Pathogenesis

Human papillomavirus (HPV) is a double stranded DNA virus, that infects squamous epithelia including the skin and mucosae of the upper respiratory and anogenital tracts. There are approximately 100 types of HPV, of which about 40 infect the genital tract. Although most infections are asymptomatic and self-limiting, genital infection by HPV is associated with genital warts and anogenital cancers in both men and women.

HPV viruses are classified as either ‘high-risk’ or ‘low-risk’ types depending on their association with the development of cancer:

• Genital HPVs are transmitted by sexual contact with an infected individual, usually through sexual intercourse.
• The risk increases with the number of sexual partners, the introduction of a new sexual partner or because of the sexual history of a new partner. The use of condoms reduces but does not eliminate the risk of sexual transmission.
• Non-sexual routes of HPV transmission include vertical transmission from mother to newborn baby.

Of the high-risk types HPV16 and HPV18 are responsible for more than 70% of all cervical cancers in Europe.^[2]  The majority of high-risk HPV infections are transient and cause no clinical problems. Persistent infection by a high-risk HPV type is the most important causal factor for the development of cervical pre-cancerous and cancerous lesions. Persistence and disease is more common for infections by HPV types 16 and 18 than for other high risk types.

Epidemiology

Surveillance of HPV is complex due to the high proportion of asymptomatic infections, the variable presentation of the different viral types and the long period between infection and disease.
A UK seroprevalence study in an unselected population showed that HPV prevalence was extremely low in girls aged 14 years but HPV infections rise sharply in the mid teens.^[2]

Prevalence of any HPV type, and particularly of HPV 16 or 18, was higher in women who had abnormal cytology.

Vaccines

There are two HPV vaccines available in the UK: Cervarix® and Gardasil®.

Cervarix® is known as a bi valent vaccine, meaning it protects against two strains of HPV. Cervarix® protects against HPV16 and HPV18 and so is aimed to reduce (in time) the number of cases of cervical cancer. When the UK first started immunising young women against HPV, this was the vaccine chosen.

Gardasil® is a quadri valent vaccine, meaning it protects against four strains of HPV. Gardasil® protects against HPV16, HPV18 and HPV6 and HPV11. This means that it also protects against genital warts as well as cervical cancer.

In November 2011, the Department of Health (DH) announced that the UK HPV immunisation programme would switch to using Gardasil® from September 2012.

Efficacy

HPV vaccines are highly effective at preventing the infection of susceptible women with the HPV types covered by the vaccine. In clinical trials, both vaccines are over 99% effective at preventing pre-cancerous lesions associated with HPV types 16 or 18 in young women.^[3] Current studies suggest that protection is maintained for at least six years. Based on the immune responses, it is expected that protection will be extended further; long term follow-up studies are in place.

Gardasil® is also 99% effective at preventing genital warts associated with vaccine types in young women.^[4]

Indications

The objective of the HPV immunisation programme is to provide three doses of HPV vaccine to females before they reach an age when the risk of HPV infection increases and they are at subsequent risk of cervical cancer.^[5]

Females aged nine to 12 years

Gardasil® is licensed for individuals from nine years old. Vaccination is not routinely recommended for those aged nine to 12 years.

Females aged 12 to 13 years

From September 2008, HPV vaccination is routinely recommended for all girls at 12 to 13 years of age (school year 8 or S2 in Scotland or school year 9 in Northern Ireland). The course of HPV vaccination should be administered according to the guidance given in the dosage and schedule section. If the course is interrupted then it should be resumed but not repeated, ideally allowing the appropriate interval between the remaining doses.

Females aged 14 to under 18 years

Initially, there will be a catch-up campaign where girls aged 14 to under 18 years will be offered the vaccination.

Females aged 18 or over

Vaccination is not routinely recommended for those aged 18 years or over.

Vaccination of females with unknown or incomplete immunisation status

Where a female in the target cohort aged over 12 and under 18 years presents with an inadequate vaccination history, every effort should be made to clarify what doses they have had. A female who has not completed the schedule should complete the vaccination course at the minimum interval (see above) where possible. Females coming to the UK from overseas may not have been offered protection against HPV in their country of origin and should be offered vaccination where appropriate.

Administration dosage and schedule

For planning purposes, a vaccination schedule of 0,1-2, 6 months is appropriate for both vaccines. All three doses should be given within a 12-month period. If the course is interrupted, it should be resumed but not repeated, ideally allowing the appropriate interval between the remaining doses.

Schedule for Gardasil® (containing HPV types 6,11,16,18):

• First dose of 0.5ml of Gardasil® HPV vaccine.
• Second dose of 0.5ml, at least one month after the first dose.
• A third dose of 0.5ml, at least three months after the second dose.

Adverse reactions

As with most vaccines, the most common side effect is mild to moderate swelling, redness and pain at the site where the injection is given.^[6] Other mild side effects eg slightly raised temperature, sickness, dizziness, diarrhoea and muscle aches have been reported.

Very rarely, as with most vaccines, some people have an allergic reaction soon after immunisation or anaphylaxis.

Individuals with immunosuppression or with HIV infection should be considered for HPV vaccines. However, individuals who are immunosuppressed may not develop a full antibody response. Re-immunisation should be considered after treatment is finished and/or recovery has occurred. Specialist advice may be required.