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Author: Sonam Vadera, Medical Student, University College London, London, United Kingdom. DermNet New Zealand Editor in Chief: Hon A/Prof Amanda Oakley, Dermatologist, Hamilton, New Zealand. Copy edited by Gus Mitchell/Maria McGivern. October 2017.
Certain subtypes of human papillomavirus (HPV), the cause of viral warts, are classified as sexually transmitted infections (STIs). These types of HPV are found on the skin and mucosa of the anogenital tract and the upper respiratory tract. In most individuals, the virus does not cause symptoms and infection resolve by itself.
Certain subtypes of HPV can persist in some people, leading to:
Low-risk HPV genotypes can cause benign cellular changes and genital warts. HPV types 6 and 11 are responsible for most genital warts.
There are approximately 13 high-risk types of HPV associated with cancer, particularly cervical cancer. HPV causes nearly all cases of cervical cancer, with subtypes HPV 16 and HPV 18 being responsible for 70% of these cases. Other HPV-associated cancers include cancers of the vulva, penis, anus and anal canal, vagina and oropharyngeal tract (oral cancer).
Lesions due to human papillomavirus
Vaccines used to protect against HPV are:
HPV infects basal keratinocytes in the cervix through small breaks between the epithelial cells. Following infection with high-risk subtypes, the immune system may clear the virus.
In some women, the infection persists, and integration of the viral genome with the human genome results in the production of the oncoproteins E6 and E7 (oncoproteins are linked to cancer tumour cell growth). The production of these oncoproteins leads to unregulated cellular proliferation, resulting in cellular dysplasia, also known as cervical intraepithelial neoplasia (CIN).
The degree of cervical dysplasia is graded from CIN1 (minimal dysplasia) through to CIN3 (full-thickness dysplasia). These cellular changes may resolve spontaneously, or they can develop into invasive cancer. The risk of cancer correlates with the CIN grade. Those who are immunosuppressed or who smoke are at a higher risk of developing cancer.
Similar processes occur less frequently in other tissues in the anogenital area and upper respiratory tract that are exposed to oncogenic HPV subtypes.
The course of HPV infection is similar in its progression to other cancers. For example, the squamous cells of the anal epithelium undergo dysplasia, leading to anal intraepithelial neoplasia, which can eventually develop into anal cancer. Such precancerous and cancerous changes have also been noted in the vulva, vagina, penis and oropharyngeal tract, and similar grading systems are used for vaginal, vulval and anal intraepithelial neoplasia.
Vaccines against HPV contain virus-like particles (VLPs) derived from HPV surface proteins. These are produced by recombinant DNA technology (the joining together of DNA molecules from two different species). VLPs are empty protein shells without a viral genome and do not infect human cells.
VLPs prime the immune system by eliciting an immune response, that produces antibodies. When later exposed to the subtypes of HPV covered by the vaccination, these antibodies neutralise the virus before it can cause infection.
To be effective, the vaccines need to be given before HPV infection has occurred, and in most people, this is before their first sexual encounter. The vaccines provide little protection for those who have already been infected with the HPV subtypes contained in the vaccines.
The vaccines are over 99% effective at protecting against CIN and cervical cancer from HPV 16 and 18, with protection lasting at least 10 years. The nine-valent Gardasil 9 also protects against less common disease resulting from HPV types 6, 11, 31, 33, 45, 52, and 58.
The vaccines are also effective at preventing in situ and invasive cancers in other anogenital sites and the oropharynx of both sexes. The nine-valent Gardasil 9 has 100% efficacy against vaginal and vulval cancers, and 75% efficacy against anal cancers.
Both forms of Gardasil 9 are also 99% effective at protecting against genital warts caused by HPV 6 and 11. In New Zealand, Gardasil 9 is also funded for treatment of some patients with recurrent respiratory papillomatosis.
The degree of protection against the HPV subtypes not included in the vaccines is unknown.
Common side effects of vaccination include:
Free vaccination schedules vary from country to country, and from year to year. The vaccine is also available privately.
This information is current from October 2017.
The HPV vaccination is recommended for all boys and girls aged 11 or 12 years old. The recommended schedule is two doses 6–12 months apart. Females up to the age of 26 years and males up to age 21 may have catch-up immunisations recommended if they have not yet been vaccinated; in such cases, three doses are required. Men who have sex with men and immunocompromised males have vaccination recommended through to age 26. The nine-valent Gardasil 9 vaccine is used and is available on a private basis.
All girls in the UK are invited for free vaccination with the quadrivalent Gardasil 9 vaccine. A two-dose schedule is required for girls under the age of 15. The first dose is given between the ages of 11 and 13 years, with a second dose given 6–24 months later. In girls over the age of 15, three doses are given.
The current programme in the UK does not cover males, although men who have sex with men have recently been added to the immunisation programme in an attempt to protect against anogenital and oropharyngeal cancers.
Immunosuppressed individuals or those with HIV may also be recommended vaccination. Specialist advice should be sought.
Boys and girls aged 12–13 years are offered free vaccination. The quadrivalent Gardasil 9 vaccine is given as three separate doses over a 6-month period. There is a catch-up programme available free of cost for boys aged 14–15 years. For all others, the vaccine is only available privately at a separate cost.
All girls and boys aged 11–12 years in New Zealand are invited for a vaccination with nine-valent Gardasil 9. The vaccine is funded for children and young adults aged 9–27 years. Two doses are required up to the age of 14 years; in individuals over 15 years old who are receiving catch-up vaccinations, three doses are required.
Vaccination is not recommended against HPV in the following circumstances:
Screening programmes worldwide aim to detect CIN and cervical cancer at the earliest possible stage using cytology and/or HPV DNA testing and subtyping. Early detection of CIN enables treatment and prevents the progression to cancer.
Cervical screening programmes for women differ worldwide.
Screening is still recommended in vaccinated women, but this is under review.
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