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 2008¹ . 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 2018² .

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

What is HPV? (Pathogenesis)

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 rising³ .

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 cancers⁶ . 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 low² .

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 men who have sex with men (MSM) 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 MSM. More than 80% of anal cancers are caused by high-risk HPV types and the incidence of anal cancer in MSM is increasing⁶ .

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 benefits⁸ . It is being rolled out in Scotland from March 2020.

How common is HPV? (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-teens⁴ .

Prevalence of any HPV type, and particularly of HPV16 or HPV18, is higher in women who have abnormal cytology. HPV is detected in 99% of cervical tumours⁵ .

HPV vaccines

There are three HPV vaccines available in the UK: Cervarix®, Gardasil® and Gardasil® 9.

Cervarix® is known as 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® is 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.

Gardasil® 9, in addition to protecting against HPV16, HPV18, HPV6 and HPV11, also protects against HPV31, HPV33, HPV45, HPV52, and HPV58. During the academic year 2021-22, the vaccine supplied for the NHS programme will change from Gardasil® to Gardasil® 9⁹ .

Efficacy

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 of¹⁰ :

• 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 women¹¹ . Studies suggest that protection is maintained for at least ten years¹² . Based on the immune responses, it is expected that protection will be extended further; long-term follow-up studies are in place¹³ . Current evidence suggests that HPV immunisation in males generates comparable immunogenicity to that seen in females² .

A World Health Organization-funded study on cost-effectiveness of the HPV vaccination across 179 countries showed it was very cost-effective in the majority of countries¹⁴ . Vaccination of 58 million 12-year-old girls in 179 countries had prevented 690,000 cases of cervical cancer and 420,000 deaths. Because of the lower incidence of HPV-related cancers in males, cost-effectiveness is less favourable but reducing the discount rate makes gender-neutral vaccination highly likely to be cost-effective at what may be a realistic price per dose² .

Gardasil® is also 99% effective at preventing genital warts associated with vaccine types in young women¹⁵ . Australia was the first country to introduce national HPV vaccination with the quadrivalent vaccine, and results after five years from sexual health clinics showed a marked reduction of genital warts in women and also heterosexual men in the vaccinated age group¹⁶ . Between 2007 and 2011, the percentage of women having genital warts in sexual health clinics in the relevant age group dropped from 11.5% to 0.85%. In 2011 no diagnoses of genital warts were made in girls who had been vaccinated. The UK can expect similar reduction, but results will be delayed as the bivalent vaccine was used until 2012.

HPV vaccination administration dosage and schedule¹²

Since the immunisation programme began, on a three-dose schedule, it has been established that a two-dose schedule is as effective as a course of three. From 2014, a two-dose schedule has been recommended, as long as vaccination is started before the young person's 15th birthday.

The NHS immunisation starts at age 12-13 (school year 8 in England and Wales, school year 9 in Northern Ireland, school year S1 in Scotland). For either vaccine, a 0.5 ml dose is given first, with the second 0.5 ml dose given 6-24 months later.

The schedule for Gardasil® (containing HPV types 6, 11, 16, 18) is two doses for young people starting the schedule at under age 15:

• First dose of 0.5 ml of HPV vaccine.

• Second dose of 0.5 ml 6-24 months after the first dose.

Vaccines are given intramuscularly in the upper arm or anterolateral thigh.

For those who start the vaccine at age 15 years or older, the schedule is three doses of 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.

While a catch-up programme was included when the immunisation was first introduced for girls, there is no catch-up programme for boys on the basis of significant herd protection as a result of pre-existing female immunisation.

HPV immunisation programme cohort¹²

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. Following the introduction of the HPV vaccine for girls, there was a catch-up programme for girls aged 13-18 at the commencement of the programme on the NHS. There is no such catch-up programme on the NHS for boys who were over 13 years at the commencement of the boys' programme on the NHS.

If the course is interrupted then it should be resumed but not repeated, ideally allowing the appropriate interval between the remaining doses. For young people who miss starting a course of vaccination in the first target year, those less than 15 years of age should still start on a two-dose schedule. Those aged 15 or over should start a three-dose schedule.

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 MSM.

Men who have sex with men

MSM have not benefited in the same way as heterosexual males from the herd immunity conferred by the NHS vaccination programme for females. MSM 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 MSM 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)¹⁷ .