Cervical Cancer Clinical Trials 2026: Recruiting Studies for HPV-Positive & Advanced Disease

Cervical cancer, caused by persistent human papillomavirus (HPV) infection, kills approximately 350,000 women annually worldwide — a statistic that stands in stark contrast to the fact that it is one of the most preventable cancers in existence. In high-income countries where screening and HPV vaccination are widespread, cervical cancer rates have fallen dramatically; globally, it remains the fourth most common cancer in women. The 2026 clinical trial landscape is focused on two distinct patient populations: women in high-income countries who developed cervical cancer despite screening access (often with aggressive or advanced disease) and women in low- and middle-income countries for whom new screening and treatment tools need to work without cold-chain vaccines or colposcopy infrastructure. The therapeutic research — particularly around tisotumab vedotin, pembrolizumab combinations, and HPV-targeted T-cell therapies — represents a genuine change in the prognosis for recurrent disease.

Tisotumab Vedotin (Tivdak) Combination Trials

Tisotumab vedotin is an antibody-drug conjugate (ADC) targeting tissue factor (TF), which is highly expressed in cervical cancer. It delivers monomethyl auristatin E (MMAE), a cytotoxin, directly to TF-expressing tumor cells. After innovaTV 301 demonstrated improved overall survival over chemotherapy in second-line recurrent cervical cancer, trials in 2026 are evaluating:

• Tisotumab vedotin + pembrolizumab in first-line metastatic disease (innovaTV 205 expansion cohorts)
• Tisotumab vedotin + carboplatin combination regimens in platinum-eligible populations
• ADC sequencing — optimal treatment sequence after prior pembrolizumab failure
• Biomarker studies — TF expression level as a predictive marker for response

The main safety concern with tisotumab vedotin is ocular toxicity (conjunctivitis, keratitis). Eye care protocols — lubricating drops and cold compresses during infusion — are now standard; trials are testing modified protocols to further reduce this risk.

Immunotherapy: Checkpoint Inhibitors and Beyond

Pembrolizumab (Keytruda) became the standard first-line addition to chemotherapy for PD-L1 CPS ≥1 recurrent/metastatic cervical cancer following KEYNOTE-826. Cemiplimab (Libtayo) is approved as monotherapy for second-line after platinum. The 2026 trial landscape is testing:

• Durvalumab + concurrent chemoradiation for locally advanced disease (CALLA trial follow-up and expansion)
• PD-L1 inhibitors for PD-L1 CPS <1 populations — where benefit has been unclear
• LAG-3 + PD-1 dual checkpoint blockade in checkpoint-refractory disease
• TIGIT inhibitors in combination with anti-PD-1 for immune-cold tumors

HPV-Targeted Cell Therapies and Therapeutic Vaccines

Because cervical cancer is driven by HPV oncoprotein expression (E6 and E7), the tumor presents HPV-derived peptides on its surface — making it a target for HPV-specific T-cell therapies unlike most solid tumors where the antigen is not so clearly defined.

TIL (Tumor-Infiltrating Lymphocyte) Therapy

The NCI Surgery Branch's TIL therapy — expanded tumor-infiltrating T-cells, reinfused after lymphodepletion — has shown dramatic responses in HPV-positive cervical cancer. Complete response rates of 10–15% in heavily pretreated patients are extraordinary for recurrent metastatic disease. Iovance Biotherapeutics is conducting Phase 3 TIL trials for cervical cancer. Eligibility typically requires adequate organ function and performance status after 1–2 prior lines of therapy.

Therapeutic HPV Vaccines

Unlike preventive HPV vaccines (Gardasil 9), therapeutic vaccines aim to generate immune responses against established HPV infection or tumor. Candidates in 2026 trials include:

• ISA101 (SLP HPV-16 peptide vaccine) — combined with pembrolizumab in KEYNOTE-A18 extension cohorts
• mRNA-based HPV vaccines (Moderna's mRNA-4157 platform adapted for HPV E6/E7 neoantigen targets)
• DNA vaccines (VGX-3100 in combination with immunotherapy for CIN3 and early cervical cancer)

Early-Stage: Fertility-Sparing and De-Escalation Trials

For women diagnosed with early-stage cervical cancer (Stage IB1–IB2), an active area of research addresses whether standard radical hysterectomy over-treats low-risk disease:

• Simple hysterectomy vs. radical hysterectomy in Stage IB1 ≤2cm tumors (ConCerv and similar trials)
• Fertility-sparing trachelectomy in young patients with early-stage disease — trials assessing oncological equivalence and fertility outcomes
• Neoadjuvant chemotherapy to downstage locally advanced disease before fertility-preserving surgery

Who Can Join a Cervical Cancer Trial?

Requirements vary significantly by trial stage and type, but common criteria for recurrent/metastatic disease trials include:

• Histologically confirmed cervical cancer (squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma)
• ECOG performance status 0–1 (ambulatory, able to carry out light work)
• Prior platinum-based chemotherapy (for second-line trials)
• Measurable disease by RECIST 1.1 criteria
• Adequate hematologic, hepatic, and renal function
• No active autoimmune disease (for immunotherapy trials)

PD-L1 expression (CPS score) is required for some pembrolizumab trials but not for ADC or TIL trials. Fresh or archival tumor biopsy is typically required for biomarker analysis.

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