p16 Improves interobserver agreement in diagnosis of anal intraepithelial neoplasia.
ABSTRACT Evaluation of anal intraepithelial neoplasia (AIN) is subjective. Previous studies have shown p16 and Ki-67 expressions to correlate with AIN grade. Biomarkers like p16 and Ki-67 may improve interobserver agreement. The objectives were (1) to determine the extent of interobserver agreement in evaluating AIN on routine hematoxylin and eosin (H&E) sections and (2) to test whether p16 and/or Ki-67 staining improve interobserver diagnostic agreement.
Seventy-seven anal specimens were retrieved. Sections were stained with monoclonal antibodies against p16 and Ki-67. Blind to the original diagnoses, 4 pathologists assessed H&E alone, p16 alone, Ki-67 alone, and all 3 simultaneously. Diagnoses were normal/reactive, AIN I/HPV, AIN II, and AIN III. Agreement was calculated using kappa and S statistics.
Pathologists were board certified and had 2 to 25 years (mean = 13.6 years) of experience. Fair agreement was observed using H&E diagnosis alone (kappa = 0.38, S = 0.56). The p16 diagnostic evaluation demonstrated the highest agreement (kappa = 0.57, S = 0.73). Interobserver agreement for Ki-67 alone and for H&E/p16/Ki-67 combined were comparable to that of H&E alone (kappa = 0.4, S = 0.54 and kappa = 0.44, S = 0.62, respectively). When the pathologists' diagnoses for all diagnostic evaluations were compared with consensus diagnoses, the lowest average magnitude of disagreement was seen with Ki-67 alone, followed by p16 alone, H&E/p16/Ki-67 combined, and H&E alone.
Interobserver agreement for diagnosis of AIN was fair when based solely on H&E preparation. p16 alone improved interobserver agreement and demonstrated superior agreement when compared with H&E, Ki-67, and H&E/p16/Ki-67 combined.
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ABSTRACT: BACKGROUND: The performance of cytologic screening and its correlation with histology and polymerase chain reaction (PCR) detection of human papillomavirus (HPV) DNA have not been evaluated in populations with a low prevalence of anal intraepithelial neoplasia (AIN). The objective of the current study was to analyze the significance of abnormal smears relative to the histology and PCR detection of HPV DNA. METHODS: A cytologic smear and a viral sample were taken in 300 consecutive patients undergoing surgery (Milligan-Morgan hemorrhoidectomy and/or fissurectomy) who gave their informed consent. RESULTS: The cytologic smear was normal in 216 of 290 patients (74.5%). Four high-grade and 19 low-grade intraepithelial neoplastic lesions were identified. In 5 patients, high-grade lesions could not be excluded, 30 lesions were of undetermined significance, and there were 16 cellular modifications with a non-neoplastic appearance. The PCR test for HPV was positive in 18.7% of patients, and a high-risk genotype was identified in 63.6% of positive samples. Histologic examination of the surgical samples was normal in 92.3% of patients. The 23 AIN samples were distributed as follows: 13 grade 1 AIN (AIN1), 6 AIN2, and 4 AIN3. The sensitivity of cytologic smears and PCR for detecting AIN was 56% and 60.8%, respectively, and specificity was 77% and 84.5%, respectively. Combining the 2 tests increased sensitivity to 78% but decreased specificity to 68%. CONCLUSIONS: Compared with a large surgical sample, anal cytologic Papanicolaou smears and HPV PCR exhibited sensitivity and specificity that varied, depending on the risk of HPV infection and AIN. Positive HPV DNA screening increased with AIN grade, and high-risk HPV testing was particularly helpful. Cancer 2012. © 2012 American Cancer Society.Cancer 06/2012; · 5.20 Impact Factor
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ABSTRACT: Cervical cancer and anal cancer share many similarities including causation by oncogenic human papillomaviruses; however, significant differences exist in their epidemiology, risk factors, biologic behavior, management, and treatment. Although rare, the incidence of anal cancer is alarmingly high and continues to increase in high-risk populations, particularly men who have sex with men regardless of their human immunodeficiency virus (HIV) status. There are no national screening guidelines for anal cancer. Using the success of cervical cancer screening as a model, anal cancer screening approaches apply anal cytology, high-resolution anoscopy, and directed biopsy to guide treatment and management strategies. Although much has been learned about the natural history and epidemiology of anal intraepithelial neoplasia (AIN), the rate of progression of high-grade anal intraepithelial neoplasia (HGAIN) to invasive squamous cell carcinomas is not known. The impact of screening and treatment of HGAIN on morbidity and mortality from anal cancer are also unknown. Because the incidence of HGAIN and anal squamous cell carcinoma continue to increase, it is imperative to find pathways for effective screening, early detection, and therapeutic intervention. This article provides an overview of anal cancer screening while highlighting its differences from cervical cancer screening and the remaining obstacles and controversies to implementation of a successful anal cancer screening program.Cancer Cytopathology 02/2011; 119(1):5-19. · 4.43 Impact Factor
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ABSTRACT: A better understanding of the reasons for diagnostic variability may help reduce the phenomenon. In preparation for a study on interpretation of breast specimens (B-Path), a panel of three experienced breast pathologists reviewed 336 cases to develop consensus reference diagnoses. After independent assessment, cases coded as diagnostic discordance were discussed at consensus meetings. Using qualitative data analysis techniques, transcripts of 16 hours of consensus meetings for a subset of 201 cases were analyzed. The reasons for diagnostic variability could be attributed to three overall root causes: 1) pathologist-related, 2) diagnostic coding/study methodology-related and 3) specimen-related. Most pathologist-related root causes were due to professional differences in pathologists' opinions about whether the diagnostic criteria for a specific diagnosis were met, most frequently in cases of atypia. Diagnostic coding/study methodology root causes were primarily miscategorizations of descriptive text diagnoses, which led to development of a standardized electronic diagnostic form (BPATH-Dx). Specimen-related causes included artifacts, limited diagnostic material and poor slide quality. After re-review and discussion, a consensus diagnosis could be assigned in all cases. In conclusion, diagnostic variability is related to multiple factors, but consensus conferences, standardized electronic reporting formats and comments on suboptimal specimen quality can be used to reduce diagnostic variability. This article is protected by copyright. All rights reserved.Histopathology 02/2014; · 2.86 Impact Factor