Human papillomavirus (HPV) vaccinations were voted by ASCO this year to be one of the top five advances in modern oncology in the past 50 years.  Nevertheless, uptake of HPV vaccinations in the United States have been slow, so much so, that early this year the President's Cancer Panel released a report entitled ?Accelerating HPV Vaccine Uptake" that recognized HPV vaccinations as one of the most important opportunities in cancer prevention today and called for a coordinated effort to increase the rates of vaccinations against HPV across the United States1.

HPV is the most common sexually transmitted infection in the United States, with most sexually active adults being infected at some point in their lives2.  HPV infection is often symptomless and is cleared by the immune system. However, persistent infection of certain strains of HPV is the primary cause of cervical, anal, vaginal and penile cancer, as well as being implicated as a cause of many head and neck cancers.  Furthermore, other strains of HPV are associated with genital warts.

Currently more than 150 different types of HPV have been identified and of these, approximately 40 are transmitted through sexual contact infecting the anogenital region and other mucosal sites of the body. Mucosal HPV types are classified as either high-risk HPV (types 16 and 18) or low-risk HPV (types 6 and 11)3. High-risk HPV causes many cancers of the cervix, vagina, vulva, penis, anus, and are also linked to many oropharyngeal cancers. Most infections are asymptomatic and are not clinically significant; however persistent infection may lead to disease or cancer. Of the cervical cancers related to HPV, about 70% are caused by two strains, HPV-16 or HPV-18. HPV can cause oral and oropharyngeal cancer and are increasing steadily in both men and women3,4.  Recent U.S. population-based studies conducted by CDC show that 66% of cervical cancers, 55% of vaginal cancers, 79% of anal cancers, and 62% of oropharyngeal cancers are attributable to HPV types 16 or 18.4

Infection with the most common high-risk strains of HPV (types 16 and 18) can now be prevented by two safe and effective HPV vaccines Merck & Co's Gardasil and GlaxoSmithKline's Cervarix. By preventing HPV infection and spread vaccinations can protect future generations from many types of HPV-associated cancers. Furthermore, the expected introduction of Merck's V503 vaccine against even more strains of HPV will most likely prevent even more cases of cancer. However, uptake of HPV-vaccinations, to date, varies significantly throughout the developed world. In the United Kingdom, which has a vaccination program in schools, vaccination rates in girls are as high as 86%5. However, in the United States only around one-third of girls were vaccinated in 2012, which is lower than in Rwanda6.  Furthermore in Japan, HPV vaccination is controversially no longer recommended by the Japanese Ministry of Heath, Labor and Welfare, due to incidences of pain during vaccinations7. Whilst the side-effects of vaccines must be taken seriously, these have to be taken into context with the cancer-preventing efficacy of the vaccines.

Most vaccination programs in developed countries are aimed at girls/women, as these are primarily aimed at preventing cervical cancer. Gardasil has been shown to be efficacious in preventing pre-cancerous anal and penile lesions in males as well. However, only the USA recommends routine vaccinations in boys, and even so coverage is lower than it is for girls.  Whilst it is anticipated that herd immunity from vaccinations in women will lead to a decrease in HPV infections in men, this would not benefit men who have sex with men (MSM), who are at higher risk of contracting anal cancer than men in general8.   Another argument for the HPV vaccination for boys is that currently the uptake of the HPV vaccine among girls is desperately low, thus uptake by boys may also help confer protection to girls. Therefore there has been increasing pressure from charities to extend routine vaccination coverage to boys in other Western countries9.

As outlined in the President's Cancer Panel report education is crucial to realizing the full potential of HPV vaccination. Parents and young adolescents much be made fully aware of the benefits of vaccinations and reassured of their safety. HPV vaccinations should be strongly recommended by health care providers and be made available by a wider variety of providers and in more locations.  Removing cost barriers is also a priority for increase uptake of the vaccines.  Notably, the federal Affordable Care Act now requires all new private insurance plans in the United States to cover HPV vaccines for the recommended age groups of males and females without consumer cost-sharing.

The discovery by Dr. Harald zur Hausen that HPV is the cause of cervical and other cancers means that HPV-associated cancers are some of the most preventable, and prevention of cancer is always more preferable than treatment. However, steps must be taken for this advance to be realized; most crucially increasing awareness and education is needed on HPV, both for young adolescents and their parents. 

The role of HPV vaccinations in cervical cancer prevention will be discussed in more detail in Decision Resources Niche Market and Rare Disease Report on Cervical Cancer, which publishes in December 2014.

References
1http://deainfo.nci.nih.gov/advisory/pcp/annualReports/HPV/PDF/PCP_Annual_Report_2012-2013.pdf
2http://www.cdc.gov/std/HPV/HPV-factsheet-March-2014.pdf 2014
3CDC. Quadrivalent human papillomavirus vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2007;56(No. RR-2).
4CDC. Human papillomavirus (HPV)-associated cancers. Atlanta, GA: US Department of Health and Human Services, 5CDC; 2013. Available at http://www.cdc.gov/cancer/hpv/statistics/cases.htm.
5https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/318686/PHE_HPV_Q_A_health_professionals.pdf

6http://www.cdc.gov/media/releases/2013/t0725-Human-papillomavirus.html
7Gilmour S, et al. HPV vaccination programme in Japan. The Lancet. 2014;382(9894):768.
8Frisch M, et al. Cancer in a population-based cohort of men and women in registered homosexual partnerships. American Journal of Epidemiology. 2003;157:966-72.
9http://www.theguardian.com/society/2014/sep/22/hpv-vaccine-schoolboys-cancer

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