Cervical cancer

Evidence chains

A lane follows one defined population and setting, where each new trial tests against what was then standard. Compare only within a lane, and read every comparison as illustrative.

Persistent, recurrent or metastatic, first-line treatment: median overall survival

Persistent, recurrent or metastatic cervical cancer not previously treated with systemic therapy for advanced disease; earlier platinum given with radiotherapy was permitted in some trials · Metastatic · endpoint: OS

Persistent, recurrent or metastatic, first-line treatment: median progression-free survival

Persistent, recurrent or metastatic cervical cancer not previously treated with systemic therapy for advanced disease; earlier platinum given with radiotherapy was permitted in some trials · Metastatic · endpoint: PFS

Recurrent or metastatic, after earlier systemic therapy: median overall survival

Recurrent or metastatic cervical cancer with progression on or after earlier systemic therapy (EMPOWER-Cervical 1: after first-line platinum-based chemotherapy; innovaTV 301: second or third line) · Metastatic · endpoint: OS

Locally advanced, curative chemoradiation: 5-year overall survival

Newly diagnosed cervical cancer treated with curative-intent radiotherapy, mostly with cisplatin chemoradiation as the control; stage definitions and eligibility differ by trial · Locally advanced · endpoint: OS

Standard of care, then and now

How the usual sequence of treatment changed for one setting. Choose a point in time; each step links to the milestone behind it.

Persistent, recurrent or metastatic cervical cancer: first-line and later treatment

Persistent, recurrent or metastatic cervical cancer · Metastatic

Early-stage cervical cancer: surgical approach

Early-stage cervical cancer treated with hysterectomy · Localised

Standard of care today

Screening

US Preventive Services Task Force recommendation page (final statement dated 21 August 2018; the page shows the topic as being updated and links a draft update, which was not used here; the text was read on 20 October 2026):

• grade A for screening every 3 years with cytology alone at age 21 to 29 years and, at age 30 to 65 years, every 3 years with cytology alone, every 5 years with high-risk HPV testing alone, or every 5 years with cotesting
• grade D against screening under 21, after hysterectomy with removal of the cervix without a history of high-grade precancer or cervical cancer, and over 65 with adequate prior screening and no other high risk. The statement describes self-collection as a possible way to raise screening rates and says rigorous comparative studies are needed. Randomised evidence: in a follow-up of four European trials (176,464 women aged 20 to 64) the rate ratio for invasive cervical carcinoma with HPV-based versus cytology-based screening was 0.60 (95% CI 0.40 to 0.89). FDA device actions read in the approval orders: the cobas HPV Test was approved on 24 April 2014 for several indications including, in women 25 years and older, use as a first-line primary screening test with genotyping for HPV 16 and 18 (supplement P100020/S008)
• on 14 May 2024 the cobas HPV Test (P100020/S055) and the BD Onclarity HPV Assay (P160037/S017) were approved for self-collected vaginal specimens obtained in a healthcare setting, as an alternative specimen type when cervical sampling is contraindicated or cervical samples otherwise cannot be obtained. The openFDA PMA record for BD Onclarity lists a further supplement (P160037/S024, 2 April 2026) described as expanding the settings in which self-collected vaginal specimens are collected and adding a processing workflow
• that approval order was not located, so only that record's statement is given. The WHO 2020 global strategy (publication page, 17 November 2020) sets 2030 targets of 90% of girls fully vaccinated against HPV by age 15, 70% of women screened with a high-performance test by age 35 and again by 45, and 90% of women with cervical disease treated, with an elimination threshold of 4 per 100,000 women-years. Guideline texts were not opened
• the American Cancer Society 2020 screening update (PMID 32729638) and the 2019 ASCCP risk-based management consensus guidelines (PMID 32243307) are cited by identifier only

US Preventive Services Task Force 2018Ronco G, Dillner J, Elfström KM, Tunesi S, Snijders PJ, Arbyn M, et al 2014US Food and Drug Administration, Center for Devices and Radiological Health 2014US Food and Drug Administration, Center for Devices and Radiological Health 2024US Food and Drug Administration, Center for Devices and Radiological Health 2024US Food and Drug Administration 2026World Health Organization 2020Fontham ETH, Wolf AMD, Church TR, Etzioni R, Flowers CR, Herzig A, et al 2020Guideline: Perkins RB, Guido RS, Castle PE, Chelmow D, Einstein MH, Garcia F, et al 2020

Prevention

The FDA licensed Gardasil on 8 June 2006 for females aged 9 to 26 years, according to the FDA news release as reprinted by the Immunization Action Coalition. Population evidence of effect on cervical cancer comes from observational registry work:

• in England the estimated relative reduction in cervical cancer rates was 87% (95% CI 72 to 94) in women offered the bivalent vaccine at age 12 to 13 years (see the hooks). Fewer-dose evidence concerns persistent HPV infection, not cancer: in KEN SHE, single-dose bivalent or nonavalent vaccine gave vaccine efficacy of 97.5% against persistent HPV 16/18 infection at 18 months in young Kenyan women, compared with meningococcal vaccine
• in ESCUDDO, one dose of a bivalent or nonavalent vaccine was noninferior to two doses for HPV 16 or 18 infection persisting at least 6 months (months 12 to 60) in girls aged 12 to 16 years
• and an Indian cohort that began as a randomised dose comparison reported vaccine efficacy of 95.4% (95% CI 85.0 to 99.9) after a single dose, 93.1% after two doses and 93.3% after three doses at about 10 years. No WHO position paper or national vaccination schedule text was read, so no current dose recommendation is stated

US Food and Drug Administration 2006Falcaro M, Castañon A, Ndlela B, Checchi M, Soldan K, Lopez-Bernal J, et al 2021Barnabas RV, Brown ER, Onono MA, Bukusi EA, Njoroge B, Winer RL, et al 2022Kreimer AR, Porras C, Liu D, Hildesheim A, Carvajal LJ, Ocampo R, et al 2025Basu P, Malvi SG, Joshi S, Bhatla N, Muwonge R, Lucas E, et al 2021

Localised

Two randomised trials define current surgical questions. In LACC (stage IA1 with lymphovascular invasion, IA2 or IB1 disease), disease-free survival at 4.5 years was 86.0% with minimally invasive radical hysterectomy and 96.5% with open abdominal radical hysterectomy, a difference of -10.6 percentage points (95% CI -16.4 to -4.7), so the trial did not show noninferiority. In SHAPE (low-risk disease:

• lesions of 2 cm or less with limited stromal invasion), pelvic recurrence at 3 years was 2.17% after radical hysterectomy and 2.52% after simple hysterectomy with lymph-node assessment (absolute difference 0.35 percentage points
• 90% CI -1.62 to 2.32
• prespecified noninferiority margin 4 percentage points), with less urinary incontinence and retention after simple hysterectomy. The intermediate-risk adjuvant question is open (CERVANTES, see the horizon). The ESGO/ESTRO/ESP guidelines (update 2023
• PMID 37127326) and the NCCN Guidelines Insights, version 1.2024 (PMID 38081139) are cited by identifier only
• their text was not opened, and no recommendation from them is stated

Ramirez PT, Frumovitz M, Pareja R, Lopez A, Vieira M, Ribeiro R, et al 2018Plante M, Kwon JS, Ferguson S, Samouëlian V, Ferron G, Maulard A, et al 2024Guideline: Cibula D, Raspollini MR, Planchamp F, Centeno C, Chargari C, Felix A, et al 2023Guideline: Abu-Rustum NR, Yashar CM, Arend R, Barber E, Bradley K, Brooks R, et al 2023

Locally advanced

Chemoradiotherapy with brachytherapy (cisplatin-based in most of these trials; CALLA also allowed carboplatin) is the control backbone of the recent phase 3 trials; no guideline text was read for this statement. INTERLACE added 6 weeks of weekly carboplatin and paclitaxel before chemoradiotherapy:

• 5-year progression-free survival 72% versus 64% (hazard ratio 0.65
• 95% CI 0.46 to 0.91) and 5-year overall survival 80% versus 72% (hazard ratio 0.60
• 95% CI 0.40 to 0.91), with more grade 3 or higher adverse events (59% versus 48%). KEYNOTE-A18 added pembrolizumab with and after chemoradiotherapy in high-risk disease (FIGO 2014 stage IB2 to IIB node-positive or III to IVA): progression-free survival hazard ratio 0.70 (95% CI 0.55 to 0.89) at the first interim analysis, and at the second interim analysis 36-month overall survival 82.6% versus 74.8% (hazard ratio 0.67
• 95% CI 0.50 to 0.90). FDA approved pembrolizumab with chemoradiotherapy on 12 January 2024 for FIGO 2014 stage III-IVA cervical cancer (the letter calls it a priority approval)
• the current US Keytruda label (effective 10 July 2026 in the openFDA record) describes the indication as locally advanced cervical cancer, FIGO 2014 stage III-IVA, in combination with chemoradiotherapy, and the EMA Keytruda page lists the same stage group for adults who have not received prior definitive therapy. Two add-ons did not improve outcomes in their primary analyses: adjuvant carboplatin and paclitaxel after chemoradiotherapy (OUTBACK
• 5-year overall survival 72% versus 71%, hazard ratio 0.90, 95% CI 0.70 to 1.17) and durvalumab with and after chemoradiotherapy (CALLA
• progression-free survival hazard ratio 0.84, 95% CI 0.65 to 1.08, p=0.17). These trials enrolled different stage groups and were not compared with one another

McCormack M, Eminowicz G, Gallardo D, Diez P, Farrelly L, Kent C, et al 2024Lorusso D, Xiang Y, Hasegawa K, Scambia G, Leiva M, Ramos-Elias P, et al 2024Lorusso D, Xiang Y, Hasegawa K, Scambia G, Leiva M, Ramos-Elias P, et al 2024U 2024U 2026European Medicines Agency 2026Mileshkin LR, Moore KN, Barnes EH, Gebski V, Narayan K, King MT, et al 2023Monk BJ, Toita T, Wu X, Vázquez Limón JC, Tarnawski R, Mandai M, et al 2023

Metastatic

First-line treatment of persistent, recurrent or metastatic disease. Bevacizumab added to chemotherapy in GOG 240 was associated with median overall survival of 17.0 versus 13.3 months (hazard ratio for death 0.71; 98% CI 0.54 to 0.95), with more hypertension, thromboembolic events and gastrointestinal fistulas; FDA approved bevacizumab for persistent, recurrent, or metastatic carcinoma of the cervix on 14 August 2014 (the letter has no accelerated-approval wording), and the openFDA Avastin label (effective 6 January 2025) lists it with paclitaxel and cisplatin or paclitaxel and topotecan. In KEYNOTE-826 (first interim analysis), pembrolizumab added to platinum chemotherapy with or without bevacizumab gave median progression-free survival of 10.4 versus 8.2 months (hazard ratio 0.62; 95% CI 0.50 to 0.77) and 24-month overall survival of 53.0% versus 41.7% (hazard ratio 0.64; 95% CI 0.50 to 0.81) in patients with a PD-L1 combined positive score of 1 or more. FDA approved this combination on 13 October 2021 for tumours with a combined positive score of 1 or more as determined by an FDA-approved test, and the EMA Keytruda page lists the same restriction (CPS of 1 or more). Atezolizumab with bevacizumab and chemotherapy (BEATcc) and cadonilimab with platinum chemotherapy with or without bevacizumab (COMPASSION-16, conducted in China) have published phase 3 results; no FDA or EMA action for either was established here. The NCCN Guidelines Insights, version 1.2024 (PMID 38081139) are cited by identifier only.

Tewari KS, Sill MW, Long HJ 3rd, Penson RT, Huang H, Ramondetta LM, et al 2014FDA 2014U 2025Colombo N, Dubot C, Lorusso D, Caceres MV, Hasegawa K, Shapira-Frommer R, et al 2021FDA 2021European Medicines Agency 2026Oaknin A, Gladieff L, Martínez-García J, Villacampa G, Takekuma M, De Giorgi U, et al 2024Wu X, Sun Y, Yang H, Wang J, Lou H, Li D, et al 2024Guideline: Abu-Rustum NR, Yashar CM, Arend R, Barber E, Bradley K, Brooks R, et al 2023

Relapsed / refractory

After first-line chemotherapy. Tisotumab vedotin-tftv:

• FDA accelerated approval (effective 20 September 2021
• corrected letter signed 22 September 2021) for recurrent or metastatic cervical cancer with disease progression on or after chemotherapy, and regular approval on 29 April 2024 (supplement S-007
• the letter states that approval fulfils the accelerated-approval commitments) after innovaTV 301, in which median overall survival was 11.5 versus 9.5 months (hazard ratio 0.70
• 95% CI 0.54 to 0.89) and the confirmed objective response rate was 17.8% versus 5.2% against investigator's-choice chemotherapy. The European marketing authorisation for Tivdak is dated 28 March 2025 (EPAR page, which words the indication as progression on or after systemic therapy)
• the current US label still words the indication as progression on or after chemotherapy. Pembrolizumab as a single agent for PD-L1 combined positive score of 1 or more after chemotherapy: accelerated approval on 12 June 2018 (supplement S-034) and regular approval on 13 October 2021 (supplement S-122). Cemiplimab (EMPOWER-Cervical 1): median overall survival 12.0 versus 8.5 months against investigator's-choice chemotherapy (hazard ratio 0.69
• 95% CI 0.56 to 0.84) in patients with progression after first-line platinum-containing chemotherapy, regardless of PD-L1 status
• the EMA Libtayo page lists monotherapy for recurrent or metastatic cervical cancer after platinum-based chemotherapy (the date of that extension was not read), and the current US Libtayo label (openFDA record effective 31 August 2026) has no cervical indication

FDA 2021FDA 2024Vergote I, González-Martín A, Fujiwara K, Kalbacher E, Bagaméri A, Ghamande S, et al 2024EMA 2025U 2025FDA 2018FDA 2021Tewari KS, Monk BJ, Vergote I, Miller A, de Melo AC, Kim HS, et al 2022EMA 2026FDA 2026

Trials to watch

• AK104-305 NCT05235516

  In locally advanced cervical cancer (FIGO 2018 stage IIIA to IVA; the record excludes prior total hysterectomy and prior immune checkpoint therapy), does AK104 added to concurrent chemoradiotherapy differ from placebo with chemoradiotherapy in progression-free survival assessed by the investigator (the registry's primary outcome)? Registry record: randomised, double-blind, placebo-controlled phase 3, 636 estimated, sponsor Akeso. Registry status: active, not recruiting; registry primary completion date 2026-05 (listed as estimated; the record was last updated 2024-08-13); no results posted. AK104 is the sponsor's code, and the registry record does not give a generic name.

• CERVANTES NCT04989647

  In early-stage (FIGO IB1 to IIA) intermediate-risk cervical cancer after radical surgery, how does no further treatment compare with adjuvant radiotherapy or chemoradiotherapy in disease-free survival (the registry's primary outcome)? Registry record: randomised phase 3 with a stated noninferiority margin, 514 estimated, sponsor Central and Eastern European Gynecologic Oncology Group. Registry status: recruiting; registry primary completion date 2029-12 (estimated); no results posted.

• PAROLA NCT05581121

  In FIGO 2018 stage IIIC1 cervical cancer with FDG-positive pelvic nodes and FDG-negative para-aortic nodes on PET/CT, does pre-treatment para-aortic lymphadenectomy followed by tailored chemoradiotherapy and brachytherapy differ from PET/CT staging only followed by chemoradiotherapy in disease-free survival (the registry's primary outcome)? Registry record: randomised, open-label phase 3, 510 estimated, sponsor Institut Claudius Regaud. Registry status: recruiting; registry primary completion date 2033-12-20 (estimated); no results posted.

• Socazolimab first-line phase 3 NCT06459687

  As first-line treatment of persistent, recurrent or metastatic cervical cancer that cannot be cured by surgery or radiotherapy, does socazolimab added to platinum-paclitaxel chemotherapy with or without bevacizumab differ from placebo with the same chemotherapy in overall survival (the registry's primary outcome)? Registry record: randomised, double-blind, placebo-controlled phase 3, 440 estimated, sponsor Lee's Pharmaceutical Limited. Registry status: recruiting; registry primary completion date 2027-09-01 (estimated); no results posted.

• AddChemo NCT05764044

  In locally advanced cervical cancer (FIGO 2018 stage IB3 to IVA) with cell-free HPV DNA detected in plasma at the end of chemoradiotherapy, do two further cycles of cisplatin and gemcitabine differ from follow-up alone in progression-free survival (the registry's primary outcome, with a registry time frame of 120 days)? Registry record: randomised phase 3, 365 estimated, sponsor Hospital do Coracao. Registry status: recruiting; registry primary completion date 2026-12-31 (estimated); no results posted.

• JSKN033 phase 3 NCT07797153

  In recurrent or metastatic cervical cancer after platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor, how does subcutaneous JSKN033 compare with investigator's-choice chemotherapy (docetaxel, topotecan, gemcitabine or pemetrexed) in progression-free survival by blinded independent review and in overall survival (the registry's two primary outcomes)? Registry record: randomised, open-label phase 3, 368 estimated, sponsor Jiangsu Alphamab Biopharmaceuticals. Registry status: not yet recruiting, start estimated 2026-09, registry primary completion date 2028-12 (estimated); no results posted. The registry record was last updated 2026-09-01.