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%. 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%) 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. 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 [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.
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.
Inflammation on Pap smear is a very common finding. Its prevalence in various Indian studies is reported to vary between 70% and 80.5%. 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. The incidence is lower than that reported by Sandmire (35.1%) and Reiter (25.3%). 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%.
According to various studies, ASCUS on Pap smear has a 10%-20% chance of harboring CIN. This is the reason why we triage women with ASCUS on Pap smear with either repeat cytology, HPV DNA testing, or colposcopy. 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. 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.
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Conflict of Interest:
1. DiBonito L, Falconieri G, Tomasic G, Colautti I, Bonifacio D, Dudine S. Cervical cytopathology: An evaluation of its accuracy based on cytohistologic comparison Cancer. 1993;72:3002–6
2. Wilkinson EJ. Paponicolou smear and screening for cervical neoplasia Obstet Gynecol. 1990;35:817–25
3. Gay JD, Donaldson LD, Goellner JR. False negative result in cervical cytological studies Acta Cytol. 1985;29:1043–6
4. Seçkin NC, Turhan NO, Ozmen S, Ersan F, Avºar F, Ustün H. Routine colposcopic evaluation of patients with persistent inflammatory cellular changes on Pap smear Int J Gynaecol Obstet. 1997;59:25–9
5. McLachlan N, Patwardhan JR, Ayer B, Pacey NF. Management of suboptimal cytological smears Acta Cytol. 1994;38:531–6
6. Parashari A, Singh V, Gupta MM, Satyanarayana L, Chattopadhya D, Sodhani P, et al Significance of inflammatory cervical smears APMIS. 1995;103:273–8
7. Eckert LO, Koutsky LA, Kiviat NB, Krone MR, Stevens CE, Eschenbach DA. The inflammatory Papnicolaou smear: What does it mean? Obstet Gynecol. 1995;86:360–6
8. WHO. Management of sexually transmitted diseases at district and PHC level. 1999 Regional publication SEARO:25
9. Walker P, Dexeus S, De Palo G, Barrasso R, Campion M, Girardi F, et al International terminology of colposcopy: An updated report from the International Federation for Cervical Pathology and Colposcopy Obstet Gynecol. 2003;101:175–7
10. Mali BN, Joshi JU, Bhave GG, Wagle UD. Cervical cytology in prostitutes of Bombay (India) Genitourin Med. 1992;68:62–3
11. Sandmire HF, Austin SD, Bechtel RL. Experience with 40,000 Papanicolaou smears Obstet Gynecol. 1976;48:56–60
12. Reiter RC. Management of initial atypical cervical cytology: A randomized, prospective study Obstet Gynecol. 1986;68:237–40
13. Wright TC, Sun XW, Loulos J. Comparison of management algorithms for the evaluation of women with low-grade cytologic abnormalities Obstet Gynecol. 1995;85:202–10
14. Lonky NM, Navarre GL, Saunders S, Sadeghi M, Wolde-Tsadik G. Low-grade Papanicolaou smears and the Bethesda system: A prospective cytohistopathologic analysis Obstet Gynecol. 1995;85:716–20
15. Wright TC, Massad LM, Dunton CJ, Spitzer M, Wilkinson EJ, Solomon D, et al 2006 consensus guidelines for the management of women with abnormal cervical cancer screening tests Am J Obstet Gynecol. 2007;197:346–55
16. Dasari P, Rajathi S, Kumar SV. Colposcopic evaluation of persistent inflammatory Pap smear: A prospective analytical study Cytojournal. 2010;7:16