TP 139 Performance of Cytology and HPV16/18 Genotyping Among a Large Cohort of HPV Positive Women Aged 30 Years and Older

Tuesday, June 10, 2014
Exhibit Hall
Megan Clarke, M.H.S.1, Sean Boyle, B.S.2, Robert Burk, M.D.3, Tina Raine-Bennett, M.D., M.P.H.4, Philip Castle, Ph.D., M.P.H.5, Nicolas Wentzensen, M.D., Ph.D.6, Julia Gage, Ph.D., M.P.H.6, Hormuzd Katki, Ph.D., M.P.H.7 and Mark Schiffman, M.D., M.P.H.6, 1Epidemiology, Johns Hopkins School of Public Health, Baltimore, MD, 2Research, Roche Molecular Systems, Pleasanton, CA, 3Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, MD, 4Division of Research, Women's Health Research Institute, Kaiser Permanente Northern California, Oakland, CA, 5Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, 6Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, 7Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville

Background:  Co-testing for HPV, the most commonly diagnosed sexually transmitted infection, has recently been incorporated into U.S. cervical cancer screening guidelines.  Currently, women who are HPV positive (HPV+) with ASC-US or worse cytology (ASC-US+) are referred to immediate colposcopy.  Those with normal cytology may be triaged with HPV16/18 genotyping and referred to colposcopy if HPV16/18+; however implementation of this approach in routine clinical practice has not been evaluated.  Here we use co-testing data from the Persistence and Progression cohort at Kaiser Permanente Northern California (KPNC) to evaluate the performance of cytology and HPV16/18 genotyping among HPV+ women 30+ years of age.

Methods:  We evaluated 34,242 women who tested HPV+ by Hybrid Capture 2 (Qiagen, Gaithersburg, MD).  Cases of cervical intraepithelial neoplasia grade 2 or worse that developed within approximately two years (CIN2+, n=4,154) plus a subset of <CIN2 (n=3,517) were genotyped using the Cobas HPV test, which separately detects HPV16/18 genotypes plus a pool of 12 additional carcinogenic HPV types (Roche Molecular Systems, Pleasanton, CA).  We calculated sensitivity and specificity, simulating the performance of cytology and HPV16/18 genotyping for triage of HPV+ women. 

Results:  Sensitivity and specificity of cytology for CIN2+ were 72.3% and 58.8%, respectively.  Among women with normal cytology, the sensitivity and specificity of HPV16/18 genotyping for CIN2+ were 41.7% and 81.1%, respectively. Sensitivity and specificity for the combination of cytology and HPV16/18 detection for CIN2+ were 84.4% and 47.7%, respectively.

Conclusions:  Among HPV+ women, a combination of ASC-US cytology and HPV16/18+ genotyping would immediately refer 84% with CIN2+ to colposcopy, leaving 16% who would be referred at 1-year follow-up.  Nearly half of HPV+ women who do not develop CIN2+ would still be sent to colposcopy. Management of HPV+ women while avoiding overtreatment remains a key challenge; whether this performance is adequate will depend on cost-effectiveness analyses.