Correlation of Pap smear and colposcopic finding with directed biopsy in detection of cervical neoplasm

Introduction: Cancer of uterine cervix is the most common genital tract malignancy. Pap smear though widely used screening test for cervical cancer has the disadvantage of low sensitivity. Colposcopy has higher sensitivity compared to Pap smear. Concurrent screening with Pap smear and colposcopy can overcome this problem. Aim: The aim of the study was correlation of Pap smear and colposcopic finding with directed biopsy in detection of cervical neoplasm. Methods: The Present study was conducted in the Department of Pathology, Gujarat Adani Institute of Medical Science, Bhuj, Kutch. During the study period in 57 symptomatic patient’s simultaneous Pap smear, colposcopic examination, followed by directed biopsy was performed. Data was recorded and analyzed. Results: In correlation between cytology and biopsy, sensitivity of cytology was 82.3%, specificity 96.9% and accuracy of 92%. In correlation between colposcopy and biopsy, sensitivity of colposcopy was 94.1%, specificity 87.8% and accuracy of 90%. Conclusion: High sensitivity in colposcopy as compared to cytology and high specificity in cytology as compared to colposcopy emphasizes the need for pairing these methods to achieve better results.


Introduction
Cancer of cervix is the leading cause of cancer-related death among women in developing countries, where more than 80% of new cases occur. Cervical cancer continues to be the most common genital tract malignancy in India. Cancer of cervix is preceded by recognizable precancerous histological and cytological changes which provide opportunity for early detection of cervical neoplasm [1,2].
Cervical cytology is the accepted method of screening for cervical cancer all over the world but it has low sensitivity. In the presence of an abnormal Pap smear, a tissue diagnosis is essential before proceeding with definitive therapy. Although cytology is accurate in predicting severity of cervical lesion, it cannot determine their location or extent. A random cervical biopsy in the absence of visible lesion may result in a false negative histologic diagnosis [3]. With the introduction of colposcope, comparative studies substantiated that it was possible to accurately localize the area of abnormal cervical epithelium by colposcopic examination for the selection of biopsy site. Colposcopy as an adjunctive screening test has high sensitivity and can provide immediate results for evaluation of cervical lesions. Executing targeted biopsy, colposcopy can be useful in defining diagnosis of preinvasive lesions and carcinoma of cervix [4,5].
Complete and accurate assessment of the nature of a cervical neoplastic lesion relies on three methods of investigation: cervical smear, examination of cervix with colposcope and histology of a biopsy specimen.
Ideally the grade of cervical neoplasia discovered during all three methods should be the same, but in practice disagreement of more than one method is not uncommon [6]. The aim of the study was correlation of Pap smear and colposcopic finding with directed biopsy to assess the advantage of concurrent testing by

Materials and Methods
Study Design and Study Settings-The Present study was conducted in the Department of Pathology, Gujarat Adani Institute of Medical Science, Bhuj, Kutch for a period of 12 months after taking approval from Institutional Ethical Committee.
Sample Collection-During the study period 57 female patients above the age of 18 years, with symptoms of vaginal discharge and other gynecological problems attending the outpatient department of OBG following informed consent were subjected for concurrent Pap smear examination, colposcopy and directed biopsy.
Inclusion and Exclusion Criteria-Pregnant women, teenage girls, hysterectomy patients, unsatisfactory smearand inadequate biopsies were excluded. Total of 50 cases were included in the study.
Methodology-Clinical details were obtained according to the structured proforma. The relevant clinical findings were collected by personal interview and examination of the patient. Pap smears were taken using Ayre's spatula from squamocolumnar junction. Material spread evenly on glass slide and fixed with cytofix containing 95% ethyl alcohol and carbowax. Fixed smears received were stained with Pap stain and reported according to The Bethesda System.
Colposcopic examination was performed using Gold way SLC-2000 video colposcope. Normal saline was applied to the cervix to remove excess mucus. Green filter of colposcope was used to appreciate vascular pattern and 3% acetic acid applied to visualize the atypical transformation zone, following which biopsies were taken using punch biopsy forceps. Biopsy specimens received in 10% formalin fixative were routinely processed and sections stained with hematoxylin and eosin. Results were categorized according to WHO.

Statistical analysis-
The data was coded and entered into Microsoft Excel spreadsheet. Analysis was done using SPSS version 15 (SPSS Inc. Chicago, IL, USA) Windows software program. Descriptive statistics included computation of percentages. For all tests, confidence level and level of significance were set at 95% and 5% respectively. Statistical analysis was carried out by calculating sensitivity, specificity, positive and negative predictive value for Pap smear and Colposcopy.
In correlation between cytology and biopsy, sensitivity of cytology was 82.3%, specificity 96.9%, false negative rate of 17.6%, false positive rate of 3% and accuracy of 92%.
In correlation between colposcopy and biopsy, sensitivity of colposcopy was 94.1%, specificity 87.8%, false negative rate of 6.25%, false positive rate of 12.1% and accuracy of 90%.

Discussion
Cancer of cervix is the fourth most common cancer in women, with an estimated 528,000 new cases in 2012. Large majority (around 85%) of the global burden occurs in the less developed regions, where it accounts for almost 12% of all female cancers.
Almost nine out of ten (87%) cervical cancer deaths occur in the less developed regions [1]. In the present study, the age of patients ranged from 20 to 70 years with the mean age of 36.4 years, which is comparable to study by Joshi C et al where the age range was 20 to 65 years, Similar distribution of patients has been observed in other studies also [5][6][7].White discharge per vagina was the most common symptom with 37(74%) cases, which was comparable to studies done by Chaudhary RD et al and Bhalerao A et al [8,9] In the present study, clinical status of cervix in majority of patients was cervical erosion with 27(54%) cases. Similar findings were observedin the studies performed by Chaudhary RD et al and Bhalerao A et al, where majority were cervical erosion with 173(86%), 156(78%) cases respectively [8,9].Most common colposcopic finding was acetowhite area with 20(40%) cases, similarly reported by Joshi C et al and Krishnegowda et al [10,11].
Cytology and colposcopy showed 100% correlation for high grade lesions. High false negative rate on cytology was seen in cases of inflammatory smear and high false positive rate on colposcopy in cases of CIN1, implying the importance of repeat smear and follow-up in these cases.

Conclusion
High sensitivity in colposcopy as compared to cytology and high specificity in cytology as compared to colposcopy emphasizes the need for pairing these methods to achieve better results.
Advantage of this study to existing knowledge-When properly used, colposcopy complements cytology by accurately defining the most suspicious area of the cervix for taking biopsy and there by increases the diagnostic accuracy.
Funding: Nil, Conflict of interest: None initiated, Permission from IRB: Yes