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Sam Hibbitts lecturer in HPV and cervical targets HPV types 16 and 18. neoplasia, HPV Research Group, Department of Obstetrics Should and Gynaecology, School of Medicine, Cardiff University, has US Food and Drug Administration approval Cardiff CF14 4XN [email protected] for use in males (9-26 years), and HPV A programme induce an equivalent immune response in boys should target and stop and girls. Preliminary studies of Gardasil and boys transmission of the Cervarix in boys reported ≥99% and 100% causative agent in order to prevent all seroconversion respectively at seven months, 1 2 associated diseases. The striking flaw in and both vaccines were well tolerated. receive human papillomavirus (HPV) vaccination Comprehensive efficacy data are expected programmes is the focus on prevention of to confirm that the can prevent HPV cervical cancer. What has been overlooked infection and associated disease in boys. is that HPV are responsible for a HPV vaccines are designed to target HPV the HPV range of non-cervical diseases in both sexes specific infections. HPV types 6, 11, 16, that have serious morbidity and contribute and 18 are prevalent in both cervical3 4 and to a substantial healthcare burden. HPV non-cervical diseases,5 6 and the vaccines can vaccine? vaccination of boys alongside girls would prevent a range of HPV associated diseases. facilitate the eradication of HPV and protect HPV types 16 and 18 contribute to 30% of boys from infection, reduce transmission, vaginal, vulval, and oropharyngeal cancers, Many countries have increase herd immunity, and effectively 20% of oral cancers, and 80% of anal implemented HPV vaccination prevent HPV associated diseases. Limiting HPV cancers,5 6 and the incidence of these cancers vaccination to girls will not lead to eradication. is steadily increasing. A US study to assess the programmes for girls. burden of HPV associated cancers in men and Benefits of HPV vaccination women found an average annual incidence Sam Hibbitts argues that Two HPV vaccines are available: Gardasil of 24 918 cases, with most (56.5%) being they will not be fully effective targets HPV types 6, 11, 16, and 18 and non-cervical: 2.4% were vaginal, 9.1% vulval, 12.1% anal or rectal, and 29.5% oropharyngeal unless extended to boys, Herd immunity obtained by vaccinating or oral cavity tumours.6 In addition, HPV but Kate Cuschieri says the only women is likely to be insufficient types 6 and 11 cause genital warts, which are to eradicate the targeted HPV types a common sexually transmitted disease with benefit is insufficient

Kate Cuschieri principal clinical scientist, Scottish HPV lesions. As a consequence, several countries Reference Laboratory, Royal Infirmary of Edinburgh, Edinburgh have introduced HPV immunisation for young EH16 4SA [email protected] girls and women. However, even female only The burden of human programmes are costly (estimated at £77m papillomavirus (HPV) mediated (€87m; $130m) a year in the UK), and some disease is borne by women in would consider them excessive in countries the form of cervical cancer and its precursor that have robust screening and low cancer rates 2 lesions. Globally, cervical cancer is the second (at least at the current vaccine price). Inclusion most common cancer in women, with an of males could be justified only if there were estimated 493 000 new cases and 274 000 significant population benefits. This is not the deaths in 2002.1 It is a devastating cancer with case. a peak incidence in young women in their 30s. Some argue that immunising males will lead HPV vaccines and associated immunisation to enhanced herd immunity and consequently programmes are hugely expensive, and reduce rates of cervical cancer. However, including boys will double the cost for a small the most consistent conclusion of the cost unjustifiable return. All efforts and resources effectiveness evaluations is that vaccinating must be channelled into ensuring high coverage males provides only small additional benefit Related articles on bmj.com rates are achieved and sustained in girls. and is not cost effective,3 especially if female • Editorial. Should the HPV vaccine be given Two HPV vaccines are currently available: programmes obtain high (>75%) coverage. to men? (BMJ 2009;339:b4127) a bivalent vaccine that protects against Such coverage rates are achievable—over 80% • Research. Cost effectiveness analysis of infection with HPV 16 and HPV 18 (the types of adolescent girls have taken up the vaccine including HPV vaccination programme in the responsible for about 70% of cervical cancer) in national programmes in Australia and US. (BMJ 2009;339:b3884) and a quadrivalent vaccine that also protects the UK.4 In resource poor settings, Kim et al • Listen to Jane Kim at podcasts.bmj.com/bmj against infection with HPV 6 and HPV 11 (using Brazil as a model) concluded that at any All references are in the version on bmj.com (which cause around 90% of genital warts). coverage level, “A decision maker faced with Data from clinical trials indicate that both are the choice of trying to expand coverage in girls WHERE DO YOU STAND ON THE ISSUE? Tell us on bmj.com highly effective in preventing incident infection v boys should always increase coverage in girls with vaccine type HPV and associated genital first.”5

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an estimated prevalence of 0.07-6.20/1000 One evaluation in the UK identified that Herd immunity obtained by vaccinating women and 0.13-5.01/1000 men in the US.7 if HPV vaccine induced immunity is short only women is likely to be insufficient The primary objective of HPV vaccination lived (10 years), a that to eradicate the targeted HPV types. In should be to eradicate HPV infection, and targets only 12 year old girls would not be cost situations where vaccine uptake in females this will be achieved only by a vaccination effective unless high coverage was achieved.10 is expected to be low, it is more cost programme for both sexes. Other studies have shown that vaccinating the effective to vaccinate males than vaccinate whole sexually active population would be hard to reach females.13 A single sex HPV Cost effectiveness more cost effective even when prevention of vaccination programme may also increase A US study evaluating the economic burden of cervical disease is the only disease outcome.11 the psychological burden on women,14 non-cervical HPV disease calculated the overall and this sex inequality could amount to an medical costs to be about $418m (£248m; Social inequity and psychological burden additional healthcare burden that could be €280m), range $160m to $1.6bn.8 More than Most cases of cervical cancer occur in low avoided if the vaccine was administered to 60% of this financial burden was attributable resource settings, and Castle and colleagues both sexes. to treating genital warts, with non-cervical speculated that “targeting young women in malignancies accounting for $164.7m. Kim et these populations for HPV vaccination and Lessons from history al assessed the cost effectiveness of including screening older women would have a bigger In 1996, the vaccine programme for boys in a routine HPV vaccination programme.9 effect on reducing the burden of cervical women was extended to cover men after the Assuming 90% vaccine efficacy in males for cancer than widespread HPV vaccination disease reappeared in men.15 Rubella and HPV types 6, 11, 16, and 18 against all disease of young men from resource rich areas.”12 HPV differ in many ways, including mode of outcomes (cervical cancer, non-cervical However, this assumes that funding for transmission. However, the rubella scenario malignancies, and genital warts) the ratio HPV vaccination and decisions about shows the potential pitfalls of a single sex for a strategy including boys was $90 870 implementation come from a central source. vaccine programme. I advocate making per quality adjusted life year (QALY), which In reality, although policies and strategies HPV vaccination available to boys and girls is below $100 000 per QALY, the threshold for vaccine implementation in low resource in order to eradicate HPV infection and for which an intervention is deemed a good countries are influenced by the World Health associated diseases in the population. economic investment in the US. If there was Organization Expanded Programme of I thank Alison Fiander, P Lewis White, and Ned Powell only 50% coverage in both sexes and lifelong Immunisation, local governments hold the for helpful comments and earlier discussions on this topic. vaccine efficacy against all disease outcomes, final decision, which is driven by economic Competing interests: None declared. 9 this ratio decreased to $62 070 per QALY. realities. Cite this as: BMJ 2009;339:b4928

19 countries showed that in most, anal cancer Boys still benefit Vaccinating males provides only 1 small additional benefit and is not is twice as common in women than men. Men To believe that by vaccinating girls, only girls cost effective who have sex with men are at higher risk of will benefit is naive. Smith et al assessed anal cancer, but it would be more sensible to the impact of the Australian programme (in Non-cervical disease use targeted measures (such as anal screening) which girls receive the quadrivalent vaccine) HPV is linked to other non-cervical neoplasms for this group than to try to vaccinate all boys. on overall HPV infection rates and predicted that affect men—namely, penile cancers, certain Furthermore, the effectiveness of the vaccine a reduction in the age standardised incidence head and neck squamous cell cancers, and in reducing male neoplasms has not yet been of HPV 16 infections of 56% by 2010 and anal cancers. However, penile cancer accounts proved in clinical trials. 92% by 2050.4 HPV 16 is the most commonly for <0.5% of male cancers worldwide and, Inequalities between the sexes regarding detected type in male (HPV associated) unlike cervical cancer, has several independent protection from genital warts apply only to cancer.1 6 9 Other, recent Australian data have causes, with HPV causing less than half of countries that use the quadrivalent vaccine. shown a reduction of genital warts in both cases.6 As for head and neck cancers, the most Nevertheless, there have been understandable vaccinated women and heterosexual men.13 potent risk factor is still smoking and alcohol calls for genital warts to be factored into cost It is inevitable that lower rates of circulating consumption. The data on prevalence and effectiveness analyses. Jit and colleagues’ virus brought about by vaccinating females attribution of HPV in head and neck cancers economic evaluation that did incorporate the will lead to a reduction in HPV associated are conflicting, but a large study of 1670 cases potential reduction of warts and non-cervical disease in men over time. found only 18% of oropharyngeal tumours were cancers still concluded that vaccinating boys There is currently no robust evidence to HPV associated.7 In addition, HPV associated was not cost effective.10 In the US, Hu and Goldie justify the expense and effort of vaccinating head and neck cancers have a better prognosis estimated the cost burden of non-cervical HPV boys with existing HPV vaccines either in than those that are HPV negative.8 associated disease to be 8%. This figure is not developed or developing countries. To do so Anal cancer is more similar to cervical cancer trivial, but does it warrant vaccinating both would constitute a misuse of resources and in that 90% of cases are attributable to HPV, sexes when the other 92% is associated with a diversion from what should be the primary but it is still comparatively rare. In the US, the cervix?11 A more recent analysis would objective— vaccinating as many young girls which has one of the highest rates, incidence indicate not—Kim and Goldie concluded that as possible. is 0.9 cases per 100 000 population compared the inclusion of boys in the US immunisation Competing interests: KC has been a speaker for Merck and with eight cases of cervical cancer per 100 000 programme would exceed “conventional received research funding from GSK. women.9 Moreover, an analysis of incidence in thresholds of good value for money.”12 Cite this as: BMJ 2009;339:b4921

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