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Human papillomavirus(HPV) vaccine efficacy and immunogenicity in women with existing HPV infections

Human papillomavirus(HPV) vaccine efficacy and immunogenicity in women with existing HPV infections

Fanghui Zhao

National Cancer Center & Cancer Hospital,Chinese Academy of Medical Sciences

05 June 2020

Human papillomavirus(HPV) infection is a common viral infection that is often spread through sexual contact. There are more than 100 different types of HPV. Many types do not cause problems in most people, but some types are linked to cancer, especially cervical cancer. These oncogenic types are called high-risk HPV(HR-HPV) types, causing nearly all cervical cancers (99.7%). Effective HPV vaccines are currently available to protect against cervical cancer caused by some of these HR-HPV types. However, these vaccines are all prophylactic and do not cure pre-existing infections. Therefore, HPV vaccines are most effective before sexual exposure and are recommended mainly in adolescent girls. However, there are a percentage of unvaccinated women who might be currently infected with HR-HPV (HR-HPV DNA positive), which raises the question about how much the HPV vaccine can benefit this population.We thus proposed research to analyze efficacy and immunogenicity purely in women who are HR-HPV DNA positive at first vaccination. In previous published papers, data in this population are always combined with data from DNA negative women. The efficacy trials for AS04-HPV-16/18 vaccine were sponsored by GSK with similar study design and registered on https://clinicaltrials.gov. This provide chance to look at the vaccine benefit in HR-HPV DNA positive women, which would not have been feasible in individual trials due to a limited sample size.By pooling the data, we propose to address the research question from the following 4 aspects: 1. In women infected with any HR-HPV types, whether the residual benefit of preventing infection associated with other non-infected HR-HPV types would be sufficient to warrant vaccination? 2. In women DNA positive for HPV-16 or HPV-18, what's the vaccine efficacy against re-infections associated with HPV-16/18 after their immune system clears the baseline infection? 3. What's the long-term immune response in women DNA positive for HPV-16 or HPV-18 at first dose? 4. In women allocated in control arm in selected trials, whether women DNA positive for one type of HR-HPV have increased risks in later years to be infected with other HR-HPV types? This research will help to address the very real confusion existing among both clinicians and adult women about HPV benefit in HR-HPV DNA positive women and thus hold promise for reinforcing the confidence for extending vaccine benefit to this population.

[{ "PostingID": 1516, "Title": "GSK-104798", "Description": "A phase II study to assess the efficacy, immunogenicity and safety of GSK Biologicals' HPV-16/18 L1 VLP AS04 (Cervarix TM) vaccine administered intramuscularly according to a 0, 1, 6 month schedule in healthy Japanese female subjects aged 20 - 25 years." },{ "PostingID": 1517, "Title": "GSK-104820", "Description": "A study to evaluate safety, immunogenicity and efficacy of GSK Biologicals HPV-16/18 L1/AS04 vaccine administered intramuscularly according to a three-dose schedule (0, 1, 6 month) in healthy adult female subjects aged 26 years and above" },{ "PostingID": 1528, "Title": "GSK-580299/008", "Description": "A phase III, double-blind, randomized, controlled, multi-center study to evaluate the efficacy of GlaxoSmithKline Biologicals. HPV-16/18 VLP AS04 vaccine compared to hepatitis A vaccine as control in prevention of persistent HPV-16 or HPV-18 cervical infection and cervical neoplasia, administered intramuscularly according to a 0, 1, 6 month schedule in healthy females 15-25 years of age." },{ "PostingID": 2794, "Title": "GSK-107638", "Description": "Efficacy, immunogenicity and safety of GlaxoSmithKline Biologicals’ HPV GSK 580299 vaccine in healthy Chinese female subjects" },{ "PostingID": 2795, "Title": "GSK-112949", "Description": "Long-term extension study of the efficacy of the 580299 vaccine in the prevention of HPV-16 and/or HPV-18 associated cervical intraepithelial neoplasia (CIN) in Japanese women vaccinated in the primary vaccination study NCT00316693" }]

Statistical Analysis Plan

Wen T-M, Xu X-Q, Zhao X-L, et al. Efficacy and immunogenicity of AS04-HPV-16/18 vaccine in females with existing cervical HR-HPV infection at first vaccination: A pooled analysis of four large clinical trials worldwide. Int J Cancer. 2024; 1-15