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Indian Journal of Cancer, Vol. 48, No. 2, April-June, 2011, pp. 220-222 Original Article Persistent inflammation on Pap smear: Does it warrant evaluation? K Bhutia1, M Puri1, N Gami1, K Aggarwal2, SS Trivedi1 1 Department of Obstetrics and Gynecology, Lady Hardinge Medical College, Delhi, India Correspondence Address: N Gami Department of Obstetrics and Gynecology, Lady Hardinge Medical College, Delhi India nehagami@hotmail.com Code Number: cn11053DOI: 10.4103/0019-509X.82901 Abstract Objective: Due to the low sensitivity of Pap smear, premalignant lesions of the cervix can be missed in women with inflammatory Pap smears. However, it is not practically possible to subject all women with inflammatory Pap smear to colposcopy. This study was carried out with the aim to evaluate whether women with persistent inflammation on Pap smear need further evaluation with colposcopy.Materials and Methods: Four hundred and twenty women were screened at a tertiary level hospital with Pap smear. Women with inflammation on Pap smear were given treatment as per WHO guidelines and Pap smear was repeated at an interval of 6-12 weeks. Women with persistent inflammation on Pap smear were then subjected to colposcopy and directed biopsy if required. Results: Of the 420 women screened, 102 (24.3%) women had a Pap smear showing inflammation. Thirty six women (8.6%) had persistent inflammatory Pap smear. Thirty women were subjected to colposcopy and 16 (53.3%) had abnormal findings on colposcopy. Five out of these 30 women (16.67%) had Cervical intraepithelial neoplasia (CIN) on biopsy. Conclusions: Nearly 16.67% women with persistent inflammation on Pap smear had cervical intraepithelial neoplasia. Hence, a large number of women with CIN would be missed if persistent inflammation on Pap smear is not evaluated further. Keywords: Colposcopy, inflammation, pap smear Introduction World over, Pap smear has been the standard test for screening of cervical cancer and its precursors. However, it suffers from low sensitivity and has a high false negative rate of 9%-40%. [1],[2],[3] To overcome this problem many algorithms have been devised to manage ASCUS or LSIL on pap-smear. These involve HPV DNA testing, colposcopy or both. However, no such algorithms are available for further management of an inflammatory Pap smear. Inflammation on Pap smear is considered a relatively benign finding. However, due to the low sensitivity and high false negative rate of Pap smear there is a possibility that an inflammatory Pap smear may miss cervical premalignant changes. Since the incidence of inflammation on Pap smear is very high (14%-19%) [4],[5],[6],[7] it may not be possible to subject all patients with inflammation to colposcopy or HPV DNA testing. This study was designed to evaluate whether persistent inflammatory changes on Pap smear could be the first indication of premalignant changes in the cervix and whether further evaluation by colposcopy would help to triage these women. Materials and Methods The study was conducted at a tertiary level teaching hospital after obtaining clearance from the Ethical Committee of the Institution. Four hundred and twenty women presenting with symptoms like discharge per vaginum, pain in lower abdomen, lower backache, pruritis vulvae or vagina were enrolled. Women who were pregnant or postmenopausal, with proven CIN or obvious cervical growth, IUCD users, with diabetes mellitus, and with multiple sexual partners were excluded from the study. Informed consent was taken from all women. After a detailed history and general physical examination, a detailed gynecological examination was carried out in all. This included examination of the breast, local examination of vulva, per speculum examination with Pap smear, and per vaginum examination. Women with inflammatory Pap smear were then included in the study. Both the patient and her partner were treated with antimicrobial and anti-inflammatory treatment according to WHO guidelines. [8] They were given doxycycline and metronidazole orally for 7-14 days and clotrimazole vaginal pessary daily for 8 days. The couple was advised abstinence or barrier contraception during the treatment period. A repeat Pap smear was taken after an interval of 6-12 weeks and the patients with a repeat report of inflammation were said to have persistent inflammatory smear. They were then subjected to colposcopy. The presence of any acetowhite or iodine negative areas was noted and classified according to colposcopic terminology by IFCPC [9] [Table - 1]. The patients with suspicious lesions on colposcopy were then subjected to cervical biopsy from these abnormal areas along with endocervical brush cytology and endocervical curettage. The biopsy specimens were fixed in 10% formalin and sent for histopathological evaluation. The results were then interpreted. The statistical analysis was done using Student′s t-test. Results Four hundred and twenty women were initially recruited from the OPD of our hospital. Of these, 102 (24.3%) women had an initial Pap smear showing inflammation. After treatment 36/420 (8.6%) women had a persistent inflammatory Pap smear. The mean age of the women with persistent inflammatory Pap smear was 30.4 ± 6.1 years. The mean age at marriage was 18.9 ± 2.6 years. A total of 30 patients underwent colposcopy and 6 were lost to follow up. Sixteen patients had abnormal colposcopic findings. The reports of the colposcopic directed cervical biopsies revealed chronic cervicitis in 11 (36.7%), CIN 1 in 4 (13.33%) and CIN 2 in 1(3.3%) women. No tissue was identified in the endocervical curettings in any patient and the endo-cervical brush cytology showed only inflammation. On correlating the histopathology reports with the colposcopic findings, it was found that the women with chronic cervicitis had grade I-II acetowhite changes and fine mosaic and punctation pattern, while the patients with CIN had grade II-III acetowhite change with coarse punctation. Discussion Inflammation on Pap smear is a very common finding. Its prevalence in various Indian studies is reported to vary between 70% and 80.5%. [6],[10] In our study the reported prevalence of 24.3% is lower probably due to the fact that the sample size being small does not represent the general population entirely. Persistent inflammatory Pap smear, i.e., a repeat report of inflammation on Pap smear even after treatment was found in 8.6% of cases. Similar results were reported by Secken et al. [4] The incidence is lower than that reported by Sandmire (35.1%) [11] and Reiter (25.3%). [12] Again this could be explained by the predominance of healthy cervix among the women included in the study. The mean age of the women with persistent inflammatory Pap smear was 30.43 ± 6.1 years. The mean age of women with CIN in our study was 30.2 years (P > 0.05 ). The mean age at marriage was 18.9 ± 2.6 years among women with persistent inflammatory smear while that with the women with CIN was 16.8 ± 2 years (P = 0.05). The mean parity was 2.5 ± 0.9 years and 2.4, respectively (P > 0.05 ). In our study, out of the 30 women with persistent inflammatory Pap smear 16 (53.3%) women had abnormal colposcopic findings and CIN was found in 5 of these 30 women (16.3%). So, 16.3% women with persistent inflammatory Pap smear were harboring CIN which included four cases of CIN 1 and one case of CIN 2. Various studies have found the possibility of CIN with a report of persistent inflammatory smear to range from 18% to 35%. [4],[5] According to various studies, ASCUS on Pap smear has a 10%-20% chance of harboring CIN. [13],[14] This is the reason why we triage women with ASCUS on Pap smear with either repeat cytology, HPV DNA testing, or colposcopy. [15] Our study has shown that a similar percentage of women with persistent inflammation on Pap smear could be harboring CIN. Hence, all women with persistent inflammation on Pap smear should be subjected to further evaluation. HPV DNA testing can be an alternative to colposcopy; however, the use of HPV DNA testing to triage women with persistent inflammatory pap smears has not been recommended. Further studies are required to establish the cost effectiveness of HPV DNA testing in triage of women with inflammatory pap smear. In our study, we found a 16.67% incidence of CIN in women with persistent inflammatory pap smear. The incidence of CIN and invasive carcinoma in women with persistent inflammatory pap smears over just 2 weeks was found to be 20.6% and 0.7%, respectively, in a study by Dasari et al. [16] Hence, by waiting for a longer period of time before repeating the pap smear may lead to a delay in diagnosis of CIN in a high percentage of cases. To conclude, one must not see a report of inflammation on Pap smear in isolation and ignore it as being absolutely insignificant. If it persists in any patient then we must consider evaluating the patient further by colposcopy. References
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