Vaccines That Can Treat HPV

In a nutshell

Therapeutic vaccines against human papillomavirus (HPV) are currently being developed and may become an important new tool in the fight against cervical cancer. Unlike prophylactic HPV vaccines, which prevent new infections, therapeutic vaccines will be developed to eliminate or treat existing HPV infections as well as HPV-related cancers or precancerous lesions. A few days ago, WHO published a report on the preferred characteristics of these vaccines, including which populations they should be useful for, safety and effectiveness, and immunization strategies, to guide researchers and manufacturers. To date, the development of these therapeutic vaccines has primarily focused on candidates targeting regression of CIN2/3 lesions and invasive cervical cancer.

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Vaccines that treat HPV could help save hundreds of thousands of lives lost to cervical cancer

Although highly effective vaccines exist to protect against human papillomavirus (HPV), the leading cause of cervical cancer, millions of women in Middle- and low-income people (who account for the majority of cervical cancer cases globally) remain at risk. HPV vaccines were only introduced in Africa a decade ago, so many women have not yet had access to the vaccine and are unlikely to have access to early detection and treatment.

“Therapeutic” HPV vaccines (vaccines given after HPV infection, rather than before) could help save hundreds of thousands of lives lost to cervical cancer.

A few days ago, the World Health Organization (WHO) published a report on the preferred characteristics of these therapeutic HPV vaccines, including which populations these vaccines should benefit, safety and efficacy, and immunization strategies, to guide researchers and manufacturers.

Therapeutic HPV vaccines

Therapeutic vaccines against human papillomavirus are currently being developed and may be an important new tool in the fight against cervical cancer. Unlike available prophylactic HPV vaccines, which prevent new infections, advances in immunotherapy are opening a new era of therapeutic vaccines designed to eliminate or treat existing HPV infections and HPV-associated cancers or precancerous lesions.

According to the published report, WHO’s Preferred Product Characteristics (PPC) provide strategic guidance on the agency’s preferences for new vaccines in priority diseases. The CFP aims to encourage innovation and development of vaccines for use in appropriate settings with unmet global public health needs.

The first therapeutic vaccine approved by the U.S. Food and Drug Administration (FDA) was Provenge in 2010, used to treat men with advanced prostate cancer. Since then, other therapeutic vaccines have been developed for HIV and HPV.

At present, There are more than 20 potential therapeutic HPV vaccines in various stages of development.and some of them are undergoing clinical trials. Various technologies have been used to develop these therapeutic vaccines, including peptide-based, protein-based, DNA/RNA vaccines, and bacterial and viral vector platforms.

Approach to therapeutic vaccines

Therapeutic HPV vaccines are designed to act in the setting of active and ongoing infection. They are therefore different from prophylactic vaccines that prevent infection. All HPV types encode “early” proteins (E proteins: E1, E2, E4-E7) and “late” virion structural proteins (L proteins: L1, L2). To cause infection, HPV virions bind to basal epithelial cells via the viral capsid protein L1. Current highly effective prophylactic HPV vaccines target L1 (figure attached).

In infected cells, E1 and E2 proteins are responsible for viral replication and transcription, while E6 and E7 proteins direct cell proliferation. Because E6 and E7 play important roles in cellular transformation, these viral proteins have so far been the primary targets of most potential therapeutic vaccines designed to treat later stages of HPV disease, such as precancerous and invasive cervical cancer (Figure attached).

To date, the development of these therapeutic HPV vaccines has primarily focused on candidates targeting regression of CIN2/3 lesions and invasive cervical cancer.

A systematic review of completed phase 2 and 3 HPV therapeutic vaccine trials targeting CIN2/3 lesions identified 12 studies published in 2022–2023 (six vector-based vaccines, three peptide-based protein vaccines, and three nucleic acid-based vaccines) (Khalil, BMJ Open 2023). In addition, at least six therapeutic vaccine candidates were registered as active in phase 1 or 2 clinical trials in June 2023.

Several studies have shown regression of high-grade (CIN2/3) and low-grade (CIN1) lesions or absence of precancerous lesions after therapeutic HPV vaccination, with modest but significant differences compared with natural regression. In a meta-analysis of controlled trials, the proportion of patients achieving regression after vaccination was approximately 50% higher than in the placebo group.

These data support the concept that A therapeutic vaccine may induce immune responses that may cause regression of high-grade precancerous lesions.although efficiency will need to be improved.

Future Prospects

Existing early studies have shown that resolution of infection (defined as loss of HPV detection by a sensitive nucleic acid amplification test) often occurs concomitantly with regression of precancerous lesions.

So far, all candidates have been multi-dose formulations (usually three doses) administered at regular intervals over several months. The most common route of administration in clinical trials has been parenteral (subcutaneous and intramuscular). Other routes of administration include oral administration and direct injection into the cervix.

Report WHO is calling on vaccine manufacturers to ensure their products are effective in low- and middle-income countries, where more than 90% of cervical cancer-related deaths occur.

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More detailed information on this website

Bibliographic references

• Canfell K, Kim JJ, Brisson M, Keane A, Simms CT, Caruana M, et al. Mortality impact of achieving the WHO cervical cancer elimination targets: a comparative modelling analysis in 78 low-income and lower-middle-income countries. The Lancet. 2020;395(10224):591–603.
• Cohen JA, Stewart RM, Lee S, Klein DJ, Kerr CC, Rao DW, et al. Understanding key determinants of a therapeutic HPV vaccine: a modeling analysis. 2023.
• Ibrahim Khalil A, Zhang L, Muwonge R, Sovaget S, Basu P. Efficacy and safety of therapeutic HPV vaccines for the treatment of CIN 2/CIN 3 lesions: a systematic review and meta-analysis of phase II/III clinical trials. BMJ Open. 2023;13(10):e069616.
• Mo Y, Ma J, Zhang H, Shen J, Chen J, Hong J, et al. Prophylactic and therapeutic HPV vaccines: current scenario and prospects. Forehead cells infect microbiol. 2022;12:909223.
• Oyuni AA. Human papillomavirus in cancer: infection, disease transmission, and progress in vaccine development. J Infect Public Health. 2023;16(4):626–31.
• Pradden HJ, Achilles SL, Schocken S, Brute N, Canfell K, Acaba H, et al. Understanding the public health value and identifying preferred characteristics of therapeutic human papillomavirus (HPV) vaccines: World Health Organization consultation, October 2021–March 2022. Vaccine. 2022;40(41):5843–55.
• Smalley Rumfield S, Roller N, Pellom ST, Schlom J, Jochems K. Therapeutic vaccines against HPV-associated malignancies. ImmunoTargets Ther. 2020;9:167–200.
• Stanley MA. Epithelial cell response to human papillomavirus infection. Clin Microbiol Rev 2012;25(2):215–22.
• Wendell Naumann R, Leet CA, 3rd. Advances in Immunotherapy for Cervical Cancer. Current Opin Oncol. 2020;32(5):481–7.
• www.clinicaltrials.gov: NCT04607850; NCT03913117; NCT04490512, last accessed June 15, 2024. NCT04607850; NCT03913117; NCT04490512; NCT00788164; NCT04131413; NCT03911076.