Grossly Abnormal Cervix: Evidence for Using Colposcopy in the Absence of Squamous Intraepithelial Lesion by Conventional Papanicolau Test

Abstract

Background: An “unhealthy cervix” or grossly abnormal cervix can harbor premalignant cervical lesions or invasive carcinoma even when the Papanicolau test report is negative for these pathologies. Methods: Colposcopic evaluation of the cervix was undertaken at a tertiary-care center in 356 women who were referred from 2000 to 2008 with “unhealthy cervix,” contact bleeding, and doubtful carcinoma of the cervix. Colposcopic directed biopsy was performed to investigate abnormal areas in these women, and the incidence of cervical intraepithelial neoplasia and invasive cervical carcinoma was determined. Results: The most common histopathologic diagnosis was chronic cervicitis. Human papilloma virus (HPV) lesions accounted for 20.5% of the cases and cervical intraepithelial neoplasia (CIN) 1 for 13% and CIN 2/3 for 11% of the cases. Invasive cervical cancer was diagnosed in 5.34% of the cases. Conclusions: It is essential to subject all cases of “unhealthy”/grossly abnormal cervix to colposcopic evaluation when the conventional Papanicolau test is negative for squamous intraepithelial 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 tertiary care institute in developing countries to get referrals from practitioners and from peripheral health centers for patients with a clinical diagnosis of “unhealthy cervix” or a doubtful diagnosis of carcinoma cervix/suspicious for cancer, etc. If, on primary screening with cytology, a squamous intraepithelial lesion (SIL) is diagnosed, management of the case is straightforward because definite protocols for treatment exist. Without a comprehensive cervical cytology screening program, one cannot dismiss the patient saying she has no SIL/carcinoma, as the sensitivity of the Papanicolau smear is only 58%. Hence, there is an obvious need to subject such women to a definitive test, such as colposcopic assessment or colposcopic directed biopsy, to ensure that there is an absence of disease. Colposcopy was undertaken at the Jawaharlal Institute of Postgraduate Medical Education and Research, in Puducherry, India, for patients with grossly abnormal cervices, whose Papanicolau smear reports were negative for SIL. The objective of this study was to find out how to detect cervical intraepithelial neoplasia when SIL is not evident on Papanicolau smears.

Materials and Methods

Colposcopy was performed on 356 women with a clinical diagnosis of “unhealthy cervix”/suspicious cervix (grossly abnormal cervix) from 2000 to 2008. The procedure and its necessity were explained to each patient and an informed consent was obtained. Inclusion criteria for this study were clinically suspicious cervix with Papanicolau smear negative for SIL/dysplastic cells/atypical cells/squamous cell carcinoma. The cervix was considered “unhealthy” or abnormal if it had abnormalities present, either singly or in various combinations, such as hypertrophy, irregularity, congestion with increased vascularity or erosion, nabothian cysts, and polyps, or appearance of clinically suspicious signs of malignancy, such as bleeding on touch. Pregnant patients, patients with obvious growths on their cervices, and patients who underwent cryosurgery or conization were excluded.

After applying 3% acetic acid to the cervix, it was studied 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 areas (RSAs), punctations, atypical vessels, acetowhite areas, ulcers, and growths were biopsied. Multiple punch biopsies were performed in all of the abnormal areas such as acetowhite areas and punctations. RSA was diagnosed when there was a localized elevation of the surface epithelium. A growth was diagnosed when there was a localized raised area with multiple heaped up epithelium, which was irregular. An ulcer was diagnosed when there was denudation or deficiency of epithelium in localized areas. Biopsies were taken from the edges of erosions when they were irregular and also when the margins were acetowhite. The incidence of cervical intraepithelial neoplasia (CIN)/invasive carcinoma cervix was reported by frequencies and percentages.

Results

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

Table 1.

Clinical Profile

Serial no.	Parameter	n
1.	Mean age in years	41.3
2.	Mean parity	2.6
3.	Clinical diagnosis
a	? Ca cervix	38 (10.7%)
b.	“Unhealthy cervix”	273 (76.7%)
c.	Contact bleeding	45 (12.6%)

The patients' colposcopic features are shown in Table 2. The most common colposcopic feature was actowhite areas (35%), followed by vascular abnormalities and a combination of findings of acetowhite areas and vascular abnormalities. Erosion was clinically diagnosed as “unhealthy cervix” in as high as 14% of cases. Growths, small sessile polyps, RSAs, and ulcers were some of the other findings in cases of “unhealthy” cervix. In 15.7% of cases, patients who were referred as having carcinoma cervix, ulcers were seen, and, in 4, cases growths were seen on colposcopy. Colposcopy showed normal cervices in only 5 cases of the 356 women. The results of colposcopic biopsy are shown in Table 3. Invasive cancer was reported in 4.3%, 2.2%, and 15.8% of cases of unhealthy cervix, contact bleeding, and patients with doubtful carcinoma of cervix, respectively (Table 4). The incidence of CIN 2/3 was approximately 11%.

Table 2.

Colposcopic Features

						Other findings ^b
Clinical diagnosis	Normal	Erosion	Acetowhite areas	Vascular changes	Acetowhite areas and vascular changes	G	RSA	P	Ulcer
“Unhealthy cervix” n = 273	3 (1.1%)	37 (13.6%)	98 + 5^a (41.4%)	68 (24.9%)	53 (19.4%)	3 (1.1%)	5 (1.8%)	4 (1.5%)	13 (4.8%)
Contact bleeding n = 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 n = 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 N = 356	5 (1.4%)	42 (11.8%)	125 (35%)	85 (23.9%)	67 (18.8%)	9 (3%)	13 (4%)	7 (2%)	26 (8%)

Leukoplakia.

Other 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.

Table 3.

Histopathologic Diagnosis by Coloposcopic Biopsy

	Histopathologic diagnosis
Clinical diagnosis	No biopsy	Normal tissue	SM	CC	SM+CC	HPV lesions	CIN	Invasive cancer
“Unhealthy cervix” n = 273	3	12 (4.4%)	6 (2.2%)	109 (40%)	3	62 (22.7%)	66 (25%)	12 (4.3%)
Contact bleeding n = 45	–	1	2	22 (48.9%)	–	7 (15.6%)	12 (27%)	1 (2.2%)
?Carcinoma cervix n = 38	2	–	–	20 (52.6%)	–	4 (10.5%)	6 (16%)	6 (16%)
Total N = 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 n = 273	40 (14.7%)	10 (3.7%)	7 (2.6%)	9 (3.3%)	12 (4.3%)
Contact bleeding n = 45	4 (8.9%)	5 (11%)	1 (2.2%)	2 (4.4%)	1 (2.2%)
? Ca cervix n = 38	2 (5.3%)	2 (5.3%)	2 (5.3%)	–	6 (15.8%)
Total N = 356	46 (12.9%)	17 (4.8%)	10 (2.8%)	11 (3%)	19 (5.34%)

CIN, cervical intraepithelial neoplasia.

Human papilloma virus (HPV) lesions accounted for 20.5% of the cases, and CIN 1 for 13% of the cases. Most of the patients with contact bleeding had chronic cervicitis, followed by HPV lesions. Although the most common colposcopic biopsy result in all three categories was chronic cervicitis and HPV lesions, a significant proportion of cases with CIN2/3 (11%) and invasive carcinoma (5.3%) existed.

Discussion

Screening for carcinoma of the cervix by employing Papanicolau smear has reduced the incidence of invasive cervical cancer and the mortality associated with it. However, clinicians still encounter cases of invasive cancer despite good screening protocols—even in developed countries. In the United Kingdom, 2800 cases of invasive cervical cancer were reported to occur every year, and 1000 women died of the disease.¹ One of the reasons for this may be the sensitivity of the conventional Papanicolau test, which is reported to be only 58%. This may be a result of sampling errors or laboratory errors. By simply repeating the Papanicolau test, one may not achieve the maximum desired outcome. The aim of any screening program should be to increase the case detection rate by using various techniques or methods whenever possible. One such approach may be to screen clinically abnormal or suspicious cervices in patients with negative Papanicolau smear test results by using better modalities, such as colposcopy. This approach is possible in institutions that serve a large number of referral patients as is the case in the Jawaharlal Institute of Postgraduate Medical Education and Research.

A prospective study undertaken recently that aimed to determine the incidence of CIN using conventional Papanicolau test in “unhealthy” and healthy cervices concluded that there was no difference (statistical significance) in the incidence of CIN although there was an increased incidence in patients with “unhealthy” cervix.² The present study did not evaluate patients with cervices that were healthy in appearance. Colpscopic evaluation of patients with “unhealthy” or grossly abnormal cervices showed a significantly high proportion of CIN and invasive cancer. A multicenter study evaluating the sensitivity of Papanicolau testing revealed that the sensitivity of the cytology for detection of high-grade lesions was 57%.³ The results of that study indicated that specificity in the range of 90%–95% corresponded to a sensitivity of 20%–35%. This analysis pointed toward the search for a more optimal method of screening.³

The major focus of colposcopic assessment is to detect cancer. To accomplish this goal, one must maintain a high index of suspicion. The colposcopist should be aware of the hallmark features of invasive cancer and look for these features in each patient who is evaluated. Colposcopically, cervical cancer can be a challenge to diagnose—especially in cases of microinvasive cancer, because atypical vessels or other signs of more-advanced disease may not be present. This reinforces the fact that one must maintain a high degree of suspicion and address effectively any discrepancies among colposcopy, cytology, and histology before therapy is initiated.⁴

Signs and symptoms that may suggest cervical cancer are intermenstrual bleeding, postcoital bleeding, postmenopausal bleeding, abnormal appearance of the cervix (suspicion of malignancy), bloodstained vaginal discharge, and pelvic pain. A women presenting with these symptoms and who has negative cytology has a greatly reduced risk of cervical cancer compared to a woman with positive cytology, but the risk is not entirely eliminated.¹ Hence there is a good rationale for undertaking evaluation of any patient who has an “unhealthy” or grossly abnormal cervix, even according to the latest guideline, and even when the patient's Papanicolau test is negative for SIL or carcinoma. Few authorities are also of the opinion that using colposcopy to evaluate “unhealthy cervix” is indicated when a patient's Papanicolau test is negative.⁵

“Unhealthy cervix” includes any one of a group of chronic conditions that affect the cervix, including chronic cervicitis, endocervicitis, erosions, lacerations, eversions, polipi, leukoplakia, and basal-cell hyperplasia. These conditions produce symptoms, and there is evidence that some patients may be harboring premalignant lesions.⁶ Cervical erosion was found to be associated with mild dysplasia in 9.75% of cases and severe dysplasia in 2.43% of cases in a cross-sectional study, undertaken in India, that used cytology.⁷ A combination of visual inspection with acetic acid (VIA) and HPV DNA was proposed to be the best screening test for premalignant and malignant lesions of the cervix for patients in developing countries; however, one cannot rely on this for treatment purposes, as the false-positive rate is high, resulting in overtreatment of 5 women for every single positive case.⁸ Ultimately, histopathologic examination, especially biopsy of abnormal areas, is the gold standard for arriving at an accurate diagnosis. In a prospective study that compared Papanicolau testing and colposcopic biopsy for screening for CIN and cervical cancer in symptomatic patients with “unhealthy” cervix, colposcopy was found to be more sensitive, with the case detection rate being four times higher than cytology.⁹ In the present study, when Papanicolau smears were negative for SIL, colposcopy detected 24% cases of CIN and 5.34% cases of invasive cancer. Cervical lesions, such as suspicious and “unhealthy” cervix and persistent vaginal discharge, were found to be contributing factors for progression of SIL in a study that aimed to discover the risk factors for progression of CIN. The researchers involved in this study suggested treating mild cervical lesions and persistent vaginal discharge to avoid or reduce the rate of progression to CIN.¹⁰

Conclusions

It is important to subject women who have an “unhealthy cervix” without an abnormal Papanicolau test report to colposcopy, as a significantly high proportion of them can harbor preinvasive and/or invasive cancer.

Disclosure Statement

No competing financial conflicts exist.

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