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Cervical cancer is the main cancer among women in sub-Saharan Africa, India and other parts of the developing world. Evaluation of screening performance of effective, feasible and affordable early detection and management methods is a public health priority. Five screening methods, naked eye visual inspection of the cervix uteri after application of diluted acetic acid (VIA), or Lugol's iodine (VILI) or with a magnifying device (VIAM), the Pap smear and human papillomavirus testing with the high-risk probe of the Hybrid Capture-2 assay (HC2), were evaluated in 11 studies in India and Africa. More than 58,000 women, aged 25-64 years, were tested with 2-5 screening tests and outcome verification was done on all women independent of the screen test results. The outcome was presence or absence of cervical intraepithelial neoplasia (CIN) of different degrees or invasive cervical cancer. Verification was based on colposcopy and histological interpretation of colposcopy-directed biopsies. Negative colposcopy was accepted as a truly negative outcome. VIA showed a sensitivity of 79% (95% CI 73-85%) and 83% (95% CI 77-89%), and a specificity of 85% (95% CI 81-89%) and 84% (95% CI 80-88%) for the outcomes CIN21 or CIN31, respectively. VILI was on average 10% more sensitive and equally specific. VIAM showed similar results as VIA. The Pap smear showed lowest sensitivity, even at the lowest cutoff of atypical squamous cells of undetermined significance (57%; 95% CI 38-76%) for CIN21 but the specificity was rather high (93%; 95% CI 89-97%). The HC2-assay showed a sensitivity for CIN21 of 62% (95% CI 56-68%) and a specificity of 94% (95% CI 92-95%). Substantial interstudy variation was observed in the accuracy of the visual screening methods. Accuracy of visual methods and cytology increased over time, whereas performance of HC2 was constant. Results of visual tests and colposcopy were highly correlated. This study was the largest ever done that evaluates the cross-sectional accuracy of screening tests for cervical cancer precursors in developing countries. The merit of the study was that all screened subjects were submitted to confirmatory investigations avoiding to verification bias. A major finding was the consistently higher sensitivity but equal specificity of VILI compared with VIA. Nevertheless, some caution is warranted in the interpretation of observed accuracy measures, since a certain degree of gold standard misclassification cannot be excluded. Because of the correlation between visual screening tests and colposcopy and a certain degree of over-diagnosis of apparent CIN21 by study pathologists, it is possible that both sensitivity and specificity of VIA and VILI were overestimated. Gold standard verification error could also explain the surprisingly low sensitivity of HC2, which contrasts with findings from other studies. ' 2008 Wiley-Liss, Inc.Key words: cervical cancer; cervical intraepithelial neoplasia; screening methods; VIA; pap smear; HPV; developing countries Cervical cancer, an eminently preventable can...

Simple and inexpensive methods based on visual examination of the cervix are currently being investigated as alternative methods of cervical screening. The test characteristics of visual inspection with 4% acetic acid (VIA), and Lugol's iodine (VILI) and conventional cytology were investigated in a crosssectional study involving 4,444 women aged 25 to 65 years in Kerala, India. While detection of any acetowhite area constituted a low-threshold positive VIA, detection of well-defined, opaque acetowhite lesions close to or touching the squamocolumnar junction constituted a high-threshold positive VIA test. Detection of definite yellow iodine nonuptake areas in the transformation zone close to or touching the squamocolumnar junction constituted a positive VILI test. Cytology was considered positive if reported as atypia or worse lesions. All screened women were evaluated by colposcopy and biopsies were directed in 1,644 women (37.0%), which allowed the direct estimation of sensitivity, specificity and predictive values. The reference diagnosis was based on a combination of histology and/or colposcopy. Cytology-based screening is not feasible in many developing countries at high risk for cervical cancer in view of the considerable financial, technical and manpower resources required for organizing such a program. Visual inspection-based screening is currently being evaluated as a potential alternative to conventional cytology in the early detection of cervical neoplasia. 1 We investigated the test characteristics of visual inspection of the cervix after application of 4% acetic acid (VIA) and visual inspection after the application of Lugol's iodine (VILI) in detecting high-grade cervical intraepithelial neoplasia (CIN 2-3) and invasive cervical cancer and compared these with that of cervical cytology, in a cross-sectional study, the results of which are reported in this article. MATERIAL AND METHODSA cross-sectional study was carried out during the years 1998 -2000 in Kerala, a southern state on the west coast of India. The study protocol was reviewed and approved by institutional review and ethics committees at the Regional Cancer Centre (RCC), Thiruvananthapuram, Kerala, and the International Agency for Research on Cancer (IARC), Lyon, France. Health education campaigns were conducted in different districts of Kerala to motivate women to seek cervical cancer prevention services in the early cancer detection clinics conducted by the community oncology division of the RCC. Apparently healthy women aged 25 to 65 years, who voluntarily attended these clinics, were invited to participate in the study. Pregnant women, and those who had already undergone hysterectomy or treatment for cervical precancer or cancer, were excluded from the study.The objectives and the methodology of the study were explained by a social worker and leaflets on cervical cancer prevention and early detection in the local language were distributed to the eligible women. A written informed consent was obtained from each woman willing to participa...

Screening for precancerous and cancerous cervical lesions using VIA is a simple, low-cost, and efficient alternative to cytologic testing in low-resource areas.

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The knowledge that cervical neoplasia are caused by human papillomavirus (HPV) infection has led to the evaluation of its role in screening. We evaluated the accuracy of HPV testing by Hybrid capture II (HC II) method in detecting cervical intraepithelial neoplasia grade 2 and 3 (CIN 2 and 3) lesions in 4 cross-sectional studies with common protocol and questionnaire in 3 different locations (Kolkata, Mumbai and Trivandrum) in India. These studies involved 18,085 women aged 25-65 years. The reference standard for final diagnosis was a combination of colposcopy/biopsy. All women were investigated with colposcopy and 3,116 received directed biopsy. The sensitivity of HPV testing for detecting CIN 2-3 lesions varied from 45.7% to 80.9% across the study sites; the specificity varied from 91.7% to 94.6% and the positive predictive value from 6.7% to 13.7%. Retesting of 298 randomly chosen denatured samples in France revealed an agreement rate of 85.9% and a -value of 0.72. Although HPV testing seems to be a promising approach for cervical cancer prevention, a large range in sensitivity was observed in our study, possibly due to variations in the quality of specimen collection and reference standards. A higher sensitivity was associated with the center performing the test well. Further developments in terms of more reproducible, less expensive and less sophisticated testing are essential to make the test feasible and effective in low-resource settings. © 2004 Wiley-Liss, Inc. II; accuracy; sensitivity; specificity; cervical neoplasia; screening; prevention It has been well established that cervical neoplasia are caused by persistent infection with certain oncogenic types of human papillomaviruses (HPVs). 1,2 This knowledge has led to the evaluation of potential applications in the prevention of cervical cancer such as vaccination and its usefulness in the primary screening, in secondary triage and in the follow-up of treated cases of cervical neoplasia. In the setting of primary screening, HPV testing is being evaluated as a potential alternative or adjunctive to cervical cytology for the early detection of cervical cancer precursors and prevention of invasive cervical cancer. HPV testing is intuitively a more objective test than cytology or visual methods, which are based on the interpretation by the readers and are subject to wide interobserver variations. In low-resource settings, where repeated testing of women at risk for cervical neoplasia may not be feasible due to logistic, organizational and financial reasons, HPV testing may provide an objective method of identifying and investing the limited resources on women at risk for disease. Key words: HPV testing; Hybrid captureWe evaluated the accuracy of HPV testing by Hybrid capture II (HC II) method (Digene, Gaithersburg, MD) in detecting cervical intraepithelial neoplasia lesions grade 2 and 3 (CIN 2-3) in 4 cross-sectional studies in 3 different locations in India. This was a joint collaborative project between the Chittaranjan National Cancer Institute (CN...

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