Can the HPV Vaccine Prevent More Than Cervical Cancer?

An Epidemiologic Perspective

Kevin GJ Pollock

Disclosures

Future Virology. 2014;9(10):887-889. 

In the UK, cervical cancer is the second most common cancer in women under 35 years.[1] HPV types 16 and 18 (both high risk) are essential precipitants in at least 70% of cervical cancers,[2] but may contribute in excess of 80% of cervical cancers in Scotland.[3] Both the prophylactic bivalent (Cervarix) and quadrivalent (Gardasil) vaccines prevent infection with HPV types 16 and 18, and have been shown to induce avid and sustained neutralizing antibody responses which prevent cervical HPV 16 and 18 infection while conferring protection against consequent viral-induced cervical intraepithelial neoplasia (CIN).[4,5]

Emerging data from population-based surveillance of HPV vaccination programs suggest that vaccination is strongly associated with a reduction in high-grade cervical abnormalities (CIN of grade 2 or worse) in young women.[5–7] Furthermore, the quadrivalent vaccine, which additionally includes HPV types 6 and 11 (both low risk) that are associated with 85–95% of genital warts (GWs) has also been shown to be strongly associated with a reduction in GW in both females and heterosexual males.[8] In Australia, the decrease in GWs in heterosexual men was observed prior to the implementation of vaccination of boys and is likely due to community (also known as herd) immunity.

In the Occidental world cancers of the anus, penis, vagina and vulva (here forth described as noncervical genital cancers) are increasing in incidence.[9] The increase in noncervical genital cancers may be associated with a concomitant rise in high-risk oncogenic HPV infections, with HPV-16 and -18 estimated to contribute between 74 and 93% of these cancers.[10] Autoinoculation of HPV occurs both from cervix to anus, and from anus to cervix in the same woman, and it appears to be quite common.[11] Although no natural history studies of anal intraepithelial neoplasia (AIN) are available in women, women with other HPV-associated lesions, including high-grade CIN and vulvar cancer, have higher rates of anal cancer. Therefore, it seems biologically plausible that girls vaccinated with the HPV vaccine will have a significantly reduced propensity in developing noncervical genital cancers.[10]

HPV has also been causally implicated in a subset of cancers of the upper aero-digestive tract, especially HPV-16 and oropharyngeal cancer.[12] A marginal role for HPV-18 was also determined, independent of HPV-16 infection, and this large case–control study also found that HPV-6 was associated with laryngeal cancer. However, there have been numerous population-based oral prevalence studies, and when one considers the heterogeneity of study populations, differences in sample preparation and viral detection methods, the range of HPV prevalence estimates (37–60%) may not accurately reflect the scope of HPV-associated oropharyngeal cancers.[13] Steinau and colleagues suggest that in their analysis of US cancer registries, 62% of oropharyngeal squamous cell carcinomas were positive for both HPV-16 and -18. While prevalence varied significantly by demography, the HPV vaccine should afford a significant protective effect against HPV-driven oropharyngeal cancers.

While the benefits of the HPV vaccine are now being realized,[6,8] efficacy is dependent on a number of critical factors. National vaccine programs that target preadolescent girls through school-based delivery are likely to be more successful in preventing HPV infection and disease.[14,15] However, such coordinated programs require a robust and well-governed infrastructure, and tend only to be a feature of high-income countries (HICs), although high HPV vaccine uptake has been achieved in Rwanda.[16] Nevertheless, the burden of disease attributable to HPV infection is significantly greater in deprived countries, where recognized barriers such as high vaccine cost must be overcome if global burden of disease is to be reduced.[17]

Gender-neutral vaccination has been recommended in the USA, Canada, Austria and Australia. Considered cost-effective modelling has preceded such decisions, suggesting that when the burden of disease in men is included in the models then, depending upon vaccine price and vaccine uptake as well as other factors, male vaccination can become cost effective.[18] Although the HPV vaccine is not currently offered to boys within the UK, the UK Joint Committee on Vaccination and Immunization is appraising the evidence as to whether vaccination of boys would be cost effective. In a recent Norwegian analysis, public health priority and cost–effectiveness appears to be directed towards increasing vaccine uptake in girls rather than expanding vaccination coverage to boys, but this is crucially dependent upon vaccine tender price.[19]

There are indirect benefits of the HPV vaccine. Achieving high HPV vaccine uptake may reduce inequalities in cervical cancer prevention by mitigating against the inequalities observed in the cervical screening program. Knowledge and awareness of HPV infection, cervical cancer and screening in young girls who have been vaccinated against the virus is surprisingly low.[20] Thus, it may be assumed that in older women knowledge and awareness of the virus and its association with cervical cancer will be even lower. By having a high-profile HPV vaccine campaign with prompt dissemination of the realized benefits, it provides an opportunity to emphasize the importance of attendance at cervical screening for both vaccinated women and older, unvaccinated women. Given that there are a small minority of mothers and daughters from disadvantaged backgrounds who do not participate in either cervical screening or HPV vaccination, it is imperative that awareness of HPV is raised through targeted efforts to reach these deprived groups.[21]

Finally, although the HPV vaccine is most effective in individuals with no prior exposure to HPV, there are sporadic reports of resolution of HPV-induced warts after quadrivalent HPV vaccination.[22,23] These studies enrolled patients who were immunocompromised and suggest that there may be clinical benefit in post-exposure treatment of persistent warts. However, in a recent case series there was no clinical improvement in immunocompetent patients with HPV-6-positive condylomas who received quadrivalent vaccine.[24] Well-designed clinical trials are required to elucidate the immunological mechanisms required for wart clearance.

Population-based surveillance data from countries such as Australia, the UK and Denmark provide early encouragement that HPV vaccination is significantly associated with a decrease in high-risk HPV infection, genital warts and precursors to cervical cancer in young women.[5–8,15] These countries in particular have achieved high HPV vaccine uptake (70–90%), and this article highlights the gains that can be achieved if action is taken to overcome recognized barriers to high vaccine uptake.

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