Grant B Ellsworth1, Elizabeth A Stier2, Elizabeth Y Chiao3, Shelly Y Lensing4, Teresa Darragh5, Naomi Jay6, J Michael Berry-Lawhorn6,7, Mark Einstein8, Luis F Barroso9, Ross D Cranston10, Rebecca Levine11, Humberto M Guiot12, Audrey L French13, Stephen E Goldstone14, Wolfgang Preiser15, Mathilda Claassen15, Joel M Palefsky6, Timothy J Wilkin1. 1. Weill Department of Medicine, Division of Infectious Diseases, Weill Cornell Medicine, New York, NY. 2. Department of Obstetrics and Gynecology, Boston University School of Medicine, Boston, MA. 3. Department of Epidemiology and Department of General Oncology, MD Anderson Cancer Center, Houston, TX. 4. University of Arkansas for Medical Sciences, Little Rock, AR. 5. Department of Pathology, University of California San Francisco, San Francisco, CA. 6. Department of Medicine, Anal Neoplasia Center for Research and Education, University of California San Francisco, San Francisco, CA. 7. Division of Hematology and Oncology. 8. Department of Obstetrics, Gynecology and Reproductive Health, Rutgers New Jersey Medical School, Newark, NJ. 9. Department of Internal Medicine, Section of Infectious Diseases, Wake Forest University Health Sciences, Winston-Salem, NC. 10. University of Vic, Hospital Germans Trias i Pujol, Barcelona, Spain. 11. Department of Surgery, Montefiore Medical Center, Bronx, NY. 12. Department of Medicine, University of Puerto Rico School of Medicine, San Juan, PR. 13. The CORE Center/Stronger Hospital of Cook County, Chicago, IL. 14. Laser Care Surgery, New York, NY; and. 15. Division of Medical Virology, Stellenbosch University, Cape Town, South Africa.
Abstract
BACKGROUND: Women living with HIV (WLWH) experience high rates of anal cancer. Screening using anal cytology, high-resolution anoscopy (HRA) with biopsies, can histologically diagnose anal cancer precursors called high-grade squamous intraepithelial lesions (HSIL). The low specificity of screening using anal cytology results in HRA referral for many WLWH without HSIL. Screening using high-risk human papillomavirus (HR-HPV) may improve specificity. METHODS: Two hundred seven WLWH (63% non-Hispanic black) were screened for anal histologic HSIL (hHSIL) using cytology, HRA-guided biopsies, and Xpert HPV. Xpert performance for predicting anal hHSIL was compared with that of cytology. Usng Xpert 5 HPV genotypic results and accompanying cycle thresholds, receiver operator characteristic curve and recursive partitioning analyses were used to create predictive models for hHSIL. RESULTS: The performance of Xpert to predict hHSIL was not different from that of cytology with a sensitivity (Sn) of 89% and specificity (Sp) of 49%. Interpretation of Xpert was modified using genotypic results and receiver operator characteristic curve analysis, which produced a screen with an Sn and Sp of 75% and 84% for hHSIL, respectively. Another reinterpretation of Xpert was created using recursive partitioning and cycle thresholds, which predicted hHSIL with an Sn and Sp of 75% and 86%, respectively. The detection of HPV-16 was highly predictive of hHSIL in all analyses. These modified screening tests would reduce HRA referral in this population by almost half compared with anal cytology. CONCLUSIONS: Xpert HPV is an alternative to anal cytology to screen for anal HSIL and can be optimized to reduce the number of unnecessary HRAs performed in WLWH.
BACKGROUND: Women living with HIV (WLWH) experience high rates of anal cancer. Screening using anal cytology, high-resolution anoscopy (HRA) with biopsies, can histologically diagnose anal cancer precursors called high-grade squamous intraepithelial lesions (HSIL). The low specificity of screening using anal cytology results in HRA referral for many WLWH without HSIL. Screening using high-risk human papillomavirus (HR-HPV) may improve specificity. METHODS: Two hundred seven WLWH (63% non-Hispanic black) were screened for anal histologic HSIL (hHSIL) using cytology, HRA-guided biopsies, and Xpert HPV. Xpert performance for predicting anal hHSIL was compared with that of cytology. Usng Xpert 5 HPV genotypic results and accompanying cycle thresholds, receiver operator characteristic curve and recursive partitioning analyses were used to create predictive models for hHSIL. RESULTS: The performance of Xpert to predict hHSIL was not different from that of cytology with a sensitivity (Sn) of 89% and specificity (Sp) of 49%. Interpretation of Xpert was modified using genotypic results and receiver operator characteristic curve analysis, which produced a screen with an Sn and Sp of 75% and 84% for hHSIL, respectively. Another reinterpretation of Xpert was created using recursive partitioning and cycle thresholds, which predicted hHSIL with an Sn and Sp of 75% and 86%, respectively. The detection of HPV-16 was highly predictive of hHSIL in all analyses. These modified screening tests would reduce HRA referral in this population by almost half compared with anal cytology. CONCLUSIONS: Xpert HPV is an alternative to anal cytology to screen for anal HSIL and can be optimized to reduce the number of unnecessary HRAs performed in WLWH.
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