On this page
Quick Reference
Overview and Recommendations
Background
- •Cervical cancer systemic management is stratified by clinical intent: curative-intent radiosensitization for locally advanced disease and palliative-intent combinations for metastatic or recurrent presentations.
- •The definitive standard for locally advanced cervical cancer (FIGO stages IB3–IVA) is concurrent chemoradiotherapy (CCRT) using weekly , which improves 5-year survival by 6% compared to radiation alone (NNT = 17).
- •The metastatic treatment paradigm was redefined by the KEYNOTE-826 trial (2021), which established the 'quadruplet' regimen—platinum, , , and —as the first-line standard for PD-L1-positive disease.
- •Angiogenesis inhibition via remains a cornerstone of therapy for advanced disease, providing a 3.7-month median overall survival benefit, though it carries specific risks of gastrointestinal fistulas and hypertension.
- •Second-line therapy has evolved with the introduction of , an antibody-drug conjugate targeting tissue factor, which provides a 30% reduction in the risk of death compared to single-agent chemotherapy in pretreated patients.
- •Human papillomavirus (HPV) integration drives the molecular landscape, but treatment selection is currently guided by PD-L1 Combined Positive Score (CPS) and prior platinum exposure rather than HPV subtype.
Evaluation
- •Suspect advanced disease in patients with persistent vaginal bleeding, pelvic pain, or obstructive uropathy; perform a thorough pelvic examination and biopsy for histological confirmation.
- •Order FIGO staging workup including pelvic MRI and PET/CT to differentiate between locally advanced disease (amenable to CCRT) and metastatic disease (requiring systemic therapy).
- •Perform PD-L1 immunohistochemistry (IHC) testing on primary or metastatic tissue to determine the Combined Positive Score (CPS); a CPS ≥1 is the threshold for initiating first-line .
- •Assess renal function via calculated creatinine clearance (CrCl) before every cycle of platinum therapy; is the preferred radiosensitizer but requires CrCl ≥60 mL/min.
- •Evaluate for contraindications to anti-angiogenic therapy, specifically checking for tumor invasion of the bladder or rectum, history of major bleeding, or non-healing wounds, which increase the risk of -induced fistulas.
- •Screen for baseline peripheral neuropathy using the performance status and physical exam, as taxanes and platinums can exacerbate pre-existing nerve damage.
- •Obtain a baseline ophthalmic examination (including visual acuity and slit-lamp exam) if considering , as ocular toxicity is a dose-limiting adverse effect.
- •Verify HIV status in all patients, as people living with HIV (PLWH) have higher mortality rates and require close coordination with infectious disease specialists to manage drug-drug interactions with antiretroviral therapy (ART).
Management
- •Initiate concurrent chemoradiotherapy for locally advanced disease: Administer 40 mg/m² IV weekly for 5–6 cycles during external beam radiotherapy.
- •Avoid adjuvant chemotherapy following CCRT; the OUTBACK trial confirmed that adding carboplatin/paclitaxel after definitive CCRT increases toxicity without improving overall survival.
- •Utilize 30 mg/m² weekly as an alternative radiosensitizer in patients with mild renal impairment or those unable to tolerate the emetogenic profile of cisplatin.
- •Prescribe the first-line 'quadruplet' for metastatic PD-L1+ (CPS ≥1) disease: 200 mg + 175 mg/m² + 50 mg/m² (or AUC 5) + 15 mg/kg every 3 weeks.
- •Omit in the first-line setting if the PD-L1 CPS is <1, utilizing the triplet of platinum, paclitaxel, and bevacizumab instead.
- •Select the platinum backbone based on prior exposure: Use AUC 5 for patients who previously received cisplatin during CCRT; use 50 mg/m² for platinum-naive metastatic disease.
- •Administer 2.0 mg/kg (max 200 mg) IV every 3 weeks as the preferred second-line agent for patients progressing on or after platinum-based chemotherapy.
- •Implement a strict ocular prophylaxis protocol for tisotumab vedotin: Use vasoconstrictor eye drops (e.g., naphazoline) during infusion, followed by steroid and lubricating drops for 72 hours post-infusion.
- •Manage immune-related adverse events (irAEs) from by monitoring for pneumonitis, colitis, and thyroiditis; initiate high-dose steroids (prednisone 1–2 mg/kg) for Grade 3+ toxicities.
- •Monitor blood pressure and urine protein-to-creatinine ratio every cycle for patients on ; withhold therapy for Grade 3 hypertension or proteinuria >2g/24h.
- •Provide aggressive emesis prophylaxis for cisplatin-containing regimens: Use a three-drug regimen of an NK-1 receptor antagonist (e.g., 150 mg), a 5-HT3 antagonist, and .
- •Treat neuropathic pain from paclitaxel or cisplatin with 300–600 mg TID or 30–60 mg daily.
- •Refer patients with persistent or recurrent pelvic-only disease for evaluation of pelvic exenteration if they are not candidates for further radiation or systemic therapy.
- •Maintain antiretroviral therapy in PLWH throughout systemic treatment; do not dose-reduce chemotherapy based solely on HIV status if the performance status is adequate.
Board Review — High Yield
- •KEYNOTE-826 — Landmark trial establishing pembrolizumab + chemotherapy ± bevacizumab as 1L standard for PD-L1+ metastatic cervical cancer.
- •GOG 240 — Trial that proved adding bevacizumab to chemotherapy doublets improves OS in metastatic disease.
- •OUTBACK Trial — Demonstrated that adjuvant chemotherapy after CCRT provides no survival benefit and should be avoided.
- •Tisotumab vedotin — Antibody-drug conjugate targeting Tissue Factor; requires strict eye drop prophylaxis to prevent conjunctivitis/keratitis.
- •Sedlis Criteria — Pathological features (tumor size, lymphovascular space invasion, depth of invasion) used to determine the need for adjuvant RT after hysterectomy.
- •Peters Criteria — High-risk features (positive margins, positive nodes, parametrial involvement) that mandate adjuvant CCRT.
- •Cisplatin Radiosensitization — Mechanism involves inhibiting the repair of radiation-induced DNA damage; standard dose is 40 mg/m² weekly.
- •PD-L1 CPS — The ratio of PD-L1 staining cells (tumor, lymphocytes, macrophages) to total viable tumor cells; CPS ≥1 is the cutoff for pembrolizumab in 1L.
Deep Dive — Evidence Details
Setting-Based Framework
- ▸Weekly cisplatin 40 mg/m² is the standard radiosensitizer for locally advanced disease, providing a 6% absolute survival benefit at 5 years.
- ▸Adjuvant chemotherapy after definitive CCRT does not improve survival and is not recommended as standard care.
- ▸First-line metastatic therapy requires a triplet or quadruplet regimen including pembrolizumab for PD-L1-positive disease.
Systemic therapy for is categorized by clinical setting, with strategies ranging from curative-intent radiosensitization to palliative-intent triplet or quadruplet regimens. The framework is dictated by disease stage, prior treatment exposure, and molecular markers such as PD-L1 status [1]A1c[50]A1c.
Definitive and Adjuvant Settings in Locally Advanced Disease
-based concurrent chemoradiotherapy (CCRT) is the definitive standard for locally advanced cervical cancer (LACC) [1]A1c[53]D5. Weekly cisplatin 40 mg/m² (up to 6 cycles) concurrent with radiation improves 5-year survival by 6% compared to radiation alone (HR 0.71, 95% CI 0.64-0.80); NNT = 17 to prevent one death at 5 years [8]A1a. While tri-weekly cisplatin 75 mg/m² is an alternative, the TACO trial supports weekly dosing as the preferred schedule due to comparable efficacy and manageable toxicity [22]A1b. Adjuvant chemotherapy after CCRT lacks a survival benefit; the OUTBACK trial showed no improvement in 5-year overall survival (OS) with the addition of and (72% vs 71%; HR 0.91, 95% CI 0.70-1.18) [24]A1b.
Neoadjuvant Strategies and Surgical Integration
Neoadjuvant chemotherapy (NACT) followed by radical surgery (NACT-S) is generally not superior to standard CCRT. The EORTC-55994 trial demonstrated 5-year OS rates of 72% for NACT-S versus 76% for CCRT, confirming CCRT as the preferred curative approach [10]A1b. NACT-S may be considered primarily in resource-limited settings where access to radiation therapy is restricted [9]A1b.
First-Line Framework for Advanced Disease
First-line treatment for persistent, recurrent, or metastatic disease utilizes platinum-based doublets combined with immunotherapy and antiangiogenic agents. The KEYNOTE-826 trial established 200 mg every 3 weeks plus chemotherapy (paclitaxel 175 mg/m² with cisplatin 50 mg/m² or carboplatin AUC 5) ± 15 mg/kg as the standard of care [28]A1b[67]A1b. This combination reduced the risk of death by 37% in patients with a PD-L1 Combined Positive Score (CPS) ≥1 (HR 0.63, 95% CI 0.52-0.77); NNT = 9 to prevent one death at 24 months [28]A1b[67]A1b.
Subsequent Lines and Targeted Salvage
Second-line options focus on antibody-drug conjugates (ADCs) and immunotherapy for patients who progressed on first-line doublets. Tisotumab vedotin 2.0 mg/kg every 3 weeks is the preferred ADC, showing a 30% reduction in the risk of death compared to single-agent chemotherapy (HR 0.70, 95% CI 0.54-0.89); NNT = 8 to prevent one death at 12 months [29]A1b. For patients who are immunotherapy-naïve, cemiplimab 350 mg every 3 weeks provides a survival benefit regardless of PD-L1 status (HR 0.69, 95% CI 0.56-0.84) [30]A1b.
Controversies and Guideline Disagreement
| Question | Position A (NCCN/ESMO) | Position B (Alternative) | Strength | Implication |
|---|---|---|---|---|
| Role of NACT-S | CCRT is the definitive standard for LACC [1]A1c[10]A1b[53]D5. | NACT-S is used where RT is unavailable [9]A1b. | Level 1b | NACT-S is not superior and may delay curative RT [10]A1b. |
Pearl: Cisplatin-based CCRT is the curative backbone for locally advanced disease, as adjuvant chemotherapy adds toxicity without survival benefit [24]A1b; in the metastatic setting, the addition of pembrolizumab to platinum-doublets has redefined first-line survival expectations [28]A1b[67]A1b.
| Setting | Regimen | Dose/Schedule |
|---|---|---|
| Concurrent (LACC) | Cisplatin | 40 mg/m² IV weekly (max 6 cycles) [1]A1c[22]A1b |
| 1st Line (Metastatic) | Pembrolizumab + Chemo ± Bevacizumab | Pembrolizumab 200 mg Q3W; Bevacizumab 15 mg/kg Q3W [28]A1b[67]A1b |
| 2nd Line (Metastatic) | Tisotumab Vedotin | 2.0 mg/kg IV Q3W [29]A1b[40]C4 |
| 2nd Line (Metastatic) | Cemiplimab | 350 mg IV Q3W [30]A1b |
Concurrent Chemotherapy with RT
- ▸Weekly cisplatin 40 mg/m² is the preferred radiosensitizer over tri-weekly dosing due to its established efficacy and toxicity profile [22, 103].
- ▸Adjuvant CCRT is indicated for high-risk post-surgical patients (Peters criteria) and increasingly for intermediate-risk patients (GOG-263) [98, 107].
- ▸Nedaplatin 30 mg/m² is a validated alternative for patients with renal impairment who cannot tolerate cisplatin [124].
Weekly at 40 mg/m² serves as the definitive radiosensitizer for locally advanced disease, a role established by multiple phase III trials demonstrating a significant survival advantage over radiation alone [103]A1b (1b). The NCCN v.3.2019 and ESMO 2024 guidelines recommend concurrent chemoradiotherapy (CCRT) as the standard of care for FIGO stages IB3–IVA [1]A1c[97]A1c[120]A1c. This approach utilizes the synergistic effects of platinum-based agents to inhibit the repair of radiation-induced DNA damage, thereby enhancing local tumor control [126]D5.
Step-by-Step Protocol
- Initial Risk Stratification: Identify patients with locally advanced (LACC) or those post- with high-risk features (positive margins, positive nodes, or parametrial involvement) [1]A1c[107]A1b.
- Initiate Weekly Cisplatin: Administer cisplatin 40 mg/m² IV weekly for 5–6 cycles concurrent with ( ) [1]A1c[22]A1b. The TACO trial (N=314) confirmed that weekly dosing is non-inferior to tri-weekly dosing (75 mg/m²) and remains the preferred schedule due to manageable toxicity [22]A1b (1b).
- Alternative for Renal Impairment: In patients with baseline renal dysfunction or intolerance to cisplatin, ESMO and NCCN suggest nedaplatin 30 mg/m² weekly [105]A1b[124]A1a. A meta-analysis of RCTs showed nedaplatin provides comparable 3-year overall survival (OS) with significantly reduced nephrotoxicity [124]A1a (1a).
- Incorporate : Ensure the completion of image-guided adaptive brachytherapy (IGABT) following EBRT to achieve a point A dose of 85 Gy [7]A1b[39]B2b. Omission of brachytherapy significantly compromises local control and OS [128]D5.
- Monitoring and Supportive Care: Monitor weekly CBC and creatinine. Administer fosaprepitant in combination with palonosetron and to prevent radiation-induced nausea and vomiting [106]A1b (1b).
Controversies and Guideline Disagreement
| Question | Position A | Position B | Strength | Implication |
|---|---|---|---|---|
| Adjuvant CRT for intermediate risk | NCCN/GOG-263 — Recommend adjuvant CRT for intermediate-risk factors (Sedlis criteria) [98]A1b | Traditional Practice — Adjuvant RT alone was standard; CRT was reserved for high-risk (Peters criteria) [130]B3b | Moderate | GOG-263 results (2025) support adding cisplatin to improve RFS in intermediate-risk disease [98]A1b. |
| Sequential vs. Concurrent Adjuvant Therapy | STARS Trial — Sequential chemoradiation (SCRT) improved 5-year OS (92% vs 86%) compared to CCRT [107]A1b | Standard Guidelines — CCRT remains the global standard for high-risk postoperative patients [1]A1c[120]A1c | Moderate | SCRT may offer superior systemic control but requires validation in non-Asian populations [107]A1b. |
| Role of Immunotherapy in LACC | CALLA Trial — Addition of to CCRT did not improve PFS [23]A1b | Ongoing Research — Meta-analyses suggest potential benefit of ICIs in specific subgroups [63]A1a[125]A1a | Mild | CCRT alone remains the standard; durvalumab is not currently recommended for LACC [23]A1b. |
Pearl: Weekly cisplatin at 40 mg/m² is the definitive radiosensitizer for LACC; adding adjuvant chemotherapy after the completion of CCRT does not improve survival and should be avoided (OUTBACK trial, HR 1.01) [24]A1b.
| Drug | Starting Dose | Target Cycles | Renal Adjustment | Key Monitoring |
|---|---|---|---|---|
| Cisplatin | 40 mg/m² IV weekly | 5–6 | eGFR <60: Consider alternative | Cr, CBC, Mg2+ |
| Nedaplatin | 30 mg/m² IV weekly | 5–6 | Reduced nephrotoxicity vs cisplatin | CBC, Cr |
| Lobaplatin | 30 mg/m² IV q3w | 2 | Preferred in elderly (≥65y) [112]A1b | Platelets, Cr |
| Strategy | Indication | Outcome (5-yr OS) | Evidence Level |
|---|---|---|---|
| CCRT (Cisplatin) | High-risk (Peters) | 86% (HR 0.65 vs RT) [107]A1b | 1b (NNT=25) |
| SCRT (Sequential) | High-risk (Peters) | 92% (HR 0.52 vs RT) [107]A1b | 1b (NNT=10) |
| RT Alone | Intermediate-risk | 82% [107]A1b | 1b |
Chemotherapy Regimens
- ▸Pembrolizumab plus platinum-paclitaxel is the first-line standard for PD-L1 CPS ≥1 recurrent or metastatic cervical cancer [28, 67].
- ▸Tisotumab vedotin is the preferred second-line agent following progression on platinum and immunotherapy [29, 137].
- ▸Adjuvant chemotherapy following definitive chemoradiotherapy does not improve survival in locally advanced disease [24].
Platinum-based doublets combined with and constitute the current standard of care for persistent, recurrent, or metastatic [3]A1b[28]A1b[31]A1b. The therapeutic landscape has transitioned from single-agent to multi-agent regimens that integrate inhibition and to overcome the relative chemoresistance often seen in patients previously treated with concurrent chemoradiotherapy (CCRT) [31]A1b[52]D5[79]D5.
First-Line Systemic Therapy
For patients with persistent, recurrent, or metastatic disease, the KEYNOTE-826 trial established the addition of pembrolizumab 200 mg every 3 weeks to platinum-based chemotherapy (cisplatin or ) and , with or without bevacizumab, as the preferred first-line regimen [28]A1b[67]A1b. In patients with a PD-L1 Combined Positive Score (CPS) ≥1, the addition of pembrolizumab reduced the risk of death by 40% (OS HR 0.60, 95% CI 0.49–0.74) compared to chemotherapy alone; NNT = 9 to prevent one death at 24 months [67]A1b (1b). This benefit was observed regardless of bevacizumab use [3]A1b.
Prior to the integration of immunotherapy, the GOG 240 trial demonstrated that adding bevacizumab 15 mg/kg to chemotherapy doublets significantly improved overall survival (OS) from 13.3 to 17.0 months (HR 0.71, 95% CI 0.54–0.95) [31]A1b[43]A1b (1b). The NCCN v1.2024 guidelines recommend the triplet of carboplatin (AUC 5), paclitaxel (175 mg/m²), and bevacizumab (15 mg/kg) as a Category 1 option, particularly for patients who have previously received cisplatin as a radiosensitizer [11]A1b[50]A1c[51]A1c.
Second-Line and Subsequent Therapies
When disease progresses after first-line therapy, options become more limited, but the emergence of (ADCs) has provided new efficacy. The innovaTV 301 trial showed that tisotumab vedotin 2.0 mg/kg every 3 weeks significantly improved OS compared to investigator's choice chemotherapy (11.5 vs 9.5 months; HR 0.70, 95% CI 0.54–0.89); NNT = 8 to prevent one death at 12 months [29]A1b[137]A1b (1b).
For patients who have not previously received immunotherapy, cemiplimab 350 mg every 3 weeks is recommended regardless of PD-L1 status based on improved OS compared to chemotherapy (HR 0.69, 95% CI 0.56–0.84) [59]C4[141]A1c (1b). Other options for later-line therapy include single-agent topotecan, vinorelbine, or , though response rates are typically low (20-30%) [27]B2b[73]D5[144]D5.
Neoadjuvant and Adjuvant Sequential Chemotherapy
The role of systemic chemotherapy outside the metastatic setting remains controversial. The EORTC-55994 trial compared neoadjuvant chemotherapy (NACT) followed by surgery against standard CCRT in stage IB2–IIB disease and found no OS benefit for the NACT-surgery approach (5-year OS 72% vs 76%, HR 1.15) [10]A1b (1b). Similarly, the OUTBACK trial demonstrated that adding 4 cycles of adjuvant carboplatin and paclitaxel after standard CCRT did not improve 5-year OS (72% vs 71%, HR 0.91, 95% CI 0.70–1.18) [24]A1b (1b). However, the STARS trial suggested that sequential chemoradiation (SCRT) might improve disease-free survival (DFS) compared to CCRT alone in early-stage patients with high-risk pathological factors (3-year DFS 90.0% vs 82.0%; NNT = 13) [107]A1b (1b).
Controversies and Guideline Disagreement
| Question | Position A | Position B | Strength | Implication |
|---|---|---|---|---|
| Preferred Platinum Backbone in 1L | JCOG0505: Carboplatin is non-inferior to cisplatin in OS (HR 0.99) and better tolerated [11]A1b. | JCOG0505 Subgroup: Cisplatin remains superior in platinum-naive patients (HR 1.57 for carboplatin) [11]A1b. | Moderate | Carboplatin is preferred for prior cisplatin exposure; cisplatin may be better for primary metastatic disease. |
| Role of NACT in LACC | NACI Study: Neoadjuvant + chemo shows high pCR rates (39.5%) and ORR (97.4%) [42]C4. | EORTC-55994: NACT followed by surgery is not superior to standard CCRT [10]A1b. | Strong | NACT is not standard of care but is an area of active investigation with immunotherapy. |
Dosing Table
| Drug | Starting dose | Target / max dose | Renal adjustment | Hepatic adjustment | Key monitoring |
|---|---|---|---|---|---|
| Cisplatin | 50 mg/m² IV | 50 mg/m² Q3W | CrCl <60: avoid or reduce | No adjustment | Cr, Mg, K, hearing |
| Carboplatin | AUC 5 IV | AUC 5–6 Q3W | eGFR <30: avoid | No adjustment | CBC, Cr |
| Paclitaxel | 175 mg/m² IV | 175 mg/m² Q3W | No adjustment | B/C: reduce | Neuropathy, ANC |
| Bevacizumab | 15 mg/kg IV | 15 mg/kg Q3W | No adjustment | No adjustment | BP, Urine protein |
| Pembrolizumab | 200 mg IV | 200 mg Q3W or 400 mg Q6W | No adjustment | No adjustment | LFTs, TSH, Glucose |
| Tisotumab vedotin | 2.0 mg/kg IV | Max 200 mg Q3W | No adjustment | Child-Pugh B/C: avoid | Ocular exam, CBC |
Caption: Figure 1: algorithm for first- and second-line systemic therapy in recurrent/metastatic cervical cancer (adapted from [28]A1b[29]A1b[50]A1c).
Pearl: The addition of pembrolizumab to platinum-paclitaxel (± bevacizumab) is the first-line standard for PD-L1 CPS ≥1 disease, reducing mortality by 40% (KEYNOTE-826) [67]A1b. For second-line therapy, tisotumab vedotin is the first ADC to demonstrate a survival benefit over conventional chemotherapy (innovaTV 301) [29]A1b.
| Regimen | Setting | Key Trial | Outcome (OS) | Evidence Level |
|---|---|---|---|---|
| Pembro + Chemo ± Bev | 1L R/M | KEYNOTE-826 | HR 0.60 (CPS ≥1) [67]A1b | 1b |
| Chemo + Bevacizumab | 1L R/M | GOG 240 | 17.0 vs 13.3 mo [31]A1b | 1b |
| Tisotumab Vedotin | 2L+ R/M | innovaTV 301 | HR 0.70 [29]A1b | 1b |
| Cemiplimab | 2L+ R/M | EMPOWER-Cervical 1 | HR 0.69 [59]C4 | 1b |
Targeted and Immune Therapy
- ▸Pembrolizumab plus chemotherapy is the first-line standard for PD-L1-positive (CPS ≥1) recurrent or metastatic cervical cancer.
- ▸Bevacizumab improves overall survival when added to chemotherapy doublets, with a median OS benefit of 3.7 months.
- ▸Tisotumab vedotin is the preferred second-line ADC for patients progressing after platinum-based therapy.
Survival in persistent, recurrent, or metastatic disease significantly improves with the addition of or to platinum-based doublets [3]A1b[31]A1b (1b). These agents target the molecular drivers of cervical carcinogenesis, specifically the pro-angiogenic vascular endothelial growth factor (VEGF) and the immune-evasive programmed death-1 (PD-1) pathway [72]D5[77]D5 (5). The NCCN v1.2024 and ESMO 2024 guidelines now mandate PD-L1 testing for all patients with advanced disease to guide the selection of first-line immunotherapy [3]A1b[28]A1b.
First-Line Targeted and Immune Combinations
Pembrolizumab 200 mg IV every 3 weeks combined with chemotherapy ( plus or ) is the standard of care for PD-L1-positive (CPS ≥1) persistent, recurrent, or metastatic [28]A1b (1b). In the KEYNOTE-826 trial (N=617), this combination reduced the risk of death by 33% (HR 0.67, 95% CI 0.54–0.84) compared to chemotherapy alone; NNT = 9 to prevent one death at 24 months [28]A1b[67]A1b. The benefit of pembrolizumab is observed regardless of bevacizumab use, although the triplet of pembrolizumab, chemotherapy, and bevacizumab remains a Category 1 NCCN recommendation for eligible patients [3]A1b[36]B2b (2b).
Bevacizumab 15 mg/kg IV every 3 weeks added to chemotherapy doublets provides a significant survival advantage in the first-line setting [31]A1b (1b). The GOG 240 trial demonstrated an improvement in median overall survival from 13.3 to 17.0 months (HR 0.71, 95% CI 0.54–0.95); NNT = 7 to prevent one death at 12 months [31]A1b[157]B2b. Bevacizumab is particularly effective in patients with extra-pelvic metastases but requires careful screening for contraindications such as rectovaginal fistulas or major bleeding risk [109]B2b[157]B2b (2b).
Second-Line and Later-Line Strategies
Tisotumab vedotin 2.0 mg/kg IV every 3 weeks is the preferred second-line therapy for patients who have progressed on or after platinum-based chemotherapy [40]C4[77]D5 (4). As a tissue factor-directed (ADC), it delivers a cytotoxic monomethyl auristatin E (MMAE) payload directly to tumor cells [166]D5[184]D5 (5). In the innovaTV 204 trial, tisotumab vedotin achieved an objective response rate (ORR) of 24% (95% CI 16–33) in heavily pretreated patients [40]C4 (4). Key toxicities include ocular events (conjunctivitis, ), which necessitate a strict prophylactic eye drop protocol [40]C4[54]C4.
Pembrolizumab monotherapy 200 mg IV every 3 weeks remains an option for PD-L1-positive (CPS ≥1) disease that has progressed after first-line chemotherapy, provided the patient did not receive an ICI in the first-line setting [32]C4[174]D5 (4). The KEYNOTE-158 study reported an ORR of 14.3% (95% CI 7.4–24.1) in this population, with all responses occurring in PD-L1-positive tumors [32]C4 (4).
Step-by-Step Protocol
- Biomarker Stratification: Perform PD-L1 IHC testing on primary or metastatic tissue. Determine the Combined Positive Score (CPS).
- First-Line Selection (CPS ≥1): Initiate pembrolizumab 200 mg IV + paclitaxel 175 mg/m² + cisplatin 50 mg/m² (or carboplatin AUC 5). Add bevacizumab 15 mg/kg if there is no high risk of fistula or hemorrhage [3]A1b[28]A1b[31]A1b.
- First-Line Selection (CPS <1): Administer chemotherapy doublet + bevacizumab 15 mg/kg [31]A1b[36]B2b.
- Monitoring: Perform CT or MRI imaging every 9 weeks for the first year to assess response per v1.1 [32]C4[40]C4.
- Second-Line Escalation: Upon progression, switch to tisotumab vedotin 2.0 mg/kg IV every 3 weeks [40]C4[77]D5.
Controversies and Guideline Disagreement
| Question | Position A | Position B | Strength | Implication |
|---|---|---|---|---|
| Necessity of Bevacizumab with Pembrolizumab | NCCN v1.2024 — Recommends the triplet (Chemo+Bev+Pembro) as a preferred Category 1 option [3]A1b. | ESMO 2024 — Notes that pembrolizumab benefit is independent of bevacizumab use in subgroup analyses [3]A1b[36]B2b. | Moderate | Clinicians may omit bevacizumab in patients at high risk for fistulas without compromising pembrolizumab efficacy. |
| PD-L1 Threshold for 1L ICI | US FDA / NCCN — Requires CPS ≥1 for pembrolizumab use in the first-line setting [28]A1b[173]D5. | Emerging Data — Some trials suggest ICIs may have activity in PD-L1-negative tumors when combined with chemo [3]A1b[62]A1a. | Mild | Current standard remains restricted to CPS ≥1; clinical trials are needed for CPS <1. |
Pearl: Add pembrolizumab to first-line chemotherapy for all PD-L1-positive (CPS ≥1) recurrent or metastatic cases to achieve a 33% reduction in mortality risk (KEYNOTE-826) [28]A1b[67]A1b.
| Drug | Starting Dose | Target / Max Dose | Renal Adjustment | Hepatic Adjustment | Key Monitoring |
|---|---|---|---|---|---|
| Pembrolizumab | 200 mg IV Q3W | 400 mg IV Q6W | No adjustment | No adjustment | Immune-related AEs (TSH, LFTs) |
| Bevacizumab | 15 mg/kg IV Q3W | 15 mg/kg IV Q3W | No adjustment | No adjustment | BP, Proteinuria, Bleeding |
| Tisotumab Vedotin | 2.0 mg/kg IV Q3W | Max 200 mg | No data for CrCl <30 | Avoid in moderate/severe impairment | Ocular exam, Neuropathy |
| Option | Indication | ORR | Key Trial | Evidence Level |
|---|---|---|---|---|
| Tisotumab Vedotin | 2L+ R/M CC | 24% | innovaTV 204 | 4 [40]C4 |
| Pembrolizumab | 2L+ CPS ≥1 | 14% | KEYNOTE-158 | 4 [32]C4 |
| Cadonilimab | 1L/2L R/M CC | 60-90% (w/ chemo) | COMPASSION-13 | 4 [55]C4[190]B2b |
Toxicity and Supportive Care
- ▸Bevacizumab increases the risk of GI fistulas (NNH=20) and grade 3+ hypertension (25% vs 2%), requiring strict blood pressure control and monitoring for bowel perforation.
- ▸Fosaprepitant (150 mg IV) combined with palonosetron and dexamethasone significantly improves complete emetic response (NNT=8) during concurrent chemoradiotherapy.
- ▸Tisotumab vedotin requires strict adherence to an ocular care bundle (topical steroids, vasoconstrictors, and cooling) to prevent severe conjunctivitis and keratitis.
Grade 3 or higher treatment-related adverse events (TRAEs) occur in approximately 48% to 82% of patients receiving modern triplet or quadruplet regimens [28]A1b[31]A1b. While significantly improves survival, it increases the risk of (GI) fistulas from 1% to 6% (NNH = 20) and grade 3+ from 2% to 25% [31]A1b[43]A1b. Immune checkpoint inhibitors (ICIs) introduce unique immune-related adverse events (irAEs), including pneumonitis, colitis, and thyroiditis, which require prompt steroid intervention [28]A1b[30]A1b[200]B2a.
Respiratory Monitoring
Monitoring for immune-related pneumonitis is critical during therapy with or cemiplimab, as early-grade symptoms often mimic infection or disease progression [28]A1b[30]A1b. Severe pneumonitis (Grade 3+) necessitates permanent discontinuation of immunotherapy and high-dose corticosteroids (1–2 mg/kg/day equivalent).
| Clinical Status | Monitoring/Action | Threshold for Intervention |
|---|---|---|
| Stable/Asymptomatic | at each visit | SpO2 <92% on room air |
| Symptomatic (G2) | High-resolution CT (HRCT) | New interstitial infiltrates |
| Severe (G3-4) | ICU admission; FVC monitoring | FVC <15 mL/kg or 30% decline |
| Impending Failure | Mechanical ventilation | PaO2 <60 mmHg or pH <7.25 |
Autonomic Complications
Autonomic dysfunction in patients typically arises from platinum-induced neuropathy or paraneoplastic syndromes [103]A1b[124]A1a. -induced may manifest as orthostatic hypotension, resting tachycardia, or severe constipation/ileus. includes adequate hydration, compression stockings, and potentially midodrine for refractory hypotension. Tri-weekly cisplatin (75 mg/m²) may increase acute toxicity compared to weekly dosing (40 mg/m²), though long-term autonomic outcomes are similar [22]A1b.
DVT/PE Prophylaxis
Cervical cancer patients are at high risk for due to pelvic tumor burden and systemic therapy [31]A1b. For hospitalized patients or those undergoing major surgery, 40 mg SC daily or Dalteparin 5000 units SC daily is the standard of care. Bevacizumab further increases the risk of arterial thromboembolism, necessitating vigilant monitoring for stroke or myocardial infarction [31]A1b[157]B2b.
Pain Management
Pain management follows the WHO analgesic ladder, addressing visceral pelvic pain, bone metastases, and neuropathic pain. Neuropathic pain from or cisplatin is managed with Gabapentin (300–600 mg TID) or Duloxetine (30–60 mg daily). Bone pain may require bisphosphonates or palliative radiotherapy in addition to opioids. Tisotumab vedotin-induced neuropathy (Grade 3+ in 2%) may require dose delays or reductions to 1.3 mg/kg [54]C4.
Rehabilitation
Early rehabilitation and physical therapy should begin during the first cycle of systemic therapy to mitigate cancer-related fatigue and functional decline. Modalities include pelvic floor physical therapy for post-radiation fibrosis and aerobic exercise to improve cardiovascular reserve. Multidisciplinary teams are essential, particularly for older women (≥65 years) who face higher rates of treatment-related morbidity [113]B2c.
Hospital-Acquired Complications
Prevention of hospital-acquired complications focuses on "bundles" for pneumonia and urinary tract infections (UTIs). Given the frequency of ureteral obstruction in advanced disease, UTI prevention is paramount in patients with nephrostomy tubes or ureteral stents. Pressure injury prevention is critical for patients with limited mobility due to advanced pelvic disease or treatment-related fatigue.
Controversies and Guideline Disagreement
| Question | Position A (NCCN/ASCO) | Position B (JGOG/East Asia) | Strength | Implication |
|---|---|---|---|---|
| Platinum Choice | Cisplatin is the gold standard [2]A1c[103]A1b. | Nedaplatin is a valid alternative [124]A1a. | Moderate | Nedaplatin reduces nephrotoxicity [124]A1a. |
| Cisplatin Schedule | Weekly 40 mg/m² is standard [2]A1c. | Tri-weekly 75 mg/m² is non-inferior [22]A1b. | High | Tri-weekly may be more convenient but toxic [22]A1b. |
Pearl: Aggressive emesis prophylaxis with NK-1 receptor antagonists like fosaprepitant (NNT=8) and vigilant monitoring for bevacizumab-induced GI fistulas (NNH=20) are essential to maintain treatment intensity and quality of life [31]A1b[106]A1b.
| Complication | Frequency | Prevention | Management |
|---|---|---|---|
| Emesis (Cisplatin) | >90% (without prophylaxis) | Fosaprepitant 150mg IV + 5-HT3 RA [106]A1b | Olanzapine 5-10mg; Rescue antiemetics |
| GI Fistula (Bevacizumab) | 6% [31]A1b | Avoid in patients with bowel invasion | Surgical consultation; Discontinue drug |
| Ocular Toxicity (TV) | 25-30% [54]C4 | Steroid drops; Cold packs; Lubricants | Dose reduction to 1.3 mg/kg; Ophthalmology referral |
| Nephrotoxicity (Cisplatin) | 20-30% | Aggressive hydration; Nedaplatin alternative [124]A1a | Dose reduction; Switch to Carboplatin |
| irAEs (ICIs) | 15-20% (Grade 3+) [28]A1b[30]A1b | Patient education; Early detection | Prednisone 1-2 mg/kg; Infliximab for colitis |
Special Populations
- ▸PLWH should receive standard-of-care systemic therapy, including immunotherapy, provided ART is maintained and drug-drug interactions are managed.
- ▸Carboplatin (AUC 5) is the mandatory substitute for cisplatin in patients with creatinine clearance <60 mL/min to prevent nephrotoxicity.
- ▸Performance status 2 patients may benefit from modified regimens or oral fluoropyrimidines like S-1 when platinum doublets are not tolerated.
HIV-infected individuals experience significantly higher mortality rates due to advanced stage at presentation and systemic treatment disparities [2]A1c[69]D5[121]B2b. While cervical cancer is a primary AIDS-defining illness, survival deficits in people living with HIV (PLWH) are often driven by the non-receipt of standard therapy (aOR 0.58, 95% CI 0.45–0.75) rather than inherent resistance to treatment [213]B2c.
Immunocompromised and HIV-Positive Populations
NCCN Guidelines mandate that PLWH receive the same stage-specific systemic therapy as HIV-negative patients, provided their performance status is adequate [2]A1c. Coordination with HIV specialists is essential to manage potential drug-drug interactions between (ART) and cytotoxic agents, particularly those involving the cytochrome P450 system [2]A1c[69]D5. Standard regimens, including 200 mg every 3 weeks and 15 mg/kg, should be utilized alongside ART to maintain CD4+ counts and prevent opportunistic infections [2]A1c[3]A1b[31]A1b.
Elderly and Poor Performance Status
Patients with an Eastern Cooperative Oncology Group ( ) performance status (PS) of 2 or higher require careful regimen selection. While pivotal trials like KEYNOTE-826 focused on PS 0–1, phase II data support the use of bevacizumab 15 mg/kg in PS 2 patients with manageable toxicity [3]A1b[157]B2b. For elderly patients or those with significant frailty, oral fluoropyrimidines such as S-1 (35 mg/m² twice daily for 28 days) offer an alternative, demonstrating an objective response rate of 30.6% [15]C4.
Renal Impairment
Cisplatin-induced nephrotoxicity is a major constraint in cervical cancer due to frequent ureteral obstruction. In patients with a creatinine clearance <60 mL/min, (AUC 5) is the preferred substitute for to mitigate the risk of acute kidney injury [27]B2b[31]A1b. Bevacizumab added to chemotherapy reduced the risk of death by 29% (HR 0.71, 95% CI 0.54–0.95); NNT is not calculable from reported data [31]A1b.
Pregnancy and Pediatrics
Systemic therapy during pregnancy is generally deferred until after the first trimester to avoid teratogenicity. Platinum-based "chemobridge" therapy may be initiated after 14 weeks gestation to delay definitive surgery or radiation until fetal maturity is reached [207]B3b. Pediatric cases are extremely rare and require weight-based dosing of adult protocols with intensive monitoring for long-term developmental sequelae.
Pearl: HIV status alone should never preclude standard-of-care systemic therapy, as survival deficits in PLWH are primarily driven by treatment inequities rather than inherent chemoresistance [2]A1c[121]B2b[213]B2c.
| Population | Clinical Modification | Rationale |
|---|---|---|
| HIV-Positive | Standard-of-care + ART | Address treatment disparities; prevent AIDS progression [2]A1c[213]B2c |
| Renal Impairment | Carboplatin (AUC 5) | Avoid cisplatin-induced nephrotoxicity [31]A1b |
| Elderly/Frailty | S-1 (35 mg/m²) or dose-reduced doublets | Balance efficacy with toxicity profile [15]C4[157]B2b |
| Pregnancy | Delay chemo until >14 weeks | Avoid first-trimester teratogenicity [207]B3b |
Related Pages
Part of the Cervical Cancer family. Cross-cutting management is split across dedicated child pages:
- Cervical Cancer — diagnostic page (definition, epidemiology, staging, biomarkers, prognosis)
- — operations by stage, fertility-sparing options, sentinel node mapping, adjuvant triggers (Sedlis / Peters)
- — EBRT + image-guided brachytherapy + concurrent chemoradiation, dose / fractionation, OAR constraints
- — early integration, symptom management, palliative procedures, end-of-life care
- — post-treatment surveillance schedule, late toxicity, survivorship, patient counselling
- — local-regional salvage, distant metastatic systemic therapy, oligometastatic disease
Pearl: Use these links to hop between management modalities; the parent Cervical Cancer page carries diagnosis + staging that informs every decision here.
References
- [1]
Koh WJ, Abu-Rustum NR, Bean S et al.. “Cervical Cancer, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology.” Journal of the National Comprehensive Cancer Network : JNCCN (2019). PMID: 30659131 ↗
L1GUIDELINECited in: Setting-Based Framework, Concurrent Chemotherapy with RT, Chemotherapy Regimens - [2]
Reid E, Suneja G, Ambinder RF et al.. “Cancer in People Living With HIV, Version 1.2018, NCCN Clinical Practice Guidelines in Oncology.” Journal of the National Comprehensive Cancer Network : JNCCN (2018). PMID: 30099375 ↗
L1GUIDELINECited in: Setting-Based Framework, Toxicity and Supportive Care, Special Populations - [3]
Lorusso D, Colombo N, Dubot C et al.. “Pembrolizumab plus chemotherapy for advanced and recurrent cervical cancer: final analysis according to bevacizumab use in the randomized KEYNOTE-826 study.” Annals of oncology : official journal of the European Society for Medical Oncology (2025). PMID: 39393777 ↗
L1RCTCited in: Setting-Based Framework, Chemotherapy Regimens, Targeted and Immune Therapy, Special Populations - [4]
Mayadev J, Vázquez Limón JC, Ramírez Godinez FJ et al.. “Ultrasensitive detection and tracking of circulating tumor DNA to predict relapse and survival in patients with locally advanced cervical cancer: phase III CALLA trial analyses.” Annals of oncology : official journal of the European Society for Medical Oncology (2025). PMID: 40500687 ↗
L1RCTCited in: Setting-Based Framework, Concurrent Chemotherapy with RT, Chemotherapy Regimens - [5]
Lissoni AA, Colombo N, Pellegrino A et al.. “A phase II, randomized trial of neo-adjuvant chemotherapy comparing a three-drug combination of paclitaxel, ifosfamide, and cisplatin (TIP) versus paclitaxel and cisplatin (TP) followed by radical surgery in patients with locally advanced squamous cell cervical carcinoma: the Snap-02 Italian Collaborative Study.” Annals of oncology : official journal of the European Society for Medical Oncology (2009). PMID: 19181826 ↗
L1RCTCited in: Setting-Based Framework, Concurrent Chemotherapy with RT, Chemotherapy Regimens - [6]
Sehouli J, Runnebaum IB, Fotopoulou C et al.. “A randomized phase III adjuvant study in high-risk cervical cancer: simultaneous radiochemotherapy with cisplatin (S-RC) versus systemic paclitaxel and carboplatin followed by percutaneous radiation (PC-R): a NOGGO-AGO Intergroup Study.” Annals of oncology : official journal of the European Society for Medical Oncology (2012). PMID: 22357252 ↗
L1RCTCited in: Setting-Based Framework, Concurrent Chemotherapy with RT, Chemotherapy Regimens, Toxicity and Supportive Care - [7]
Cetina L, González-Enciso A, Cantú D et al.. “Brachytherapy versus radical hysterectomy after external beam chemoradiation with gemcitabine plus cisplatin: a randomized, phase III study in IB2-IIB cervical cancer patients.” Annals of oncology : official journal of the European Society for Medical Oncology (2013). PMID: 23609186 ↗
L1RCTCited in: Setting-Based Framework, Concurrent Chemotherapy with RT - [8]
. “Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: a systematic review and meta-analysis of individual patient data from 18 randomized trials.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2008). PMID: 19001332 ↗
L1SR_OBSCited in: Setting-Based Framework, Chemotherapy Regimens - [9]
Gupta S, Maheshwari A, Parab P et al.. “Neoadjuvant Chemotherapy Followed by Radical Surgery Versus Concomitant Chemotherapy and Radiotherapy in Patients With Stage IB2, IIA, or IIB Squamous Cervical Cancer: A Randomized Controlled Trial.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2018). PMID: 29432076 ↗
L1RCTCited in: Setting-Based Framework, Concurrent Chemotherapy with RT, Chemotherapy Regimens - [10]
Kenter GG, Greggi S, Vergote I et al.. “Randomized Phase III Study Comparing Neoadjuvant Chemotherapy Followed by Surgery Versus Chemoradiation in Stage IB2-IIB Cervical Cancer: EORTC-55994.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2023). PMID: 37656948 ↗
L1RCTCited in: Setting-Based Framework, Concurrent Chemotherapy with RT, Chemotherapy Regimens - [11]
Kitagawa R, Katsumata N, Shibata T et al.. “Paclitaxel Plus Carboplatin Versus Paclitaxel Plus Cisplatin in Metastatic or Recurrent Cervical Cancer: The Open-Label Randomized Phase III Trial JCOG0505.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2015). PMID: 25732161 ↗
L1RCTCited in: Setting-Based Framework, Concurrent Chemotherapy with RT, Chemotherapy Regimens - [12]
Xia L, Zhang K, Tang Y et al.. “Camrelizumab Plus Famitinib versus Camrelizumab Alone and Investigator's Choice of Chemotherapy in Recurrent or Metastatic Cervical Cancer: A Randomized, Phase II Study.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2025). PMID: 40561369 ↗
L1RCTCited in: Setting-Based Framework, Chemotherapy Regimens - [13]
Zhang J, Liu R, Wang S et al.. “Bulumtatug Fuvedotin (BFv, 9MW2821), a next-generation Nectin-4 targeting antibody-drug conjugate, in patients with advanced solid tumors: a first-in-human, open-label, multicenter, phase I/II study.” Annals of oncology : official journal of the European Society for Medical Oncology (2025). PMID: 40288679 ↗
L4TRIAL_NONRANDOMCited in: Setting-Based Framework, Targeted and Immune Therapy - [14]
Lorusso D, Ferrandina G, Pignata S et al.. “Evaluation of pemetrexed (Alimta, LY231514) as second-line chemotherapy in persistent or recurrent carcinoma of the cervix: the CERVIX 1 study of the MITO (Multicentre Italian Trials in Ovarian Cancer and Gynecologic Malignancies) Group.” Annals of oncology : official journal of the European Society for Medical Oncology (2010). PMID: 19605508 ↗
L4TRIAL_NONRANDOMCited in: Setting-Based Framework, Toxicity and Supportive Care - [15]
Katsumata N, Hirai Y, Kamiura S et al.. “Phase II study of S-1, an oral fluoropyrimidine, in patients with advanced or recurrent cervical cancer.” Annals of oncology : official journal of the European Society for Medical Oncology (2011). PMID: 21345941 ↗
L4TRIAL_NONRANDOMCited in: Setting-Based Framework, Toxicity and Supportive Care, Special Populations - [16]
Thaker PH, Salani R, Brady WE et al.. “A phase I trial of paclitaxel, cisplatin, and veliparib in the treatment of persistent or recurrent carcinoma of the cervix: an NRG Oncology Study (NCT#01281852).” Annals of oncology : official journal of the European Society for Medical Oncology (2017). PMID: 27998970 ↗
L4TRIAL_NONRANDOMCited in: Setting-Based Framework, Concurrent Chemotherapy with RT, Chemotherapy Regimens - [17]
Zagouri F, Korakiti AM, Zakopoulou R et al.. “Taxanes during pregnancy in cervical cancer: A systematic review and pooled analysis.” Cancer treatment reviews (2019). PMID: 31442939 ↗
L4SR_OBSCited in: Setting-Based Framework, Chemotherapy Regimens - [18]
Andrade MO, Al-Alam OCM, Kim HJS et al.. “Induction chemotherapy followed by chemoradiotherapy for locally advanced cervical cancer: A systematic review and meta-analysis.” Cancer treatment reviews (2025). PMID: 40408847 ↗
L1SR_OBSCited in: Setting-Based Framework, Concurrent Chemotherapy with RT, Chemotherapy Regimens - [19]
Tzioras S, Pavlidis N, Paraskevaidis E et al.. “Effects of different chemotherapy regimens on survival for advanced cervical cancer: systematic review and meta-analysis.” Cancer treatment reviews (2007). PMID: 17112673 ↗
L1SR_OBSCited in: Setting-Based Framework, Concurrent Chemotherapy with RT, Chemotherapy Regimens - [20]
Petrelli F, Riboldi V, Bruschieri L et al.. “First-line treatment of locally advanced cervical carcinoma: An updated systematic review and Bayesian network meta-analysis.” Cancer treatment reviews (2025). PMID: 40086103 ↗
L1SR_OBSCited in: Setting-Based Framework, Concurrent Chemotherapy with RT, Chemotherapy Regimens, Targeted and Immune Therapy - [21]
Azim HA, Peccatori FA, Pavlidis N. “Treatment of the pregnant mother with cancer: a systematic review on the use of cytotoxic, endocrine, targeted agents and immunotherapy during pregnancy. Part I: Solid tumors.” Cancer treatment reviews (2010). PMID: 20015593 ↗
L4SR_OBSCited in: Setting-Based Framework, Targeted and Immune Therapy - [22]
Ryu SY, Nam BH, Kim MH et al.. “A randomized phase III clinical trial of weekly versus tri-weekly cisplatin-based chemoradiotherapy for locally advanced cervical cancer: results of the TACO (GCIG/KGOG 1027/THAI 2012) study.” ESMO open (2026). PMID: 41812622 ↗
L1RCTCited in: Setting-Based Framework, Concurrent Chemotherapy with RT, Toxicity and Supportive Care - [23]
Monk BJ, Toita T, Wu X et al.. “Durvalumab versus placebo with chemoradiotherapy for locally advanced cervical cancer (CALLA): a randomised, double-blind, phase 3 trial.” The Lancet. Oncology (2023). PMID: 38039991 ↗
L1RCTCited in: Setting-Based Framework, Concurrent Chemotherapy with RT, Chemotherapy Regimens, Special Populations - [24]
Mileshkin LR, Moore KN, Barnes EH et al.. “Adjuvant chemotherapy following chemoradiotherapy as primary treatment for locally advanced cervical cancer versus chemoradiotherapy alone (OUTBACK): an international, open-label, randomised, phase 3 trial.” The Lancet. Oncology (2023). PMID: 37080223 ↗
L1RCTCited in: Setting-Based Framework, Concurrent Chemotherapy with RT, Chemotherapy Regimens, Special Populations - [25]
Oaknin A, Moore K, Meyer T et al.. “Nivolumab with or without ipilimumab in patients with recurrent or metastatic cervical cancer (CheckMate 358): a phase 1-2, open-label, multicohort trial.” The Lancet. Oncology (2024). PMID: 38608691 ↗
L2RCTCited in: Setting-Based Framework, Chemotherapy Regimens, Special Populations - [26]
Monk BJ, Tewari KS, Dubot C et al.. “Health-related quality of life with pembrolizumab or placebo plus chemotherapy with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer (KEYNOTE-826): a randomised, double-blind, placebo-controlled, phase 3 trial.” The Lancet. Oncology (2023). PMID: 36878237 ↗
L1RCTCited in: Setting-Based Framework, Chemotherapy Regimens, Targeted and Immune Therapy, Special Populations - [27]
Symonds RP, Gourley C, Davidson S et al.. “Cediranib combined with carboplatin and paclitaxel in patients with metastatic or recurrent cervical cancer (CIRCCa): a randomised, double-blind, placebo-controlled phase 2 trial.” The Lancet. Oncology (2015). PMID: 26474517 ↗
L2RCTCited in: Setting-Based Framework, Chemotherapy Regimens, Special Populations - [28]
Colombo N, Dubot C, Lorusso D et al.. “Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer.” The New England journal of medicine (2021). PMID: 34534429 ↗
L1RCTCited in: Setting-Based Framework, Chemotherapy Regimens, Targeted and Immune Therapy, Toxicity and Supportive Care - [29]
Vergote I, González-Martín A, Fujiwara K et al.. “Tisotumab Vedotin as Second- or Third-Line Therapy for Recurrent Cervical Cancer.” The New England journal of medicine (2024). PMID: 38959480 ↗
L1RCTCited in: Setting-Based Framework, Chemotherapy Regimens - [30]
Tewari KS, Monk BJ, Vergote I et al.. “Survival with Cemiplimab in Recurrent Cervical Cancer.” The New England journal of medicine (2022). PMID: 35139273 ↗
L1RCTCited in: Setting-Based Framework, Toxicity and Supportive Care - [31]
Tewari KS, Sill MW, Long HJ et al.. “Improved survival with bevacizumab in advanced cervical cancer.” The New England journal of medicine (2014). PMID: 24552320 ↗
L1RCTCited in: Setting-Based Framework, Concurrent Chemotherapy with RT, Chemotherapy Regimens, Targeted and Immune Therapy, Toxicity and Supportive Care, Special Populations - [32]
Chung HC, Ros W, Delord JP et al.. “Efficacy and Safety of Pembrolizumab in Previously Treated Advanced Cervical Cancer: Results From the Phase II KEYNOTE-158 Study.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2019). PMID: 30943124 ↗
L4TRIAL_NONRANDOMCited in: Setting-Based Framework, Targeted and Immune Therapy, Toxicity and Supportive Care, Special Populations - [33]
Vergote I, Van Nieuwenhuysen E, O'Cearbhaill RE et al.. “Tisotumab Vedotin in Combination With Carboplatin, Pembrolizumab, or Bevacizumab in Recurrent or Metastatic Cervical Cancer: Results From the innovaTV 205/GOG-3024/ENGOT-cx8 Study.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2023). PMID: 37651655 ↗
L4TRIAL_NONRANDOMCited in: Setting-Based Framework, Chemotherapy Regimens, Targeted and Immune Therapy - [34]
Frenel JS, Le Tourneau C, O'Neil B et al.. “Safety and Efficacy of Pembrolizumab in Advanced, Programmed Death Ligand 1-Positive Cervical Cancer: Results From the Phase Ib KEYNOTE-028 Trial.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2017). PMID: 29095678 ↗
L4TRIAL_NONRANDOMCited in: Setting-Based Framework, Chemotherapy Regimens, Targeted and Immune Therapy, Toxicity and Supportive Care - [35]
Xu Q, Wang J, Sun Y et al.. “Efficacy and Safety of Sintilimab Plus Anlotinib for PD-L1-Positive Recurrent or Metastatic Cervical Cancer: A Multicenter, Single-Arm, Prospective Phase II Trial.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2022). PMID: 35192397 ↗
L4TRIAL_NONRANDOMCited in: Setting-Based Framework, Chemotherapy Regimens - [36]
Tewari KS, Colombo N, Monk BJ et al.. “Pembrolizumab or Placebo Plus Chemotherapy With or Without Bevacizumab for Persistent, Recurrent, or Metastatic Cervical Cancer: Subgroup Analyses From the KEYNOTE-826 Randomized Clinical Trial.” JAMA oncology (2024). PMID: 38095881 ↗
L2RCTCited in: Setting-Based Framework, Concurrent Chemotherapy with RT, Chemotherapy Regimens, Targeted and Immune Therapy - [37]
Birrer M, Li G, Yunokawa M et al.. “Bintrafusp Alfa for Recurrent or Metastatic Cervical Cancer After Platinum Failure: A Nonrandomized Controlled Trial.” JAMA oncology (2024). PMID: 39052242 ↗
L4RCTCited in: Setting-Based Framework - [38]
Tabernero J, Andre F, Blay JY et al.. “Phase II multicohort study of atezolizumab monotherapy in multiple advanced solid cancers.” ESMO open (2022). PMID: 35305400 ↗
L4TRIAL_NONRANDOMCited in: Setting-Based Framework - [39]
Pötter R, Tanderup K, Schmid MP et al.. “MRI-guided adaptive brachytherapy in locally advanced cervical cancer (EMBRACE-I): a multicentre prospective cohort study.” The Lancet. Oncology (2021). PMID: 33794207 ↗
L2TRIAL_NONRANDOMCited in: Setting-Based Framework, Concurrent Chemotherapy with RT - [40]
Coleman RL, Lorusso D, Gennigens C et al.. “Efficacy and safety of tisotumab vedotin in previously treated recurrent or metastatic cervical cancer (innovaTV 204/GOG-3023/ENGOT-cx6): a multicentre, open-label, single-arm, phase 2 study.” The Lancet. Oncology (2021). PMID: 33845034 ↗
L4TRIAL_NONRANDOMCited in: Setting-Based Framework, Chemotherapy Regimens, Targeted and Immune Therapy, Special Populations - [41]
Gao X, Xu N, Li Z et al.. “Safety and antitumour activity of cadonilimab, an anti-PD-1/CTLA-4 bispecific antibody, for patients with advanced solid tumours (COMPASSION-03): a multicentre, open-label, phase 1b/2 trial.” The Lancet. Oncology (2023). PMID: 37797632 ↗
L4TRIAL_NONRANDOMCited in: Setting-Based Framework, Chemotherapy Regimens, Toxicity and Supportive Care, Special Populations - [42]
Li K, Chen J, Hu Y et al.. “Neoadjuvant chemotherapy plus camrelizumab for locally advanced cervical cancer (NACI study): a multicentre, single-arm, phase 2 trial.” The Lancet. Oncology (2024). PMID: 38048802 ↗
L4TRIAL_NONRANDOMCited in: Setting-Based Framework, Concurrent Chemotherapy with RT, Chemotherapy Regimens - [43]
Penson RT, Huang HQ, Wenzel LB et al.. “Bevacizumab for advanced cervical cancer: patient-reported outcomes of a randomised, phase 3 trial (NRG Oncology-Gynecologic Oncology Group protocol 240).” The Lancet. Oncology (2015). PMID: 25638326 ↗
L1TRIAL_NONRANDOMCited in: Setting-Based Framework, Concurrent Chemotherapy with RT, Chemotherapy Regimens, Targeted and Immune Therapy, Toxicity and Supportive Care - [44]
Youn JW, Hur SY, Woo JW et al.. “Pembrolizumab plus GX-188E therapeutic DNA vaccine in patients with HPV-16-positive or HPV-18-positive advanced cervical cancer: interim results of a single-arm, phase 2 trial.” The Lancet. Oncology (2020). PMID: 33271094 ↗
L4TRIAL_NONRANDOMCited in: Setting-Based Framework, Targeted and Immune Therapy, Toxicity and Supportive Care - [45]
Mayadev JS, Enserro D, Lin YG et al.. “Sequential Ipilimumab After Chemoradiotherapy in Curative-Intent Treatment of Patients With Node-Positive Cervical Cancer.” JAMA oncology (2020). PMID: 31774464 ↗
L4TRIAL_NONRANDOMCited in: Setting-Based Framework, Concurrent Chemotherapy with RT - [46]
Lan C, Zhang P, Zhao J et al.. “Spatiotemporal Immune Determinants of Response to Immune Rechallenge in Advanced Cervical Cancer.” Cancer discovery (2026). PMID: 41511850 ↗
L4TRIAL_NONRANDOMCited in: Setting-Based Framework, Chemotherapy Regimens - [47]
Xu Q, Deng Z, Liu J et al.. “Molecular and Immune Correlates of Response to First-Line De-escalated Chemotherapy plus Penpulimab and Anlotinib in Advanced Cervical Cancer.” Cancer discovery (2026). PMID: 41297028 ↗
L4TRIAL_NONRANDOMCited in: Setting-Based Framework, Chemotherapy Regimens - [48]
Zhong J, Wu L, Song Z et al.. “TROP-2-targeted antibody-drug conjugate SHR-A1921 for advanced or metastatic solid tumors: A first-in-human phase 1 study.” Cancer cell (2025). PMID: 41135519 ↗
L4TRIAL_NONRANDOMCited in: Setting-Based Framework, Targeted and Immune Therapy - [49]
Han K, Fyles A, Shek T et al.. “A Phase II Randomized Trial of Chemoradiation with or without Metformin in Locally Advanced Cervical Cancer.” Clinical cancer research : an official journal of the American Association for Cancer Research (2022). PMID: 36037303 ↗
L2RCTCited in: Setting-Based Framework - [50]
Abu-Rustum NR, Yashar CM, Arend R et al.. “NCCN Guidelines® Insights: Cervical Cancer, Version 1.2024.” Journal of the National Comprehensive Cancer Network : JNCCN (2023). PMID: 38081139 ↗
L1OTHERCited in: Setting-Based Framework, Chemotherapy Regimens - [51]
Koh WJ, Greer BE, Abu-Rustum NR et al.. “Cervical Cancer, Version 2.2015.” Journal of the National Comprehensive Cancer Network : JNCCN (2015). PMID: 25870376 ↗
L1OTHERCited in: Setting-Based Framework, Chemotherapy Regimens - [52]
Moore DH. “Chemotherapy for advanced, recurrent, and metastatic cervical cancer.” Journal of the National Comprehensive Cancer Network : JNCCN (2008). PMID: 18267059 ↗
L5REVIEW_NARRATIVECited in: Setting-Based Framework, Chemotherapy Regimens - [53]
Flint ML, Byrne ME, Friedman CF. “Locally Advanced Cervical Cancer: What is the Preferred Systemic Treatment?” Journal of the National Comprehensive Cancer Network : JNCCN (2025). PMID: 41671446 ↗
L5REVIEW_NARRATIVECited in: Setting-Based Framework, Concurrent Chemotherapy with RT, Chemotherapy Regimens, Targeted and Immune Therapy - [54]
Hong DS, Concin N, Vergote I et al.. “Tisotumab Vedotin in Previously Treated Recurrent or Metastatic Cervical Cancer.” Clinical cancer research : an official journal of the American Association for Cancer Research (2020). PMID: 31796521 ↗
L4TRIAL_NONRANDOMCited in: Setting-Based Framework, Chemotherapy Regimens, Targeted and Immune Therapy, Toxicity and Supportive Care - [55]
Lou H, Cai H, Huang X et al.. “Cadonilimab Combined with Chemotherapy with or without Bevacizumab as First-Line Treatment in Recurrent or Metastatic Cervical Cancer (COMPASSION-13): A Phase 2 Study.” Clinical cancer research : an official journal of the American Association for Cancer Research (2024). PMID: 38372727 ↗
L4TRIAL_NONRANDOMCited in: Setting-Based Framework, Chemotherapy Regimens, Targeted and Immune Therapy - [56]
Oaknin A, Ghamande SA, Kasamatsu Y et al.. “Phase I Trial of First-line Bintrafusp Alfa in Patients with Locally Advanced or Persistent/Recurrent/Metastatic Cervical Cancer.” Clinical cancer research : an official journal of the American Association for Cancer Research (2024). PMID: 38165683 ↗
L4TRIAL_NONRANDOMCited in: Setting-Based Framework, Concurrent Chemotherapy with RT, Chemotherapy Regimens - [57]
Feng J, Tang D, Wang J et al.. “SHR-1701, a Bifunctional Fusion Protein Targeting PD-L1 and TGFβ, for Recurrent or Metastatic Cervical Cancer: A Clinical Expansion Cohort of a Phase I Study.” Clinical cancer research : an official journal of the American Association for Cancer Research (2022). PMID: 35653122 ↗
L4TRIAL_NONRANDOMCited in: Setting-Based Framework - [58]
An J, Tang J, Li BX et al.. “Efficacy and Safety of the Anti-PD-L1 mAb Socazolimab for Recurrent or Metastatic Cervical Cancer: a Phase I Dose-Escalation and Expansion Study.” Clinical cancer research : an official journal of the American Association for Cancer Research (2022). PMID: 36136294 ↗
L4TRIAL_NONRANDOMCited in: Setting-Based Framework - [59]
Papadopoulos KP, Johnson ML, Lockhart AC et al.. “First-In-Human Study of Cemiplimab Alone or In Combination with Radiotherapy and/or Low-dose Cyclophosphamide in Patients with Advanced Malignancies.” Clinical cancer research : an official journal of the American Association for Cancer Research (2020). PMID: 31796520 ↗
L4TRIAL_NONRANDOMCited in: Setting-Based Framework, Concurrent Chemotherapy with RT, Chemotherapy Regimens - [60]
Mi X, Lin T, Zhu X et al.. “Efficacy and safety of cadonilimab for malignant solid tumor treatment: a systematic review and meta-analysis.” Frontiers in immunology (2026). PMID: 42292353 ↗
L1SR_OBSCited in: Setting-Based Framework, Toxicity and Supportive Care - [61]
Zhang D, Meng Y, Dong X et al.. “Efficacy and safety of immune checkpoint inhibitors combined with antiangiogenic agents in advanced cervical cancer: a systematic review and meta-analysis.” Frontiers in immunology (2026). PMID: 42253994 ↗
L1SR_OBSCited in: Setting-Based Framework, Chemotherapy Regimens, Toxicity and Supportive Care - [62]
Wang X, Zhang Y, Wang C et al.. “Efficacy and safety of first-line therapies for persistent, recurrent, or metastatic cervical cancer: a systematic review and exploratory network meta-analysis of immunotherapy.” Frontiers in immunology (2026). PMID: 42079658 ↗
L1SR_OBSCited in: Setting-Based Framework, Chemotherapy Regimens, Targeted and Immune Therapy, Toxicity and Supportive Care - [63]
Zhou L, Sun C, Diao P et al.. “Efficacy and safety of adding immune checkpoint inhibitors to standard chemotherapy or chemoradiotherapy for advanced or recurrent cervical cancer: a meta-analysis.” Frontiers in immunology (2026). PMID: 41869324 ↗
L1SR_OBSCited in: Setting-Based Framework, Concurrent Chemotherapy with RT, Chemotherapy Regimens, Toxicity and Supportive Care - [64]
Park JY, Kim DY, Kim JH et al.. “Management of occult invasive cervical cancer found after simple hysterectomy.” Annals of oncology : official journal of the European Society for Medical Oncology (2010). PMID: 19858083 ↗
L3OTHERCited in: Setting-Based Framework, Chemotherapy Regimens - [65]
Soonthornthum T, Arias-Pulido H, Joste N et al.. “Epidermal growth factor receptor as a biomarker for cervical cancer.” Annals of oncology : official journal of the European Society for Medical Oncology (2011). PMID: 21325449 ↗
L5REVIEW_NARRATIVECited in: Setting-Based Framework - [66]
Cho Y, Kim KH, Yoon HI et al.. “Tumor-related leukocytosis is associated with poor radiation response and clinical outcome in uterine cervical cancer patients.” Annals of oncology : official journal of the European Society for Medical Oncology (2016). PMID: 27502717 ↗
L3OTHERCited in: Setting-Based Framework, Concurrent Chemotherapy with RT - [67]
Monk BJ, Colombo N, Tewari KS et al.. “First-Line Pembrolizumab + Chemotherapy Versus Placebo + Chemotherapy for Persistent, Recurrent, or Metastatic Cervical Cancer: Final Overall Survival Results of KEYNOTE-826.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2023). PMID: 37910822 ↗
L1OTHERCited in: Setting-Based Framework, Chemotherapy Regimens, Targeted and Immune Therapy - [68]
Schmid MP, Lindegaard JC, Mahantshetty U et al.. “Risk Factors for Local Failure Following Chemoradiation and Magnetic Resonance Image-Guided Brachytherapy in Locally Advanced Cervical Cancer: Results From the EMBRACE-I Study.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2023). PMID: 36599120 ↗
L2OTHERCited in: Setting-Based Framework - [69]
Lurain K. “Treating Cancer in People With HIV.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2023). PMID: 37267514 ↗
L5REVIEW_NARRATIVECited in: Setting-Based Framework, Special Populations - [70]
Ogasawara A, Suzuki S, Oda K et al.. “Phase II study of pembrolizumab plus olaparib in recurrent cervical cancer progressing after platinum-based chemotherapy (GOTIC-025).” Gynecologic oncology (2026). PMID: 42013608 ↗
L4TRIAL_NONRANDOMCited in: Setting-Based Framework, Chemotherapy Regimens, Targeted and Immune Therapy, Toxicity and Supportive Care - [71]
Van Nieuwenhuysen E, Vergote I, Randall LM et al.. “Tisotumab vedotin plus carboplatin or pembrolizumab in recurrent or metastatic cervical cancer: 5-year results from the innovaTV 205/ENGOT-cx8/GOG-3024 study.” Gynecologic oncology (2026). PMID: 42000372 ↗
L4TRIAL_NONRANDOMCited in: Setting-Based Framework, Chemotherapy Regimens, Targeted and Immune Therapy - [72]
Garcia J, Hurwitz HI, Sandler AB et al.. “Bevacizumab (Avastin®) in cancer treatment: A review of 15 years of clinical experience and future outlook.” Cancer treatment reviews (2020). PMID: 32335505 ↗
L5REVIEW_NARRATIVECited in: Setting-Based Framework, Chemotherapy Regimens, Targeted and Immune Therapy - [73]
Pectasides D, Kamposioras K, Papaxoinis G et al.. “Chemotherapy for recurrent cervical cancer.” Cancer treatment reviews (2008). PMID: 18657909 ↗
L5REVIEW_NARRATIVECited in: Setting-Based Framework, Concurrent Chemotherapy with RT, Chemotherapy Regimens - [74]
Attademo L, Tuninetti V, Pisano C et al.. “Immunotherapy in cervix cancer.” Cancer treatment reviews (2020). PMID: 32827839 ↗
L5REVIEW_NARRATIVECited in: Setting-Based Framework - [75]
Wenzel HHB, Olthof EP, Bekkers RLM et al.. “Primary or adjuvant chemoradiotherapy for cervical cancer with intraoperative lymph node metastasis - A review.” Cancer treatment reviews (2022). PMID: 34773774 ↗
L5REVIEW_NARRATIVECited in: Setting-Based Framework, Concurrent Chemotherapy with RT - [76]
Ventriglia J, Paciolla I, Pisano C et al.. “Immunotherapy in ovarian, endometrial and cervical cancer: State of the art and future perspectives.” Cancer treatment reviews (2017). PMID: 28800469 ↗
L5REVIEW_NARRATIVECited in: Setting-Based Framework, Targeted and Immune Therapy - [77]
Monk BJ, Enomoto T, Kast WM et al.. “Integration of immunotherapy into treatment of cervical cancer: Recent data and ongoing trials.” Cancer treatment reviews (2022). PMID: 35413489 ↗
L5REVIEW_NARRATIVECited in: Setting-Based Framework, Chemotherapy Regimens, Targeted and Immune Therapy - [78]
Crowley FJ, O'Cearbhaill RE, Collins DC. “Exploiting somatic alterations as therapeutic targets in advanced and metastatic cervical cancer.” Cancer treatment reviews (2021). PMID: 34082256 ↗
L5REVIEW_NARRATIVECited in: Setting-Based Framework - [79]
Gennigens C, Jerusalem G, Lapaille L et al.. “Recurrent or primary metastatic cervical cancer: current and future treatments.” ESMO open (2022). PMID: 36108558 ↗
L5REVIEW_NARRATIVECited in: Setting-Based Framework, Concurrent Chemotherapy with RT, Chemotherapy Regimens, Targeted and Immune Therapy - [80]
Man I, Georges D, de Carvalho TM et al.. “Evidence-based impact projections of single-dose human papillomavirus vaccination in India: a modelling study.” The Lancet. Oncology (2022). PMID: 36174583 ↗
L2OTHERCited in: Setting-Based Framework - [81]
Du Q, Liu Q, Zhou Y et al.. “Primary prophylaxis with pegylated G-CSF is associated with improved treatment completion and progression-free survival in locally advanced cervical cancer undergoing concurrent chemoradiotherapy: a retrospective cohort study.” Future oncology (London, England) (2026). PMID: 41930746 ↗
L3COHORTCited in: Setting-Based Framework, Chemotherapy Regimens - [82]
Wang Y, Farmer M, Izaguirre EW et al.. “Association of Definitive Pelvic Radiation Therapy With Survival Among Patients With Newly Diagnosed Metastatic Cervical Cancer.” JAMA oncology (2018). PMID: 30054609 ↗
L3OTHERCited in: Setting-Based Framework, Concurrent Chemotherapy with RT - [83]
Lheureux S, Butler MO, Clarke B et al.. “Association of Ipilimumab With Safety and Antitumor Activity in Women With Metastatic or Recurrent Human Papillomavirus-Related Cervical Carcinoma.” JAMA oncology (2018). PMID: 29145543 ↗
L4OTHERCited in: Setting-Based Framework - [84]
. “Reducing cervical cancer mortality in India.” Cancer discovery (2013). PMID: 23847374 ↗
L2OTHERCited in: Setting-Based Framework - [85]
Ishida S, McCormick F, Smith-McCune K et al.. “Enhancing tumor-specific uptake of the anticancer drug cisplatin with a copper chelator.” Cancer cell (2010). PMID: 20541702 ↗
L5OTHERCited in: Setting-Based Framework, Concurrent Chemotherapy with RT - [86]
. “Strong HPV Vaccine Response Predicts Better Survival with Chemotherapy.” Cancer discovery (2020). PMID: 32220926 ↗
L5OTHERCited in: Setting-Based Framework - [87]
Zeng Z, Yang X, Wang W et al.. “Effect of Cisplatin Cycles on Prognosis for Cervical Cancer Patients Treated With Concurrent Chemoradiotherapy: A Retrospective Cohort Study.” Technology in cancer research & treatment (2026). PMID: 42015673 ↗
L3COHORTCited in: Setting-Based Framework - [88]
Chen Y, Liu L, Chen Y et al.. “Prognostic factors influencing the cure rate of 5-Aminolevulinic acid photodynamic therapy (ALA-PDT) of High-grade squamous intraepithelial lesions (HSIL): A retrospective cohort study.” Photodiagnosis and photodynamic therapy (2026). PMID: 41941918 ↗
L3COHORTCited in: Setting-Based Framework - [89]
Friedman CF, Ravichandran V, Miller K et al.. “Assessing the Genomic Landscape of Cervical Cancers: Clinical Opportunities and Therapeutic Targets.” Clinical cancer research : an official journal of the American Association for Cancer Research (2023). PMID: 37643132 ↗
L2OTHERCited in: Setting-Based Framework - [90]
Bonfill-Teixidor E, Neva-Alejo A, Arias A et al.. “Cervical Cancer Evades the Host Immune System through the Inhibition of Type I Interferon and CXCL9 by LIF.” Clinical cancer research : an official journal of the American Association for Cancer Research (2024). PMID: 39078728 ↗
L5OTHERCited in: Setting-Based Framework - [91]
Lyng H, Skipar K, Hompland T. “Targeted Therapy on the Screen: Do We Hit the Target?” Clinical cancer research : an official journal of the American Association for Cancer Research (2022). PMID: 36240006 ↗
L5OTHERCited in: Setting-Based Framework - [92]
Tewari KS, Monk BJ. “New strategies in advanced cervical cancer: from angiogenesis blockade to immunotherapy.” Clinical cancer research : an official journal of the American Association for Cancer Research (2014). PMID: 25104084 ↗
L5REVIEW_NARRATIVECited in: Setting-Based Framework, Chemotherapy Regimens, Targeted and Immune Therapy - [93]
Lin Z, Bazzaro M, Wang MC et al.. “Combination of proteasome and HDAC inhibitors for uterine cervical cancer treatment.” Clinical cancer research : an official journal of the American Association for Cancer Research (2009). PMID: 19147762 ↗
L5OTHERCited in: Setting-Based Framework - [94]
Cantidio FS, Costa Diniz PH, Gil G et al.. “Bone marrow-sparing radiotherapy in women with cervical cancer treated with radiochemotherapy.” The Cochrane database of systematic reviews (2026). PMID: 42273975 ↗
L5SR_OBSCited in: Setting-Based Framework - [95]
Yao H, Hao Z, Zhang X et al.. “Severe immune checkpoint inhibitor-induced 3M syndrome: a case report.” Frontiers in immunology (2026). PMID: 42292465 ↗
L4CASE_REPORTCited in: Setting-Based Framework - [96]
Lin J, He H, Liu B et al.. “The exploration of iparomlimab and tuvonralimab combined with de-escalated chemotherapy as an innovative neoadjuvant treatment strategy for locally advanced cervical cancer: a case report from the NICE-CC trial.” Frontiers in immunology (2026). PMID: 42112362 ↗
L4CASE_REPORTCited in: Setting-Based Framework, Chemotherapy Regimens - [97]
Koh WJ, Greer BE, Abu-Rustum NR et al.. “Cervical cancer.” Journal of the National Comprehensive Cancer Network : JNCCN (2013). PMID: 23486458 ↗
L1GUIDELINECited in: Concurrent Chemotherapy with RT - [98]
Ryu SY, Deng W, Albuquerque K et al.. “Randomized phase III trial of adjuvant radiation versus chemoradiation in intermediate-risk, early-stage cervical cancer following radical hysterectomy and lymphadenectomy: results from NRG Oncology/GOG-263/KGOG 1008.” Annals of oncology : official journal of the European Society for Medical Oncology (2025). PMID: 40947016 ↗
L1RCTCited in: Concurrent Chemotherapy with RT - [99]
Sugiyama T, Fujiwara K, Ohashi Y et al.. “Phase III placebo-controlled double-blind randomized trial of radiotherapy for stage IIB-IVA cervical cancer with or without immunomodulator Z-100: a JGOG study.” Annals of oncology : official journal of the European Society for Medical Oncology (2014). PMID: 24569914 ↗
L1RCTCited in: Concurrent Chemotherapy with RT, Toxicity and Supportive Care - [100]
da Costa SCS, Bonadio RC, Gabrielli FCG et al.. “Neoadjuvant Chemotherapy With Cisplatin and Gemcitabine Followed by Chemoradiation Versus Chemoradiation for Locally Advanced Cervical Cancer: A Randomized Phase II Trial.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2019). PMID: 31449470 ↗
L2RCTCited in: Concurrent Chemotherapy with RT - [101]
Zuliani AC, Esteves SC, Teixeira LC et al.. “Concomitant cisplatin plus radiotherapy and high-dose-rate brachytherapy versus radiotherapy alone for stage IIIB epidermoid cervical cancer: a randomized controlled trial.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2014). PMID: 24449243 ↗
L1RCTCited in: Concurrent Chemotherapy with RT, Toxicity and Supportive Care - [102]
Blohmer JU, Paepke S, Sehouli J et al.. “Randomized phase III trial of sequential adjuvant chemoradiotherapy with or without erythropoietin Alfa in patients with high-risk cervical cancer: results of the NOGGO-AGO intergroup study.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2011). PMID: 21860000 ↗
L1RCTCited in: Concurrent Chemotherapy with RT - [103]
Rose PG, Ali S, Watkins E et al.. “Long-term follow-up of a randomized trial comparing concurrent single agent cisplatin, cisplatin-based combination chemotherapy, or hydroxyurea during pelvic irradiation for locally advanced cervical cancer: a Gynecologic Oncology Group Study.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2007). PMID: 17502627 ↗
L1RCTCited in: Concurrent Chemotherapy with RT, Toxicity and Supportive Care - [104]
Dueñas-González A, Zarbá JJ, Patel F et al.. “Phase III, open-label, randomized study comparing concurrent gemcitabine plus cisplatin and radiation followed by adjuvant gemcitabine and cisplatin versus concurrent cisplatin and radiation in patients with stage IIB to IVA carcinoma of the cervix.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2011). PMID: 21444871 ↗
L1RCTCited in: Concurrent Chemotherapy with RT - [105]
Yang X, Ren H, Li Z et al.. “A phase III randomized, controlled trial of nedaplatin versus cisplatin concurrent chemoradiotherapy in patients with cervical cancer.” ESMO open (2022). PMID: 35994789 ↗
L1RCTCited in: Concurrent Chemotherapy with RT - [106]
Ruhlmann CH, Christensen TB, Dohn LH et al.. “Efficacy and safety of fosaprepitant for the prevention of nausea and emesis during 5 weeks of chemoradiotherapy for cervical cancer (the GAND-emesis study): a multinational, randomised, placebo-controlled, double-blind, phase 3 trial.” The Lancet. Oncology (2016). PMID: 26952945 ↗
L1RCTCited in: Concurrent Chemotherapy with RT, Toxicity and Supportive Care - [107]
Huang H, Feng YL, Wan T et al.. “Effectiveness of Sequential Chemoradiation vs Concurrent Chemoradiation or Radiation Alone in Adjuvant Treatment After Hysterectomy for Cervical Cancer: The STARS Phase 3 Randomized Clinical Trial.” JAMA oncology (2021). PMID: 33443541 ↗
L1RCTCited in: Concurrent Chemotherapy with RT, Chemotherapy Regimens - [108]
Cho WK, Park W, Kim SW et al.. “Postoperative Hypofractionated Intensity-Modulated Radiotherapy With Concurrent Chemotherapy in Cervical Cancer: The POHIM-CCRT Nonrandomized Controlled Trial.” JAMA oncology (2024). PMID: 38662364 ↗
L2RCTCited in: Concurrent Chemotherapy with RT - [109]
Tewari KS, Sill MW, Monk BJ et al.. “Prospective Validation of Pooled Prognostic Factors in Women with Advanced Cervical Cancer Treated with Chemotherapy with/without Bevacizumab: NRG Oncology/GOG Study.” Clinical cancer research : an official journal of the American Association for Cancer Research (2015). PMID: 26672085 ↗
L2RCTCited in: Concurrent Chemotherapy with RT, Chemotherapy Regimens, Targeted and Immune Therapy, Special Populations - [110]
Marchetti C, Fagotti A, Tombolini V et al.. “Survival and toxicity in neoadjuvant chemotherapy plus surgery versus definitive chemoradiotherapy for cervical cancer: A systematic review and meta-analysis.” Cancer treatment reviews (2020). PMID: 31838220 ↗
L1SR_OBSCited in: Concurrent Chemotherapy with RT - [111]
Corbeau A, Spampinato S, Charnalia M et al.. “Normal tissue complication probability models for gastrointestinal toxicity after adjuvant (chemo)radiotherapy for cervical cancer in the PARCER trial.” Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology (2026). PMID: 41698508 ↗
L2RCTCited in: Concurrent Chemotherapy with RT - [112]
Hu L, Li J, Du Y et al.. “Lobaplatin versus cisplatin in concurrent chemoradiotherapy for elderly cervical cancer: randomized controlled phase II study.” Journal of gynecologic oncology (2026). PMID: 41381401 ↗
L1RCTCited in: Concurrent Chemotherapy with RT, Chemotherapy Regimens - [113]
Xiang M, Kidd EA. “Benefit of Cisplatin With Definitive Radiotherapy in Older Women With Cervical Cancer.” Journal of the National Comprehensive Cancer Network : JNCCN (2019). PMID: 31390586 ↗
L2OTHERCited in: Concurrent Chemotherapy with RT, Toxicity and Supportive Care - [114]
Dyer BA, Zamarin D, Eskandar RN et al.. “Role of Immunotherapy in the Management of Locally Advanced and Recurrent/Metastatic Cervical Cancer.” Journal of the National Comprehensive Cancer Network : JNCCN (2019). PMID: 30659133 ↗
L5REVIEW_NARRATIVECited in: Concurrent Chemotherapy with RT, Targeted and Immune Therapy - [115]
Kidd EA, Grigsby PW. “Intratumoral metabolic heterogeneity of cervical cancer.” Clinical cancer research : an official journal of the American Association for Cancer Research (2008). PMID: 18698042 ↗
L2TRIAL_NONRANDOMCited in: Concurrent Chemotherapy with RT - [116]
Nogueira-Rodrigues A, do Carmo CC, Viegas C et al.. “Phase I trial of erlotinib combined with cisplatin and radiotherapy for patients with locally advanced cervical squamous cell cancer.” Clinical cancer research : an official journal of the American Association for Cancer Research (2008). PMID: 18829516 ↗
L4TRIAL_NONRANDOMCited in: Concurrent Chemotherapy with RT, Chemotherapy Regimens - [117]
Kunos CA, Waggoner S, von Gruenigen V et al.. “Phase I trial of pelvic radiation, weekly cisplatin, and 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, NSC #663249) for locally advanced cervical cancer.” Clinical cancer research : an official journal of the American Association for Cancer Research (2010). PMID: 20145183 ↗
L4TRIAL_NONRANDOMCited in: Concurrent Chemotherapy with RT, Chemotherapy Regimens - [118]
Tewari KS. “Immune Checkpoint Blockade in PD-L1-Positive Platinum-Refractory Cervical Carcinoma.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2019). PMID: 31026210 ↗
L4CASE_REPORTCited in: Concurrent Chemotherapy with RT - [119]
. “Prophylactic para-aortic irradiation vs pelvic radiotherapy in pelvic node-positive carcinoma cervix in the setting of concurrent chemoradiation: a phase II open-label multi centric randomized controlled trial (PRO-PARA).” Trials (2026). PMID: 41792812 ↗
L5RCTCited in: Concurrent Chemotherapy with RT - [120]
Chargari C, Martinez A, Michels J et al.. “[French recommendations for clinical practice, Nice/Saint-Paul-de-Vence 2024-2025: Management of localized cervical cancer].” Bulletin du cancer (2026). PMID: 41617621 ↗
L1GUIDELINECited in: Concurrent Chemotherapy with RT - [121]
Dryden-Peterson S, Bvochora-Nsingo M, Suneja G et al.. “HIV Infection and Survival Among Women With Cervical Cancer.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2016). PMID: 27573661 ↗
L2OTHERCited in: Concurrent Chemotherapy with RT, Special Populations - [122]
Wei S, Li X, Liu Z et al.. “Nimotuzumab plus concurrent chemoradiotherapy sequential maintenance treatment for locally advanced cervical squamous cell carcinoma (NOTABLE-306): a multicenter, prospective, randomized, double-blind, placebo-controlled trial.” Journal of gynecologic oncology (2026). PMID: 41514314 ↗
L5TRIAL_NONRANDOMCited in: Concurrent Chemotherapy with RT - [123]
Yokoi A, Machida H, Okazawa-Sakai M et al.. “Optimal adjuvant strategy in intermediate-risk cervical cancer: a systematic review and meta-analysis.” International journal of clinical oncology (2026). PMID: 42012622 ↗
L1SR_OBSCited in: Concurrent Chemotherapy with RT - [124]
Umemiya M, Kou K, Inayama Y et al.. “Comparison of nedaplatin and cisplatin in concurrent chemoradiotherapy for cervical cancer: a systematic review and meta-analysis.” International journal of clinical oncology (2026). PMID: 41612081 ↗
L1SR_OBSCited in: Concurrent Chemotherapy with RT, Toxicity and Supportive Care - [125]
Piya IJ, Riya IJ, Sharma V. “Efficacy and safety of immune checkpoint inhibitors with chemoradiotherapy/chemotherapy in locally advanced cervical cancer patients: a systematic review and single-arm meta-analysis.” Journal of gynecologic oncology (2026). PMID: 41267534 ↗
L1SR_OBSCited in: Concurrent Chemotherapy with RT, Toxicity and Supportive Care - [126]
Wieringa HW, van der Zee AG, de Vries EG et al.. “Breaking the DNA damage response to improve cervical cancer treatment.” Cancer treatment reviews (2016). PMID: 26643553 ↗
L5REVIEW_NARRATIVECited in: Concurrent Chemotherapy with RT - [127]
Cabel L, Bonneau C, Bernard-Tessier A et al.. “HPV ctDNA detection of high-risk HPV types during chemoradiotherapy for locally advanced cervical cancer.” ESMO open (2021). PMID: 34022731 ↗
L2OTHERCited in: Concurrent Chemotherapy with RT - [128]
Westerveld H, Nesvacil N, Fokdal L et al.. “Definitive radiotherapy with image-guided adaptive brachytherapy for primary vaginal cancer.” The Lancet. Oncology (2020). PMID: 32135119 ↗
L5REVIEW_NARRATIVECited in: Concurrent Chemotherapy with RT - [129]
Gouy S, Morice P, Narducci F et al.. “Nodal-staging surgery for locally advanced cervical cancer in the era of PET.” The Lancet. Oncology (2012). PMID: 22554549 ↗
L5REVIEW_NARRATIVECited in: Concurrent Chemotherapy with RT - [130]
Agustí N, Viveros-Carreño D, Wu CF et al.. “Adjuvant Chemoradiotherapy vs Radiotherapy Alone for Patients With Intermediate-Risk Cervical Cancer.” JAMA oncology (2025). PMID: 40079948 ↗
L3OTHERCited in: Concurrent Chemotherapy with RT - [131]
Zhao X, Singhal A, Park S et al.. “Cancer Mutations Converge on a Collection of Protein Assemblies to Predict Resistance to Replication Stress.” Cancer discovery (2024). PMID: 38236062 ↗
L5OTHERCited in: Concurrent Chemotherapy with RT - [132]
Mondini M, Deutsch E. “(Chemo)Radiotherapy-Immunotherapy Combinations: Time to Get Tailored?” Clinical cancer research : an official journal of the American Association for Cancer Research (2021). PMID: 33986023 ↗
L5OTHERCited in: Concurrent Chemotherapy with RT, Targeted and Immune Therapy - [133]
Seo A, Xiao W, Gjyshi O et al.. “Human Papilloma Virus Circulating Cell-Free DNA Kinetics in Patients with Cervical Cancer Undergoing Definitive Chemoradiation.” Clinical cancer research : an official journal of the American Association for Cancer Research (2025). PMID: 39680029 ↗
L2OTHERCited in: Concurrent Chemotherapy with RT - [134]
Chaudary N, Pintilie M, Jelveh S et al.. “Plerixafor Improves Primary Tumor Response and Reduces Metastases in Cervical Cancer Treated with Radio-Chemotherapy.” Clinical cancer research : an official journal of the American Association for Cancer Research (2017). PMID: 27697997 ↗
L5OTHERCited in: Concurrent Chemotherapy with RT - [135]
Sannigrahi MK, Sharma R, Singh V et al.. “Role of Host miRNA Hsa-miR-139-3p in HPV-16-Induced Carcinomas.” Clinical cancer research : an official journal of the American Association for Cancer Research (2017). PMID: 28143871 ↗
L5OTHERCited in: Concurrent Chemotherapy with RT - [136]
O'Malley DM, Neffa M, Monk BJ et al.. “Dual PD-1 and CTLA-4 Checkpoint Blockade Using Balstilimab and Zalifrelimab Combination as Second-Line Treatment for Advanced Cervical Cancer: An Open-Label Phase II Study.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2022). PMID: 34932394 ↗
L2TRIAL_NONRANDOMCited in: Chemotherapy Regimens - [137]
Yonemori K, Nishio S, Suzuki S et al.. “Tisotumab vedotin in Japanese patients with recurrent or metastatic cervical cancer: results from the innovaTV 301/ENGOT-cx12/GOG-3057 trial.” International journal of gynecological cancer : official journal of the International Gynecological Cancer Society (2026). PMID: 41644383 ↗
L1RCTCited in: Chemotherapy Regimens - [138]
Jones R, Plummer R, Moreno V et al.. “A Phase I/II Trial of Oral SRA737 (a Chk1 Inhibitor) Given in Combination with Low-Dose Gemcitabine in Patients with Advanced Cancer.” Clinical cancer research : an official journal of the American Association for Cancer Research (2023). PMID: 36378548 ↗
L2TRIAL_NONRANDOMCited in: Chemotherapy Regimens - [139]
Kelly RJ, Draper D, Chen CC et al.. “A pharmacodynamic study of docetaxel in combination with the P-glycoprotein antagonist tariquidar (XR9576) in patients with lung, ovarian, and cervical cancer.” Clinical cancer research : an official journal of the American Association for Cancer Research (2011). PMID: 21081657 ↗
L2TRIAL_NONRANDOMCited in: Chemotherapy Regimens - [140]
Zhou J, Ye W, Ranarisoa SN et al.. “Comparison of drug regimens for recurrent or metastatic cervical cancer: a systematic review and network meta-analysis.” Frontiers in immunology (2026). PMID: 41822503 ↗
L1SR_OBSCited in: Chemotherapy Regimens, Targeted and Immune Therapy - [141]
Sabatier R, Hennequin C, Martin-Babau J et al.. “[French recommendations for clinical practice, Nice/Saint-Paul-de-Vence 2024-2025: Management of advanced cervical cancer].” Bulletin du cancer (2026). PMID: 41620326 ↗
L1GUIDELINECited in: Chemotherapy Regimens - [142]
Liu Y, Ren T, Wang X et al.. “Efficacy and safety of PARP inhibitors monotherapy or combination therapy with anti-angiogenics in ovarian cancer: a network meta-analysis.” Frontiers in oncology (2025). PMID: 41669254 ↗
L1SR_OBSCited in: Chemotherapy Regimens - [143]
Monk BJ, Tewari KS, Koh WJ. “Multimodality therapy for locally advanced cervical carcinoma: state of the art and future directions.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2007). PMID: 17617527 ↗
L5REVIEW_NARRATIVECited in: Chemotherapy Regimens - [144]
Long HJ. “Management of metastatic cervical cancer: review of the literature.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2007). PMID: 17617528 ↗
L5REVIEW_NARRATIVECited in: Chemotherapy Regimens - [145]
Ismaili N. “Major Advances in Gynecologic Oncology in 2025: Systematic Review and Synthesis of Conference and Published Evidence.” Biomedicines (2026). PMID: 41751194 ↗
L1SR_OBSCited in: Chemotherapy Regimens - [146]
Mountzios G, Soultati A, Pectasides D et al.. “Developments in the systemic treatment of metastatic cervical cancer.” Cancer treatment reviews (2013). PMID: 22727690 ↗
L5REVIEW_NARRATIVECited in: Chemotherapy Regimens - [147]
Vora C, Gupta S. “Targeted therapy in cervical cancer.” ESMO open (2018). PMID: 30997156 ↗
L5OTHERCited in: Chemotherapy Regimens - [148]
Riggenbach E, Mose L, Imboden S et al.. “Intensified radiochemotherapy with cisplatin and gemcitabine for cervical cancer in the modern era: a retrospective cohort study.” Journal of gynecologic oncology (2026). PMID: 41413788 ↗
L3COHORTCited in: Chemotherapy Regimens - [149]
Zhou J, Cai J, Li X et al.. “Pelvic radiotherapy combined with immunotherapy and chemotherapy for stage IVB cervical cancer: a retrospective study.” International journal of gynecological cancer : official journal of the International Gynecological Cancer Society (2026). PMID: 41411697 ↗
L3COHORTCited in: Chemotherapy Regimens - [150]
. “FDA Approves First Biosimilar to Treat Cancer.” Cancer discovery (2017). PMID: 28982661 ↗
L5OTHERCited in: Chemotherapy Regimens, Targeted and Immune Therapy - [151]
Nakashima T, Matsumoto K, Yoshitake T et al.. “Impact of high-dose pelvic radiotherapy combined with chemotherapy on local control, symptom relief, and safety in patients with stage IVB cervical cancer (FIGO 2018): a two-center retrospective study.” Japanese journal of radiology (2026). PMID: 41441948 ↗
L4COHORTCited in: Chemotherapy Regimens - [152]
Rotman J, Heeren AM, Gassama AA et al.. “Adenocarcinoma of the Uterine Cervix Shows Impaired Recruitment of cDC1 and CD8+ T Cells and Elevated β-Catenin Activation Compared with Squamous Cell Carcinoma.” Clinical cancer research : an official journal of the American Association for Cancer Research (2020). PMID: 32220890 ↗
L3OTHERCited in: Chemotherapy Regimens - [153]
Wiwekananda IGNA, Malek NANN, Endharti AT et al.. “Nab-paclitaxel for the treatment of cervical cancer: a systematic review of clinical safety and effectiveness.” Journal of chemotherapy (Florence, Italy) (2026). PMID: 41655064 ↗
L2SR_OBSCited in: Chemotherapy Regimens - [154]
Li H, Wu M, Xing Y et al.. “Sacituzumab govitecan combined with tislelizumab as second-line therapy for recurrent or metastatic cervical cancer: a case report and literature review.” BMC women's health (2026). PMID: 42015186 ↗
L4CASE_REPORTCited in: Chemotherapy Regimens, Targeted and Immune Therapy - [155]
Sun L, Lang J, Wu X et al.. “Complete remission of recurrent human papillomavirus-associated cervical cancer managed with camrelizumab and nanoparticle albumin-bound paclitaxel as second-line treatment: a case report.” Frontiers in immunology (2025). PMID: 41409282 ↗
L4CASE_REPORTCited in: Chemotherapy Regimens - [156]
Chang HA, Armenian SH, Dellinger TH. “Secondary Neoplasms of the Female Lower Genital Tract After Hematopoietic Cell Transplantation.” Journal of the National Comprehensive Cancer Network : JNCCN (2018). PMID: 29439180 ↗
L5SR_OBSCited in: Targeted and Immune Therapy - [157]
Monk BJ, Sill MW, Burger RA et al.. “Phase II trial of bevacizumab in the treatment of persistent or recurrent squamous cell carcinoma of the cervix: a gynecologic oncology group study.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2009). PMID: 19139430 ↗
L2TRIAL_NONRANDOMCited in: Targeted and Immune Therapy, Toxicity and Supportive Care, Special Populations - [158]
Lu YC, Parker LL, Lu T et al.. “Treatment of Patients With Metastatic Cancer Using a Major Histocompatibility Complex Class II-Restricted T-Cell Receptor Targeting the Cancer Germline Antigen MAGE-A3.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2017). PMID: 28809608 ↗
L2TRIAL_NONRANDOMCited in: Targeted and Immune Therapy, Toxicity and Supportive Care - [159]
Stevanović S, Helman SR, Wunderlich JR et al.. “A Phase II Study of Tumor-infiltrating Lymphocyte Therapy for Human Papillomavirus-associated Epithelial Cancers.” Clinical cancer research : an official journal of the American Association for Cancer Research (2019). PMID: 30518633 ↗
L2TRIAL_NONRANDOMCited in: Targeted and Immune Therapy - [160]
Welters MJ, Kenter GG, Piersma SJ et al.. “Induction of tumor-specific CD4+ and CD8+ T-cell immunity in cervical cancer patients by a human papillomavirus type 16 E6 and E7 long peptides vaccine.” Clinical cancer research : an official journal of the American Association for Cancer Research (2008). PMID: 18172269 ↗
L2TRIAL_NONRANDOMCited in: Targeted and Immune Therapy - [161]
Kenter GG, Welters MJ, Valentijn AR et al.. “Phase I immunotherapeutic trial with long peptides spanning the E6 and E7 sequences of high-risk human papillomavirus 16 in end-stage cervical cancer patients shows low toxicity and robust immunogenicity.” Clinical cancer research : an official journal of the American Association for Cancer Research (2008). PMID: 18172268 ↗
L2TRIAL_NONRANDOMCited in: Targeted and Immune Therapy - [162]
Basu P, Malvi SG, Joshi S et al.. “Vaccine efficacy against persistent human papillomavirus (HPV) 16/18 infection at 10 years after one, two, and three doses of quadrivalent HPV vaccine in girls in India: a multicentre, prospective, cohort study.” The Lancet. Oncology (2021). PMID: 34634254 ↗
L2COHORTCited in: Targeted and Immune Therapy - [163]
Xu MA, Pant S, DiClemente RJ. “Factors affecting human papillomavirus vaccination: A review of individual, interpersonal, and structural factors affecting vaccine uptake among adolescents.” Vaccine (2026). PMID: 41965976 ↗
L2SR_OBSCited in: Targeted and Immune Therapy - [164]
Xiao C, Zeng S, Li L et al.. “Efficacy and safety of immune checkpoint inhibitors combined with chemoradiotherapy in locally advanced cervical cancer: a systematic review and meta-analysis.” Frontiers in pharmacology (2026). PMID: 41859340 ↗
L1SR_OBSCited in: Targeted and Immune Therapy - [165]
Giannone G, Giuliano AR, Bandini M et al.. “HPV vaccination and HPV-related malignancies: impact, strategies and optimizations toward global immunization coverage.” Cancer treatment reviews (2022). PMID: 36265336 ↗
L5REVIEW_NARRATIVECited in: Targeted and Immune Therapy - [166]
Tolcher A, Hamilton E, Coleman RL. “The evolving landscape of antibody-drug conjugates in gynecologic cancers.” Cancer treatment reviews (2023). PMID: 37023499 ↗
L5REVIEW_NARRATIVECited in: Targeted and Immune Therapy - [167]
Sankaranarayanan R, Basu P, Kaur P et al.. “Current status of human papillomavirus vaccination in India's cervical cancer prevention efforts.” The Lancet. Oncology (2019). PMID: 31674322 ↗
L5REVIEW_NARRATIVECited in: Targeted and Immune Therapy - [168]
Lowy DR, Herrero R, Hildesheim A. “Primary endpoints for future prophylactic human papillomavirus vaccine trials: towards infection and immunobridging.” The Lancet. Oncology (2015). PMID: 25943067 ↗
L5REVIEW_NARRATIVECited in: Targeted and Immune Therapy - [169]
Simms KT, Steinberg J, Caruana M et al.. “Impact of scaled up human papillomavirus vaccination and cervical screening and the potential for global elimination of cervical cancer in 181 countries, 2020-99: a modelling study.” The Lancet. Oncology (2019). PMID: 30795950 ↗
L2OTHERCited in: Targeted and Immune Therapy - [170]
Lei J, Ploner A, Elfström KM et al.. “HPV Vaccination and the Risk of Invasive Cervical Cancer.” The New England journal of medicine (2020). PMID: 32997908 ↗
L2OTHERCited in: Targeted and Immune Therapy - [171]
Ozdemir S, Caglayan R. “Health education on HPV vaccination and cervical cancer prevention: A randomised controlled trial on knowledge, attitudes, beliefs, and behaviours.” JPMA. The Journal of the Pakistan Medical Association (2026). PMID: 41830346 ↗
L1RCTCited in: Targeted and Immune Therapy - [172]
. “Cervical Cancer Analysis Reveals New Mutations.” Cancer discovery (2017). PMID: 28179363 ↗
L5OTHERCited in: Targeted and Immune Therapy - [173]
. “Pembrolizumab May Substantially Up Cervical Cancer Survival.” Cancer discovery (2021). PMID: 34561245 ↗
L5OTHERCited in: Targeted and Immune Therapy - [174]
. “Pembrolizumab OK'd for Cervical Cancer.” Cancer discovery (2018). PMID: 29967015 ↗
L5OTHERCited in: Targeted and Immune Therapy - [175]
Norberg SM, Hinrichs CS. “Engineered T cell therapy for viral and non-viral epithelial cancers.” Cancer cell (2023). PMID: 36400016 ↗
L5REVIEW_NARRATIVECited in: Targeted and Immune Therapy - [176]
Wang X, Xiong D, Cui S et al.. “Immunoconjugates in cervical cancer: a bibliometric and thematic mapping analysis of global research trends, 2015-2024.” Frontiers in oncology (2026). PMID: 42109675 ↗
L5SR_OBSCited in: Targeted and Immune Therapy - [177]
Ferrall L, Lin KY, Roden RBS et al.. “Cervical Cancer Immunotherapy: Facts and Hopes.” Clinical cancer research : an official journal of the American Association for Cancer Research (2021). PMID: 33888488 ↗
L5REVIEW_NARRATIVECited in: Targeted and Immune Therapy - [178]
Miller KM, Friedman CF. “Bifunctional Blockade: A Novel Immunotherapy Approach for Cervical Cancer.” Clinical cancer research : an official journal of the American Association for Cancer Research (2022). PMID: 35947045 ↗
L5OTHERCited in: Targeted and Immune Therapy - [179]
Kang Z, Stevanović S, Hinrichs CS et al.. “Circulating Cell-free DNA for Metastatic Cervical Cancer Detection, Genotyping, and Monitoring.” Clinical cancer research : an official journal of the American Association for Cancer Research (2017). PMID: 28899967 ↗
L4OTHERCited in: Targeted and Immune Therapy - [180]
Chambers L, Haight P, Chalif J et al.. “Bridging the Gap from Bench to Bedside: A Call for In Vivo Preclinical Models to Advance Endometrial Cancer and Cervical Cancer Immuno-oncology Research.” Clinical cancer research : an official journal of the American Association for Cancer Research (2024). PMID: 38662438 ↗
L5OTHERCited in: Targeted and Immune Therapy - [181]
Choi YW, Kang MC, Seo YB et al.. “Intravaginal Administration of Fc-Fused IL7 Suppresses the Cervicovaginal Tumor by Recruiting HPV DNA Vaccine-Induced CD8 T Cells.” Clinical cancer research : an official journal of the American Association for Cancer Research (2016). PMID: 27407095 ↗
L5OTHERCited in: Targeted and Immune Therapy - [182]
Sun YY, Peng S, Han L et al.. “Local HPV Recombinant Vaccinia Boost Following Priming with an HPV DNA Vaccine Enhances Local HPV-Specific CD8+ T-cell-Mediated Tumor Control in the Genital Tract.” Clinical cancer research : an official journal of the American Association for Cancer Research (2016). PMID: 26420854 ↗
L5OTHERCited in: Targeted and Immune Therapy - [183]
Bae SH, Park YJ, Park JB et al.. “Therapeutic synergy of human papillomavirus E7 subunit vaccines plus cisplatin in an animal tumor model: causal involvement of increased sensitivity of cisplatin-treated tumors to CTL-mediated killing in therapeutic synergy.” Clinical cancer research : an official journal of the American Association for Cancer Research (2007). PMID: 17200373 ↗
L5OTHERCited in: Targeted and Immune Therapy - [184]
Barquin A, Kasherman L, Lheureux S et al.. “Antibody-drug conjugates in gynecologic cancers.” Cancer (2026). PMID: 42226034 ↗
L5REVIEW_NARRATIVECited in: Targeted and Immune Therapy - [185]
Kao PY, Chen JH, Chen KH. “The Role of HPV and Hormone in Cervical Precancer and Cancer: Molecular Pathophysiology and Cell Biology of Disease and Treatment.” Oncology research (2026). PMID: 42220428 ↗
L5REVIEW_NARRATIVECited in: Targeted and Immune Therapy - [186]
Li M, Chen Q, Wang F et al.. “Factors influencing Chongqing nurses' HPV vaccination: a cross-sectional survey based on the 5C model.” Frontiers in public health (2026). PMID: 42180508 ↗
L4OTHERCited in: Targeted and Immune Therapy - [187]
Brand-Wiita S, Tsai CJ, Liu YH et al.. “Cost-effectiveness of pembrolizumab as a treatment for FIGO 2014 stage III-IVA cervical cancer in the United States.” Gynecologic oncology (2026). PMID: 42150374 ↗
L2OTHERCited in: Targeted and Immune Therapy - [188]
Plačková K, Fialová A. “The immune microenvironment of HPV-associated cancers: from viral oncogenesis to immunotherapy response.” Frontiers in immunology (2026). PMID: 42148142 ↗
L5REVIEW_NARRATIVECited in: Targeted and Immune Therapy - [189]
Opaleye OO, Esan DT. “Mobile health strategies to improve HPV vaccination uptake among parents of adolescent girls: a scoping review.” Vaccine (2026). PMID: 42134133 ↗
L5REVIEW_NARRATIVECited in: Targeted and Immune Therapy - [190]
Lian X, Qi H, Lin D et al.. “Real-world efficacy, safety, and associated biomarkers of cadonilimab in cervical cancer: a prospective observational study.” Frontiers in immunology (2026). PMID: 42125658 ↗
L2OTHERCited in: Targeted and Immune Therapy - [191]
Meynard C, Fardeau E, Lambert T et al.. “Immunotherapy in Locally Advanced Cervical Carcinoma: A Narrative Review.” Cancers (2026). PMID: 42122204 ↗
L5REVIEW_NARRATIVECited in: Targeted and Immune Therapy - [192]
Stefanos R, Gargano JW, Niccolai LM et al.. “Decreases in Human Papillomavirus Vaccine Types 16 and 18 in Cervical Precancers: HPV-IMPACT, 2008 to 2019.” Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology (2026). PMID: 42089801 ↗
L2OTHERCited in: Targeted and Immune Therapy - [193]
Monk BJ, Mas Lopez L, Zarba JJ et al.. “Phase II, open-label study of pazopanib or lapatinib monotherapy compared with pazopanib plus lapatinib combination therapy in patients with advanced and recurrent cervical cancer.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2010). PMID: 20606083 ↗
L2RCTCited in: Toxicity and Supportive Care - [194]
Naumann RW, Hollebecque A, Meyer T et al.. “Safety and Efficacy of Nivolumab Monotherapy in Recurrent or Metastatic Cervical, Vaginal, or Vulvar Carcinoma: Results From the Phase I/II CheckMate 358 Trial.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2019). PMID: 31487218 ↗
L4TRIAL_NONRANDOMCited in: Toxicity and Supportive Care - [195]
Vicier C, Isambert N, Cropet C et al.. “MOVIE: a phase I, open-label, multicenter study to evaluate the safety and tolerability of metronomic vinorelbine combined with durvalumab plus tremelimumab in patients with advanced solid tumors.” ESMO open (2022). PMID: 36521418 ↗
L4TRIAL_NONRANDOMCited in: Toxicity and Supportive Care - [196]
Maschmeyer G, Fehm T, Loibl S et al.. “Onkopedia: What's New? Systemic Tumor Treatment in Pregnancy.” Oncology research and treatment (2026). PMID: 40602390 ↗
L1GUIDELINECited in: Toxicity and Supportive Care - [197]
Strauss J, Heery CR, Schlom J et al.. “Phase I Trial of M7824 (MSB0011359C), a Bifunctional Fusion Protein Targeting PD-L1 and TGFβ, in Advanced Solid Tumors.” Clinical cancer research : an official journal of the American Association for Cancer Research (2018). PMID: 29298798 ↗
L4TRIAL_NONRANDOMCited in: Toxicity and Supportive Care - [198]
Diaz-Padilla I, Duran I, Clarke BA et al.. “Biologic rationale and clinical activity of mTOR inhibitors in gynecological cancer.” Cancer treatment reviews (2012). PMID: 22381585 ↗
L5REVIEW_NARRATIVECited in: Toxicity and Supportive Care - [199]
Zhuang Q, Liu Y. “Efficacy and safety of Cadonilimab in the treatment of recurrent/metastatic and advanced cervical cancer: a systematic review and meta-analysis.” Frontiers in immunology (2025). PMID: 41601625 ↗
L2SR_OBSCited in: Toxicity and Supportive Care - [200]
Zhang Z, Yu J, Zhang Z et al.. “The Safety of Cadonilimab: A Systematic Review and Single-Arm Meta-Analysis.” Cancer medicine (2025). PMID: 40899424 ↗
L2SR_OBSCited in: Toxicity and Supportive Care - [201]
Kitami K, Kuji S, Kamiya N et al.. “Real-world safety and efficacy of immune checkpoint inhibitors in Japanese patients with persistent, recurrent, or metastatic cervical cancer: a multicenter prospective and retrospective study.” International journal of clinical oncology (2026). PMID: 41504989 ↗
L2COHORTCited in: Toxicity and Supportive Care, Special Populations - [202]
Da Silva DM, Enserro DM, Mayadev JS et al.. “Immune Activation in Patients with Locally Advanced Cervical Cancer Treated with Ipilimumab Following Definitive Chemoradiation (GOG-9929).” Clinical cancer research : an official journal of the American Association for Cancer Research (2020). PMID: 32816895 ↗
L4OTHERCited in: Toxicity and Supportive Care - [203]
Reid E, Suneja G, Ambinder RF et al.. “AIDS-Related Kaposi Sarcoma, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology.” Journal of the National Comprehensive Cancer Network : JNCCN (2019). PMID: 30787130 ↗
L1GUIDELINECited in: Special Populations - [204]
Guiguet M, Boué F, Cadranel J et al.. “Effect of immunodeficiency, HIV viral load, and antiretroviral therapy on the risk of individual malignancies (FHDH-ANRS CO4): a prospective cohort study.” The Lancet. Oncology (2009). PMID: 19818686 ↗
L2COHORTCited in: Special Populations - [205]
Palefsky JM, Lee JY, Jay N et al.. “Treatment of Anal High-Grade Squamous Intraepithelial Lesions to Prevent Anal Cancer.” The New England journal of medicine (2022). PMID: 35704479 ↗
L1RCTCited in: Special Populations - [206]
Ayeni OA, Mmereki D, Mistry H et al.. “Disease characteristics, treatment, and overall survival outcomes of patients with locally advanced cervical cancer referred for radiation therapy in Johannesburg, South Africa: a 2-year retrospective study.” BMC women's health (2026). PMID: 42310589 ↗
L3COHORTCited in: Special Populations - [207]
Amubuomombe PP, Itsura P, Tonui PK et al.. “Pregnancy outcomes among women with and without HIV infections who underwent excisional treatment for high-grade cervical intraepithelial neoplasia: a retrospective cohort study in low-resource settings.” BMJ open (2026). PMID: 41708173 ↗
L3COHORTCited in: Special Populations - [208]
Asare M, Ebu Enyan NI, Sencherey VL et al.. “Culturally adapting and evaluating an evidence-based communication intervention with HPV self-sampling to improve cervical cancer screening among women living with HIV in Ghana: a mixed-methods study.” BMJ open (2025). PMID: 41475829 ↗
L4RCTCited in: Special Populations - [209]
Kabarambi A, Kizito S, Girma AZ et al.. “Preliminary Impact of Public Health Messaging on HPV Vaccine Uptake Among Adolescent Girls and Young Women Living with HIV in Central Uganda.” AIDS and behavior (2026). PMID: 41251868 ↗
L2RCTCited in: Special Populations - [210]
Waldecker M, Taghavi K, Pasin C et al.. “Factors associated with uptake of gynaecological care and cervical cancer screening among women in the Swiss HIV Cohort Study.” HIV medicine (2025). PMID: 41216952 ↗
L2COHORTCited in: Special Populations - [211]
Wang X, Wu Y, Huang J et al.. “Bispecific antibodies (PD-1/CTLA-4) vs. PD-1 inhibitors with platinum-based chemotherapy±bevacizumab as first-line therapy for persistent, recurrent, or metastatic cervical cancer: a retrospective matched cohort study.” Cancer immunology, immunotherapy : CII (2025). PMID: 41136631 ↗
L3COHORTCited in: Special Populations - [212]
Pellegrino RA, Tu S, Ville-Benavides R et al.. “Incidence and outcomes of anal and cervical cancer among adults with HIV in Latin America: a retrospective cohort study.” Journal of the International AIDS Society (2025). PMID: 41074705 ↗
L3COHORTCited in: Special Populations - [213]
McGee-Avila JK, Suneja G, Engels EA et al.. “Cancer Treatment Disparities in People With HIV in the United States, 2001-2019.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2024). PMID: 38513161 ↗
L2OTHERCited in: Special Populations - [214]
Rose PG, Java J, Whitney CW et al.. “Nomograms Predicting Progression-Free Survival, Overall Survival, and Pelvic Recurrence in Locally Advanced Cervical Cancer Developed From an Analysis of Identifiable Prognostic Factors in Patients From NRG Oncology/Gynecologic Oncology Group Randomized Trials of Chemoradiotherapy.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2015). PMID: 25732170 ↗
L2OTHERCited in: Special Populations - [215]
D'Souza G, Gross ND, Pai SI et al.. “Oral human papillomavirus (HPV) infection in HPV-positive patients with oropharyngeal cancer and their partners.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2014). PMID: 24778397 ↗
L3OTHERCited in: Special Populations - [216]
Yarchoan R, Uldrick TS. “HIV-Associated Cancers and Related Diseases.” The New England journal of medicine (2018). PMID: 29539283 ↗
L5REVIEW_NARRATIVECited in: Special Populations