Key learning points:
– In the UK, liquid-based cytology with human papilloma virus triage of low-grade cytological results are used for cervical screening
– Women aged 25-49 should attend screenings every three years and women aged 50-64 should attend every five years
– High coverage of the target population is essential for the cervical screening programme to be successful
Cervical cancer is the fourth most common cancer in women worldwide.1 There is consistent evidence that high-risk human papillomavirus (HR-HPV) infection, a common sexually transmitted disease, is a necessary cause of cervical cancer.2 At least 13 HPV sub-types have been identified as being high risk (or cancer causing). However, around 70% of cervical cancers are caused by HR-HPV 16 and 18.3 Although HR-HPV is a necessary cause of cervical cancer, it is not sufficient and many women will clear the virus without developing disease. Co-factors that appear to increase the risk of developing cervical cancer in HR-HPV infected women include the use of oral contraceptives, smoking, high parity, previous exposure to sexually transmitted diseases (chlamydia and herpes simplex virus type 2) and potentially some unidentified genetic factors related to immunity.4
Organised call/recall cervical screening in England was introduced in 1988 and has been so effective that the incidence of cervical cancer has been reduced by 46% and mortality by 65%. By 2010 a woman’s lifetime risk of developing cervical cancer in the UK was estimated to be one-in-139 (or 0.7%).5 In fact, in the UK cervical cancer is no longer among the top 10 cancers in women. By 2012, the age standardised incidence was 9.5 per 100,000 women (equivalent to 3,044 women diagnosed with cancer) and the age standardised mortality (ASR) was 2.2 per 100,000 (or 919 deaths). Making cervical cancer the 12th cause of cancer and the 17th cause of cancer death in women.6,7 This is in stark contrast to less developed regions with no organised screening, such as Eastern Africa where cervical cancer remains the most common cancer in women and the lifetime risk of developing it is 4.6%.8
Target population for cervical screening
The aim of the cervical screening programme is to detect and treat high-grade pre-invasive disease (cervical intraepithelial neoplasia (CIN) grade 2 or 3). When the programme was first introduced women aged 20-64 were invited every three years for cervical screening (in Scotland women were invited up to age 60). However, research published in 20039 showed that screening is less effective at preventing cancer in young women than it is for older women. The same study also found screening was not effective at preventing cancer in those aged 20-24.
In England, the screening policy changed in 2009 and women are now invited aged 25-49 for three yearly screens and women aged 50-64 for five yearly screens. Wales changed its policy to come in line with the English programme in September 201310 and Scotland is expected to change its policy as of April 2016.11
What cervical screening is used in the UK?
Currently, cytology is used for cervical screening. Cytology is the collection, staining and microscopic examination of cells from the cervix. Since October 2008 the programme has screened using liquid based cytology (where the cells are deposited directly into a small glass vial containing preservative fluid before being transferred onto a glass slide). This leads to lower rates of inadequate samples when compared to conventional cytology.12 Another benefit of liquid based cytology is that the same sample can be used both to examine the cells from the cervix and to test for the presence of HR-HPV virus (also known as reflex testing). This is key since as of April 2012 all samples with a cytological diagnosis of low-grade dyskaryosis or borderline changes are also tested for the presence of HR-HPV virus at the laboratory. This approach is called cytology screening with HPV triage of low-grade cytological results.
There is a wealth of evidence suggesting that HR-HPV testing is better at identifying those at risk of disease (CIN2 or worse) but not those who actually have abnormalities that can be treated (ie it is more sensitive but less specific than cytology testing).13 This is because for 90% of women the body’s immune system will clear a cervical HPV infection within a year or two.14 Hence, by using both tests together, one can better identify women who have both low-grade cytological changes in the cervix and a HR-HPV infection. The risk of developing CIN2 among those who are HR-HPV negative and have low-grade cytological changes is low (the cumulative five year risk is 1.3%), therefore these women can be returned to routine recall every three or five years.15 However, the five-year risk of CIN2 or worse among those who test HR-HPV positive is more than 10% and referral to colposcopy for further follow up is warranted.15 The introduction of HPV triage of low-grade or borderline cytology has eliminated the need for repeat cytology testing in such women, leading to swifter investigation of those at high risk of developing disease and requiring treatment.
It is expected that testing for HR-HPV will become the primary screening test in the near future. This approach is currently being piloted in the UK.16 In primary care the change from cytology screening with HPV triage to HPV primary testing will not change current sample taking practices. Sample takers will continue to use liquid-based cytology to obtain samples from the cervix. However, the laboratory will carry out the HR-HPV test first, and then – only if it is positive – perform a reflex cytology test as triage.
Why should women attend cervical screening?
Women who attend screening regularly are between 60% and 80% less likely to develop cancer compared to women who don’t (depending on age).9 Therefore, it is essential to the success of the programme that all eligible women attend screening regularly. Maintaining high coverage in the programme has been particularly challenging in recent years. National statistics have shown a decrease in coverage in England over the last five years among women eligible for screening.17 Coverage has fallen among those aged 50-64 (from 80.1% in 2011 to 78.4% in 2015), but it is particularly noticeable among women aged 25-49 where the proportion of attending every 3.5 years has fallen from 73.7% in 2011 to 71.2% in 2015.
Vaccination against high-risk HPV types 16 and 18 was rolled out nationally in 2008 to girls aged 12-13 with a catch-up programme in girls aged 15 to 18.18 Around 2016 the first vaccinated cohorts will reach the age of 25 and become eligible for screening. Vaccinated women will still need to attend screening. This is because the vaccine does not protect against all HR-HPV types and those in the catch-up cohort may not be fully protected since the vaccine is not effective among those who have already been exposed to the virus.
The falling coverage among older women is particularly worrying. The average time between HPV infection and the development of cancer varies but it is unusual for cancer to develop in less than seven years. Moreover, it is not uncommon for it to develop more than 30 years after infection,19 so the longer women remain unscreened the more vulnerable they are to developing cancer. Additionally, these women will not benefit from the introduction of vaccination.
Role of the primary care nurse
There is work to be done regarding the lack of knowledge among women when it comes to understanding the relationship between the HPV virus, HPV vaccination and the development of cervical cancer. An international study of 18-70 year olds found that 38% of women in the UK had not heard of HPV before and nearly all of those who had heard of HPV did not know that ‘HPV usually doesn’t need any treatment’.20 Moreover, 28% of women thought that once vaccinated against HPV they could not develop cervical cancer. In the same study 18% of women wrongly thought that a HPV positive test would definitely lead to the development of cancer.21
The role of the primary care nurse is not only to be a competent sample taker but to have a good understand of why screening is important, what the programme is testing for and what the risks of not being screened are.
Primary care nurses are the face of the screening programme and having a good understanding of the issues raised here should allow them to provide adequate support, advice and reassurance to women who engage with the screening programme.
Resources
Cancer Research UK. Cervical cancer statistics–
cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/cervical-cancer
NHS Cervical Screening Programme. Public Health England–
gov.uk/topic/population-screening-programmes/cervical
Cervical Screening Wales–
cervicalscreeningwales.wales.nhs.uk/about-screening
ICO HPV Information Centre–
hpvcentre.net
References
1. Ferlay J, Soerjomataram I, Ervik M et al. Cervical Cancer: Estimated Incidence, Mortality and Prevalence Worldwide in 2012. Secondary Cervical Cancer: Estimated Incidence, Mortality and Prevalence Worldwide in 2012.
2. Bosch FX, Iftner T. The aetiology of cervical cancer. NHSCSP Publication No 22. Sheffield, UK, 2005.
3. World Health Organization. Human papillomavirus (HPV) and cervical cancer. Secondary Human papillomavirus (HPV) and cervical cancer. who.int/mediacentre/factsheets/fs380/en/ (accessed 9 December 2015).
4. Castellsague X, Munoz N. Cofactors in human papillomavirus carcinogenesis role of parity, oral contraceptives, and tobacco smoking. Journal of the National Cancer Institute Monographs 2003(31):20-8.
5. Cancer research UK. CRUK lifetime risk of cervical cancer. Secondary CRUK lifetime risk of cervical cancer, 2015. cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/cervical-cancer/incidence#heading-Three. (accessed 9 December 2015).
6. Cancer Research UK. Cervical cancer incidence statistics. cancerresearchuk.org/cancer-info/cancerstats/types/cervix/incidence/. (accessed 9 December 2015).
7. Cancer Research UK. Cervical cancer mortality statistics. cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/cervical-cancer/mortality#heading-Zero. (accessed 9 December 2015).
8. Ferlay J SI, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, F. Bray. Cancer Incidence and Mortality Worldwide: IARC CancerBase No.11 [Internet]. http://globocan.iarc.fr. (accessed 9 December 2015).
9. Sasieni P, Adams J, Cuzick J. Benefit of cervical screening at different ages: evidence from the UK audit of screening histories. British Journal of Cancer 2003;89(1):88-93.
10. Cervical Screening Wales. Changes to screening age explained. cervicalscreeningwales.wales.nhs.uk/empty-1. (accessed 9 December 2015).
11. NHS Health Scotland. Cervical screening. healthscotland.com/topics/health-topics/screening/cervical.aspx (accessed 9 December 2015).
12. Department of Health. NHS cervical screening programme. cancerscreening.nhs.uk/cervical/lbc.html (accessed 9 December 2015).
13. Cuzick J, Clavel C, Petry KU, et al. Overview of the European and North American studies on HPV testing in primary cervical cancer screening. International Journal of Cancer 2006;119(5):1095-101.
14. Sherman ME, Lorincz AT, Scott DR et al. Baseline cytology, human papillomavirus testing, and risk for cervical neoplasia: a 10-year cohort analysis. Journal of the National Cancer Instute 2003;95(1):46-52.
15. Katki HA, Kinney WK, Fetterman B, et al. Cervical cancer risk for women undergoing concurrent testing for human papillomavirus and cervical cytology: a population-based study in routine clinical practice. Lancet Oncology 2011;12(7):663-72.
16. Wise J. Pilot study will assess whether HPV test should replace smears to screen for cervical cancer. British Medical Journal 2012;344:e3744.
17. Screening and Immunisations Team HaSCIC. Cervical Screening Programme, England – 2014-2015.
18. NHS choices. HPV vaccine. nhs.uk/conditions/vaccinations/pages/hpv-human-papillomavirus-vaccine.aspx (accessed 9 December 2015).
19. Schiffman M, Wentzensen N, Wacholder S, et al. Human papillomavirus testing in the prevention of cervical cancer. Journal of the National Cancer Institute 2011;103(5):368-83.
20. Marlow LA, Zimet GD, McCaffery KJ et al. Knowledge of human papillomavirus (HPV) and HPV vaccination: an international comparison. Vaccine 2013;31(5):763-9.
21. Dodd RH, McCaffery KJ, Marlow LA et al. Knowledge of human papillomavirus (HPV) testing in the USA, the UK and Australia: an international survey. Sexually Transmitted Infections 2014;90(3):201-7.
