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. 2013 Apr;17(5 Suppl 1):S28-35.
doi: 10.1097/LGT.0b013e318285423c.

Benchmarking CIN 3+ risk as the basis for incorporating HPV and Pap cotesting into cervical screening and management guidelines

Hormuzd A Katki  1 , Mark Schiffman, Philip E Castle, Barbara Fetterman, Nancy E Poitras, Thomas Lorey, Li C Cheung, Tina Raine-Bennett, Julia C Gage, Walter K Kinney
Affiliations

Benchmarking CIN 3+ risk as the basis for incorporating HPV and Pap cotesting into cervical screening and management guidelines

Hormuzd A Katki et al. J Low Genit Tract Dis. 2013 Apr.

Abstract

Objective: In 2012, the US Preventive Services Task Force (USPSTF) and a consensus of 25 organizations endorsed concurrent cytology and human papillomavirus (HPV) testing ("cotesting") for cervical cancer screening. Past screening and management guidelines were implicitly based on risks defined by Pap-alone, without consideration of HPV test results. To promote management that is consistent with accepted practice, new guidelines incorporating cotesting should aim to achieve equal management of women at equal risk of cervical intraepithelial neoplasia grade 3 and cancer (CIN 3+).

Methods: We estimated cumulative 5-year risks of CIN 3+ for 965,360 women aged 30 to 64 years undergoing cotesting at Kaiser Permanente Northern California over 2003 to 2010. We calculated the implicit risk thresholds for Pap-alone and applied them for new management guidance on HPV and Pap cotesting, citing 2 examples: HPV-positive/atypical squamous cells of undetermined significance (ASC-US) and HPV-negative/Pap-negative. We call this guidance process "benchmarking."

Results: A low-grade squamous intraepithelial lesion result, for which immediate colposcopy is prescribed, carries a 5-year CIN 3+ risk of 5.2%, suggesting that test results with similar risks should be managed with colposcopy. Similarly, ASC-US (2.6% risk) is managed with a 6- to 12-month follow-up visit and Pap-negative (0.26% risk) is managed with a 3-year follow-up visit. The 5-year CIN 3+ risk for women with HPV-positive/ASC-US was 6.8% (95% confidence interval = 6.2%-7.6%). This is greater than the 5.2% risk implicitly leading to referral to colposcopy, consistent with current management recommendations that HPV-positive/ASC-US should be referred for immediate colposcopy. The 5-year CIN 3+ risk for women with HPV-negative/Pap-negative was 0.08% (95% confidence interval = 0.07%-0.09%), far below the 0.26% implicitly required for a 3-year return and justifying a longer (e.g., 5-year) return.

Conclusions: Using the principle of "equal management of equal risks," benchmarking to implicit risk thresholds based on Pap-alone can be used to achieve safe and consistent incorporation of cotesting.

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Conflict of interest statement

Conflicts of Interest: Dr. Schiffman and Dr. Gage report working with Qiagen, Inc. on independent evaluations of non-commercial uses of care HPV (a low-cost HPV test for low-resource regions) for which they have received research reagents and technical aid from Qiagen at no cost. They have received HPV testing for research at no cost from Roche. Dr. Castle has received compensation for serving as a member of a Data and Safety Monitoring Board for HPV vaccines for Merck. Dr. Castle has received HPV tests and testing for research at a reduced or no cost from Qiagen, Roche, MTM, and Norchip. Dr. Castle is a paid consultant for BD, GE Healthcare, and Cepheid, and has received a speaker honorarium from Roche. No other authors report any conflicts of interest.

Figures

Figure 1
Figure 1
Cumulative risk of CIN2+ (left panel), CIN3+ (middle panel), and cancer (right panel) among women aged 30–64 by baseline Pap result alone (regardless of HPV test result). Note that the y-axes have different scales for different panels.
Figure 2
Figure 2
Cumulative risks of CIN2+ (left panel), CIN3+ (middle panel), and cancer (right panel), among women aged 30–64, by baseline test results of HPV+/ASC-US, LSIL alone (regardless of HPV test result), Pap-negative (Pap−) alone (regardless of HPV test result) and HPV-negative/Pap-negative. Note that the y-axes have different scales for different panels.
See this image and copyright information in PMC

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