Vaccines against human papilloma virus
What is sexually acquired human papilloma virus?
Certain subtypes of human papilloma virus (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 resolves by itself.
Certain subtypes of HPV can persist in some people, leading to:
- Precancerous squamous intraepithelial lesions, such as vulval intraepithelial neoplasia (IN), vaginal IN, penile IN, anal IN
- Invasive cancers, such as vulvar squamous cell carcinoma and oral cancer.
Low–risk HPV genotypes can cause benign cellular changes and genital warts. HPV types 6 and 11 are responsible for most genital warts.
Approximately 13 high–risk types of HPV are associated with cancer, particularly cervical cancer. HPV causes nearly all cases of cervical cancer, with subtypes HPV 16 and HPV 18 responsible for 70% of these cases. Other HPV–associated cancers include cancers of the vulva, penis, anus, vagina and oropharyngeal tract.
Cancer is more common in patients with immunosuppression, due to viruses such as human immunodeficiency virus (HIV), or drugs as a result of an organ transplant.
Lesions due to human papillomavirus
What vaccines are available to protect against human papilloma virus?
Vaccines used to protect against HPV are:
- Cervarix®: bivalent; protects against HPV 16 and 18. Protects against cervical cancer.
- Gardasil®; protects against cervical cancer and genital warts.
- Quadrivalent. Protects against HPV 6, 11, 16 and 18.
- Nine–valent (Gardasil® 9). Protects against HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58.
How does human papillomavirus cause cervical cancer?
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 production of oncoproteins E6 and E7. These lead 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) 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 of the anogenital area and upper respiratory tract that are exposed to oncogenic HPV subtypes.
The course of HPV infection is similar in the progression to other cancers. For example, the squamous cells of the anal epithelium undergo dysplasia, leading to anal intraepithelial neoplasia (AIN), 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, vulvar and anal intraepithelial neoplasia.
How do vaccines work against human papilloma virus?
Vaccines against HPV contain virus–like particles (VLP) derived from HPV surface proteins. These are produced by recombinant technology. VLP are empty protein shells without a viral genome and do not infect human cells.
VLP prime the immune system by eliciting an immune response, which produces antibodies. When later exposed to the subtypes of HPV covered by the vaccination, 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 that have already been infected with the relevant HPV subtypes.
What are the benefits of vaccination?
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 form of Gardasil® also protects against less common disease from HPV 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 males and females. The nine–valent form of Gardasil® has 100% efficacy against vaginal and vulvar cancers, and 75% efficacy against anal cancers.
Both forms of Gardasil® are also 99% effective at protecting against genital warts caused by HPV 6 and 11.
The degree of protection against HPV subtypes not included in the vaccine is unknown.
What are the possible side effects and risks of vaccination?
Common side effects of vaccination include:
- Swelling, pain and redness at the injection site for a few days
- Mild muscle aches, fatigue and headaches for a few hours to a few days
- Anaphylaxis, a rare complication encountered by a few individuals.
Who gets vaccinated?
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.
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 and males up to the age 21 may be recommended ‘catch–up’ immunisations if they have not yet been vaccinated; in such cases, three doses are required. Men who have sex with men and immune compromised males are recommended vaccination through age 26. The nine–valent Gardasil® vaccine is used and is available on a private basis.
All girls in the UK are invited for free vaccination with the quadrivalent Gardasil® vaccine. A two–dose schedule is required for girls under the age of 15. The first is given between ages 11–13, 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, though 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 are offered free vaccination. The quadrivalent Gardasil® vaccine is given as three separate doses over a six month period. There is a catch up programme available free of cost for boys aged 14–15. For all others, the vaccine is only available privately at a separate cost.
All girls and boys aged 11–12 in New Zealand are invited for vaccination with nine–valent Gardasil®. The vaccine is funded for children and young adults aged 9 to 27. Two doses are required up to the age of 14; in individuals over 15 years old who are receiving catch–up vaccinations, three doses are required.
What are the contraindications to vaccination?
Vaccination is not recommended against HPV in the following circumstances.
- History of previous anaphylaxis to the vaccine components. This includes allergy to yeast products, a component of the vaccine.
- Vaccination against HPV is avoided in pregnancy, although there is no evidence that it is unsafe in pregnancy.
Should I have a cervical screening?
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 progression to cancer.
Details of cervical screening programmes for women differ worldwide.
- USA. Cytology screening at age 21–29 every three years. Cytology screening with HPV testing at age 30–65 every five years.
- UK. Cytology, potentially followed by HPV testing depending on findings, at age 25–49 years every three years. Subsequently, every 5 years for women age 50–64.
- Australia. Cytology screening in females aged 18–70 years every two years. This is due to change in December 2017.
- New Zealand. Cytology testing every three years in women aged 20–69.
Screening is still recommended in vaccinated women, but this is under review.
Other screening programmes
Male and female immunosuppressed patients, for example those with HIV infection, are recommended to undergo regular anal cytological or HPV screening.