Human Papillomavirus Vaccination and Cervical Cancer Risk

The progression of high-risk human papillomavirus (hrHPV) to cervical cancer is well characterized, and risk factors for hrHPV including genetic predisposition, hormonal factors, host immune response, and cigarette smoking are well documented. Prevention of cervical cancer primarily relies on preventing hrHPV infection through vaccination, as well as treatment of precancerous lesions (high-grade cervical intraepithelial neoplasia [CIN2/3] or adenocarcinoma in situ [ACIS]). Bivalent, quadrivalent, and nonavalent HPV vaccines are prequalified by the World Health Organization (WHO) and widely licensed; however, less than 25% of low-income countries have HPV vaccination as part of their national immunization schedules. The WHO set a target for 194 countries to adopt HPV vaccination by 2030, and this article summarizes clinical data on the efficacy and effectiveness of HPV vaccination, its potential impact on incidence of invasive cervical squamous cell carcinoma (ICC), and strategies to increase access to and uptake of vaccination. Large online databases were searched for randomized control trials and population-based cohort studies in which HPV vaccination and pathologic diagnosis were documented in the data set. Several large-scale studies including a Cochrane review of 73,428 participants and a meta-analysis of more than 60 million, and data from National registries in Sweden, Japan, and the United Kingdom demonstrated that HPV vaccination is safe and leads to prevention of cervical precancer. In April 2022, the WHO updated its recommendation to be 1 or 2 doses for girls aged 9-14 years; 1 or 2 doses for girls aged 15-20 years; and 2 doses separated by 6 months for women older than 21. Eight of every 10 cases of IIC occur in low- and middle-income countries (LMICs), and ICC is the leading cause of death from cancer among women in sub-Saharan Africa. Disparities among these countries are driven by inequity in access to prevention and treatment of cancer. Global HPV vaccination coverage for girls is approximately 18% for a first dose and 13% for series completion. On the supply side, barriers to vaccination include prohibitive cost of vaccines for many LMICs and the requirement for refrigeration of all licensed vaccines. Promisingly, a new quadrivalent prophylactic HPV vaccine is becoming available in 2023 in India that may significantly reduce the cost of vaccine doses and may not require refrigeration. On the demand side, misinformation, cultural views on sex, and mistrust of the medical system are major barriers. According to data from 37 registries in 20 countries, without changing the rate of HPV vaccination or cervical cancer screening, the global burden will increase from an estimated 600,000 in 2020 to 1.3 million in 2069. Models demonstrate that a rapid scale up of HPV vaccination to more than 80% of adolescent girls and continued or increased screening could result in 13 million cases of ICC averted in LMICs and an incidence of ICC less than 4 per 100,000 women worldwide. Robust literature and extensive modeling show us that HPV vaccination is effective in preventing infection with the virus, cervical precancers, ICC, and with the help of biomedical and policy innovation; the near elimination of cervical cancer is possible in countries with robust uptake of the vaccine.