Interrater agreement of anal cytology
ABSTRACT BACKGROUND: The majority of anal cancers are caused by persistent infections with carcinogenic human papillomaviruses (HPV). Similar to cervical carcinogenesis, the progression from HPV infection to anal cancer occurs through precancerous lesions that can be treated to prevent invasion. In analogy to cervical cytology, anal cytology has been proposed as a screening tool for anal cancer precursors in high-risk populations. METHODS: The authors analyzed the interobserver reproducibility of anal cytology in a population of 363 human immunodeficiency virus (HIV)-infected men who have sex with men (MSM). Liquid-based cytology (LBC) specimens were collected in the anal dysplasia clinic before the performance of high-resolution anoscopy on all patients. Papanicolaou-stained LBC slides were evaluated by 2 cytopathologists, each of whom was blinded to the clinical outcome and the other pathologist's results, using the revised Bethesda terminology. RESULTS: Overall agreement between the 2 observers was 66% (kappa, 0.54; linear-weighted kappa, 0.69). Using dichotomizing cytology results (atypical squamous cells of undetermined significance [ASC-US] or worse vs less than ASC-US), the agreement increased to 86% (kappa, 0.69). An increasing likelihood of testing positive for markers associated with HPV-related transformation, p16/Ki-67, and HPV oncogene messenger RNA was observed, with increasing severity of cytology results noted both for individual cytologists and for consensus cytology interpretation (P value for trend [ptrend] < .0001 for all). CONCLUSIONS: Moderate to good agreement was observed between 2 cytopathologists evaluating anal cytology samples collected from HIV-positive MSM. A higher severity of anal cytology was associated with biomarkers of anal precancerous lesions. Anal cytology may be used for anal cancer screening in high-risk populations, and biomarkers of HPV-related transformation can serve as quality control for anal cytology.
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ABSTRACT: OBJECTIVE:: Anal cancer incidence is high in HIV-infected men who have sex with men (MSM). Screening for anal intraepithelial lesions and cancers is performed at specialized clinics and relies on high resolution anoscopy (HRA) and anal cytology. Both approaches have limited reproducibility and sensitivity for detecting anal cancer precursors. We evaluated biomarkers for HPV-related disease in a population of HIV-infected MSM. METHODS:: A cross-sectional screening study with passive follow-up included 363 MSM followed at a HIV/AIDS clinic. All men had anal cytology samples taken and were evaluated using HRA and anal biopsies. Using a composite endpoint of biopsy results and cytology, we compared the performance of HPV16/18 genotyping, HPVE6/E7 mRNA expression, and p16/Ki-67 cytology to detect high grade anal intraepithelial neoplasias (AIN). RESULTS:: For all biomarkers analyzed, there was a significant trend of increasing percentage of men testing positive with increasing severity of disease (p < 0.001). HPV DNA testing had the highest sensitivity for AIN2 and AIN3, followed by p16/Ki-67, HPVE6/E7 mRNA testing, and HPV16/18 genotyping. The highest Youden's index was observed for HPVE6/E7 mRNA testing, followed by HPV16/18 genotyping, p16/Ki-67 cytology, and HPV DNA testing. Increasing the threshold for positivity of p16/Ki-67 to 5 or more positive cells led to significantly higher specificity, but unchanged sensitivity for detecting AIN3. CONCLUSIONS:: Molecular features of anal disease categories are similar to those of corresponding cervical lesions. Biomarkers evaluated for cervical cancer screening may be used for primary anal cancer screening or to decide who should require immediate treatment versus expectant management.AIDS (London, England) 09/2012; 26(17). DOI:10.1097/QAD.0b013e328359f255 · 6.56 Impact Factor
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ABSTRACT: BACKGROUND: Human papillomavirus (HPV) RNA detection is reportedly more specific for the detection of anogenital precancer than HPV DNA but it is unknown whether this is due to detection of RNA or due to HPV genotype restriction. MATERIALS AND METHODS: 363 human immunodeficiency virus (HIV)-positive men who have sex with men had two anal cytology samples taken and were evaluated using high-resolution anoscopy and biopsies of visible lesions. Anal specimens were tested for E6/E7 RNA for 5 carcinogenic HPV genotypes (HPV16, 18, 31, 33, and 45) and tested for the DNA of 13 carcinogenic HPV genotypes. RESULTS: DNA testing was more likely to be positive than RNA testing (53% vs. 48%, p = 0.02) for the same 5 HPV genotypes in aggregate. When restricted to 5 HPV genotypes targeted by the RNA test, the sensitivity to detect anal precancer was the same for DNA and RNA (81%) while RNA was more specific than DNA (65% vs. 58%, p = 0.007). By comparison, DNA detection of all 13 carcinogenic HPV genotypes was more sensitive (96% vs. 81%, p = 0.001) but much less specific (65% vs. 33%, p < 0.001) compared to RNA detection of the 5 HPV genotypes. CONCLUSIONS: After controlling for HPV genotypes, RNA was only slightly more specific than DNA detection for anal precancer Impact:DNA or RNA testing for a subset of the most carcinogenic HPV genotypes may be useful for distinguishing between those HPV-positive men at higher and lower risk of anal precancer and cancer.Cancer Epidemiology Biomarkers & Prevention 11/2012; 22(1). DOI:10.1158/1055-9965.EPI-12-0984 · 4.32 Impact Factor
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ABSTRACT: Background. Carcinogenic human papillomaviruses (HPV) cause a large proportion of anal cancers. HIV-infected men who have sex with men (MSM) are at increased risk of HPV infection and anal cancer compared to HIV-negative men. We evaluated risk factors for HPV infection and anal precancer in a population of HIV-infected MSM.Methods. Our study included 305 MSM at an HIV/AIDS clinic in the Kaiser Permanente Northern California Health Maintenance Organization. Logistic regression was used to estimate associations of risk factors comparing (1) men without anal HPV infection, (2) men with anal HPV infection, but no precancer, and (3) men with anal precancer.Results. Low CD4 count (<350 cells/mm(3)) and previous Chlamydia infection were associated with an increased risk of carcinogenic HPV infection (OR 3.65 95%CI 1.28-10.40, OR 4.24 95%CI 1.16-15.51, respectively). History of smoking (OR 2.71 95%CI 1.43-5.14), duration, recency, and dose of smoking, increased the risk of anal precancer among carcinogenic HPV-positive men, but had no association with HPV infection.Conclusions. We found distinct risk factors for anal HPV infection and anal precancer. Risk factors for HPV infection and anal precancer are similar to established risk factors for cervical cancer progression.The Journal of Infectious Diseases 08/2013; DOI:10.1093/infdis/jit374 · 5.78 Impact Factor