Should we be vaccinating boys too?
Current medical students will have been among the first UK cohort to receive the human papillomavirus (HPV) vaccine in 2008. All 12-13 year old girls in the United Kingdom are now vaccinated in a series of three doses over six months. However, Australia is the only country that has extended its vaccination programme routinely to boys. Australia’s leading non-governmental cancer control organisation, Cancer Council Australia, believes that extending the programme to boys will “bring with it the added benefit of greater herd immunity for those girls who are yet to complete the three-dose vaccine course,” as well as protecting men against “most penile and anal cancers” and genital warts caused by HPV infection.  Some doctors have called for the rest of the world to follow suit,    and the Joint Committee on Vaccination and Immunisation (JCVI) is currently reviewing the evidence for vaccination programmes aimed at both sexes and vaccination of homosexual men in the UK. But what are the arguments for and against universal vaccination?
What is HPV?
Human papillomaviruses are DNA viruses that infect skin or mucosal cells. There is international consensus that infection with high risk genotypes, including types 16 and 18, is a necessary but not sufficient cause of cervical cancer, and is “associated with other mucosal anogenital and head and neck cancers” in both men and women. HPV types 16 and 18 were found in 71% of patients with invasive cervical cancer in a large retrospective cross sectional study, with similar figures found in a meta-analysis by Smith et al.
Infections with “low risk” genotypes such as type 6 and 11 can cause “benign or low-grade cervical tissue changes and genital warts,” which are growths on the cervix, vagina, vulva, penis, scrotum, or anus. According to a Lancet article, HPV 6 and HPV 11 are responsible for about 90% of genital warts.
Two vaccines have been approved for use by the US Food and Drug Administration (FDA) and the Medicines and Healthcare Products Regulatory Agency (MHRA) in the UK.  Gardasil (Merck) is a quadrivalent vaccine protective against HPV genotypes 6, 11, 16, and 18. The other vaccine, Cervarix (GlaxoSmithKline) protects against only genotypes 16 and 18. Both vaccines are licensed in countries around the world.
Enhanced herd immunity?
Herd immunity is defined as “the resistance of a group to invasion and spread of an infectious agent, based on the resistance to infection of a high proportion of individual members of this group.” Some argue that immunising boys will lead to enhanced herd immunity and reduce the rates of cervical cancer.
In an article in The BMJ arguing for male vaccination, Sam Hibbitts, lecturer in HPV infection and cervical neoplasia, writes that the “herd immunity obtained by vaccinating only women is likely to be insufficient to eradicate the targeted HPV types.” However, according to Kate Cushieri, principal clinical scientist at the Royal Infirmary of Edinburgh, “vaccinating males provides only small additional benefit and is not cost effective, especially if female programmes obtain high (>75%) coverage.” The UK has high coverage, with the most recent report finding that 90.4% of the intended population received their first dose and that 80.8% completed the programme.
Genital warts and other cancers
Another argument for boys receiving the HPV vaccine is that they are at risk of genital warts, which are almost exclusively caused by HPV infection. Penile cancers, certain head and neck squamous cell cancers, and anal cancers are also caused by HPV infection in some cases. However, some think that boys will be protected from these diseases by the herd immunity achieved by vaccinating women. Cushieri writes. “It is inevitable that lower rates of circulating virus brought about by vaccinating females will lead to a reduction in HPV associated disease in men over time.”
The non-cervical cancers associated with HPV have several independent causes, with HPV causing “less than half of all cases” of penile cancer, for example. And although 90% of anal cancers are attributable to HPV, the disease is comparatively rare (0.9 cases/100 000 population compared with 8/100 000 women for cervical cancer), and the incidence in women is twice that in men in the UK.
In the case of head and neck cancers, “the most potent risk factor is still smoking and alcohol consumption,” and a study by Hererro and colleagues found that only 18% of oropharangeal tumours were associated with HPV. However, a recent paper by Chaturvedi et al suggests that the proportion of HPV positive oropharyngeal cancers has risen from about 16.3% during the 1980s to 72.7% during the 2000s in the US.
Although herd immunity may protect most men from HPV, even if 100% of women take up the vaccine, men who have sex with men (MSM) will continue to be at risk of HPV infection and related diseases. Men who have sex with men are disproportionately affected by HPV related cancer, particularly anal cancer, for which rates are over 15 times higher than in heterosexual men (odds ratio=17.3; 95% confidence interval 8.2 to 36.1). An Australian study found a significant decline in anogenital warts in women and heterosexual men just one year after the vaccination of women with the quadrivalent vaccine, but there was no change in incidence among men who were homosexual.
Studies have found that the vaccine is of greater benefit in men who have not been exposed to HPV 16 or 18, but it is still of substantial benefit in those who have been exposed. Targeting homosexual boys before sexual activity could be difficult because the boys might not have identified sexually. Therefore, the US Centres for Disease Control and Prevention (CDC) recommends “universal vaccination for boys aged 11 and 12, and vaccination for gay men up to the age of 26.” However, this has not yet resulted in any policy change in the US.
When might HPV vaccination for boys be cost effective?
Cost effectiveness analysis “compares the costs and health effects of an intervention to assess the extent to which it can be regarded as providing value for money.” Decision makers use it to help them determine where to allocate limited healthcare resources. In the UK, the National Institute of Health and Care Excellence (NICE) uses an internationally recognised method to assess cost effectiveness: quality adjusted life years (QALYs). Generally, treatment that costs more than £20 000-£30 000 per QALY would not be considered cost effective.
Lawton and colleagues claim there are ample data showing the increased burden of HPV related conditions in men who have sex with men. Although Cushieri argues that “it would be more sensible to use targeted measures (such as anal screening) for this group than to try to vaccinate all boys,” Lawton and colleagues point out that there is no reliable screening method. They advocate, in the absence of universal vaccination of boys, the introduction of targeted vaccination for men who have sex with men up to the age of 26, stating that “modelling using conservative analyses suggests vaccination is cost effective.”
In the UK, the JVCI is reviewing the evidence on vaccinating homosexual men. This includes the results from a study being run at a London genitourinary medicine clinic to estimate the prevalence of HPV infection and incidence of HPV related disease in men who have sex with men and the potential effect vaccination would have on this, as well as assessing the cost effectiveness of vaccinating this population. Public Health England aims to have the results by October 2014, but the JVCI has concerns that they are likely to show a “large amount of uncertainty” since “HPV related cancers in men are not so well understood in terms of progression.” HIV status also affects the rates of HPV related cancer and there is “uncertainty over what proportion of HPV associated cancers in men occurs in MSM.”
Countries with low uptake in females
Universal vaccination may have an important role in countries where the coverage of vaccination in females is low. In the US, parents have remained cautious about letting their daughters have the vaccination, and uptake is about 30%. One reason is that some parents think that allowing their daughters to receive the vaccine encourages them to engage in premarital sex. Possibly a greater concern is the absence of HPV vaccination programmes in many developing countries, particularly since more than 80% of the 500 000 annual cases of cervical cancer occur in these low resource settings. Hibbitts believes that when vaccine uptake in females is expected to be low, “it is more cost effective to vaccinate males than vaccinate hard to reach females,” although others maintain that “the best policy is to ensure that preadolescent females are vaccinated worldwide.”
In January, the JCVI’s HPV subcommittee acknowledged that more modelling is necessary to determine the cost effectiveness of including teenage boys in vaccination programmes and recommended finishing modelling work on men who have sex with men “to inform any short term decision that might be made for a targeted vaccination programme while results are awaited for the work looking at universal vaccination.” Until then, it is important that girls continue to be vaccinated against HPV in order to reduce the prevalence of the disease in the community.Katy Bettany, fifth year medical student1, Isabella Laws, second year medical student2
1Imperial College London, London, UK , 2St George’s Medical School, London, UK
Correspondence to: firstname.lastname@example.org
Competing interests: I have read and understood BMJ policy on declaration of interests and have no relevant interests to declare.
See editorial doi:10.1136/sbmj.g4089
Provenance and peer review: Not commissioned; externally peer reviewed.
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Cite this as: Student BMJ 2014;22:g4015