Human Papillomavirus Immunization and the Elimination of Cervical Carcinoma

Cervical Carcinoma I their current report, Baussano and colleagues describe how a human papillomavirus (HPV) immunization program in Bhutan is pointing the way toward realizing the World Health Organization (WHO) goal of eliminating cervical cancer (1). Bhutan achieved a high uptake of HPV vaccination (approximately 90%) in girls and women aged 12 to 18 years through a schoolbased program, with “catch-up” vaccination in older age groups. Through use of the quadrivalent vaccine, Bhutan saw an 88% reduction in vaccine-related high-risk HPV over 7 years, despite observed changes in sexual behavior associated with risk for HPV-related disease. These results are extremely encouraging considering the global burden of cervical cancer. A recent assessment placed cervical cancer among the top 3 cancer types affecting women younger than 45 years in nearly 80% of the 185 countries surveyed (2). This finding has major consequences in terms of lost productivity and disruption of families. By far, lowand middleincome countries (LMICs) bear the greatest burden. Understanding that nearly all cervical cancer cases are the result of HPV infection and elucidating the mechanism by which HPV causes cancer have led to the development of highly effective vaccines and molecular methods for screening populations for HPV infection. Given the breakthroughs in both primary and secondary prevention, the WHO has identified the elimination of carcinoma of the cervix as a worldwide public health challenge (3). The current vaccines are most effective in persons who have not been exposed to HPV infection. Their administration is generally limited to young persons (aged <18 years), meaning that many women will not benefit directly. However, the licensed vaccines do not protect against all HPV types that cause cervical cancer. Therefore, immunization alone, although fundamental in eliminating cervical cancer, is unlikely to be sufficient; a combination of screening and vaccination is crucial. In addition to the implementation of vaccination programs, the WHO has set a goal that by 2030, 70% of women aged 35 to 45 years should have been screened at least once in their lifetime and 90% of all detected lesions should have been treated. Effective cervical screening programs currently require considerable resources for organization and delivery of a test (the Papanicolaou [Pap] test). Given that Pap tests require skilled interpretation and rigorous quality control, such programs are not generally sustainable in LMICs. Molecular HPV testing is an exciting and important development, especially for LMICs. It offers the possibility of rapid, low-complexity HPV detection that can be performed on self-taken samples (4, 5). However, effective screening mandates affordable, accessible, and effective treatment, which may be challenging in LMICs. Notwithstanding these difficulties, a combination of HPV immunization and limited screening with HPV testing offers the best chance of eliminating cervical cancer worldwide. Implementing and sustaining an effective HPV immunization program has not been trouble-free. Some countries—Australia, Finland, and the United Kingdom, for example—have managed to achieve high (>70%) and sustained uptake. Other programs that initially had high uptake subsequently had dramatic reductions in adherence. In Japan, HPV vaccination rates dropped from more than 70% to less than 1% (6). In high-income countries, such factors as cohesive political endorsement, school-based delivery, and free-of-charge vaccination have contributed to success. Equally important has been effective and objective communication of the benefits to girls and women, and to their families, to counter and challenge information promulgated by the antivaccine lobby. Monitoring of immunization programs, preferably at the individual level, is essential to provide information that is specific to the population being targeted. Baussano and colleagues demonstrate that a successful immunization program is achievable in an LMIC given the appropriate political and financial resources. Their work was supported by the Bill & Melinda Gates Foundation and the International Agency for Research on Cancer, and Gavi (The Vaccine Alliance) has received pledges to support HPV vaccination programs in LMICs (7). An immunization program requires an infrastructure to deliver the vaccines, the choice of an appropriate vaccine, availability of the vaccine, and an agreed-on schedule for administration. After several successful worldwide campaigns, many LMICs now have the necessary infrastructure. Three effective vaccines are available for use: the quadrivalent vaccine, which protects against HPV 6, 11, 16, and 18; the bivalent vaccine, which protects against HPV 16 and 18 and provides substantial crossprotection against HPV 31, 33, and 45; and the nonavalent vaccine, which has the same spectrum as the quadrivalent vaccine with additional protection against HPV 31, 33, 45, 52, and 58 (8, 9). The choice of vaccine for a country is determined partly by the spectrum of HPV types associated with cancer cases in that region and partly by cost. Vaccines generally are administered on a 2-dose schedule (0 and 6 months), but increasing evidence shows that 1 dose generates substantially more persistent immunity than natural infection and may be sufficient for protection (10). The implications of this option for affordability and sustainability of immunization are clear. These factors are irrelevant, however, without the willingness of the population to be vaccinated. Achieving and sustaining the level of uptake needed for elimination of cervical cancer requires communicating to