Visual inspection with acetic acid in the early detection of cervical cancer and precursors

Organized cytology screening programs are not feasible in many developing countries where four-fifths of the world burden of cervical cancer occurs. Among other possible approaches to prevention, the performance of unaided visual inspection (to detect lesions of the cervix) has been shown to be unsatisfactory, particularly in detecting pre-invasive lesions (Neneet al.,1997; Wesleyet al.,1997; Sankaranarayanan et al., 1997). Unmagnified, naked eye inspection of the cervix, after the application of 3–4% acetic acid [termed visual inspection with acetic acid (VIA) or cervicoscopy] has been reported to detect lesions missed by cytology (Cecchini et al.,1993; Leet al.,1993). Aceto-whitening of cervical epithelium may reflect the presence of an abnormal transformation zone as a result of increased cellular density with increased abnormal nuclei and DNA content. Acetic acid application is routinely used in colposcopic examination to visualize abnormal epithelium. Here, we report a comparison of the performance of VIA and cervical cytology in detecting cervical lesions in a clinic-based study in Kerala, India. The study subjects were 1,351 women aged 22–70 years attending the Early Cancer Detection Centre (ECDC), Ernakulam, Kerala, India, during 1995–1997. These women presented themselves for a routine examination or were referred from elsewhere to rule out cervical pathology. Their mean age was 38.9 years (SD 7.3 years). Their educational levels were as follows: nil: 66 (4.9%), primary school: 305 (22.6%), middle school: 221 (16.4%), high school: 495 (36.6%), college and above: 260 (19.2%), not known: 4 (0.3%). They were subjected to speculum examination by a nurse trained in recognizing cervical abnormalities and aceto-white lesions after acetic acid application. The nurse initially recorded the findings of unaided visual inspection, and then took a cervical smear using Ayre’s spatula. This was followed by application of 3–4% freshly prepared acetic acid using a cotton swab and the cervix was examined after 1–2 min under adequate light. If aceto-white areas were detected in the cervix, the test outcome was recorded as being positive. Cervical smears were examined by the cytopathologist (B.S.) of the ECDC, who is also an experienced colposcopist. Cytology was considered to be positive if it revealed any of the following lesions: atypia, mild dysplasia, severe dysplasia, carcinomain situand invasive cancer. Subjects with positive VIA or with a positive cervical smear were referred for colposcopy. In addition, women with grossly abnormal looking cervix (bleeding on touch, hypertrophied elongated irregular edematous cervix, stippled cervix, suspected growth/ulcer) but with negative VIA and cytology were also referred for colposcopy/biopsy, in order to increase the number of participants subjected to verification of their true disease status and thereby to reduce ‘‘verification bias’’. Those with normal looking cervix, features of inflammation and squamous metaplasia on colposcopy were assumed to be false positives and were not subjected to biopsy. Directed biopsies were performed for those with colposcopic diagnosis of atypia or worse lesions. Those with normal findings or inflammation or squamous metaplasia or mild dysplasia on histological examination of biopsy specimens were also considered to be false positives. Those revealing moderate dysplasia or severe dysplasia or carcinomain situ or invasive cancer on histology were considered to be true positives. Thus, negative colposcopy and the results of histological diagnosis of colposcopically guided biopsy were considered the gold standard to evaluate the performance of the tests. Sensitivity and specificity measure the effıcacy of a screening (or diagnostic) test and the positive and negative predictive values measure its accuracy. Sensitivity and specificity of the screening tests could not be calculated directly as the reference test (colposcopy with or without biopsy) was not applied to all women who were negative on screening. Estimated sensitivity and specificity may be biased (‘‘verification bias’’) if all study participants are not subjected to the reference test to determine their true disease status. The performances of 2 tests (cervicoscopy and cytology) can, nevertheless, be compared by means of the following parameters (Schatzkin et al.,1987):