Immunotherapy
For Cervical Cancer

How is Immunotherapy for Cervical Cancer Changing the Outlook for Patients?

Reviewed by:

Dmitriy Zamarin, MD, PhD
Memorial Sloan Kettering Cancer Center

Immunotherapy for cervical cancer shows promise with preventive vaccines and new treatment directions.

Cervical cancer is the fourth most common cancer in the world for women, affecting over half a million people every year. Almost all cases of cervical cancer are associated with human papilloma virus (HPV) infection. This prevalent virus is also linked to anal, genital, and head and neck cancers. Most people infected by HPV do not develop cancers associated with the virus.

During the early stages, cervical cancer can usually be detected early with regular Pap smear, also called a Pap test, a procedure in which cells are scraped from the cervix and looked at under a microscope. Mortality rates have been decreasing in United States, thanks largely to widespread use of the Pap smear as a screening tool. In addition to the Pap smear, DNA tests can also detect HPV strains that pose a cervical cancer risk. Cervical cancer incidence and mortality, however, remain significantly higher in low-income countries.

Symptoms of this disease often go undetected until the cancer becomes invasive. Abnormal vaginal bleeding is the most common sign of cervical cancer.

There are an estimated 570,000 new cases of cervical cancer diagnosed and 310,000 cervical cancer-related deaths each year globally, and in 2023 there will be an estimated 14,000 new cases and 4,000 deaths in the United States alone. If cervical cancer is caught while it is still localized, the five-year survival rate is 92%. The five-year survival rates for patients with regional and distant disease are 57% and 17%, respectively.

Three immunotherapy vaccines (below) are FDA-approved to prevent HPV infection. Since the introduction of the first HPV vaccine in 2006, the number of new cases of cervical cancer has dropped significantly in the United States. Recent studies have begun to provide evidence that vaccination may also provide some benefit to people who have been infected previously with HPV. While these vaccines are effective in preventing HPV infection, there is no evidence that the vaccines are effective against established cancers.

Preventive Vaccines

• Cervarix®: a vaccine approved for use in preventing infection by the two strains of HPV that cause most cervical cancers, HPV types 16 and 18; can help prevent the development of HPV-related cervical, vulvar, vaginal, and anal cancers
• Gardasil®: a vaccine that protects against infection by HPV types 16, 18, 6, and 11; can help prevent the development of HPV-related cervical, vulvar, vaginal, and anal cancers
• Gardasil-9®: a vaccine approved for the prevention of infection by HPV types 16, 18, 31, 33, 45, 52, and 58, and for the prevention of genital warts caused by HPV types 6 or 11; can help prevent the development of HPV-related cervical, vulvar, vaginal, and anal cancers

Cervical Cancer Treatment Options

Standard treatment options for cervical cancer are surgery, radiation therapy, chemotherapy, and targeted therapy.

Immunotherapy is class of treatments that take advantage of a person’s own immune system to help kill cancer cells. There are currently three FDA-approved immunotherapy options for the treatment of cervical cancer.

Targeted Antibodies

• Bevacizumab (Avastin®): a monoclonal antibody that targets the VEGF/VEGFR pathway and inhibits tumor blood vessel growth; approved for subsets of patients with advanced cervical cancer in combination with chemotherapy
• Tisotumab vedotin (Tivdak™): an antibody-drug conjugate that targets tissue factor (TF); approved for subsets of patients with advanced cervical cancer

Immunomodulators

• Pembrolizumab (Keytruda®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with advanced cervical cancer that has PD-L1 expression, high microsatellite instability (MSI-H), DNA mismatch repair deficiency (dMMR), or high tumor mutational burden (TMB-H)

Other vaccines and immunotherapies that target HPV-infected tumors are also currently being tested in clinical trials.

CRI’s Impact in Cervical Cancer

Since 1953, the Cancer Research Institute has dedicated more than $10 million in funding to develop and discover immunotherapies that can treat gynecologic cancers, including cervical cancer. CRI’s support of cervical cancer and human papillomavirus research has led to several breakthroughs in treatment, including paving the way for more effective prevention methods.

• In 1999, CRI awarded the first of several grants to Ian H. Frazer, MD, FRCPA, for work on “virus-like particles” (VLP) based papillomavirus vaccines—crucial to the development of the first preventive cervical cancer vaccine, Gardasil®.

“This new vaccine that prevents cervical cancer grew out of research funded by CRI.”

Professor Ian Frazer, 2003 CRI Annual Report

• In 2009, Sjoerd van der Burg, PhD, and Cornelis (Kees) Melief, MD, PhD, at Leiden University Medical Center, found in a CRI-sponsored study that a vaccine composed of HPV long peptides could result in durable complete responses in some women with HPV 16+ vulvar intraepithelial neoplasias (VINs), a disease that normally has a spontaneous regression rate of less than 2%.
• In 2014, W. Martin Kast, PhD, was awarded a Clinic and Laboratory Integration Program (CLIP) grant from CRI to test a treatment that combines chemoradiation and the immunotherapy ipilimumab (Yervoy®) to trigger a targeted immune attack against cervical cancer cells and lead to a much-needed treatment for cervical cancer patients.
• In 2020, Sjoerd van der Burg, PhD, and Cornelis (Kees) Melief, MD, PhD, at Leiden University Medical Center, revealed the benefits of a vaccine-chemotherapy combination in advanced, HPV-associated cervical cancer.

You can explore CRI’s current funding for cervical cancer research in our funding directory.