Journal of the National Cancer Institute Advance Access originally published online on January 13, 2009
JNCI Journal of the National Cancer Institute 2009 101(2):88-99; doi:10.1093/jnci/djn444
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© The Author 2009. Published by Oxford University Press.
ARTICLES |
Efficacy of HPV DNA Testing With Cytology Triage and/or Repeat HPV DNA Testing in Primary Cervical Cancer Screening
Affiliations of authors: Department of Medical Microbiology, Malmö University Hospital, Lund University, Sweden (PN, OF, B-GH, JD); Department of Pathology and Clinical Cytology (WR), Department of Obstetrics and Gynecology (TR, BS), and Oncology Centre (BS), Sahlgrenska University Hospital, Gothenburg, Sweden; Cancer Screening Unit, Oncology Centre (ST) and Department of Obstetrics and Gynecology (KE), Karolinska University Hospital, Stockholm, Sweden; Department of Medicine, Dermatology and Venereology, University Hospital, Uppsala, Sweden (AS); Department of Virology, University of Northern Sweden, Umeå, Sweden (GW); Division of Gynecology at Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden (ER); Department of Pathology, National Hospital of Norway, Oslo, Norway (BH); Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital at Huddinge, Stockholm, Sweden (BJ)
Correspondence to: Joakim Dillner, MD, Department of Medical Microbiology, Lund University, Malmö University Hospital, S-20502 Malmö, Sweden (e-mail: joakim.dillner{at}med.lu.se).
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.
| CONTEXT AND CAVEATS Prior knowledge Data from randomized controlled trials comparing the efficacy of human papillomavirus (HPV) DNA–based primary cervical screening with that of screening by cytology for the prevention of cervical cancer indicate that the former has higher sensitivity than the latter (ie, it detects more high-grade cervical intraepithelial neoplasia lesions) but lower specificity, raising concerns that HPV DNA–based primary screening could lead to unnecessary testing and follow-up for many women. Alternative combinations of cytology and HPV DNA testing–based screening strategies may have greater specificity than those tested in these trials. Study design Data from the intervention arm of a randomized trial of HPV DNA testing as an add-on to primary cervical cancer screening by cytology were used to explore the efficacy of 11 different screening strategies based on HPV DNA testing alone, cytology alone, and HPV DNA testing combined with cytology. Contribution Primary HPV DNA testing followed by triaging with cytology and screening for persistent HPV type-specific infection had a considerably higher sensitivity for detecting cervical intraepithelial neoplasia grade 3 or worse than screening by cytology alone and led to only a modest increase in the number of screening tests and referrals. Implications Using HPV DNA testing as primary screening followed by cytological triage and repeat HPV DNA testing of women with normal cytology who are HPV DNA positive after at least 1 year is a feasible strategy in primary cervical screening. Limitations The study population was limited to women aged 32–38 years. Not all women in the cohort were referred to colposcopy. From the Editors
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Manuscript received July 1, 2008; revised October 14, 2008; accepted November 3, 2008.
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J Natl Cancer Inst 2009 101: 69.
J Natl Cancer Inst 2009 101: 69.
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