Original Articles

Grossly Abnormal Cervix: Evidence for Using Colposcopyin the Absence of Squamous Intraepithelial Lesion

by Conventional Papanicolau Test

Papa Dasari, MD, DGO, FICOG, PDCR

Abstract

Background: An ‘‘unhealthy cervix’’ or grossly abnormal cervix can harbor premalignant cervical lesions orinvasive carcinoma even when the Papanicolau test report is negative for these pathologies. Methods: Colpo-scopic evaluation of the cervix was undertaken at a tertiary-care center in 356 women who were referred from2000 to 2008 with ‘‘unhealthy cervix,’’ contact bleeding, and doubtful carcinoma of the cervix. Colposcopicdirected biopsy was performed to investigate abnormal areas in these women, and the incidence of cervicalintraepithelial neoplasia and invasive cervical carcinoma was determined. Results: The most common histo-pathologic diagnosis was chronic cervicitis. Human papilloma virus (HPV) lesions accounted for 20.5% of thecases and cervical intraepithelial neoplasia (CIN) 1 for 13% and CIN 2=3 for 11% of the cases. Invasive cervicalcancer was diagnosed in 5.34% of the cases. Conclusions: It is essential to subject all cases of ‘‘unhealthy’’=grosslyabnormal cervix to colposcopic evaluation when the conventional Papanicolau test is negative for squamousintraepithelial lesion=carcinoma to rule out CIN or invasive cancer. ( J GYNECOL SURG 27:5)

Introduction

It is very common for a gynecologist working in a tertiarycare institute in developing countries to get referrals

from practitioners and from peripheral health centers forpatients with a clinical diagnosis of ‘‘unhealthy cervix’’ or adoubtful diagnosis of carcinoma cervix=suspicious forcancer, etc. If, on primary screening with cytology, asquamous intraepithelial lesion (SIL) is diagnosed, man-agement of the case is straightforward because definiteprotocols for treatment exist. Without a comprehensivecervical cytology screening program, one cannot dismissthe patient saying she has no SIL=carcinoma, as the sen-sitivity of the Papanicolau smear is only 58%. Hence, thereis an obvious need to subject such women to a definitivetest, such as colposcopic assessment or colposcopic di-rected biopsy, to ensure that there is an absence of disease.Colposcopy was undertaken at the Jawaharlal Institute ofPostgraduate Medical Education and Research, in Pu-ducherry, India, for patients with grossly abnormal cervi-ces, whose Papanicolau smear reports were negative forSIL. The objective of this study was to find out how todetect cervical intraepithelial neoplasia when SIL is notevident on Papanicolau smears.

Materials and Methods

Colposcopy was performed on 356 women with a clinicaldiagnosis of ‘‘unhealthy cervix’’=suspicious cervix (grosslyabnormal cervix) from 2000 to 2008. The procedure and itsnecessity were explained to each patient and an informedconsent was obtained. Inclusion criteria for this study wereclinically suspicious cervix with Papanicolau smear negativefor SIL=dysplastic cells=atypical cells=squamous cell carci-noma. The cervix was considered ‘‘unhealthy’’ or abnormal ifit had abnormalities present, either singly or in variouscombinations, such as hypertrophy, irregularity, congestionwith increased vascularity or erosion, nabothian cysts, andpolyps, or appearance of clinically suspicious signs of ma-lignancy, such as bleeding on touch. Pregnant patients, pa-tients with obvious growths on their cervices, and patientswho underwent cryosurgery or conization were excluded.

After applying 3% acetic acid to the cervix, it was stud-ied using a binocular colposcope (OLYMPUS OSC 3-FLA,M=s Olympus Optical Co. Ltd., Tokyo, Japan) under 40�magnification. Abnormal areas, such as raised surface ar-eas (RSAs), punctations, atypical vessels, acetowhite areas,ulcers, and growths were biopsied. Multiple punch biop-sies were performed in all of the abnormal areas such as

Department of Obstetrics and Gynecology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India.

JOURNAL OF GYNECOLOGIC SURGERYVolume 27, Number 1, 2011ª Mary Ann Liebert, Inc.DOI: 10.1089=gyn.2010.0035

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acetowhite areas and punctations. RSA was diagnosedwhen there was a localized elevation of the surface epithe-lium. A growth was diagnosed when there was a localizedraised area with multiple heaped up epithelium, which wasirregular. An ulcer was diagnosed when there was denuda-tion or deficiency of epithelium in localized areas. Biopsieswere taken from the edges of erosions when they wereirregular and also when the margins were acetowhite.The incidence of cervical intraepithelial neoplasia (CIN)=invasive carcinoma cervix was reported by frequencies andpercentages.

Results

The clinical profiles of the patients are shown in Table 1.The mean age of the patients was 41.3 years and the oldestpatient was 68 years old. The mean parity was 2.6 years andthe highest parity was 7. Of the 356 patients, suspicious or‘‘unhealthy’’ cervix constituted 76.7%; 12.6% had evidence ofcontact bleeding, including postcoital bleeding, and 10.7%had a referral diagnosis of doubtful carcinoma of the cervix.

The patients’ colposcopic features are shown in Table 2.The most common colposcopic feature was actowhite areas(35%), followed by vascular abnormalities and a combinationof findings of acetowhite areas and vascular abnormalities.Erosion was clinically diagnosed as ‘‘unhealthy cervix’’ in ashigh as 14% of cases. Growths, small sessile polyps, RSAs,and ulcers were some of the other findings in cases of ‘‘un-healthy’’ cervix. In 15.7% of cases, patients who were referredas having carcinoma cervix, ulcers were seen, and, in 4, casesgrowths were seen on colposcopy. Colposcopy showednormal cervices in only 5 cases of the 356 women. The resultsof colposcopic biopsy are shown in Table 3. Invasive cancerwas reported in 4.3%, 2.2%, and 15.8% of cases of unhealthycervix, contact bleeding, and patients with doubtful carci-

noma of cervix, respectively (Table 4). The incidence of CIN2=3 was approximately 11%.

Human papilloma virus (HPV) lesions accounted for20.5% of the cases, and CIN 1 for 13% of the cases. Most ofthe patients with contact bleeding had chronic cervicitis,followed by HPV lesions. Although the most common col-poscopic biopsy result in all three categories was chroniccervicitis and HPV lesions, a significant proportion of caseswith CIN2=3 (11%) and invasive carcinoma (5.3%) existed.

Discussion

Screening for carcinoma of the cervix by employing Pa-panicolau smear has reduced the incidence of invasive cer-vical cancer and the mortality associated with it. However,clinicians still encounter cases of invasive cancer despitegood screening protocols—even in developed countries. Inthe United Kingdom, 2800 cases of invasive cervical cancerwere reported to occur every year, and 1000 women died ofthe disease.1 One of the reasons for this may be the sensi-tivity of the conventional Papanicolau test, which is reportedto be only 58%. This may be a result of sampling errors orlaboratory errors. By simply repeating the Papanicolau test,one may not achieve the maximum desired outcome. Theaim of any screening program should be to increase the casedetection rate by using various techniques or methodswhenever possible. One such approach may be to screenclinically abnormal or suspicious cervices in patients withnegative Papanicolau smear test results by using better mo-dalities, such as colposcopy. This approach is possible ininstitutions that serve a large number of referral patients as isthe case in the Jawaharlal Institute of Postgraduate MedicalEducation and Research.

A prospective study undertaken recently that aimed todetermine the incidence of CIN using conventional Papani-colau test in ‘‘unhealthy’’ and healthy cervices concluded thatthere was no difference (statistical significance) in the inci-dence of CIN although there was an increased incidence inpatients with ‘‘unhealthy’’ cervix.2 The present study did notevaluate patients with cervices that were healthy in ap-pearance. Colpscopic evaluation of patients with ‘‘un-healthy’’ or grossly abnormal cervices showed a significantlyhigh proportion of CIN and invasive cancer. A multicenterstudy evaluating the sensitivity of Papanicolau testingrevealed that the sensitivity of the cytology for detectionof high-grade lesions was 57%.3 The results of that study

Table 1. Clinical Profile

Serial no. Parameter n

1. Mean age in years 41.32. Mean parity 2.63. Clinical diagnosis

a ? Ca cervix 38 (10.7%)b. ‘‘Unhealthy cervix’’ 273 (76.7%)c. Contact bleeding 45 (12.6%)

Table 2. Colposcopic Features

Other findingsb

Clinical diagnosis Normal ErosionAcetowhite

areasVascularchanges

Acetowhiteareas and

vascular changes G RSA P Ulcer

‘‘Unhealthy cervix’’n¼ 273

3 (1.1%) 37 (13.6%) 98þ 5a (41.4%) 68 (24.9%) 53 (19.4%) 3 (1.1%) 5 (1.8%) 4 (1.5%) 13 (4.8%)

Contact bleedingn¼ 45

– 3 (6.7%) 15 (33.3%) 11 (24.4%) 8 (17.78%) 2 (4.4%) 5 (11%) 1 (2.2%) 7 (15.6%)

? Ca cervix n¼ 38 2 (5.3%) 2 (5.3%) 7 (18.4%) 6 (15.7%) 6 (15.7%) 4 (10.5%) 3 (7.9%) 2 (5.3%) 6 (15.7%)Total N¼ 356 5 (1.4%) 42 (11.8%) 125 (35%) 85 (23.9%) 67 (18.8%) 9 (3%) 13 (4%) 7 (2%) 26 (8%)

aLeukoplakia.bOther findings noted either alone or in association with acetowhite areas or vascular changes. Hence total findings will not be equal to N.G, growth; RSA, raised surface area; P, polyp.

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indicated that specificity in the range of 90%–95% corre-sponded to a sensitivity of 20%–35%. This analysis pointedtoward the search for a more optimal method of screening.3

The major focus of colposcopic assessment is to detectcancer. To accomplish this goal, one must maintain a highindex of suspicion. The colposcopist should be aware of thehallmark features of invasive cancer and look for these fea-tures in each patient who is evaluated. Colposcopically,cervical cancer can be a challenge to diagnose—especially incases of microinvasive cancer, because atypical vessels orother signs of more-advanced disease may not be present.This reinforces the fact that one must maintain a high degreeof suspicion and address effectively any discrepanciesamong colposcopy, cytology, and histology before therapy isinitiated.4

Signs and symptoms that may suggest cervical cancer areintermenstrual bleeding, postcoital bleeding, postmeno-pausal bleeding, abnormal appearance of the cervix (suspi-cion of malignancy), bloodstained vaginal discharge, andpelvic pain. A women presenting with these symptoms andwho has negative cytology has a greatly reduced risk ofcervical cancer compared to a woman with positive cytology,but the risk is not entirely eliminated.1 Hence there is a goodrationale for undertaking evaluation of any patient who hasan ‘‘unhealthy’’ or grossly abnormal cervix, even accordingto the latest guideline, and even when the patient’s Papani-colau test is negative for SIL or carcinoma. Few authoritiesare also of the opinion that using colposcopy to evaluate‘‘unhealthy cervix’’ is indicated when a patient’s Papanicolautest is negative.5

‘‘Unhealthy cervix’’ includes any one of a group of chronicconditions that affect the cervix, including chronic cervicitis,endocervicitis, erosions, lacerations, eversions, polipi, leuko-plakia, and basal-cell hyperplasia. These conditions produce

symptoms, and there is evidence that some patients may beharboring premalignant lesions.6 Cervical erosion was foundto be associated with mild dysplasia in 9.75% of cases andsevere dysplasia in 2.43% of cases in a cross-sectional study,undertaken in India, that used cytology.7 A combination ofvisual inspection with acetic acid (VIA) and HPV DNA wasproposed to be the best screening test for premalignant andmalignant lesions of the cervix for patients in developingcountries; however, one cannot rely on this for treatmentpurposes, as the false-positive rate is high, resulting in over-treatment of 5 women for every single positive case.8 Ulti-mately, histopathologic examination, especially biopsy ofabnormal areas, is the gold standard for arriving at an accuratediagnosis. In a prospective study that compared Papanicolautesting and colposcopic biopsy for screening for CIN andcervical cancer in symptomatic patients with ‘‘unhealthy’’cervix, colposcopy was found to be more sensitive, with thecase detection rate being four times higher than cytology.9 Inthe present study, when Papanicolau smears were negative forSIL, colposcopy detected 24% cases of CIN and 5.34% cases ofinvasive cancer. Cervical lesions, such as suspicious and ‘‘un-healthy’’ cervix and persistent vaginal discharge, were foundto be contributing factors for progression of SIL in a study thataimed to discover the risk factors for progression of CIN. Theresearchers involved in this study suggested treating mildcervical lesions and persistent vaginal discharge to avoid orreduce the rate of progression to CIN.10

Conclusions

It is important to subject women who have an ‘‘unhealthycervix’’ without an abnormal Papanicolau test report to col-poscopy, as a significantly high proportion of them canharbor preinvasive and=or invasive cancer.

Table 3. Histopathologic Diagnosis by Coloposcopic Biopsy

Histopathologic diagnosis

Clinical diagnosis No biopsy Normal tissue SM CC SMþCC HPV lesions CIN Invasive cancer

‘‘Unhealthy cervix’’ n¼ 273 3 12 (4.4%) 6 (2.2%) 109 (40%) 3 62 (22.7%) 66 (25%) 12 (4.3%)Contact bleeding n¼ 45 – 1 2 22 (48.9%) – 7 (15.6%) 12 (27%) 1 (2.2%)?Carcinoma cervix n¼ 38 2 – – 20 (52.6%) – 4 (10.5%) 6 (16%) 6 (16%)Total N¼ 356 5 (1.4%) 13 (3.7%) 8 (2.2%) 151 (42.4%) 3 (0.8%) 73 (20.5%) 84 (24%) 19 (5.34%)

SM, squamous metaplasia; CC, chronic cervicitis; HPV, human papilloma virus; CIN, cervical intraepithelial neoplasia.

Table 4. Incidence of CIN=Carcinoma Cervix

Incidence of CIN & invasive carcinoma

Clinical diagnosis CIN 1 (%) CIN 2 (%) CIN 3 (%) Carcinoma in situ (%) Invasive carcinoma (%)

‘‘Unhealthy’’ cervix n¼ 273 40 (14.7%) 10 (3.7%) 7 (2.6%) 9 (3.3%) 12 (4.3%)Contact bleeding n¼ 45 4 (8.9%) 5 (11%) 1 (2.2%) 2 (4.4%) 1 (2.2%)? Ca cervix n¼ 38 2 (5.3%) 2 (5.3%) 2 (5.3%) – 6 (15.8%)Total N¼ 356 46 (12.9%) 17 (4.8%) 10 (2.8%) 11 (3%) 19 (5.34%)

CIN, cervical intraepithelial neoplasia.

COLPOSCOPY OF GROSSLY ABNORMAL CERVIX 7

Disclosure Statement

No competing financial conflicts exist.

References

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2. Pradhan N, Giri K, Rana A. Cervical cytological study inunhealthy and healthy looking cervix. Nepal J Obstet Gy-necol 2007;2:42.

3. Jenuja A, Shegal A, Sharma S, Pandey A. Cervical Cancerscreening in India: Strategies revisited. Indian J Med Sci2007;61:34.

4. ASCCP. ASCCP Practice Recommendations: The Cervix.Invasive Cancer of Cervix. Online document at: www.asccp.org=edu=practice=cervix=cancer Accessed February 4, 2010.

5. Hammond I. Women’s Health Education and Research So-ciety Inc. 2004–2009. Online document at: www.whers.com.au=conference-2006=your-questions-answered-2006 AccessedApril 13, 2010.

6. Read DH.The treatment of the non-malignant unhealthycervix. Br J Obstet Gynecol 2005;62:796.

7. Kulakarni RN, Durge PM. Role of socio-economic factorsand cytology in cervical erosion in reproductive age groupwomen. Indian J Med Sci 2002;56:598.

8. Bhatla N, Mukopadhayay A, Kripalni A, et al. Evaluation ofadjunctive tests for cervical cancer screening in low resourcesettings. Indian J Cancer 2007;44:51.

9. Singh SL, Dastur NA, Nanavathi MS. A comparision ofcolposcopy and Papanicolaou smear: Sensitivity, specific-ity and positive predictive value. Bombay Hospital J 2010;52:1.

10. Misra JS, Das V, Srivastava AN, et al. Role of different eti-ological factors in the progression of cervical intra-epithelial neoplasia. Diagn Cytopathol 2006;34:682.

Address correspondence to:Papa Dasari, MD, DGO, FICOG, PDCRDepartment of Obstetrics and Gynecology

Jawaharlal Institute of Postgraduate Medical Educationand Research

Dhanvanthri NagarPuducherry, 605006

India

E-mail: dasaripapa@gmail.com

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