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SCREENING FOR PRECANCEROUS ANAL LESIONS WITH P16/KI67 DUAL STAIN CYTOLOGY IN HIV
Sergio Serrano-Villar1, Beatriz Hernández-Novoa2, Amparo de Benito1, Jorge Romero3, Antonio Ocampo4, Laura Pérez-Martínez5, Mar Masia6, Elena Sendagorta7, Gonzalo Sanz8, José Antonio Pérez-Molina1
1Hosp Univ Ramón y Cajal, Madrid, Spain,2Brystol-Myers-Squibb, Madrid, Spain,3Centro Sandoval, Madrid, Spain,4Hosp Xeral de Vigo, Vigo, Pontevedra,5Hosp San Pedro, Logroño, Spain,6Hosp General Univ de Elche, Elche, Spain,7Hosp Univ La Paz, Madrid, Madrid,8Hosp Clínico San Carlos, Madrid, Spain
Anal cancer is among the most prevalent neoplasias in HIV-infected MSM. Screening with anal citology results yields to high rates of false positive results and elevated burden of high-resolution anoscopies (HRA) with anal biopsies. High risk HPV up-regulate p16 expression and increase proliferation (Ki67 expression) in epithelial cells. We assessed the usefulness of P16/Ki-67 dual staining cytology for the diagnosis of precancerous anal lesions.
Prospective multi-center cohort study in 6 HIV clinics. Concomitant anal liquid cytology with p16/Ki-67 dual staining (CINtec® PLUS, Roche) and HRA with biopsy of acetowhite lugol-negative lesions was performed. We compared the diagnostic performance of an abnormal anal cytology (atypical squamous cells [ASC], LSIL or HSIL) and p16/Ki-67 dual positivity relative to HRA-guided biopsy. We calculated the independent predictive values of anal cytology and p16/Ki-67 positivity in multivariate logistic regression models adjusted by potential confounders.
A total of 328 HIV-infected MSM underwent 386 full examinations. Mean age was 39±10 years, median nadir CD4 367 (258-510) cells/uL, 57% had detectable plasma HIV RNA and 30% reported unprotected anal sex in the prior 3 months. Sixty-three % of anal cytologies were abnormal: 24(6.2%) ASC, 143(37%) LSIL and 74(19.2%) HSIL. HSIL was histologically diagnosed in 80 subjects (24.1%), and 2 (0.6%) were diagnosed with anal cancer, in whom the cytology had showed LSIL and HSIL, respectively. An abnormal citology showed the following statistics for the diagnosis of biopsy proven HSIL: sensitivity 95.6% (CI95%, 91.2-99.9), specificity 58.8% (CI95%, 52.2-65.4), positive predictive value 39.8% (CI95%, 33.2-46.4), negative predictive value 95.8% (CI95%, 91.6-99.9). P16/Ki67 dual positivity was not associated with higher rates of biopsy-proven HSIL (Table 1). After adjustment by potential confounders (age, nadir CD4, detectable HIV RNA, tobacco use), an abnormal anal citology, but not a positive P16/Ki67 stain, was an independent predictor of HSIL (OR, 12.1; CI95% 3.5-41.3 and OR, 1.2; CI95% 0.6-2.5, respectively).
P16/Ki67 dual staining does not improve the diagnostic accuracy of anal cytology, which shows a high sensitivity yet poor specificity. Other approaches aimed at improving the diagnostic accuracy of current techniques for the diagnostic of precancerous anal lesions are warranted.