Anal prevalence of HPV in women with pre-malignant lesion or cancer in the cervix and anal canal simultaneously: cross-sectional study.

OBJECTIVE: To determine the prevalence of anal HPV genotypes and associated factors in women with pre-malignant lesion or cancer in the cervix and anal canal. METHODS: A prospective, cross-sectional study analyzed DNA samples taken from women with cervical pre-malignant lesions or cancer to identify anal HPV by polymerase chain reaction (PCR). The prevalence of high-risk HPV (HR-HPV) in women with intraepithelial neoplasia and anal cancer was calculated; sociodemographic and clinical risk factors were identified using multivariate analysis. RESULTS: A total of 152 patients were included (mean age 37.8 ± 10.01 years), of whom 101 (66.4%) had anal HR-HPV. Fourteen different anal HPV types were identified. HPV 16 and 18 were found in 30 (52.6%) anal high-grade squamous intraepithelial lesions (HSIL), and HPV 31 and 33 in 21 (36.8%) lesions. In the logistic regression analysis, the factors that remained associated with HR-HPV types were: an anal histopathology report of HSIL or invasive carcinoma (odds ratio [OR] 8.96, 95% confidence interval [CI] 3.40-23.57; P<0.0001) and alcohol consumption (OR 2.20, 95% CI 1.01-4.80; P=0.04). CONCLUSION: Prevalence of HR-HPV is high in the anal canal of women with cervical and anal pre-malignant lesions simultaneously or cancer of the cervix and/or anal canal. HPV 16, 31, 33, and 18 were the four major genotypes identified.

Cervical determinants of anal HPV infection and high-grade anal lesions in women: a collaborative pooled analysis.

BACKGROUND: Cervical cancer screening might contribute to the prevention of anal cancer in women. We aimed to investigate if routine cervical cancer screening results-namely high-risk human papillomavirus (HPV) infection and cytohistopathology-predict anal HPV16 infection, anal high-grade squamous intraepithelial lesions (HSIL) and, hence, anal cancer. METHODS: We did a systematic review of MEDLINE, Embase, and the Cochrane library for studies of cervical determinants of anal HPV and HSIL published up to Aug 31, 2018. We centrally reanalysed individual-level data from 13 427 women with paired cervical and anal samples from 36 studies. We compared anal high-risk HPV prevalence by HIV status, cervical high-risk HPV, cervical cytohistopathology, age, and their combinations, using prevalence ratios (PR) and 95% CIs. Among 3255 women with anal cytohistopathology results, PRs were similarly calculated for all anal HSIL and HPV16-positive anal HSIL. FINDINGS: Cervical and anal HPV infections were highly correlated. In HIV-negative women, anal HPV16 prevalence was 41% (447/1097) in cervical HPV16-positive versus 2% (214/8663) in cervical HPV16-negative women (PR 16·5, 95% CI 14·2-19·2, p<0·0001); these values were 46% (125/273) versus 11% (272/2588) in HIV-positive women (4·4, 3·7-5·3, p<0·0001). Anal HPV16 was also associated with cervical cytohistopathology, with a prevalence of 44% [101/228] for cervical cancer in HIV-negative women (PR vs normal cytology 14·1, 11·1-17·9, p<0·0001). Anal HSIL was associated with cervical high-risk HPV, both in HIV-negative women (from 2% [11/527] in cervical high-risk HPV-negative women up to 24% [33/138] in cervical HPV16-positive women; PR 12·9, 95% CI 6·7-24·8, p<0·0001) and HIV-positive women (from 8% [84/1094] to 17% [31/186]; 2·3, 1·6-3·4, p<0·0001). Anal HSIL was also associated with cervical cytohistopathology, both in HIV-negative women (from 1% [5/498] in normal cytology up to 22% [59/273] in cervical HSIL; PR 23·1, 9·4-57·0, p<0·0001) and HIV-positive women (from 7% [105/1421] to 25% [25/101]; 3·6, 2·5-5·3, p<0·0001). Prevalence of HPV16-positive anal HSIL was 23-25% in cervical HPV16-positive women older than 45 years (5/20 in HIV-negative women, 12/52 in HIV-positive women). INTERPRETATION: HPV-based cervical cancer screening programmes might help to stratify anal cancer risk, irrespective of HIV status. For targeted secondary anal cancer prevention in high-risk groups, HIV-negative women with cervical HPV16, especially those older than 45 years, have a similar anal cancer risk profile to that of HIV-positive women. FUNDING: International Agency for Research on Cancer.

Cross-sectional study of anal intraepithelial lesions in women with cervical neoplasia without HIV.

OBJECTIVE: To evaluate the prevalence of anal intraepithelial lesions and associated risk factors in women with cervical neoplasia. METHODS: The present cross-sectional study enrolled patients with intraepithelial or invasive cervical neoplasia who had been referred to the lower genital tract pathology outpatient department of the Instituto de Medicina Integral Prof. Fernando Figueira, Recife, Brazil, between December 1, 2008, and December 31, 2009; patients with HIV infections were excluded. All participants underwent anal cytology and high-resolution anoscopy; sociodemographic and clinical risk factors were identified using multivariate analysis. RESULTS: There were 324 patients included and 37 (11.4%) had anal intraepithelial neoplasia. Factors associated with anal intraepithelial neoplasia in the multivariate analysis were being older than 35 years of age (P=0.002), having completed no more than 4 years of education (P=0.012), anomalous anal cytology (P=0.003), and anomalous high-resolution anoscopy findings (P<0.001); subclinical HPV lesions on vulvoscopy (P=0.057) were not associated with anal intraepithelial neoplasia. CONCLUSION: The prevalence of anal intraepithelial neoplasia was high among patients with cervical neoplasia who did not have HIV, particularly patients older than 35 years.

Validating competencies for an undergraduate training program in rural medicine using the Delphi technique.

INTRODUCTION: Worldwide, half the population lives in rural or remote areas; however, less than 25% of doctors work in such regions. Despite the continental dimensions of Brazil and its enormous cultural diversity, only some medical schools in this country offer students the opportunity to acquire work experience focused on medicine in rural or remote areas. The objective of the present study was to develop a framework of competencies for a longitudinal medical training program in rural medicine as an integrated part of medical training in Brazil. METHODS: Two rounds of a modified version of the Delphi technique were conducted. Initially, a structured questionnaire was elaborated, based on a literature review. This questionnaire was submitted to the opinion of 20 panelists affiliated with the Rural Medicine Working Party of the Brazilian Society of Family and Community Medicine. The panelists were asked to evaluate the relevance of the competencies using a five-point Likert-type scale. In this study, the consensus criterion for a competency to be included in the framework was it being deemed 'very important' or 'indispensable' by a simple majority of the participants, while the criterion for excluding a competency was that a simple majority of the panel members considered that it 'should not be included' or was 'of little importance'. When a consensus was not reached regarding a given competency, it was submitted to a second round to enable the panelists to re-evaluate the now dichotomized questions. RESULTS: Compliance in responding to the questionnaire was better among the panelists predominantly involved in teaching activities (85%; n=12) compared to those working principally in patient care (45%; n=8). The questionnaire consisted of 26 core competencies and 165 secondary competencies. After evaluation by the specialists, all the 26 core competencies were classified as relevant, with none being excluded and only eight secondary competencies failing to achieve a consensus. No new competencies were suggested. Of the competencies that failed to reach a consensus in the first round, seven were excluded from the framework in the second round, with most of these being associated with hospital procedures. CONCLUSIONS: A framework of competencies for a program in rural medicine was developed and validated. It consists of 26 core competencies and 158 secondary competencies that should be useful when constructing competency-based curricula in rural medicine for medical education in Brazil.

Anal cytology in women with cervical intraepithelial or invasive cancer: interobserver agreement / Citologia anal em mulheres com neoplasia intraepitelial ou invasiva cervical: concordância interobservadores

ABSTRACTIntroduction:Incidence rates of anal cancer have been rising worldwide in the last 20 years. Due to embryological, histological and immunohistochemical similarities between the anal canal and the cervix, routine screening with anal cytology for precursor lesions in high-risk groups has been adopted. Objective: To determine interobserver agreement for the diagnosis of anal neoplasia by anal cytology.Material and methods:A cross-sectional observational study was conducted in 324 women with cervical intraepithelial or invasive cancers, for screening of anal cancer, from December 2008 to June 2009. Three hundred twenty-four cytological samples were analyzed by three cytopathologists. Cytological evaluation was based on the revised Bethesda terminology; samples were also classified into negative and positive for atypical cells. We calculated the kappa statistic with 95% confidence interval (95% CI) to assess agreement among the three cytopathologists.Results:Interobserver agreement in the five categories of the Bethesda terminology was moderate (kappa for multiple raters: 0.6). Agreement among cytopathologists 1, 2 and 3 with a consensus diagnosis was strong (kappa: 0.71, 0.85 and 0.82, respectively).Conclusion:Interobserver agreement in anal cytology was moderate to strong, indicating that cervical cytomorphological criteria are reproducible also in anal samples.

RESUMOIntrodução:O número de casos de câncer de canal anal vem aumentando nos últimos 20 anos no mundo. Devido às similaridades embriológicas, histológicas e imuno-histoquímicas do canal anal com o colo uterino, adotou-se a citologia anal para rastreamento das lesões precursoras desse tipo de câncer em grupos de risco.Objetivo:Determinar a concordância interobservadores na citologia anal e a concordância entre os diagnósticos citológico e histopatológico no rastreamento das neoplasias anais.Material e métodos:Foi realizado um estudo observacional do tipo corte transversal para rastreamento de câncer anal em 324 mulheres com neoplasias intraepiteliais ou invasivas cervicais, no período de dezembro de 2008 a junho de 2009. Foram colhidas amostras citológicas anais, as quais foram analisadas por três citopatologistas; a seguir, elas foram classificadas de acordo com o consenso Bethesda 2001, sendo agrupadas em negativas e positivas para células atípicas. Biópsias e reação em cadeia de polimerase (PCR) para papilomavírus humano (HPV) foram realizadas para verificar a concordância interobservadores. Foi aplicado o coeficiente kappa múltiplo e simples, bem como o seu intervalo de confiança de 95%.Resultados:A concordância interobservadores, incluindo todas as categorias diagnósticas, foi moderada (coeficiente kappa múltiplo: 0,6). A concordância para identificar citologias anormais entre os citopatologistas 1, 2 e 3 com o diagnóstico de consenso foi forte (coeficiente de kappa simples: 0,71; 0,85 e 0,82; respectivamente).Conclusão:A concordância interobservadores na citologia anal foi de moderada a forte, indicando que os critérios citomorfológicos são reprodutíveis na interpretação de material anal.

High-resolution anoscopy in women with cervical neoplasia.

OBJECTIVE: To describe high-resolution anoscopy (HRA) findings and compare them with histopathology results. METHODS: In a cross-sectional, observational study performed between December 2008 and December 2009, women receiving care at a center in Recife, Brazil, after a histopathologic diagnosis of cervical intraepithelial neoplasia or cervical cancer were screened for anal neoplasia by HRA. Patients with anal lesions were divided into groups A (metaplasia and/or human papillomavirus infection) and B (anal intraepithelial neoplasia [AIN]). Patients with squamous cell atypia in group A and all patients in group B underwent histopathologic analysis. Agreement between HRA and histopathology findings was estimated for group B. RESULTS: HRA was done in 324 women, 204 (63.0%) of whom had anal lesions. Overall, 169 cases (82.8%) were classified as group A and 35 (17.2%) as group B. Histopathologic data were obtained for 28 of the 35 group B cases. Histopathology was suggestive of AIN in 19 (67.9%), resulting in a κ coefficient of 0.45 (95% confidence interval [CI] 0.26-0.65; P<0.001). Relative to histopathology, HRA had sensitivity of 57.6% (95% CI 40.8%-72.7%), specificity of 86.1% (95% CI 75.7%-92.5%), positive likelihood ratio of 4.1 (95% CI 3.1-5.5), negative likelihood ratio of 0.5 (95% CI 0.4-0.5), and accuracy of 76.5% (95% CI 67.2%-83.8%). CONCLUSION: HRA findings can be systematized, reducing the subjectivity of interpretation.