Cervical cancer is a potentially preventable cancer. It is preceded by premalignant lesions which may take 5-15 ys to progress to invasive cancer. If detected and treated timely, pre-invasive disease has nearly 100 per cent cure rate with simple surgical procedure, while advanced cancers have less than 35 per cent survival rates3
. However, in developing countries like India, universal screening has not been achieved. The main screening method (Pap smear) is available to a small percentage of population. Cytology based screening programmes are difficult to organize owing to limited infrastructure, trained personnel and funds4
. It has been estimated that in India, even with a major effort to expand cytology services, it will not be possible to screen even one-fourth of the population once in a lifetime5
. Moreover, screening programmes in India are mostly institution based and are restricted to urban centres6
. Thus, in developing countries, there is a need for alternative strategies for early detection of premalignant cervical lesions.
In the current study, women from all the age groups were included. A large study done by Luthra et al7
revealed mean ages for mild, moderate and severe dysplasia to be 33.8, 35.2 and 40.2 years. In another study8
, the average age of mild dysplasia was 31.4 years, severe dysplasia 34.3, carcinoma in situ
34.7 and invasive carcinoma 42.2 years. Therefore, screening for cervical carcinoma should start ideally at the onset of sexual activity and all women should be screened at least once by the age of 30-35 yr. Since visibility of the squamo-columnar junction is age related, a higher proportion of VIA-positive women are of lower age compared to women testing positive on cytology or HPV testing9
The occurrence of abnormal smears was 3.7 per cent in our study. This correlated well with the 1.5 to 5.4 per cent reported in previous Indian studies7,10
. With CIN1 as cut-off, the sensitivity of Pap smear ranged from 40 to 77 per cent and for CIN2 as cut-off, the sensitivity ranges from 33 to 86 per cent (). This low sensitivity results in a high false negative rate ranging from 6-55 per cent24,25
. The sensitivity of Pap smear has been found to be lower in developing countries, probably due to the large percentage of inflammatory smears which may mask mild dysplasia. A multi-centric study in India, evaluating the accuracy of conventional cytology, found sensitivity to vary from 37.8-81.3 per cent for ASCUS, 28.9-76.9 per cent for LSIL and 24.4-72.3 per cent for HSIL, between the centres26
Sensitivity ' specificity of Pap smear, visual inspection with acetic acid (VIA), Lugol's iodine (VILI)
Pap smear has various limitations besides low sensitivity. These include the need for repeated visits for screening, collection of report, evaluation of abnormal results and treatment, and requirement for laboratory infrastructure, highly trained cytopathologists and staff for large scale screening. This hinders the use of Pap smear on a large scale in low resource settings. This has led to the need for alternate methods which are cheap, easy to perform, can be done by paramedical workers and give immediate results.
Unaided visual inspection of cervix (downstaging) to identify cases suspicious for precancer and cancer has low positive predictive value (2-6%)27
. Luthra et al7
found that nearly 44 per cent dysplasias, 13.6 per cent carcinoma in situ
and 4.3 per cent of invasive carcinomas may be found in an apparently normal looking cervix. However, in cases of higher grade dysplasias and malignancy there is higher percentage of clinically abnormal cervix28
. The same was observed in our study. Acetowhite areas delineated on VIA may represent cervicitis, HPV infection, premalignant or malignant lesions. The prevalence of VIA positive cases has been reported to vary from 12.5 to 53.0 per cent9,10,16,18
. This wide variation is because of different criteria used to specify test positivity. The VIA positive rate in our study was similar to other Indian studies (12 to 16%)9,10
VIA is more sensitive than conventional cytology in detecting intraepithelial lesions, though it has a lower specificity. The sensitivity and specificity of VIA in our study was comparable to that of other studies (). The large variation in these results indicates that several variables affect the test characteristics of visual inspection with acetic acid. These are observer training, criteria for test positivity, inter-observer variation, light source, presence of co-existing infection, inflammation and metaplasia.
Iodine negative areas include columnar epithelium (lacking glycogen), patchy uptake peripheral areas due to cervicitis, and immature metaplasia. These can be mistaken by inexperienced workers as VILI positive. Mustard yellow areas with distinct borders suggest more severe disease. The colour changes with VILI are more easy to appreciate than the changes after VIA20,29
Advantages of VILI are that it is easily available, can be easily performed by paramedical workers and doctors, test results are immediately available and hence “see and treat” policy can be used, low cost, need not be freshly prepared (as compared to acetic acid), and longer shelf life (1 month) as compared to acetic acid. In the present study, results of VILI positive CIN1 and CIN2 cases corroborated well with other studies, while the percentage of VILI positive cases which turned out to be benign on histopathology was lower20,21
. This low test positivity could be due to the fact that only mustard yellow areas were taken as VILI positive, and partial iodine uptake was considered as VILI negative. The visual impression in VILI negative cases was based on the charts published by IARC27
. In a study conducted in 11 centres in India and Africa, VILI had a greater sensitivity (91%) compared to VIA (75%)30
. In another study conducted at Mumbai4
, sensitivity of VILI (75.4%) was higher, though not statistically significant, compared to VIA (59.7%), visual inspection of cervix with acetic acid under magnification (VIAM) (64.9%), HPV (62%) and cytology (57.4%). The specificities were 84.3 per cent for VILI, 88.4 per cent for VIA, 86.3 per cent for VIAM, 93.5 per cent for HPV and 98.6 per cent for cytology4
. Among the visual tests assessed, VILI seemed to be particularly promising, detecting 75 per cent of all cases of HSIL compared to VIA and VIAM, which detected less than two-thirds of cases. Another advantage of visual techniques is a very high negative predictive value (>99%). A woman negative by VIA/VILI need not further undergo any investigation. However, these women are advised to undergo a VIA or VILI after a minimum interval of 3 years. Only 10-15 per cent women who are test positive with visual techniques require further evaluation5
In conclusion, in low resource settings, screening of carcinoma cervix by Pap smear can be replaced by cheaper and easily available visual methods like VILI, which has the high sensitivity to detect any grade of dysplasia, with a reasonable specificity. Even when screening with Pap smear is available, it should be combined with visual screening methods like VILI, as many cases of CIN missed by Pap smear were picked up by the visual tests, and combined testing reduced the number of biopsies taken based on either test alone.