The global impact of Pap cytology screening in women's health cannot be understated. Since its introduction, the use of regular Pap 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 However, approximately 275,000 women worldwide still die of cervical cancer each year.
While the incidence has been greatly reduced, data shows that sensitivity of Pap cytology is low for the detection of pre-cancerous cervical lesions.2
There are a number of women who are screened regularly yet remain at high-risk despite having normal cytology. The practice of co-testing for hrHPV adds to the predictive value of Pap cytology by identifying women truly at high-risk that are missed by cytology alone.
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 Pap cytology.3, 4
These limitations can be addressed by the introduction of high-risk HPV testing and HPV 16 and HPV 18 genotyping.
False negative Pap results are common with adenocarcinomas because they tend to be difficult to detect cytologically and they can arise high up in the endocervical canal where it is not easy to sample them, even with cytobrushes.9 HPV 16 and 18 account for 70% of cervical cancers and >80% of adenocarcinomas.10
A systematic evidence review of randomized studies of HPV testing conducted for the U.S. Preventive Services Task Force showed that HPV screening was consistently more sensitive than Pap for the detection of ≥ CIN2 and ≥CIN3.11
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. 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.
4. 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.
5. 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.
6. Herzog TJ, Monk BJ. Reducing the burden of glandular carcinomas of the uterine cervix. Am J Obstet Gynecol. 2007;197(6):566-571.
7. The American Congress of Obstetricians and Gynecologists. ACOG Practice Bulletin. Clinical Management Guidelines for Obstetrician-Gynecologists: Screening for Cervical Cancer. November, 2012.
8. 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.
9. 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.
10. Bosch FX, de Sanjosé S. Human papillomavirus and cervical cancer — burden and assessment of causality. J Natl Cancer Inst Monogr. 2003;31:3-13.
11. 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.