|Year : 2018 | Volume
| Issue : 1 | Page : 10-16
Comparing the efficacy of visual inspection of cervix with acetic acid and Lugol's iodine with Pap smear cytology in screening for cancer cervix
Snehil Sinha1, Vinita Singh1, Byasdev Mishra1, Anu Singh2
1 Department of Obstetrics and Gynaecology, AIIMS, Raipur, Chhattisgarh, India
2 Department of Pathology, AIIMS, Raipur, Chhattisgarh, India
|Date of Submission||21-Sep-2017|
|Date of Acceptance||23-Nov-2017|
|Date of Web Publication||25-May-2018|
Department of Obstetrics and Gynaecology, AIIMS, Raipur, Chhattisgarh
Source of Support: None, Conflict of Interest: None
Background: Cervical cancer, despite being a preventable disease endangers the lives of significant number of women every year and also its incidence is growing with time. Cervical cytology which is a well-accepted standard screening tool in developed countries but in developing countries like India it fails not only due to the lack of awareness but also due to financial and technical constraints. Visual inspection with acetic acid (VIA) and visual inspection with Lugol's iodine (VILI) have been evaluated in a number of large clinical trials and is considered to be a possible alternative to cervical cytology for primary cervical cancer screening in low-resource settings.
Aim of the Study: (1) The aim of the present study was to compare the efficacy of VIA and Lugol's iodine with Pap smear cytology in screening for cancer cervix and evaluate their usefulness as tools for screening of premalignant and malignant lesions of cervix so that VIA can be used in peripheral areas where cytology is not available. (2) Early detection of pre-cancerous conditions and treating them before they progress to invasive cancer.
Methodology: This clinical study was conducted on 200 gynecological patients who were nonpregnant or who had no history suggestive of cervical intraepithelial neoplasia or carcinoma cervix. After taking informed and written consent each woman who fulfilled the inclusion criteria were subjected to Pap smear examination, VIA and VILI. A biopsy was taken in patients with abnormal findings or suspicious findings on VIA/VILI.
Results: In the present study, the sensitivity of VIA and VILI was 88.23%, specificity 78.68%, positive predictive value was 53.57%, and negative predictive value was 96% with biopsy as the reference standard. The sensitivity and specificity of cytology in our study were 88% and 52.63%, respectively.
Conclusion: VIA and VILI are simple, inexpensive, and low-technology test. Both when combined have high sensitivity as well as specificity. This can be practiced by clinicians and paramedics on a wide scale. Another advantage is immediate availability of results and hence that treatment can be started during the same visit.
Keywords: Cervical cancer, Pap smear, visual inspection with acetic acid, visual inspection with Lugol's iodine
|How to cite this article:|
Sinha S, Singh V, Mishra B, Singh A. Comparing the efficacy of visual inspection of cervix with acetic acid and Lugol's iodine with Pap smear cytology in screening for cancer cervix. J Curr Res Sci Med 2018;4:10-6
|How to cite this URL:|
Sinha S, Singh V, Mishra B, Singh A. Comparing the efficacy of visual inspection of cervix with acetic acid and Lugol's iodine with Pap smear cytology in screening for cancer cervix. J Curr Res Sci Med [serial online] 2018 [cited 2018 Oct 21];4:10-6. Available from: http://www.jcrsmed.org/text.asp?2018/4/1/10/233192
| Introduction|| |
Cervical cancer is one of the leading causes of death for middle-aged women in the developing world, yet it is almost completely preventable if precancerous lesions are identified and treated in a timely manner. Since over 70% of the Indian population resides in the rural areas, cancer cervix still continues to be the number one cancer. Approximately 9710 new cases of invasive cervical cancer are diagnosed each year. About 3700 deaths were anticipated in the year 2006 in United States. 5 years survival rate is 90% for localized cervical cancer and is considerably lower (14%) for persons with advanced stage 1V disease.
Carcinoma cervix is one cancer which has a treatable, curable precursor lesion that can be detected using an effective screening procedure, and thus, the incidence and morbidity due to it can be reduced. In other words, screening for carcinoma cervix is one of the most prevalent and successful public health measures for prevention of cancer. Importance of cervical screening is repeatedly emphasized because invasive cervical cancer is preceded by a long phase of the precancerous lesion which is easily detectable by routine screening and can be treated effectively by simple methods. This makes cervical cancer easily preventable if routinely screened., Pap smear is well-known to be effective in reducing the population-wide incidence of invasive cervical carcinoma when at least 70% population is screened with good quality Pap smears on a regular basis. However, this 70% population coverage is difficult to achieve in developing countries. In India, Pap smear facilities are largely restricted to urban areas only. Visual inspection with acetic acid (VIA) and visual inspection with Lugol's iodine (VILI) have been shown to be a feasible alternative to cytology in low-resource settings., In India, all the urban population-based Cancer Registries at Bangalore, Bhopal, Chennai, Delhi, and Mumbai have shown a statistically significant decrease in incidence rates of this site of the cancer.
VIA and VILI has been evaluated in a number of large clinical trials and is considered to be a possible alternative to cervical cytology for primary cervical cancer screening in low-resource settings. The advantages of VIA and VILI compared with cervical cytology are that they are inexpensive, does not require a laboratory infrastructure, and provides an immediate result, allowing the use of “screen and treat” protocol.
In low-resource settings, screening of carcinoma cervix by Pap smear can be replaced by cheaper and easily available visual methods such as VILI and VIA 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 such as VILI and VIA as many cases of cervical intraepithelial neoplasia (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. The inception of cervical cancer screening was with Pap smear. Even though Pap smear has worked excellently as a screening procedure to bring down the incidence and mortality from carcinoma cervix, it is not totally free of drawbacks. The reported sensitivity of Pap smear in various studies ranges from 51%–80% which has led to various improvements over conventional cytology. Further repeated cytology-based screening is not feasible in low-resource setting which has led to trials with various low technology alternatives as screening tools.
The concept of downstaging was introduced in the year 1987 by the WHO in an attempt to decrease the carcinoma cervix burden in places like India where no screening programs exist.
Studies have shown that VIA and VILI are more sensitive than conventional cytology in detecting intraepithelial lesions, although it has a lower specificity. Pap smear has high specificity but low sensitivity; however, VIA and VILI are the most cost-effective approach to downstage carcinoma cervix.
In spite of a series of tests available for cervical cancer screening, no single test has been found to have both high sensitivity and high specificity and hence ideal.
Aim of the study
- The aim of the present study was to compare the efficacy of VIA and Lugol's iodine with Pap smear cytology in screening for cancer cervix and evaluate their usefulness as tools for screening of premalignant and malignant lesions of the cervix so that VIA can be used in peripheral areas where cytology is not available
- Early detection of precancerous conditions and treating them before they progress to invasive cancer.
| Methodology|| |
The study was conducted in the gynecology department of KVG Medical College, Sullia, in the period between January 1, 2012, and December 31, 2012 (1 year). The patients for the study were selected from those attending outpatient department considering the inclusion criteria.
Sample size = 200 patients taking level of confidence of 95%, based on formula:
n = Z 2P (1−P)/d 2
Where, n – sample size; Z - statistic for a level of confidence (1.96), P = expected prevalence or proportion (0.072); d = precision (0.03)
This was a prospective study conducted on 200 gynecological patients to compare the efficacy of cervix VIA and VILI with Pap smear in screening for cancer cervix and also for early detection of precancerous conditions and treating them before they progress to invasive carcinoma. From every woman who participated in the study and fulfilled the inclusion criteria, an informed and written consent was obtained following which they were subjected to Pap smear examination followed by VIA and VILI.
Characteristics of visual inspection with acetic acid positive cases [Figure 1]
- Low-grade lesion:
- Detection of any acetowhite area.
- Detection of well-defined, opaque acetowhite areas close to or touching squamocolumnar junction (SCJ).
Positive visual inspection with Lugol's iodine [Figure 2]
The outcome was scored positive if dense, thick bright mustard yellow or saffron yellow iodine non uptake areas are seen in the transformation zone close to or abutting SCJ or when the entire cervix is densely yellow.
A biopsy was taken in all women with abnormal or suspicious findings on VIA or visual inspection of the cervix with Lugol's iodine.
Taking into consideration that on a global level, 75% of women with abnormal cervical cytology at least once in their lifetime may progress to cervical cancer, randomly 50 patients (taking confidence interval 95%) were selected from VIA/VILI negative cases and they were subjected to four quadrant cervical biopsy for comparing efficacy. Cervical biopsy was used as gold standard in our study.
- Women who are sexually active with intact uterus and cervix
- No history suggestive of CIN/cancer cervix
- No bleeding per vagina at the time of examination
- No treatment history for cervical lesions(cryo, cautery, laser).
- Unmarried women
- Pregnant women
- The previous colposcopy done
- Women who have done therapy for cervical lesions
- Hysterectomised patients.
Collection of data
- The patient was explained about the procedure and its screening value.
- Consent was taken for the procedure
- The patient was put in the lithotomy position
- Unlubricated sim's speculum was inserted into the vagina and cervix is examined
- Two smears were taken from each patient from the ectocervix and endocervix usingAyre's spatula
- Smears were fixed with cytofix spray fixture
- Once the smear was taken the cervix was applied with 3%–5% acetic acid using cotton swab
- Within 30 s, direct visualization of the cervix was done to look for any significant acetowhite areas
- The patient was subjected to VILI 1 min later to the previous procedure
- Lugol's iodine was applied to the cervix and within 30 s direct visualization of the cervix was done
- If any abnormality detected in visual inspection of the cervix with acetic acid or Lugol's iodine, punch biopsy was taken from that area
- Biopsy specimen were fixed in formaldehyde and was sent for histopathological examination
| Results|| |
[Table 1], in the present study, shows that total 17 cases were detected positive on Pap smear examination. Out of those 17 cases, 10 cases were low-grade squamous intraepithelial lesion and seven cases were reported as high-grade squamous intraepithelial lesion. Another 63 cases were reported as inflammatory smear.
From [Table 2], out of the total of 200 patients, VIA was positive in 28 cases group and also 28 cases were positive on VILI. This constitutes 12% of the total study group. Nearly 88% of the study groups were reported normal on VIA and VILI.
|Table 2: Number of visual inspection with acetic acid and visual inspection with Lugol's iodine positive cases|
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As per [Table 3], total number of VIA positive cases are 28. Out of those 28 VIA positive cases (i.e., those cases in which acetowhite areas were noticed on the application of acetic acid) 15 cases were showing abnormality even on biopsy. These 15 cases comprise of 35% of the total VIA positive cases. Furthermore, out of the total 28 VILI positive cases, biopsy was performed. Fifteen cases were positive even on biopsy (i.e., abnormality was detected which was either reported as mild dysplasia or moderate dysplasia.) These positive biopsy cases also include 35% of the total VILI positive cases.
|Table 3: Biopsy result in visual inspection with acetic acid positive cases|
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From [Table 4]a, total of cases screened were 200. Out of 200 cases, 28 cases showed acetowhite areas on the application of acetic acid. Out of these 28 VIA/VILI positive cases, 15 cases were positive even on biopsy. 13 cases did not show any premalignant lesions. For comparing the efficacy, from VIA/VILI negative cases, 50 patients were randomly selected. Out of these 78 cases, biopsy was positive in 17 cases. From the randomly selected 50 cases of VIA/VILI negative group, two cases were positive on cervical biopsy. From [Table 4]b, we can see that among 28 VIA/VILI positive case, 17 patients had positive cytology report. Among them, 8 patients were reported positive for biopsy. One case which was missed by Pap smear, was detected biopsy positive.
[Table 5] highlights and compares the statistical outcomes of the two tests Pap's and VILA/VILI.
| Discussion|| |
Cervical cancer is a potentially preventable cancer. It is preceded by premalignant lesions which may take 5–15 years to progress to invasive cancer. If detected and treated timely, pre-invasive disease has nearly 100% cure rate with the simple surgical procedure while advanced cancers have <35% survival rates. 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 the population. Cytology-based screening programs are difficult to organize due to limited infrastructure, trained personnel, and funds. Patients find it unnecessary to come and collect cytology report in subsequent visits and are usually lost to follow-up. It is also difficult for them to pay the charges of cytology. 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 lifetime. Moreover, screening programs in India are mostly institution based and are restricted to urban centers. Thus, in developing countries, there is a need for alternative strategies for early detection of premalignant cervical lesions. In the present study, the sensitivity of VIA and VILI is 88.23%, specificity 78.68%, positive predictive value was 53.57%, and negative predictive value was 96% with biopsy as the reference standard. The sensitivity and specificity of cytology in our study are 88% and 52.63%, respectively. The study is comparable to study done by Agrawal et al. in which the sensitivity of VIA and VILI was 94.70%, and specificity was 48.30%, and the sensitivity of cytology was 84.20%, and specificity was 62%. Our study also correlates with Cronjé et al. study, wherein sensitivity was 78.9% and specificity was 48.9%, taking biopsy as the reference standard. The sensitivity and specificity of our study are comparable to the study done by Sankaranarayanan et al., where in sensitivity of VIA to vary between 54.4% to 78.7% and specificity to vary between 88.6% and 90.9% in different centers. Basu et al. in his study comparing the performance of VIA and cytology for detection of high-grade cervical cancer precursor lesion, found VIA to have sensitivity of 57.7% and specificity of 82.1% and cytology with sensitivity of 29.5% and specificity of 92.3%. Megevand et al. in their study found VIA to detect 54% of high-grade lesions and hence concluded that in location where access to cytopathologist is limited, naked eye visual examination of the cervix after application of dilute acetic acid can be a good alternative. In a study done by Ghosh et al., it was concluded that in low-resource settings, cervical cancer screening by Pap smear can be replaced by visual methods like VILI, which has the highest sensitivity (100%) to detect any grade of dysplasia, and a good specificity (93.3%). According to the study done by Consul et al. named comparative study of effectiveness of Pap smear versus visual application of acetic acid and VILI for mass screening of premalignant and malignant lesion of cervix showed that VIA and VILI had sensitivity comparable to Pap smear and can thus be a suitable potential alternative/adjunctive screening test not only in poor resource setting but also in well-equipped centers. In a study by Yadav et al., VIA when compared with histopathological report (HPR) had sensitivity and specificity of 80% and 67%, respectively while that of VILI was found to be 80% and 87%, respectively. An attempt has been made in the present study to increase awareness of women about cervical cancer and preventive health-seeking behavior, screen all women of the reproductive age group at least once a year and motivate them for annual screening until three negative Pap smears, to provide a screening test with high sensitivity as women have less frequent opportunities for repeated screening and treating women with high-grade dysplasia and cancer. Women continue to ignore symptoms of irregular bleeding, postmenopausal bleeding, and postcoital bleeding. Therefore, in our study, we aimed at educating women about these signs and symptoms and to seek immediate medical care. Thus, an attempt has been made to target the disease before its onset at the level of primary prevention by providing education and counseling and secondary prevention by effective screening and treatment. VIA and VILI have other advantages too like it is very cheap. A study by Mandelblatt et al. comparing cost-effectiveness of VIA, HPV testing, cytology, and combination of tests show that VIA performed at 5 year intervals in women aged 35–55 years is the least expensive option. Most important advantage, particularly in a population like that seen in our study with high illiteracy rate and poor follow-up is immediate availability of the test result. This facilitates diagnosis and treatment to be carried out in the first visit. Hence, option of VIA and VILI as an alternative to cytology for screening in less developed countries cannot be overlooked. Pap's smear has its own limitations like screening is expensive for low-resource settings, results are not available immediately when compared to VIA and VILI, requires a laboratory setting for the procedure and also it requires highly trained cytopathologists and staff for large-scale screening so cheaper and easily available visual methods such as VIA and VILI can be a useful alternative. A very recent study by Kaur et al. concluded that in low resource settings, screening by Pap smear has not been successful in reducing incidence of cervical cancer. VIA and VILI are cheaper and easily available and can be used by medical and paramedical personnel on a large scale basis. A study by Yagnik Ami and Singh et al. also came up with the views that in comparison to Pap smear, VILI is more sensitive. Specificity is also high for this objective test with good evidence and of low cost. The study was better in a way that it also detected efficacy of Pap's smear which other studies have not done.
[Table 6] summarizes the outcome of various related studies to that of our study.
|Table 6: Comparison of diagnostic value of visual inspection with acetic acid with other studies|
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| Conclusion|| |
Carcinoma cervix is more prevalent among women living in poor conditions with low income and limited education and awareness. In our study, comparing the results of VIA and VILI and Pap smear the sensitivity of VIA and VILI was comparable to Pap smear. Hence, VIA and VILI can be used as an alternative for the screening of carcinoma cervix. VIA and VILI is an attractive test in low resource setting like India. The majority of women in India who belong to the low socioeconomic strata of society remain devoid of any screening test as Pap smear has its own limitations like it is difficult to reach remote areas which comprise the majority of Indian population. There is always constraint of infrastructure and resources required for cytological screening in developing countries. Through screening tools such as VIA and VILI a large number of population that go undetected can be screened at an affordable cost with higher sensitivity and specificity.
Limitation of our study
This is a hospital-based study. The study sample is small and the classification of the cervix into normal and suspicious is subjective. Further studies are needed to evaluate the correlation between visual inspection of the cervix with unaided eyes and Pap smears result.
The authors would like to thank women who agreed to participate in this study.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]