Accuracy of human papillomavirus testing in primary screening of cervical neoplasia: Results from a multicenter study in India

Abstract

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...

A cluster randomized controlled trial of visual, cytology and human papillomavirus screening for cancer of the cervix in rural India

“…In a multicenter cross-sectional study in India, HPV testing had similar sensitivity to detect CIN 2=3 lesions as cytology and VIA. 26 Our present findings indicate that the detection rates of HPV testing did not show any improvement over cytology. Furthermore, the currently available test (HC II) is expensive and requires a relatively sophisticated laboratory infrastructure.…”

Accuracy of human papillomavirus testing in primary screening of cervical neoplasia: Results from a multicenter study in India

“…The article by Sankaranarayanan et al 1 reported the results from 4 cervical cancer screening projects performed in 3 different regions in India. Their study of 18,085 previously unscreened women aged 25-65 years compared the effectiveness of 4 screening strategies: human papillomavirus (HPV) DNA testing, conventional Papanicolaou cytology, visual inspection after the application of acetic acid (VIA) and Lugol's iodine (VILI).…”

“…Our concern is not about the study itself, but about possible over-concern by readers regarding the mediocre performance of HPV testing compared to the other screening techniques (particularly VILI) and compared to other reports on the efficacy of HPV testing in the literature. Specifically, Sankaranarayanan et al 1 observed HPV test sensitivities in their 4 projects ranging from only 45.7-80.9% for detection of cervical intraepithelial neoplasia grade 2 or worse (CIN21). In contrast, research studies have estimated sensitivity for detection of CIN21 of >85% for HPV testing.…”

“…Sankaranarayanan et al 1 trained local health workers to collect cervical specimens for conventional cytology and for HPV DNA testing, to provide VIA and VILI and to treat lesions by cryotherapy. But training and quality monitoring were not at all intensive or prolonged.…”

“…Even if subsequent disease diagnosis in the community will not be as intensive, misclassification of disease when evaluating a new test can lead to false conclusions. As a surrogate for prevention of invasive cervical cancers, Sankaranarayanan et al 1 relied on local colposcopy and guided biopsies for all 18,085 women. They assessed the reliability of this reference standard by reviewing 182 histology slides with a categorical outcome grouping normal, inflammation, atypia, and CIN1 as one category and CIN2, CIN3 and invasive cancer as the second category.…”