Cervical cancer remains one of the most common cancers affecting women worldwide. It is strongly linked to long-term infection with high-risk types of human papillomavirus (HPV), especially HPV16 and HPV18. Vaccination against HPV 16 and HPV 18 are effective in preventing cervical cancer, especially when given in adolescence. However, once cervical cancer occurs, surgery, chemotherapy, and radiation can be effective in early stages, but outcomes are still poor for advanced or recurrent disease.
A 2025 review published in Exploration of Targeted Anti-tumor Therapy highlights how immunotherapy is changing the treatment landscape. By helping the immune system recognize and attack cancer cells, these newer approaches are offering new hope for better outcomes
Why Cervical Cancer Is a Good Target for Immunotherapy
HPV plays a major role in the development of cervical cancer. The virus produces proteins called E6 and E7. These proteins interfere with important tumor suppressor genes such as p53 and Rb. When these genes are disrupted, cells grow out of control and become cancerous
Because HPV-related cancer cells carry viral proteins, they can be recognized by the immune system. This makes cervical cancer a strong candidate for immunotherapy. However, tumors often develop ways to hide from immune attack. They create an immunosuppressive tumor microenvironment, which means they block or weaken immune responses
Immunotherapy aims to remove these “brakes” on the immune system and restore its ability to fight cancer.
Immune Checkpoint Inhibitors: Releasing the Brakes
One of the most important breakthroughs has been immune checkpoint inhibitors (ICIs). These drugs block proteins such as PD-1 and PD-L1. Normally, these proteins help prevent the immune system from attacking healthy tissue. But cancer cells can use them to hide from immune attack
Drugs like pembrolizumab, nivolumab, atezolizumab, durvalumab, and cemiplimab target these pathways. By blocking PD-1 or PD-L1, they allow T cells (a type of immune cell) to stay active and attack tumor cells
In metastatic or recurrent cervical cancer, pembrolizumab showed meaningful response rates in clinical trials. Cemiplimab improved overall survival compared with chemotherapy in patients whose disease had returned
Checkpoint inhibitors have also been tested in combination with chemotherapy, radiation, or anti-angiogenic drugs like bevacizumab. Some large trials showed improved progression-free survival and overall survival when immunotherapy was added
However, response rates are still limited. Not all patients benefit, and some experience immune-related side effects because the immune system becomes overactive.
Combining Radiation and Immunotherapy
Radiation therapy does more than kill cancer cells. It can also stimulate the immune system. When radiation damages tumor cells, it releases tumor antigens. These antigens help activate immune cells and attract them to the tumor site
Radiation can also change the tumor microenvironment, making it less suppressive and more immune-friendly. When combined with checkpoint inhibitors, this may create a stronger anti-tumor effect
Some clinical trials have shown promising results using immunotherapy alongside chemoradiation in locally advanced cervical cancer. In certain studies, adding a PD-1 inhibitor reduced the risk of progression or death
Researchers are still working to determine the best timing and dosing strategies for these combinations.
Therapeutic HPV Vaccines: Training the Immune System
Unlike preventive HPV vaccines, therapeutic vaccines are designed to treat existing HPV infections or cancer. These vaccines target the HPV E6 and E7 proteins that remain active in cancer cells
Several types are being studied, including:
- DNA vaccines
- Peptide-based vaccines
- Protein-based vaccines
- Dendritic cell (DC) vaccines
Some trials have shown lesion regression and improved immune responses in patients with high-grade precancerous lesions
These vaccines aim to generate strong cytotoxic T-cell responses. While still largely investigational, they represent an important area of ongoing research.
Adoptive Cell Therapy: Engineering the Immune Response
Adoptive cell therapy (ACT) takes a more personalized approach. In this method, a patient’s own T cells are removed, modified or expanded in the lab, and then reinfused to target cancer cells
There are several types of ACT:
- Tumor-infiltrating lymphocytes (TILs)
- T-cell receptor (TCR) engineered T cells
- Chimeric antigen receptor (CAR)-T cells
Some early studies have shown tumor regression in patients with HPV-associated cervical cancer using T cells targeting E6 and E7 proteins
However, solid tumors like cervical cancer present challenges. The tumor microenvironment can block immune cell access, and tumors may vary in the antigens they express. Researchers are working to overcome these barriers.
Challenges and the Road Ahead
Despite encouraging progress, several challenges remain. PD-L1 is not a perfect biomarker for predicting who will respond to treatment. Immune-related side effects require careful monitoring. High costs also limit access, especially in low- and middle-income countries where cervical cancer rates are highest
The scientific review also highlights the growing role of antibody-drug conjugates (ADCs), such as tisotumab vedotin. These drugs deliver chemotherapy directly to cancer cells while limiting damage to healthy tissue
Future progress will likely depend on better biomarkers, smarter combination strategies, and more personalized treatment plans.
A Transforming Treatment Landscape
Immunotherapy has already expanded options for patients with cervical cancer, especially in advanced stages. While it is not a cure for everyone, it represents a major step forward.
As research continues, combining immune checkpoint inhibitors, vaccines, adoptive cell therapies, radiation, and targeted drugs may further improve outcomes. The growing understanding of the immune system’s role in cervical cancer is opening the door to more effective and lasting treatments.
Source
Dey T, Agrawal S. Immunotherapy in cervical cancer: an innovative approach for better treatment outcomes. Explor Target Antitumor Ther. 2025;6:1002296. Available from https://pmc.ncbi.nlm.nih.gov/articles/PMC11886377/
