|Ahead of print publication
Role of various screening techniques in detecting preinvasive lesions of the cervix among symptomatic women and women having unhealthy cervix
Prasanta Kumar Nayak1, Subarna Mitra2, Sarita Agrawal1, Nighat Hussain1, Pushpawati Thakur1, Byasdev Mishra3
1 Department of Obstetrics and Gynecology, All India Institute of Medical Sciences, Raipur, Chhattisgarh, India
2 Department of Obstetrics and Gynecology, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
3 Department of Obstetrics and Gynecology, SCB Medical College, Cuttack, Odisha, India
|Date of Submission||14-Jan-2019|
|Date of Decision||15-Apr-2019|
|Date of Acceptance||22-Aug-2019|
|Date of Web Publication||28-Jan-2020|
Prasanta Kumar Nayak,
Qtr. No 302, Block C, Jainam Planet, Tatibandh, Raipur, Chhattisgarh
Source of Support: None, Conflict of Interest: None
Introduction: Cervical cancer which is preventable, occurs due to humanpapiloma virus infection and results in a preinvasive condition called cervical intraepithelial neoplasm (CIN) before the development of cancer. Majority of the patients with CIN or early stage of cervical cancer present with symptoms such as abnormal vaginal discharge or bleeding, and unhealthy looking cervix. Selectively screening these symptomatic patients, can detect more number of positive cases and also most effective screening technique for these selective patients can be advocated.
Materials and Methods: All married women between 21 and 65 years attending gynecology outpatient department of a tertiary care health center in Central India and having unhealthy cervix or abnormal vaginal discharge were included. All women were subjected to Pap smear, visual inspection under acetic acid (VIA), visual inspection under Lugol's iodine (VILI) and colposcopy. Biopsy was taken in all cases. Diagnostic value of each screening method was determined in terms of sensitivity, specificity, positive predictive value and negative predictive value.
Results: Out of 352 patients, around 20% of them were found to have abnormal cytology. The sensitivity and specificity of Pap smear was found to be 34% and 94%. But colposcopy has high sensitivity and low specificity, i.e., 99% and 31%, respectively. On the other hand the sensitivity and specificity of VIA and VILI are comparable i.e., 65% and 45% and 64% and 48% respectively. Pap smear shows high positive predictive value among all, i.e., 85% and colposcopy shows 58% for the same.
Conclusion: Pap smear carries low sensitivity but high positive predictive value. As compared to Pap smear, VIA and VILI are more sensitive and are of low cost. Colposcopy can be considered as a preferred method of screening due to its extremely high sensitivity.
Keywords: Cancer cervix, diagnostic value, symptomatic patient, unhealthy cervix
|How to cite this URL:|
Nayak PK, Mitra S, Agrawal S, Hussain N, Thakur P, Mishra B. Role of various screening techniques in detecting preinvasive lesions of the cervix among symptomatic women and women having unhealthy cervix. J Can Res Ther [Epub ahead of print] [cited 2020 Aug 15]. Available from: http://www.cancerjournal.net/preprintarticle.asp?id=276988
| > Introduction|| |
Cervical cancer is the most common cause of cancer death among women in developing countries. Every year in India, 96,922 women are diagnosed with cervical cancer and 60,078 die from this disease. In India, it is the second-most common cancer in women aged 15–44 years with the highest age standardized incidence of cervical cancer in South Asia at 22, compared to 19.2 in Bangladesh, 13 in Sri Lanka, and 2.8 in Iran. Therefore, it is vital to adapt ideal preventive methods including screening techniques. human papiloma virus DNA testing is the most reproducible test among all screening methods but it is expensive and requires sophisticated laboratories.,, Conventional Pap smear which is the primary and most widely used screening tool, has low sensitivity and carries 10%–70% false negative rate., In low-resource settings, visual inspection with acetic acid (VIA) and Lugol's iodine (VILI) are promising alternatives owing to their simplicity, rapidity of results, cost-effectiveness and comparable performance in mass screening for cervical cancer., Assessment of women with colposcopy impressions of the cervical transformation zone and histological appraisal of directed punch biopsies is an excellent method but less commonly used. The reported sensitivity of colposcopy in some Indian study has been shown to be, 60%–98% for the detection of intraepithelial disease. Although implementation of several screening strategies has led to a remarkable decline in the cervical cancer incidence and mortality worldwide, still the prevalence of screening is very less in our country and varies between 6.9% and 0.002% as reported from different states.,, The important reason of this low prevalence of screening in our country can be attributed to the nonavailability of adequate health care professionals to cater a very large number of population. On the other hand, to choose an ideal method of screening is also a dilemma, since data on effectiveness of all these screening methods, which are less expensive and less resource-intensive, are limited from this geographical territory. Although universal screening for cancer cervix is recommended for sexually active women above the age of 21 years, but to maximize the detection of preinvasive lesions we have conducted a study among symptomatic women and those having clinical features of unhealthy cervix such as those having erosion, ulceration, chronic cervicitis, healed lacerations, hypertrophic cervix, bleeds on touch, suspicious lesion on the cervix, presenting with abnormal vaginal discharge, irregular menstrual bleeding, postmenopausal bleeding, and postcoital bleeding. Some authors have described it as bad cervix. We have subjected all our patients to Pap smear, VIA, VILI and colposcopy. We have compared the results of individual screening methods with the gold standard test, i.e., histopathology report. This study will help to provide insights into the diagnostic performance of these techniques and also in assessing the disease status among this selective group of patients, in a hospital based screening when used alone or in combination.
| > Materials and Methods|| |
This cross-sectional study was undertaken at a tertiary care center in Central India from February 2016 to October 2017 after taking approval from the institute's ethical committee. A total of 352 married women between 21 and 65 years of age attending gynecology outpatient department of our hospital and having features of unhealthy cervix were included after informed consent.
Women satisfying the following criteria were included in the study: sexually active female of age 21–65 years, features of suspicious cervix on visual inspection (erosion, ulceration, chronic cervicitis, healed lacerations, hypertrophic cervix, bleeds on touch, suspicious lesion on the cervix), presenting with abnormal vaginal discharge, irregular menstrual bleeding, postmenopausal bleeding, postcoital bleeding.
Women having the following criteria were excluded from the study such as unmarried women, women with diagnosed cervical or endometrial cancer, pregnant women, use of vaginal medications within last 7 days, history of vaginal surgery/diagnostic procedures since Lat menstrual period (LMP), menstruating or immediate premenstrual, within 4 weeks of abortion or those having acute vulvitis, vaginitis, cervicitis or pelvic inflammatory disease. Objectives of the study were to determine the diagnostic value of various screening methods for cancer cervix such as: Pap smear, VIA, VILI and colposcopy and to compare the effectiveness of these screening modalities in detection of preinvasive lesions of the cervix. A detailed history was taken and physical examination was performed in each case. All women were subjected to conventional Pap smear using Ayre's spatula. Revised Bethesda systemg was used for describing Pap smear results. Pap smear results were classified as negative for intra epithelial lesion or malignancy, atypical squamous cells of undetermined significance (ASCUS), low grade squamous intra epithelial lesion (LSIL), high grade squamous intraepithelial lesion (HSIL) and carcinoma. Presence of LSIL, HSIL, ASCUS and cancer lesions were considered as positive on cytology. After that 5% acetic acid was applied to the cervix for 1 min and the results were noted as VIA positive or negative depending on presence or absence of acetowhite lesions, respectively. Subsequently, visual inspection with Lugol's iodine application was performed and findings were noted as positive if there is iodine nonuptake area detected and negative if there is iodine uptake (Maghony brown discoloration) area detected in visual inspection. Finally colposcopy was performed in all of them. Colposcopic morphology of the atypical epithelium harboring cervical intraepithelial neoplasm (CIN) is dependent on following factors, i.e., thickness of the epithelium, variations in blood vessel patterns, alterations in surface contour and any associated changes in the covering epithelium like keratinization. Abnormal colposcopic findings are noted based upon the presence of lesion after application of acetic acid and Lugol's iodine, vessel abnormalities and presence of gross lesions. Systematic methods for predicting colposcopically the severity of lesions by discriminatory analysis of unique colposcopic signs. Aggregate colposcopic signs are more accurately predictive of the clinical severity than individual signs. Hence we have used modified Reid colposcopic index (1985) for scoring of suspicious lesions. This scoring is based on four colposcopic findings, i.e., color of the acetowhite lesion, margin and surface configuration of the lesion, vascular pattern of the lesion and iodine staining. Point zero is scored to low-intensity acetowhite lesions with transparent surface, point one is scored to intermediate acetowhite lesions with shiny surface and point two is scored to oyster white and opaque lesions. Similarly point zero is scored to flat lesions with indistinct margins, point one is scored to regular shaped symmetrical lesions with straight outlines and point two is scored to lesions with peeling out and rolled edges. Point zero is scored to fine and uniform caliber vessels, point one is scored for absent vessels and point two is scored for sharply demarcated, abnormal forms of vessels with coarse mosaicism and punctuations. Similarly, point zero is scored when there is positive iodine staining, point one is scored for partial iodine uptake with variegated or speckled appearance and point two is scored for negative iodine uptake of an already diagnosed significant lesion by above criteria. Cases with Reid's scoring one or above were considered as positive for colposcopy and those having a score of zero were considered as negative for colposcopy. Directed biopsy was taken if any positive lesion was detected on colposcopy or four quadrant biopsy if no abnormality found. The specimen was sent for histopathological examination in formalin solution and slides were analysed by consultant pathologists. Results of cytology, VIA, VILI and colposcopy were compared against the gold standard diagnostic method, i.e., histopathology report of biopsy specimen. Statistical analysis was done using SPSS software version 17. The continuous variables were expressed as mean ± standard deviation and categorical variables as percentages. Student's t-test was used to compare continuous variables. Chi-square and Fisher's exact test were used for comparison of categorical variables. P < 0.05 was considered as statistically significant. Diagnostic value of each screening method was determined in terms of sensitivity, specificity, positive predictive value, and negative predictive value.
| > Results|| |
Out of 352 participants, 346 (98.3%) were parous ladies and 6 (1.7%) were nulliparous. The average age of detection of preinvasive lesions or cervical cancer was 37.16 (±9.8) years. Half of the women, i.e., 176 (50%) had positive lesion in the cervix. Around 72% of our patients presented with abnormal cervix and 70% of the patients presented with abnormal vaginal discharge. There is a significant difference present in the disease of different age groups as shown in [Table 1]. Maximum number of diseased cases were found in the age group >60 years (68.1%) followed by 40–49 years and least in 21–39 years age group. On the other hand highest number of patients presented with features of unhealthy cervix in the age group of 30–39 years and the probability of disease occurrence was increased from younger to older age groups [Table 1].
In Pap smear, only 20% patients had positive findings for disease, whereas majority of the patients showed positive findings with application of acetic acid (60.5%) and lugol's iodine (57.7%) respectively [Table 2]. Although colposcopy detected positive lesions in 84% of the cases only 50% of the cases were confirmed to have either CIN or cervical cancer [Table 2].
In all the colposcopic procedures, Reid's scoring for abnormal findings were noted. Majority of our patients had a Reid's scoring of 2 as shown in [Table 3].
An analysis was carried out to find out a cut off in Reid's scoring for the diagnosis of preinvasive lesions of cervix in colposcopy. It seems from the receiver operating characteristic (ROC) that Reid's score is a good indicator to detect preinvasive lesions of cervix. The best cut-off that maximizes (sensitivity + specificity) is 1.5 [Table 4]. At this count, the sensitivity is 0.914 and specificity is 0.443 (1 – specificity = 0.557).
|Table 4: Coordinates of the receiver operating characteristic curve (sensitivity and [1 - specificity] for Reid's score for diseased and nondiseased patients)|
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The ROC curve obtained by ploting at different cutoffs is shown in [Figure 1]. It was found that the area under the curve is C = 0.742 with standard error = 0.026 and 95% confidence interval from 0.691 to 0.793 with P < 0.001.
|Figure 1: Receiver operating characteristic curve showing cut off value of Reid's scoring to diagnose preinvasive lesions of cervix|
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The sensitivity and specificity of Pap smear was found to be 34% and 94%, at the same time colposcopy has high sensitivity and low specificity, i.e., 98.9% and 31% respectively [Table 5]. On the other hand, the sensitivity and specificity of VIA and VILI are comparable, i.e., 65% and 45% and 64% and 48% respectively. Although it shows a low sensitivity, Pap smear shows a high positive predictive value i.e., 85% as compared to colposcopy (58%) and visual inspection methods (55%). When we combine Pap smear with visual inspection methods (VIA, VILI) the sensitivity increased up to 73.8%, whereas combining all the four methods of screening obtained a highest sensitivity, i.e., 99.4%. Colposcopy alone has the highest diagnostic accuracy (65%) over all other screening methods performed alone or in combination.
| > Discussion|| |
In the present study, 50% of the patients were found to have CIN or malignancy in these selected group of patients who are symptomatic or having features of unhealthy cervix. With Pap smear alone we have detected 20% of the patients having positive findings. But in one study from India where they have performed Pap smear on 4703 random patients in a population screening program, only 3.2% of the patients showed cellular abnormalities. Hence it is essential to understand that subjecting the selected group of women (symptomatic or having unhealthy cervix) to screening increases the detection rate by Pap smear even if it has a low sensitivity but also using screening methods such as colposcopy alone or in combination with other methods substantially increases the detection rates as shown in our results. In our study it is seen that majority of the patients belonged to the age group of 30–39 years which is similar to, other studies reported across India., In our study group majority of the patients (70%) were symptomatic for abnormal vaginal discharge which was similar to few other studies reported from this country based on similar criteria., The diagnostic values of screening tests in various studies reported from across the world where they have included the symptomatic patients and patients with unhealthy cervix as their study participants, is shown in [Table 6]. Here, it is clearly seen that sensitivity of Pap smear is low whereas the sensitivity is high in visual inspection methods and in colposcopy, except the study results of Agrawal et al., which shows a high sensitivity (70%) for Pap smear. Similarly the sensitivity of colposcopy is very high across all the study results. We have shown a higher diagnostic accuracy of colposcopy (65%), which is supported by all other studies too.
|Table 6: Diagnostic efficacy of different screening tests in various studies|
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None of the studies have shown the combined diagnostic performances of all the four methods of screening as we have shown in our study [Table 5], which clearly shows that there is an increased sensitivity. Similarly, no study have shown the importance of Reid's scoring and the cutoff value to maximize the diagnosis. In the present study, we have shown the cut off of Reid's scoring as 1.5 for the prediction of preinvasive lesions by plotting ROC curve. In the absence of a nationwide screening program in many developing countries including India, there are disparities in screening techniques and treatment. An analysis of population-based surveys indicates that coverage of cervical cancer screening in developing countries is 19% compared to 63% in developed countries and ranges from 1% in Bangladesh to 73% in Brazil. The actual prevalence of screening for cancer cervix is not available in India. Only figures from opportunistic screening in various regions of India are available which varied from 6.9% in Kerala to 0.006% and 0.002% in the western state of Maharashtra and southern state of Tamil Nadu, respectively.,, Although recommendations are at place for universal screening of sexually active women after the age of 21 years, the goal is far from achieving. Hence, we can encourage the health care providers to throw special focus on women who are symptomatic or having features of unhealthy cervix. Such women can be directly subjected to colposcopy and biopsy if this facility is available. We have also shown in our study that visual inspection methods are having good diagnostic values in comparison to Pap smear. It is simple and cheap and sophisticated laboratories or trained pathologist is not required. Hence doctors and health workers working in developing countries can be trained in visual inspection methods, so that large number of population can avail the benefit. Usually colposcopy is the second step in screening. An abnormal Pap smear is an indication for colposcopy, endocervical curettage, and cervical biopsy for detecting cervical cancer. In our study, we have taken it as the first line for patients with unhealthy cervix or those are symptomatic and have found its diagnostic superiority. In situ ations colposcopy can be the first step of evaluation rather than waiting for the Pap smear report and thereby reducing the number of visits, time spent and financial expenses. Moreover, colposcopy can be reserved as an ideal tool for screening either for all women or specifically in those presenting with unhealthy cervix depending on availability of infrastructure. Hence, more and more doctors should be trained in colposcopy.
| > Conclusion|| |
Visual inspection of cervix by simple speculum examination is an important step in detecting unhealthy cervix, thereby subjecting them for colposcopy guided biopsy if feasible. As compared to Pap smear there is a need to investigate alternative strategies which are more practical, feasible, and effective. VIA and VILI are more sensitive and are of low cost. Colposcopy can be considered as a preferred method of screening for selective group of patients such as those having unhealthy cervix and abnormal vaginal discharge due to its extremely high sensitivity (98.9%). While doing colposcopy, Reid's scoring can be used as a valid scoring system for diagnosing positive cases. A Reid's scoring of 1.5 can be considered as an ideal cut off to diagnose disease cases. Combination of methods always leads to increase in the sensitivity and hence maximizes the detection rate. Hence there is a need to adapt alternative strategies which are more practical, feasible, effective, and whose results are available immediately for symptomatic and patients having unhealthy cervix.
The authors sincerely acknowledge Dr. Amit Bugalia, Dr. Pavan B.C, and Dr. Zameer Lone for their help.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]