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Background Primary cervical screening with both human papillomavirus (HPV) DNA testing and cytological examination of cervical cells with a Pap test (cytology) has been evaluated in randomized clinical trials. Because the vast majority of women with positive cytology are also HPV DNA positive, screening strategies that use HPV DNA testing as the primary screening test may be more effective. Methods We used the database from the intervention arm (n = 6257 women) of a population-based randomized trial of double screening with cytology and HPV DNA testing to evaluate the efficacy of 11 possible cervical screening strategies that are based on HPV DNA testing alone, cytology alone, and HPV DNA testing combined with cytology among women aged 32-38 years. The main outcome measures were sensitivity for detection of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) within 6 months of enrollment or at colposcopy for women with a persistent type-specific HPV infection and the number of screening tests and positive predictive value (PPV) for each screening strategy. All statistical tests were two-sided. Results Compared with screening by cytology alone, double testing with cytology and for type-specific HPV persistence resulted in a 35% (95% confidence interval [CI] = 15% to 60%) increase in sensitivity to detect CIN3+, without a statistically significant reduction in the PPV (relative PPV = 0.76, 95% CI = 0.52 to 1.10), but with more than twice as many screening tests needed. Several strategies that incorporated screening for high-risk HPV subtypes were explored, but they resulted in reduced PPV compared with cytology. Compared with cytology, primary screening with HPV DNA testing followed by cytological triage and repeat HPV DNA testing of HPV DNA-positive women with normal cytology increased the CIN3+ sensitivity by 30% (95% CI = 9% to 54%), maintained a high PPV (relative PPV = 0.87, 95% CI = 0.60 to 1.26), and resulted in a mere 12% increase in the number of screening tests (from 6257 to 7019 tests). Conclusions Primary HPV DNA-based screening with cytology triage and repeat HPV DNA testing of cytology-negative women appears to be the most feasible cervical screening strategy.

Background The effectiveness of cervical cancer screening programs differs widely in different populations. The reasons for these differences are unclear. Routine and comprehensive audits have been proposed as an ethically required component of screening. We performed a nationwide audit of the effectiveness of the Swedish cervical cancer screening program. Methods We identified all invasive cervical cancer cases that were diagnosed in Sweden from January 1, 1999, through December 31, 2001, and had been reported to the Swedish Cancer Registry (n = 1230 cases). We verified the diagnoses by histopathologic rereview and matched each case subject to five (population-based) age-matched control subjects who were identified from the National Population Register. The Pap smear screening histories for case and control subjects were reviewed for a 6-year period using the National Cervical Cancer Screening Register, which contains data on essentially all relevant cytological and histological diagnoses in Sweden. Odds ratios (ORs), and their 95% confidence intervals (CIs), of cervical cancer according to screening history were calculated in conditional logistic regression models. All statistical tests were two-sided. Results Women who had not had a Pap smear within the recommended screening interval had higher risk of cervical cancer than women who had been screened (OR = 2.52, 95% CI = 2.19 to 2.91). This risk was similarly increased for all age groups (Phomogeneity = .96). The risk for nonsquamous cell cervical cancers (OR = 1.59, 95% CI = 1.20 to 2.11) was also increased. Women who had not had a Pap smear within the recommended screening interval had a particularly high risk of advanced cancers (OR = 4.82, 95% CI = 3.61 to 6.44). Among women who had been screened within the recommended interval, those with abnormal Pap smears had a higher risk of cervical cancer than those with normal smears (OR = 7.55, 95% CI = 5.88 to 9.69) and constituted 11.5% of all women with cervical cancer. Conclusions Nonadherence to screening intervals was the major reason for cervical cancer morbidity. The screening program was equally effective for women of all ages and was also effective against nonsquamous cancers.

Evaluation of colposcopic and histopathological findings in women screened for cervical human papillomavirus deoxyribonucleic acid persistence is presented. Histopathology from colposcopically directed biopsies confirmed cervical intraepithelial neoplasia grade 2 or 3 in 28 of 100 of the women with human papillomavirus deoxyribonucleic acid persistence and in 2 of 95 among controls.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajog.2009.04.006 Byline: Lena Silfverdal (a), Levent Kemetli (b), Bengt Andrae (c), Par Sparen (d), Walter Ryd (e), Joakim Dillner (g), Bjorn Strander (f), Sven Tornberg (b) Keywords: cervical cancer risk; histologic assessment; management of abnormal Pap smear results; population-based case control study; repeated cytology Abstract: We sought to evaluate the management of women with abnormal cytology in terms of subsequent risk of invasive cervical cancer. Author Affiliation: (a) Department of Obstetrics and Gynecology, UmeA[yen] University Hospital, UmeA[yen], Sweden (b) Cancer Screening Unit, Oncologic Center, Karolinska University Hospital, Stockholm, Sweden (c) Department of Obstetrics and Gynecology, Gavle Hospital, Gavle, Sweden (d) Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden (e) Department of Pathology and Clinical Cytology, Sahlgrenska University Hospital, Goteborg, Sweden (f) Oncologic Center, Sahlgrenska University Hospital, Goteborg, Sweden (g) Department of Medical Microbiology, Lund University, Malmo University Hospital, Malmo, Sweden Article History: Received 1 October 2008; Revised 24 January 2009; Accepted 10 April 2009 Article Note: (footnote) Funded by the Swedish Cancer Society., Reprints not available from the authors., Cite this article as: Silfverdal L, Kemetli L, Andrae B, et al. Risk of invasive cervical cancer in relation to management of abnormal Pap smear results. Am J Obstet Gynecol 2009;201:188.e1-7.