A significant impact on women's health
The global impact of cervical cytology screening in women's health must not be underestimated. Since its introduction, the use of regular cervical cytology screening, together with the diagnosis and treatment of pre-cancerous lesions, has contributed to an 80% reduction in the incidence and mortality of cervical cancer in countries with systematic screening.1
While the incidence has been greatly reduced, data shows that sensitivity of cytology screening is low for the detection of pre-cancerous cervical lesions.2 In the UK cervical screening, using liquid based cytology (LBC), leads to early detection and treatment that can prevent 75 percent of cancers developing.3
Normal cytology doesn't always mean cancer or precancer free.
Up to one-third of cervical cancers occur in screened women.4,5
Audits of the well-respected screening programs of Kaiser Permanente and the Swedish healthcare system demonstrated that 32% and 24%, respectively, of invasive cervical cancer occurred in women with normal cytology screening results.4,5 In addition UK data also suggest that around 50% of cervical cancer (women aged 20-64) occurred in women who have been screened following cervical screening guidelines.6
There are multiple limitations in using cytology alone:
There are a number of women who are screened regularly yet remain at high risk despite having normal cytology.
HPV Triage of borderline and low-grade dyskaryosis (mild dyskaryosis) adds to the predictive value of cervical cytology by identifying women truly at high risk and leading to faster referral to colposcopy and earlier treatment before development of cervical cancer.
However, the limits of cytology screening affect women at both ends of the diagnostic spectrum:
These limitations can be addressed by the introduction of high-risk HPV testing as primary screen and HPV 16 and HPV 18 genotyping.
Despite well-established screening programmes, adenocarcinoma incidence is still rising in industrialised nations.11,12
False negative cytology results are common with adenocarcinomas. They tend to be difficult to detect cytologically as they can arise high up in the endocervical canal, where it is not easy to sample them, even with cytobrushes.13 HPV 16 and 18 account for 70% of cervical cancers and >80% of adenocarcinomas.14 HPV 18 is commonly associated with a third of cervical adenocarcinomas.14
A systematic evidence review of randomised studies, conducted for the US Preventive Services Task Force, showed that HPV screening was consistently more sensitive than cytology for the detection of ≥CIN2 and ≥CIN3.15 Cervical cytology screening saves around 5,000 lives every year in the UK, but an improvement on this can be achieved. The UK HART study showed that with hrHPV testing a 20% increase in screening sensitivity can be achieved.16
1. National Cancer Institute. Cervical Cancer Screening (PDQ®). http://www.cancer.gov/cancertopics/pdq/screening/cervical/HealthProfessional#Section_115 . Accessed June 2011.
2. Herbert A, Anshu, Gregory M, Gupta SS, Singh N. Invasive cervical cancer audit: a relative increase in interval cancers while coverage increased and incidence declined. BJOG. 2009;116(6):845-853.
3. PNHS Cervical Screening Programme: About Cervical Screening; http://www.cancerscreening.nhs.uk/cervical/about-cervical-screening.html. Nov 2012.
4. Leyden WA, Manos MM, Geiger AM, et al. Cervical cancer in women with comprehensive health care access: attributable factors in the screening process. J Natl Cancer Inst. 2005;97(9):675-683.
5. Andrae B, Kemetli L, Sparén P, et al. Screening-preventable cervical cancer risks: evidence from a nationwide audit in Sweden. J Natl Cancer Inst. 2008;100(9):622-629.
6. Sasieni P, Cuzick J, Lynch-Farmery E. Estimating the efficacy of screening by auditing smear histories of women with and without cervical cancer. The National Co-ordinating Network for Cervical Screening Working Group. Br J Cancer.1996;73:1001-1005.
7. Castle PE, Stoler MH, Wright TC Jr., Sharma A, Wright TL, Behrens CM. Performance of carcinogenic human papillomavirus (HPV) testing and HPV16 or HPV18 genotyping for cervical cancer screening of women aged 25 years and older: a subanalysis of the ATHENA study. Lancet Oncol. 2011;12(9):880–890 plus supplementary tables.
8. Herzog TJ, Monk BJ. Reducing the burden of glandular carcinomas of the uterine cervix. Am J Obstet Gynecol. 2007;197(6):566-571.
9. Kelly RS, Patnick J, Kitchener HC and Moss SM on behalf of the NHSCSP HPV Special Interest Group. HPV testing as a triage for borderline or mild dyskaryosison cervical cytology: results from the Sentinel Sites study. Br J Cancer. 2011;105: 983–988. doi:10.1038/bjc.2011.326.
10. The American Congress of Obstetricians and Gynecologists. ACOG Practice Bulletin. Clinical Management Guidelines for Obstetrician-Gynecologists: Screening for Cervical Cancer. November, 2012.
11. Smith HO, Tiffany MF, Qualls CR, Key CR. The rising incidence of adenocarcinoma relative to squamous cell carcinoma of the uterine cervix in the U.S. — a 24-year population-based study. Gynecol Oncol. 2000;78(2):97-105.
12. IARC. World Cancer Report 2008: Edited by Boyle P and Levin B. IARC; 2008
13. Ault KA, Joura EA, Kjær SK, et al. Adenocarcinoma in situ and associated human papillomavirus type distribution observed in two clinical trials of a quadrivalent human papillomavirus vaccine. Int J Cancer. 2011;128(6):1344-1353.
14. de Sanjosé S, Quint WG, Alemany L, et al. Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. Lancet Oncol. 2010;11(11):1048-1056
15. Whitlock EP, Vesco KK, Eder M, Lin JS, Senger CA, Burda BU. Liquid-Based Cytology and Human Papillomavirus Testing to Screen for Cervical Cancer: A Systematic Review for the U.S. Preventive Services Task Force. Ann Intern Med. 2011;155(10):687-697.
16. Cuzick J, Szarewski A, Cubie H, Hulman G, Kitchener H, Luesley D, McGoogan E, Menon U, Terry G, Edwards R, Brooks C, Desai M, Gie C, Ho L, Jacobs I, Pickles C, Sasieni P. Management of women who test positive for high-risk types of human papillomavirus: the HART study. Lancet. 2003;362:1871–1876.