Key learning points:
– Most sexually active adults will be exposed to HPV during their lifetime
– High risk HPV types are responsible for 99.7% of all cases of cervical cancer as well as being a cause of some head and neck, vulval, vagina, anal and penile cancers
– The two dose quadrivalent HPV vaccine Gardasil provides protection against two types that cause 70% of cervical cancers and two types that cause 90% of genital warts
Human papillomavirus is a very common virus that can be transmitted by skin-to-skin contact and infects the skin or mucous membranes. There are more than 100 different identified genotypes of HPV, each assigned a specific number. This article will focus on those genotypes that can be transmitted by sexual contact and are responsible for the development of a range of cancers (cervix, vulva, vagina, penis, anus, head and neck) and genital warts.1 Most sexually active adults will be infected with HPV during their lifetime.2 In the majority of cases the HPV infection regresses given time. But where infection with a high-risk infection type(s) is persistent, changes can occur in the skin or mucous membranes, which can result in the development of pre-cancerous cells that have the potential to progress into cancer, given time. This process typically takes years, which is why cervical screening every three or five years in order to detect abnormal cells has been so successful in reducing the number of cervical cancers diagnosed in the UK.
Since HPV can be sexually transmitted an individual’s risk of contracting HPV increases with the number of sexual partners they have and the number of sexual partners their partner has had. However, a HPV infection does not necessarily imply promiscuity since having sex with one infected partner is sufficient for transmission. The time between exposure to the virus and developing warts or pre-cancerous changes varies greatly, so if an individual tests positive for HPV that does not necessarily implicate their current or most recent partner. In addition, it has been proposed that HPV can lie dormant for some time and be reactivated at a later date.3 This may account for some of the cases of cervical cancer observed in older women. Because HPV is passed from one person to another during skin-to-skin contact, wearing a condom will reduce the risk of transmission. However, it does not provide full protection since condoms do not prevent all genital skin-to-skin contact. As well as practising safe sex and limiting the number of sexual partners they have, an individual can also protect themselves by not smoking. Smoking has been shown to increase the risk of developing pre-cancer and cancer of the cervix.
Infection with the low risk HPV types (typically 6 and 11) can result in genital warts, however, not all of those infected will develop symptoms. Likewise, while cervical infection with a high-risk HPV type can result in pre-cancerous lesions (only visible on colposcopy), there are no symptoms, making it impossible to know whether a person is currently carrying the infection or not without being tested. The presence of HPV in the absence of disease does not require treatment. HPV testing has been incorporated into the NHS cervical screening programme (see HPV triage and HPV test of cure sections) but is not otherwise available on demand in the UK. There is currently no reliable HPV test for men although they may be offered an anal smear.4
HPV is responsible for 99.7% of cases of cervical cancer.5 In 2008, the HPV vaccination programme was introduced in the UK for girls aged 12 to 13, with catch-up programmes aiming to offer the vaccine to all girls born on or after September 1 1990. The vaccine currently used in schools (Gardasil), protects against four types of HPV: HPV16 and HPV18, which are responsible for more than 70% of worldwide cervical cancer cases; and HPV6 and HPV11, which are responsible for most cases of genital warts.6 The current vaccination schedule requires just two doses to be administered (three doses for girls aged 15 and older). A nonavalent vaccine (Gardasil 9) is currently in production which will provide an even greater degree of protection (against 9 HPV types instead of 4: HPV 6/11/16/18/31/33/45/52/58).7
The rationale for targeting this age group is that the vaccine needs to be given to those who have not yet been sexually active in order for it to be most effective. In addition, antibody responses to the vaccine are higher before the onset of puberty.8 When the vaccination was first introduced there was some concern expressed among parents that the vaccine would lead to the early sexualisation of teenage girls and to promiscuous behaviour. Research suggests that this has not been the case.9 As of yet, boys in the UK are not routinely vaccinated, but there is increasing lobbying for this to change (see Men and HPV section).
One common misconception about the HPV vaccination is that girls and women who have received the HPV vaccination are no longer at risk of developing cervical cancer.10,11 Currently, the vaccination in the UK primarily protects against two high-risk HPV types and two low-risk HPV types and there is evidence of some cross-protection against other types.12 Although these two high-risk types are responsible for 70% of cases of cervical cancer, they are not responsible for all cases, therefore vaccinated women will still need to be screened.
Since the 1980s the NHS has had a very effective cervical screening programme (NHSCSP). When a woman has an abnormal screening (cytology/smear test) result, she will be referred to colposcopy for assessment and if necessary, treatment in order to prevent the cervical abnormalities progressing into cancer. More recently, HPV testing has been introduced alongside cervical screening. In England and Northern Ireland, women whose cervical screening cytology shows low grade changes (borderline/mild dyskaryosis) will have a HPV test performed on their smear, known as HPV triage. If the high-risk HPV test is negative, then the risk of developing high-grade changes (moderate/severe dyskaryosis) or cervical cancer is low and therefore they are discharged to routine screening recall.13 A positive HPV test will result in a referral for colposcopy. Women whose cytology shows a high-grade abnormality are referred for colposcopy without a HPV test being performed.14
HPV test of cure
Before the introduction of the HPV test, women who underwent treatment for cervical pre-cancer, known as cervical intraepithelial neoplasia (CIN) would have a follow-up smear test at six months, one year and then annually for the next nine years before being returned to the regular screening programme. A HPV test has been added to the first six-month smear test (test of cure) since it has been shown to be more sensitive at detecting CIN than cytology alone.15 If this HPV test is negative, the likelihood of further CIN is low and the woman will be recalled in three years.14 If the HPV test is positive, even if the cytology is normal, the woman will be referred back for colposcopic assessment.
Primary HPV screening
Since 2013, the NHSCSP has been trialling the use of HPV testing as the primary screening tool in six sites across England as it has been shown to be more sensitive than traditional cytology in detecting high grade cells (CIN II+).16 The protocol is in contrast to the current programme with cytology only being carried out on cervical screening samples following a positive HPV test instead of being the primary screening test. Should this pilot be successful, the intention is to roll it out across the UK.
Older women and HPV
Although the prevalence of high-risk HPV is greatest in young sexually active women and decreases with age,17 it is still important that older women continue to attend for cervical screening. Twenty per cent of all new cases of cervical cancer in the UK and 50% of all deaths occur in women aged 65 years and above. Despite this, attendance is declining in women aged 55 and older. One reason for this may be that they feel cervical cancer is a young woman’s disease. However, as mentioned before it has been proposed that HPV can lie dormant for many years and may have the potential to become reactivated, although the mechanisms for this are not yet understood. As a result even when women have been with the same partner for many years or are no longer sexually active, they are still at risk of developing cervical cancer if they were exposed to HPV at an earlier time in their life.
The cervical screening programme in the UK currently ends at 64 years of age (60 in Scotland but they will come in line with the rest of the UK from 2016) yet there is a six-fold protective effect of having three consecutive negative smear tests before leaving the screening programme.18 Women need to attend screening to benefit from this (see reference Sherman et al 19 for a review).
Men and HPV
Currently, boys in the UK are not routinely vaccinated against HPV. The rationale for vaccinating girls only is that this should provide herd immunity to boys. However, this does not benefit men who have sex with men, or those who have sex with the estimated 15% of girls who have not been vaccinated. In addition to causing cervical cancer, HPV is also responsible for a high proportion of head and neck, anal and penile cancers. Across Europe, the incidence of head and neck cancers attributable to HPV16/18 is five-fold higher in men (12,707 new cases yearly) than women (2,531 new cases yearly) and is increasing.20 As a result, there has been extensive lobbying for the vaccination programme to be extended to boys (as it is in Australia, Austria, Canada and the US). Moreover, in 2014 the Joint Committee on Vaccination and Immunisation recommended that men in England, aged 16 to 40, who have sex with men should be offered the vaccine in genitourinary (GUM) and HIV clinics.21
Role of primary care nurses
As research has shown, practice nurses are a key source of both information and advice for patients about HPV infection, vaccination and testing.22 They are also likely to be a source of support for women who are distressed by the diagnosis of HPV and abnormal cervical smear results.
Research suggests that while knowledge about HPV is increasing in the general population, there is still a considerable amount of confusion and incorrect information that persists. A recent international survey (US, Australia and UK) found that a significant minority of UK respondents believed that: HPV is very rare, always has visible signs or symptoms, can cause HIV/Aids and that men cannot get it. While a majority falsely believe it can be cured with antibiotics.23 Primary care nurses have a key role to play in combatting these misunderstandings.
To conclude, HPV is an extremely common sexually transmitted virus, which has the potential to induce malignant change in those cases where high-risk infection persists. There is a lack of knowledge about the virus in the general population and primary care nurses have an important role to play in educating and supporting patients around this issues.
Jo’s Cervical Cancer Trust – jostrust.org.uk/
1. Bouvard V, Baan R, Straif K, Grosse Y, Secretan B, El Ghissassi F et al. A review of human carcinogens – part B: biological agents. The Lancet Oncology 2009;10:321-2. dx.doi.org/10.1016/S1470-2045(09)70096-8 (accessed 13 October 2015).
2. World Health Organization. Human papillomavirus (HPV) and cervical cancer. who.int/mediacentre/factsheets/fs380/en/ (accessed 23 September 2015).
3. Brogaard KA, Munk C, Iftner T, Frederiksen K, Kjaer SK. Detection of oncogenic genital human papillomavirus (HPV) among HPV negative older and younger women after 7 years of followup. Journal of Medical Virology 2014;86(6):975-982.
4. NHS. Can genital HPV infection be tested for? nhs.uk/chq/Pages/2382.aspx?CategoryID=118&SubCategoryID=125 (accessed 13 September 2015).
5. Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PJ, Peto J, Meijer CJ, Munoz N. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. The Journal of Pathology 1999;189(1):12-19.
6. World Health Organization. Human papillomavirus (HPV). who.int/immunization/topics/hpv/en/ (accessed 23 September 2015).
7. Joura EA, Giuliano AR, Iversen OE, Bouchard C, Mao C, Mehlsen J et al. A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women. The New England Journal of Medicine 2015;372(9):711-23.
8. Stanley M, Lowy DR, Frazer I. Prophylactic HPV vaccines: underlying mechanisms. Vaccine 2006;24:106-113.
9. Forster AS, Marlow LA, Stephenson J, Wardle J, Waller J. Human papillomavirus vaccination and sexual behaviour: cross-sectional and longitudinal surveys conducted in England. Vaccine 2012;30(33):4939-4944. DOI: 10.1016/j.vaccine.2012.05.053 (accessed 13 October 2015).
10. Bowyer HL, Marlow LA, Hibbitts S, Pollock KG, Waller J. Knowledge and awareness of HPV and the HPV vaccine among young women in the first routinely vaccinated cohort in England. Vaccine 2013;31(7):1051-1056.
11. Sherman SM, Nailer E, Minshall C, Coombes R, Cooper J, Redman CWE. Awareness and knowledge of HPV and cervical cancer in female students: a survey (with a cautionary note). Journal of Obstetrics and Gynaecology in press.
12. Moreman C, Redman CWE, Moss EL. Human Papillomavirus and its Role in Cervical Cancer Screening and Treatment. Current Treatment Options in Infectious Diseases 2015;7(3):217-229.
13. Arbyn M, Roelens J, Simoens C, Buntinx F, Paraskevaidis E, Martin-Hirsch PP et al. Human papillomavirus testing versus repeat cytology for triage of minor cytological cervical lesions. Cochrane Database Systematic Reviews 2013;3:CD008054. DOI: 10.1002/14651858.CD008054.pub2 (accessed 13 October 2015).
14. NHSCSP. Screening Protocol Algorithm for HPV Triage and TOC. cancerscreening.nhs.uk/cervical/hpv-triage-test-flowchart-201407.pdf (accessed 23 September 2015).
15. Van der Heijden E, Lopes AD, Bryant A, Bekkers R, Galaal. Follow-up strategies after treatment (large loop excision of the transformation zone (LLETZ)) for cervical intraepithelial neoplasia (CIN): impact of human papillomavirus (HPV) test. Cochrane Database Systematic Reviews 2015;1:CD010757.
16. Cuzick J, Clavel C, Petry KU, Meijer CJ, Hoyer H, Ratnam S, Iftner T. Overview of the European and North American studies on HPV testing in primary cervical cancer screening. International Journal of Cancer 2006;119(5):1095-1101.
17. Leinonen M, Nieminen P, Kotaniemia-Talonen L, Malila N, Tarkkanen J, Laurila P et al. Age-specific evaluation of primary human papillomavirus screenings vs conventional cytology in a randomized setting. Journal of National Cancer Institute 2009;101:1612-23.
18. Castanon A, Landy R, Cuzick J, Sasieni P. Cervical Screening at Age 50-64 Years and the Risk of Cervical Cancer at Age 65 Years and Older: Population-Based Case Control Study. PLoS Medicine 2014;11(1):e1001585.
19. Sherman SM, Castanon A, Moss E, Redman CWE. Cervical cancer is not just a young woman’s disease. British Medical Journal 2015;350:h2729. DOI:10.1136/bmj.h2729 (accessed 13 October 2015).
20. Hartwig S, Syrjänen S, Dominiak-Felden G, Brotons M, Castellsagué X. Estimation of the epidemiological burden of human papillomavirus-related cancers and non-malignant diseases in men in Europe: a review. BMC Cancer 2012;12(1):30.
21. Department of Health. Joint Committee on Vaccination and Immunisation (JCVI) interim position statement on HPV vaccination of men who have sex with men (MSM). gov.uk/government/uploads/system/uploads/attachment_data/file/373531/JCVI_interim_statement_HPV_vacc.pdf (accessed 12 October 2015).
22. McSherry LA, Dombrowski SU, Francis JJ, Murphy J, Martin CM, O’Leary JJ, Sharp L. ‘It’s a can of worms’: understanding primary care practitioners’ behaviours in relation to HPV using the theoretical domains framework. Implementation Science 2012;7(1):73.
23. Marlow LAV, Zimet GD, McCaffery KJ, Ostini R, Waller J. Knowledge of human papillomavirus (HPV) and HPV vaccination: An international comparison. Vaccine 2013;31:763-769. DOI: 10.1016/j.vaccine.2012.11.083 (accessed 13 October 2015).