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...

Visual inspection of the cervix after application of 3-5% acetic acid (VIA) is a potential alternative to cytology for screening in low-resource countries. The present study evaluated the performance of VIA, magnified visual inspection after application of acetic acid (VIAM), and cytology in the detection of high-grade cervical cancer precursor lesions in Kolkata (Calcutta) and suburbs in eastern India. Trained health workers with college education concurrently screened 5881 women aged 30-64 years with VIA, VIAM, and conventional cervical cytology. Detection of well-defined, opaque acetowhite lesions close to the squamocolumnar junction; well-defined, circumorificial acetowhite lesions; or dense acetowhitening of ulceroproliferative growth on the cervix constituted a positive VIA or VIAM. Cytology was considered positive if reported as mild dysplasia or worse lesions. All screened women (N = 5881) were evaluated by colposcopy, and biopsies were directed in those with colposcopic abnormalities (N = 1052, 17.9%). The final diagnosis was based on histology (if biopsies had been taken) or colposcopic findings, which allowed direct estimation of sensitivity, specificity, and predictive values. Moderate or severe dysplasia or carcinoma in situ (CIN 2-3 disease) was considered as true positive disease for the calculation of sensitivity, specificity, and predictive values of screening tests. 18.7%, 17.7% and 8.2% of the women tested positive for VIA, VIAM, and cytology. One hundred twenty two women had a final diagnosis of CIN 2-3 lesions. The sensitivities of VIA and VIAM to detect CIN 2-3 lesions were 55.7% and 60.7%, respectively; the specificities were 82.1% and 83.2%, respectively. The sensitivity and specificity of cytology were 29.5% and 92.3%, respectively. All the tests were associated with negative predictive values above 98%. VIA and VIAM had significantly higher sensitivity than cytology in our study; the specificity of cytology was higher than that of VIA and VIAM.

No abstract

Objective:We conducted a multi-centre cross-sectional study in India to evaluate the accuracy of conventional cytology to detect high-grade squamous intraepithelial lesions (HSIL). Setting:Cross-sectional studies in Jaipur, Kolkata, Mumbai and Trivandrum, India, during 1999-2003. Methods: A common protocol and questionnaire were used to test 22,663 women aged 25-65 years with conventional cytology in ve cross-sectional studies. Three thresholds were used to de ne test positivity: atypical squamous cells of uncertain signi cance (ASCUS), low-grade squamous intraepithelial lesion (LSIL), or HSIL. All screened women were investigated with colposcopy, and biopsies were taken when necessary. The reference standard for nal disease status was histology or negative colposcopy. Data from the studies were pooled to evaluate the test characteristics for the detection of histologically con rmed HSIL. Results:The test positivity rates of cytology were 8.8% at ASCUS, 6.2% at LSIL and 1.8% at HSIL thresholds, and 355 women had histologically con rmed HSIL while 74 had invasive cancer. The pooled sensitivity, speci city, positive and negative predictive values at ASCUS threshold were 64.5%, 92.3%, 11.8% and 99.4% respectively. The corresponding values at LSIL threshold were 58.0%, 94.9%, 15.2% and 99.3%, while at the HSIL threshold they were 45.4%, 99.2%, 46.3% and 99.1%. The sensitivity varied between 37.8-81.3% at ASCUS , 28.9-76.9% at LSIL and 24.4-72.3% at HSIL thresholds. A signi cantly low sensitivity was observed in women aged 25-39 years (p<0.001). The wide variation in sensitivity across study sites persisted even after age standardisation. Conclusion:The sensitivity of cytology varied widely between the study sites. Findings from our study and other reviews indicate that sustained efforts in improving sampling, preparation and reading of cytological specimens and improvements in clinical judgement are essential to achieve concurrently high sensitivity and speci city. Cervical cytology screening programmes in developed countries of Western and Northern Europe, North America and Australia have been followed by a substantial reduction in disease burden. However, no signicant reduction in incidence and mortality from cervical cancer has been observed in developing countries where cytology screening programmes exist.2,3 The reasons for the lack of success include poor quality cytology and suboptimal coverage of target women with testing and treatment. Insuf cient sampling of cervical cells, imperfect preparation and staining of smears or failure to correctly identify cellular abnormalities in the smear lead to errors and a high frequency of false-negative reporting. The best estimates of the accuracy of conventional cytology screening based on the currently available data from cross-sectional studies, mostly conducted in developed countries, suggest that the range of sensitivity to detect cervical neoplasia is wide. There have been very few studies in developing countries addressing the test characteristics of cytology.W...

Unaided visual inspection or "downstaging" has been suggested as a potential alternative method for cervical cancer screening in developing countries. Our study was designed to evaluate the accuracy of downstaging to detect cervical neoplasia in a low-resource setting. A total of 6,399 women aged 30 -64 years were screened with downstaging by trained nonmedical health workers. Two thresholds were used to define positive downstaging: "low threshold" when any visible abnormality on the cervix was considered positive and "high threshold" when selected abnormalities such as bleeding on touch, bleeding erosion, hypertrophied oedematous cervix, congested stippled cervix and growth or ulcer constituted the positive test. All women underwent a colposcopy examination. Biopsies were directed when colposcopy revealed abnormal lesions. True disease status was defined as histologically proven moderate dysplasia and worse lesions. Since all the participants received a diagnostic (reference) investigation (biopsy and/or colposcopy), sensitivity, specificity and predictive values were estimated directly. Low-and high-threshold downstaging were positive in 1,585 (24.8%) and 460 (7.2%) women, respectively. Cytology screening for cervical cancer has been successful in reducing the incidence of and mortality from cervical cancer in many developed countries. 1-3 On the other hand, cervical cancer incidence and mortality rates have either remained unchanged or slowly declined in many low-resource developing countries. 4 -7 The primary reason for this is that most of these countries and regions lack effective cervical cancer screening programmes. Some of them have implemented cytology-based screening programmes nationally or regionally that have had very little impact on the incidence and mortality from cervical cancer. 7-9 The prerequisites for the success of cytology-based screening programmes are high coverage of the target population, preparation of goodquality cytology smears, well-equipped laboratory service with internal and external quality-control measures, adequate numbers of well-trained technical personnel, stringent quality assurance, efficient referral system and treatment and follow-up of those with precursor lesions, most of which are not feasible in underdeveloped countries. Therefore, the need for a relatively inexpensive and low-technology alternative to detect cervical neoplasia in low-resource settings has long been felt.Naked-eye visualization of the cervix (without application of acetic acid) by trained health workers has been considered as an option for low-resource countries to detect cervical cancer early and to improve the survival from the disease. 10,11 This approach, known as downstaging or unaided visual inspection (UVI), has been defined as "the detection of the disease in an earlier stage when still curable, by nurses and other nonmedical health workers using a speculum for visual inspection of the cervix". 11Here we report the findings from a cross-sectional study that evaluated the performance of d...