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HPV vaccination in boys and men

Key learning points:

- Analysis of the cost effectiveness of the HPV vaccine

- Is it right to rely on the vaccination of women as a way to prevent the spread of disease?

- Is the failure to vaccinate boys a missed public health opportunity

Infection with one of a subset of mucosal high risk Human papilloma virus (HPV), principally 16 and 18, is the cause of almost all cervical cancers in women, it is the major aetiological agent in squamous cell carcinoma of the anus, tonsil and base of tongue and a significant contributor to squamous cell carcinoma of the vulva, vagina, penis, larynx and head and neck.1 Altogether HPV is estimated to be the causal agent in 5% of all human cancers with HPV16 by far and away the major player. The contribution to the cancer burden is very significant but the disease burden of the “benign” or low risk HPVs - mainly 6 and 11 - should not be underestimated. Genital warts are the commonest viral sexually transmitted disease with a lifetime risk of acquisition of 10% representing a huge disease burden in men and women.2

HPV vaccines

There are two commercial prophylactic HPV vaccines that are licensed globally. These are Cervarix®, a bivalent product from Glaxo Smith Kline targeting HPV 16 and 18, and Gardasil® a quadrivalent product from MSDMerck that targets HPV 6,11,16 and 18. These vaccines are highly efficacious and national HPV immunisation programmes for girls and women have been recommended in more than 68 countries with national funding in 52. The UK has had a national HPV immunisation programme since 2008. This is a school based-programme with Year 8 (12-13 year old) girls as the ongoing cohort. In September 2014 a revised two-dose schedule dose - one at the beginning of vaccination and a second dose at 12 months - was implemented for the 12-13 year old cohort. A three-dose schedule remains in place for all girls and women 14 years and older. The UK programme is highly successful with coverage in 2012-13 of 86% for all three doses. The UK programme is restricted to females and, indeed, only three countries - USA, Australia and Austria - have funded programmes for boys and men.

Male vaccination

Gender-neutral vaccination is a controversial issue. If the reduction in female cancer is the only outcome to be considered then male vaccination provides only a small added benefit in the rate of disease reduction since, with a sexually transmitted infection (STI), immunising one gender at high coverage should with time block transmission and engender herd protection3. However, as in women, men develop HPV-attributable cancers of the anus, the oral cavity and the oropharynx and they have an equivalent burden to women of genital warts.

Anal carcinoma is a rare cancer but the incidence worldwide is increasing.4 Women have a higher incidence than men in age groups greater than 50, but men dominate the 20-49 year age group and this incidence is rising. Rates of anal cancer are highest in men who have sex with men (MSM), 37/100,000 and is even higher in HIV infected MSM at 131/100,000).5 Oropharyngeal squamous cell carcinomas (OSCC) associated with HPV have increased dramatically in men and women in developed countries over the past two to three decades6. In the USA, incidence of HPV OSCC is higher in men than women, as is the prevalence of oral HPV infection and it is projected that in the US the annual number of HPV-positive OSCC will surpass that of cervical cancers by the year 2020.7 Trials with the quadrivalent vaccine Gardasil have shown efficacy against infection and disease in men who have sex with women (MSW) and MSM, preventing 6/11 genital warts8 and 6/11/16/18 anal intraepithelial neoplasia9 respectively.

Male vaccination cost effectiveness issues

Men will clearly benefit from HPV vaccination but is it cost-effective? Most health economic models conclude that vaccination of boys is not cost-effective when female vaccination coverage is high.10 However MSM receive little benefit from herd immunity and remain vulnerable to preventable HPV associated disease.11 The cost-effectiveness case is a stark one.

With time, men who have sex with women (MSW) will be protected since they are the partners of vaccinated women (providing female vaccine coverage is high - at least 70-80%). MSM represent too small a fraction of the population to justify general male vaccination but targeting MSM would be cost effective.12

Targeted vaccination of high risk groups does not have a good track record and implementation of an MSM targeted strategy would be challenging. HPV vaccines are prophylactic not therapeutic and emerging evidence shows clearly that HPV immunisation before the sexual debut gives maximum vaccine impact.11,13 For optimal cost-effectiveness and clinical efficacy MSM would need to be reached before the sexual debut in early adolescence, a quite unrealistic scenario.

Sexual preferences are not firmly established in early adolescence and questioning the sexual orientation in such a group would elicit parental outrage. If older groups are targeted - for example 20 year old men - clinical efficacy is less because of prevalent infection and disease in this HPV-exposed population,14 and cost-effectiveness is therefore reduced. Also, the ethics of requiring disclosure of sexual orientation prior to receiving immunisation are questionable.

These questions have been carefully considered by the UK Joint Committee on Vaccines and Immunisation (JCVI) and they concluded “a programme to vaccinate MSM age 16-40 should be considered, provided that the programme could be undertaken at a price (administration and vaccines costs) which was cost effective. Vaccinating MSM aged 16-40 was preferred because of the greater uncertainty around a strategy of vaccinating only HIV positive MSM”.

Unresolved questions

However, the issues of equity remain. If 16-40 year old MSM are to be offered the vaccine, why should 16-40 year old women be denied this intervention? Furthermore, in developed countries such as those in Western Europe, the burden of HPV-associated cancers in men is comparable to that in women.

Why should heterosexual men be discriminated against? The cost-effectiveness case is that gender neutral vaccination is not justified since, with time, MSW will be protected because they are the partners of vaccinated women.

This scenario seems to be supported with data from Australia where, after vaccination, the incidence of genital warts in young (90% over a three year period but no decline occurred in MSM or older, presumably non-vaccinated women.11 In contrast, in Denmark, despite high vaccine coverage and a precipitous decline in genital warts in young women

Despite achieving high vaccine coverage and evidence of herd protection, Australia has now introduced HPV immunisation of 13 year old boys.

Careful cost-effective modelling has preceded this decision, showing that when the burden of disease in men is included in the models then, depending upon coverage, cost and other factors, male vaccination can become cost-effective. Cervical cancer, the dominant cancer in women, can be prevented both by vaccination to prevent infection and screening to treat precancerous lesions, but there is no screening for anal cancer and OSCC, the malignancies increasing in incidence, particularly in men.

Furthermore, compared to HPV-negative cancers at these sites, HPV-associated cancers tend to occur in younger age groups - 40-60 years - present at a later stage with associated mortality and show a very significant morbidity after treatment with impaired quality of life. All men, irrespective of sexual orientation, have a significant burden of HPV-associated disease. This burden is increasing in developed countries but could be substantially reduced if boys were immunised. Failure to do so looks like a missed public health opportunity.


1. Forman D, de Martel C, Lacey CJ, Soerjomataram I, Lortet-Tieulent J, Bruni L, et al. Global burden of human papillomavirus and related diseases. Vaccine. 2012;30 Suppl 5:F12-23.

2. Kjaer SK, Tran TN, Sparen P, Tryggvadottir L, Munk C, Dasbach E, et al. The burden of genital warts: a study of nearly 70,000 women from the general female population in the Four Nordic countries. J Infect Dis. 2007;196(10):1447-54.

3. Brisson M, van de Velde N, Franco EL, Drolet M, Boily MC. Incremental impact of adding boys to current human papillomavirus vaccination programs: role of herd immunity. J Infect Dis. 2011;204(3):372-6.

4. Brewster DH, Bhatti LA. Increasing incidence of squamous cell carcinoma of the anus in Scotland, 1975-2002. Br J Cancer. 2006;95(1):87-90.

5. Shiels MS, Pfeiffer RM, Gail MH, Hall HI, Li J, Chaturvedi AK, et al. Cancer burden in the HIV-infected population in the United States. J Natl Cancer Inst. 2011;103(9):753-62.

6. Chaturvedi AK, Anderson WF, Lortet-Tieulent J, Curado MP, Ferlay J, Franceschi S, et al. Worldwide trends in incidence rates for oral cavity and oropharyngeal cancers. J Clin Oncol. 2013;31(36):4550-9.

7. Chaturvedi AK, Engels EA, Pfeiffer RM, Hernandez BY, Xiao W, Kim E, et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol. 2011;29(32):4294-301.

8. Giuliano AR, Palefsky JM, Goldstone S, Moreira ED, Penny ME, Aranda C, et al. Efficacy of Quadrivalent HPV Vaccine against HPV Infection and Disease in Males. The New England Journal of Medicine. 2011;364(5):401-11.

9. Palefsky JM, Giuliano AR, Goldstone S, Moreira ED, Jr., Aranda C, Jessen H, et al. HPV vaccine against anal HPV infection and anal intraepithelial neoplasia. The New England Journal of Medicine. 2011;365(17):1576-85.

10. Canfell K, Chesson H, Kulasingam SL, Berkhof J, Diaz M, Kim JJ. Modeling Preventative Strategies against Human Papillomavirus-Related Disease in Developed Countries. Vaccine. 2012;30 Suppl 5:F157-67.

11. Ali H, Donovan B, Wand H, Read TR, Regan DG, Grulich AE, et al. Genital warts in young Australians five years into national human papillomavirus vaccination programme: national surveillance data. Bmj. 2013;346:f2032.

12. Kim JJ. Targeted human papillomavirus vaccination of men who have sex with men in the USA: a cost-effectiveness modelling analysis. Lancet Infect Dis. 2010.

13. Gertig DM, Brotherton JM, Budd AC, Drennan K, Chappell G, Saville AM. Impact of a population-based HPV vaccination program on cervical abnormalities: a data linkage study. BMC Med. 2013;11(1):227.

14. Machalek DA, Grulich AE, Jin F, Templeton DJ, Poynten IM. The epidemiology and natural history of anal human papillomavirus infection in men who have sex with men. Sex Health. 2012;9(6):527-37.

15. Baandrup L, Blomberg M, Dehlendorff C, Sand C, Andersen KK, Kjaer SK. Significant decrease in the incidence of genital warts in young danish women after implementation of a national human papillomavirus vaccination program. Sex Transm Dis. 2013;40(2):130-5.