Cervical cancer is evidently the most important, but by no means the only, health risk that vaccination against HPV aims to avert. The potential impact of vaccination on other cancers (not to mention genital warts) may also be a factor in estimating the cost benefit of achieving higher vaccination coverage, as well as determining priorities for vaccination programmes (e.g. the relative importance of achieving high coverage for males). Recent studies have investigated the role of HPV in the rising incidence of head and neck – especially oropharyngeal – cancers (Field & Lechner/STIs; King & Sonnenberg/STIs), and in the development of anal cancers amongst MSM (Poynten & Garland/STIs). The dramatic impact of vaccination programmes on the prevalence of genital warts has already been attested both in Australia, where vaccination was introduced in 2007 (Chow & Fairley/STIs ), and, more recently in the UK (Canvin & Mesher/STIs ).
In addition to these benefits of HPV vaccination, a recent Danish nationwide cohort study (Sand & Kjaer (S&K)) draws attention to another relatively limited, but nevertheless significant, benefit in the shape of a range of anogenital cancers in women – i.e. anal, vaginal and vulvar cancers. These seem to be strongly associated with the occurrence of high grade cervical intraepithelial neoplasia (CIN2 & 3), and should therefore be numbered amongst the adverse effects of HPV that vaccination may help to prevent. Given the relative rarity of these cancers (total yearly incidence in UK, both male and female, is currently about a quarter of that of oropharyngeal cancers), an important advantage of S&K’s study is its impressive scale. It investigates no less than 2.8 million women born 1918-1990 over the period from 1978 to 2012. Also, unlike similar studies, it is able to control not only for age, but for a range of potential confounders such as socio-economic status and smoking. The use of CIN2/CIN3 as a proxy for HPV infection seems well supported by the evidence (Tachezy & Vonka/STIs; Azwa & Harun (STIs)).
The key findings of the study were as follows. Relative risk of anal, vulvar and vaginal cancers following CIN2/3 as against no such history was found to be greatly increased: RR 2.8, 2.5, 8.3 after CIN2; 4.1, 3.9, 17.4 after CIN3. Risk was particularly high in the first year after CIN; but the increased risk persisted, suggesting the effect could not be attributed to surveillance bias. So, for example, analysis showed increased risks of anal, vulvar and vaginal cancers at ≥25 years after CIN3 diagnosis of RR 4.8, 3.2, and 5.5, respectively. In non-cervical anogenital cancer, HPV16 was the most frequently detected HPV type. The fact that cancer risk following CIN3 is substantially greater than it was following CIN2 suggests to the authors that the cause of both may be attributable to an inadequate immune response to HPV in certain women, leading to a failure to clear the infection. The propensity of persistent HPV to spread to the entire anogenital region explains the range of cancers (anal, vaginal, vulvar) in respect to which these women seem to be at heightened risk (see Simpson & Turner/STIs ).