Human papillomavirus (HPV) vaccination

See also the separate Anogenital warts article.

What is human papillomavirus (HPV) vaccination?

Human papillomavirus (HPV) vaccination was introduced into the immunisation schedule for females aged 12-13 years in September 2008.¹ Following a review of the evidence by the Joint Committee on Vaccination and Immunisation (JCVI), the programme was extended to males aged 12-13 years in 2018.²

HPV immunisation is also available through sexual health and HIV clinics to gay and bisexual men who have sex with men (GBMSM) including trans, as well as to trans women who have a similar risk to GBMSM, unless they are over 45.

HPV is a double-stranded DNA virus, which 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, both in men and in women. It has also been more recently shown that HPV can cause oropharyngeal cancers, and prevalence of these tumours is rising.³

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, with 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 two thirds of all cervical cancers globally.^{4 5} and more than 8 in 10 anal cancers.⁶

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 are more common for infections by HPV types 16 and 18 than for other high-risk types. The reduction of cervical cancer was the original aim in the widespread introduction of HPV vaccination, but other benefits have rapidly become apparent.

In males, HPV infection can progress to cause anal, penile, oropharyngeal, and oral cavity cancers as well as anogenital warts. The high-risk HPV types 16 and 18 are strongly implicated in anal/genital cancers (penis, vagina and vulva, anus) although the incidence of these cancers in the general population is low.²

While the incidence of anal and penile cancer is low at 1.5 and 2.2 per 100,000 population respectively and high coverage for girls provides substantial herd protection for boys, infection rates are higher (and continue to be higher into older age groups) in gay and bisexual men who have sex with men (GBMSM) than in heterosexual males, as are rates of HPV-associated disease, particularly for anal cancer.

HIV infection is associated with much higher incidence of HPV-associated disease, which further increases the risk amongst GBMSM. More than 80% of anal cancers are caused by high-risk HPV types and the incidence of anal cancer in GBMSM is increasing.⁶

Primary HPV testing as part of the cervical cancer screening programmes was rolled out across Wales from September 2018 and across England from December 2019⁷ as studies have shown the benefits.⁸ It was introduced in Scotland from March 2020.

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.

Before the introduction of the HPV vaccination programme, a study of women having routine cervical screening in 2007-9 found evidence of current high-risk HPV infection (indicated by the presence of HPV DNA) in 29% of women aged 25 to 29 years undergoing cervical screening, with prevalence declining with increasing age after 30 years.⁹ Prevalence of any HPV type, and particularly of HPV 16 or 18, was higher in women who had abnormal cytology.

A cross-sectional study of gay, bisexual and other men who have sex with men (GBMSM) aged 18–40 years attending a London sexual health clinic indicated a quarter (25.1%) had evidence of infection with one HPV type in the quadrivalent vaccine (HPV16, 18, 6 & 11), 7.4% had two or three types and none had all four types. The prevalence of the high-risk HPV vaccines types 16 and 18 was 17%.¹⁰

These prevalence rates have now reduced - see Efficacy.

Efficacy

More than a decade after introduction of the national HPV immunisation programme, evidence of the impact of vaccination has shown reductions in HPV type 16/18 infection, genital warts, pre-cancerous lesions and cervical cancer among vaccinated cohorts.¹¹ Evidence of herd protection among unvaccinated groups is now emerging both in the UK and globally.

In 2021, a review of the incidence of cervical cancer in comparable cohorts in England before and after introduction of the NHS HPV immunisation programme for girls revealed a relative risk reduction in cervical cancer rates of:¹²

• 87% among females vaccinated at age 12-13 years.

• 64% among females vaccinated at age 14-16 years.

• 34% among females vaccinated at age 16-18 years.

HPV vaccines are highly effective at preventing the infection of susceptible people 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.¹³¹⁴ Studies suggest that protection is maintained for at least ten years and, based on the immune responses, it is expected that protection will be extended further (possibly lifelong).¹⁴ Current evidence suggests that HPV immunisation in males generates comparable immunogenicity to that seen in females.²

There are currently three different HPV vaccine products available globally, however since July 2022 only Gardasil®9 is available for use in the UK immunisation programme.¹⁵

Gardasil® 9, in addition to protecting against HPV16, HPV18, HPV6, and HPV11, also protects against HPV31, HPV33, HPV45, HPV52, and HPV58. It is active against 9 HPV subtypes.

The other two vaccine products available worldwide and formerly used in the UK are:

• Cervarix; a bivalent 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®; a quadrivalent 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, as HPV6 and HPV11 cause the majority of cases of genital warts.

The immunisation programme initially recommended a three-dose schedule, but from 2014, a two-dose schedule was used. The move to a single-dose HPV schedule occurred throughout 2021/2022.

HPV vaccination is routinely recommended for all girls and boys from 11 years of age with vaccination offered in school year 8 in England and Wales, S1 in Scotland, and school year 9 in Northern Ireland.

• One-dose schedule (for children, adolescents and adults less than 25 years old)
  Gardasil®, Gardasil®9 and Cervarix®:

  • One dose of 0.5 ml of HPV vaccine.

• Two-dose schedule (adults aged 25 years and above)
  Gardasil®, Gardasil®9 and Cervarix®:

  • First dose of 0.5 ml of HPV vaccine.

  • Second dose of 0.5 ml six to 24 months after the first dose.

For those aged 25 years and above, JCVI recommends a two-dose schedule of 0, 6-24 months for all HPV vaccines. Any gap between doses of between 6 and 24 months is clinically acceptable. If the course is interrupted, it should be resumed but not repeated, even if more than 24 months have elapsed since the first dose.

• Three-dose schedule (for HIV-positive or immunocompromised populations) with Gardasil®9 and Gardasil®:

  • First dose of 0.5 ml of HPV vaccine.

  • Second dose of 0.5 ml at least one month after the first dose.

  • Third dose of 0.5 ml at least three months after the second dose.

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, so three-dose schedules are advised in this group. Re-immunisation should be considered after treatment is finished and/or recovery has occurred. Specialist advice may be required.

The objective of the HPV immunisation programme is to provide two 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.

Young people aged 9 to 11 years

Gardasil, Gardasil 9, and Cervarix are licensed for individuals from the age of 9 years. Vaccination is not routinely recommended for those aged 9 to 11 years and is not covered by the national immunisation programme.

Young people aged 12 to 13 years

HPV vaccination is routinely recommended for all girls and boys at age 12 to 13 years.

If the course is interrupted then it should be resumed but not repeated, ideally allowing the appropriate interval between the remaining doses.

Young people aged 13-24

Both males and females who missed the course at age 12-13 are eligible for NHS catch-up - either through school or through the GP practice - until they reach 25 years.

Adults aged 25 or over

Vaccination against HPV should not be offered on the NHS to people over 25, unless they are GBMSM.

Gay and bisexual men who have sex with men

GBMSM have not benefited in the same way as heterosexual males from the herd immunity conferred by the NHS vaccination programme for females. GBMSM up to and including age 45 years are eligible for free HPV vaccination on the NHS from sexual health or HIV clinics if they have not been immunised. This includes trans MSM who did not have the course at school.

Trans women who are assessed as having a similar risk of contracting HPV to GBMSM are also eligible for the HPV vaccine up to and including age 45 years.

Adverse reactions

All suspected adverse drug reactions, no matter how minor, should be reported in children under 18 years (even if the black triangle symbol has been removed), using the Yellow Card reporting scheme (www.mhra.gov.uk/yellowcard).¹⁶