Evaluation of Colposcopic and Histopathological Findings in Precancerous Cervical Lesions

Background: Cervical cancer is the most frequent cancer in women worldwide. It is a preventable and curable disease with proper screening. After primary screening Colposcopy is a valuable tool in the detection and treatment of precancerous cervical lesions. Histopathology is the gold standard method of diagnosis of precancerous lesions. Objective: The objective of this study was to evaluate the performance of colposcopy in the diagnosis and to make correlation between colposcopic & histopathological findings in precancerous cervical neoplasia (CIN). Materials and Method: It was a cross sectional study, conducted at the Colposcopy Clinic, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka. Study was done for a period of one year from January, 2016 to December, 2016. Sixty two married women having following complaints: positive visual inspection of cervix (VIA + ve) with 3-5% acetic acid, postcoital bleeding, postmenopausal bleeding, and intermenstrual bleeding were recruited for the study. Written informed consent was obtained from the participants. The questionnaire was pretested, corrected and finalized. The data collection was done using the interviewer administered questionnaire. Colposcopic examination of cervix was done in 62 participants. Colposcopy guided punch biopsy/Loop electrosurgical excision procedure (LEEP) from acetowhite area was taken in cases of VIA +ve women and random four quadrants (1, 5, 7 & 11 O’ clock position) cervical biopsy in cases of VIA – ve women having other indications. Histopathological examinations of specimens were done in the Department of Pathology, BSMMU. Descriptive analysis, chi-square test and Fisher’s exact test were performed. p value<0.05 was taken as statistically significant. Result: The mean age of the study population was 36.8±11.9 years ranging from 20 to72 years. Out of 62 participants, 40.3% (n=25) had VIA positive, 41.9% (n=26) had postcoital bleeding among which 24 was VIA positive and 2 was VIA negative, 8.1% (n=5) had intermenstrual bleeding with positive VIA and 9.7% (n=6) post-menopausal bleeding among which 4 was VIA positive and 2 was VIA negative. Among total 62 participants. Sensitivity of colposcopy to diagnose histopathologically confirmed CIN I was 82.6%, CIN II was 25% and CIN III was also 25%. The specificity to diagnose CIN I was 42.4%, CIN II was 91.4% and CIN III was 93.1%. PPV of colposcopy to diagnose histologically confirmed CIN I was 55.8%, CIN II was 16.7% and CIN III was 20%. The NPV to diagnose CIN I was 73.7%, CIN II was 94.6% and CIN III was 94.7%. The colposcopic accuracy to diagnose CIN I was 61.3%, CIN II was 87.1% and CIN III was 90.3%. There was statistically significant (p value <0.05) correlation for colposcopic diagnosis of histopathologically confirmed CIN I,CIN II and III. Conclusion: The accuracy of colposcopy to diagnose histopathologically confirmed precancerous cervical lesions was quite high. Patients presenting with postcoital bleeding and postmenopausal bleeding should have colposcopy and biopsies even if the screening test result normal. Moreover colposcopy has high sensitivity, so we can easily adopt the see and treat method to reduce the dropout.


Introduction
Cervical cancer is most frequent cancer in women worldwide. In 2012, there was an estimated 5, 30,000 new cases. Every year, it causes estimated more than 2, 70,000 deaths. More than 85% of these deaths occur in less developed regions. 1 In 2012, there was an estimated 4, 45,000 new cases in the less developed regions. Cervical cancer is second most common cancer among females of Bangladesh with an estimated 11,956 new cases and 6,582 deaths in 2012. 2 In Bangladesh, cervical cancer is the most common reproductive cancer in women, and most women present when it is too late. 3 Cervical cancer is responsible for the highest rate of mortality among Bangladeshi women. 4 More than 80% of patients diagnosed with this eminently preventable cancer presents at clinically advanced and inoperable stages. 5  the International Agency for Research on Cancer (IARC's) projections for coming decades, deaths from cervical cancer will continue to rise. 6 Cervical cancer is by far the most common HPV related disease. HPV 16 and 18 are responsible for 70% of precancerous cervical lesions and cervical cancer. Dr. Zur Hausen was awarded the Nobel Prize in Physiology or Medicine because of his pioneering work in demonstrating the role of HPV in cervical cancer on2008. 7,8 Symptoms begin when the precancerous lesions become true cancer and invade surrounding tissues. The common symptoms include abnormal vaginal discharge which may be blood stained and foul smelling, post coital bleeding, postmenopausal bleeding, inter menstrual bleeding, excessive vaginal bleeding etc. Postcoital bleeding is regarded as a cardinal symptom of cervical cancer. 9 As per USPSTF (United States Preventive Services Task Force) recommendation for cervical cancer screening: women aged 21 to 65 years are recommended to undergo screening with Papanicolaou smear every 3 years or, for those women between 30 to 65 years who want to lengthen their screening interval are recommended to screen with a combination of cytology and HPV testing every 5 years. 10 National cervical cancer screening programme of Bangladesh was initiated in 2004 as a pilot study and as a national programme in 2005. 3 In Bangladesh, government programme of screening test is VIA. Screening test is done in women aged at and above 30 years. There was good compliance for colposcopy but nearly half of patients with high grade precancerous lesions did not receive treatment. Cryotherapy use was infrequent and the policy of "see and treat" was rarely followed. Bangladesh is one of the first countries in the world to introduce VIA as the screening test for its national cervical cancer screening program. 11 Conventional cervical cancer screening and prevention programmes require the woman to make at least two visits if the test is negative and frequent visits if the test is positive. However, the multiple visit based screening programmes has not been successful in reducing cancer rates in low resource settings. To improve the outcomes, unique single visit approach of "Screen and Treat" or "See and Treat" has been developed. A "See and treat" strategy minimises risk of loss of follow up though overtreatment may happened. 12 There are studies that have demonstrated benefits of "see and treat" especially in low resource countries. [13][14][15] VIA and cryotherapy were implemented for screening and treatment by the government partners at demonstration sites in Peru, Uganda and Vietnam. Evaluations in these three countries to explore barriers and facilitating factors showed that use of VIA and cryotherapy is a feasible approach in these settings for cervical cancer prevention services . 13 The most important role of cervical cancer screening tests is to identify the woman with high grade squamous intra-epithelial lesions (HSIL) because the LSIL are frequently regressive. 16 WHO expert panel recommended "screen and treat" strategies for patients with cervical intraepithelial lesions. The recommended screening methods are VIA alone, HPV test alone, HPV test followed by VIA and HPV test/cytology. The recommended treatment method is cryotherapy or LEEP. The expert panel did not recommend the use of cold knife conization (CKC) as treatment in a screen-andtreat strategy. 17 There is no national guideline recommending either "see and treat" or "screen and treat" approaches in Bangladesh. However, Nessa et al. 5 concluded that treatmentsshould be offered by cryotherapy or LEEP immediately following colposcopy at first visit instead of receiving treatment after confirmation by biopsy. Such an approach would benefit more women due to improved treatment compliance but it could also result in over treatment.

Materials and Methods
It was a cross sectional study, conducted at the Colposcopy Clinic, Bangabandhu Sheikh Mujib Medical University (BSMMU). Study was done for a period of one year from 1 st January, 2016 to 31 st December, 2016. Sampling technic was purposive sampling. All consecutive clients attending at colposcopy clinic BSMMU full filing inclusion criteria have been included. Sixty two married women having following complaints: positive visual inspection of cervix with 3-5% Acetic acid (VIA+ve), postcoital bleeding, postmenopausal bleeding, and intermenstrual bleeding were recruited for the study. Women having cervical growth, previously underwent treatment for precancerous lesion, pregnant women and women who didn't give consent to participate in the study were excluded.Written informed consent was obtained from the participants. The questionnaire was pretested, corrected and finalised. The data collection was done using the interviewer administered questionnaire. Colposcopic examination of cervix was done in 62 participants. Colposcopic guided punch biopsy from acetowhite area were taken in Bangladesh Med Res Counc Bull 2020; 46:48-54 cases of VIA +ve women and random four quadrants cervical biopsy was taken in cases of VIA -ve women having other indications. Histopathological examinations of specimens were done in the Department of Pathology, BSMMU. Descriptive analysis, chi-square test and Fisher's exact test were performed. p value<0.05 was taken as statistically significant.

Results
The mean age (±SD) of the study population was 36.8±11.9 year ranging from 20 to 72 years. Maximum 71% (n=44) participants were in age range from 20 to 40 years. Regarding educational status 59.7% (n=37) participants had primary level education, 12.9% (n=8) were illiterate and remaining had SSC, HSC or higher degree. About their occupational status 90.3% (n=56) participants were house wives and others were employed. About socioeconomic status, 51.6% (n=32) of the study population were in the category of lower middle income group and 27.4% (n=17) were poor. bout 96.8% (n=60) of the participants were sexually active and 3.2% (n=2) were widows. The mean age at marriage was 15.6±2.99 year ranging from 11 to 25 years. Among the study population 61.3% (n=38) were married at the age of 10 to 15 years, 30.6% (n=19) at 16 to 20 years and the remaining 8.1% (n=5) at 21 to 25 years of age.
The mean age at first childbirth was 17.37± 2.98 years and ranging from 12 to 27 years. Regarding parity, 37.1% (n=23) were para 2 and others having para 3 or more.

Discussion
Cervical cancer is the fourth most common cancer in women worldwide. 1 In a study conducted by Parvin et al. 2016, the mean age of the study population was 37.57 ± 9.41 years, range from 20 to 60 years. The mean age of marriage of the study population was 16.33±3.35 years, range 10-30 years and mean age of delivery was 19.24±3.91 years, range 13-38 years. 18 Present study showed the mean age of the study population was 36.8±11.9 years, range from 20-72 years. The mean age of marriage was 15.6±2.99 years, range 11-25 years. The mean age at first childbirth was 17.4 years and the mean parity was 2.8. The early age at marriage and early childbirth at young age and repeated pregnancies contributes to the risk of cervical cancer. All cases of invasive squamous cell carcinoma of cervix in present study was in age ranges of 31-50 years and were married at 15-17 years of age ranges.
In a study conducted by Rosenthal et al. 2001 in 314 women presenting with postcoital bleeding, 3% (n=9) had cervical cancer, 5% (n=17) had CIN I, 12% (n=37) had CIN II-III and rest of them having others disease. In the same study, the authors reported cervical cancer in 0.6% of women with postcoital bleeding who had normal looking cervices and normal smear. 9 Present study showed 26 women with postcoital bleeding 16% (n=4) had normal, 60% (n=15) had CIN I, 8% (n=2) had CIN II, 4% (n=1) had CIN III, 3.8% (n=1) had CIS and 12% (n=3) had invasive squamous cell carcinoma of cervix on histopathology. Among 3 women diagnosed as cervical cancer with post coital bleeding, 3.8 % (n=1) of them presented normal looking cervices and normal smear.

Conclusion
In conclusion, the sensitivity and negative predictive value of colposcopy to diagnose LSIL were high but the specificity and positive predictive value were low. On the contrary, its specificity and negative predictive value to diagnose HSIL were high but sensitivity and positive predictive value were low. The accuracy of colposcopy to diagnose histopathologically confirmed precancerous cervical lesions was high.
In women presenting with postcoital bleeding and postmenopausal bleeding, cervical biopsy should be taken for histopathological confirmation, irrespective of colposcopic diagnosis. Endocervical curettage (ECC) should be done in women presenting with postmenopausal bleeding. Otherwise, significant numbers of highgrade lesions or invasive cancer will be missed if only colposcopy is considered.