Colposcopic Cervical Biopsy Research Articles

Discrepancy in the interpretation of cervical histology by gynecologic pathologists

OBJECTIVE:To determine if subspecialty review of cervical histology improves diagnostic consensus of cervical intraepithelial neoplasia (CIN).METHODS:After routine histologic assessment within the hospital pathology department, 119 colposcopic cervical biopsies were interpreted by two subspecialty-trained gynecologic pathologists (GYN I and GYN II) blinded to each other’s interpretations and to the interpretations of the hospital general pathologists (GEN). Biopsies were classified as normal (including cervicitis), low grade (LG, including CIN I and human papillomavirus changes), and high grade (HG, including CIN II/III). The interobserver agreement rates between GEN and GYN I, between GEN and GYN II, and between GYN I and GYN II were described using the κ statistic. The proportions of biopsies assigned to each biopsy class were compared using McNemar test.RESULTS:Interobserver agreement rates between GEN and GYN I were moderate for normal (κ = 0.53) and LG (κ = 0.46) and excellent for HG (κ = 0.76). There were no significant differences in the classifications between GEN and GYN I. Interobserver agreement rates between GEN and GYN II were moderate for normal (κ = 0.50) and LG (κ = 0.44) and excellent for HG (κ = 0.84). Also, GYN II was significantly more likely to classify biopsies as normal (P < .001) and less likely to classify biopsies as LG (P < .001). The interobserver agreement rates between GYN I and GYN II were moderate for normal (κ = 0.61) and LG (κ = 0.41) and excellent for HG (κ = 0.84). Also, GYN II was significantly more likely to classify biopsies as normal (P < .001) and less likely to classify biopsies as LG (P = .01).CONCLUSION:Interobserver agreement between two gynecologic pathologists was no better than that observed between general and gynecologic pathologists. Subspecialty review of cervical histology does not enhance diagnostic consensus of CIN.

Repeat Cervical Cytology at the Time of Colposcopy

To determine if repeating the Pap smear (PS) at colposcopy offers added benefit in the detection of cervical squamous intraepithelial lesions (SILs). Eight hundred fifty-two women were subjects of this study. Patients with cervical SIL were defined as women with SIL on the repeat PS, or SIL on the colposcopic cervical biopsy (bx) or a negative repeat PS and bx but confirmed SIL on both the previous and follow-up PS or bx. The sensitivities of repeat PS and bx in detecting SIL were calculated. The chi 2 test was used to assess statistical significance. The total cost of repeating the PS was calculated by multiplying the total number of patients (852) by the estimated cost of a single PS ($25). The sensitivities of repeat PS, bx and PS/bx combined were .89, .69 and .92 for low grade SIL (LSIL) and .74, .77 and .98 for high grade SIL (HSIL), respectively (P < .0001). Sixteen percent of the HSIL and 28% of the LSIL cases were diagnosed on repeat PS only (negative bx). If repeat PS was omitted, $21,300 would have been saved.

Ineffectiveness of Topical Benzocaine Spray During Colposcopy

BACKGROUND Colposcopic evaluation can cause patients to experience pain and anxiety. This study investigated the use of benzocaine spray, a topical anesthetic, and its effects on pain and anxiety associated with colposcopy and colposcopic biopsy. METHODS The study was a double-blind, placebo-controlled trial of the effectiveness of benzocaine spray applied to the cervix immediately before colposcopic examination, cervical biopsy, or endocervical curettage in patients of a family practice center. Prior to the gynecologic procedure the patient's cervix was sprayed with either benzocaine spray or matching placebo spray. After waiting at least 30 seconds the clinician started the procedure. Pain and anxiety, measured on 10-cm visual analog scales, were determined at the following times: (1) before the start of the gynecologic examination; (2) immediately before using the spray; (3) immediately after using the spray; and, (4) after the procedure was completed. RESULTS Of 58 consecutive patients who underwent colposcopy, 36 patients were eligible for the trial and were evaluated. Participants were similar to patients not participating with regard to race, gravidity, and parity. Statistical analysis found significant differences in both pain and anxiety scores over time (repeated measures multivariate ANOVA, P < .0001), but no difference between the use of active drug and placebo. Pain scores increased significantly after application of either benzocaine or placebo spray before the start of the procedure (average increase 1.3 cm, P < .0001). CONCLUSIONS Benzocaine, in a spray vehicle, confers no benefit when used to decrease pain and anxiety in women undergoing colposcopic procedures.

The Cytological Prediction of Cervical Intraepithelial Neoplasia In Colposcopically Directed Biopsies

The tissue sections and preceding cervical smears of 1262 women who had colposcopic cervical biopsies were reviewed and the reports correlated. Close correlation between the cytological and histological findings, to within one histological grade of cervical intraepithelial neoplasia (CIN), was noted in 86% of cases. However, the biopsy was negative, or contained evidence of wart virus infection only, in 24% of cases where dyskaryotic cells had been observed in the cervical smear. Of particular concern was the fact that negative histological findings were recorded in 13% of cases where the smear contained cells showing a moderate dyskaryosis and in 1.26% of cases where the smear showed severe dyskaryosis. This suggests that colposcopically directed biopsies do not always reflect the underlying pathological changes in the cervix. Management of these cases is discussed. In 45 women with a normal cervical smear prior to biopsy, histology revealed seven cases of CIN 3 and one case of invasive squamous carcinoma. This indicates that referral for colposcopy is advisable whenever there is clinical suspicion of cancer, even if the cervical smear report is normal.

Demonstration of Chlamydia trachomatis in colposcopic cervical biopsy specimens by an immunoperoxidase method.

A total of 31 cervical biopsy specimens were taken from 29 women attending a genitourinary medicine clinic, nine women (11 biopsy specimens) were known to have Chlamydia trachomatis cervicitis and 20 women were known to be free of chlamydial infection. The specimens were routinely processed to paraffin wax and stained by an anti-Chlamydia immunoperoxidase technique to localise the organisms. Of the 11 positive biopsy specimens three showed positive staining of elementary/reticulate bodies. In one case the surface endocervical cells showed large inclusions which were packed with chlamydial bodies. The diagnosis of chlamydial infection is difficult to make clinically and in routine cytological and histological specimens but immunoperoxidase staining can clearly identify C trachomatis inclusions in cervical biopsy specimens provided infection is severe.

Cytologic diagnosis of human papillomavirus infection: Spindled nuclei

The classic cytologic criteria, koilocytotic atypia and dyskeratocytosis, fail to identify most cases with colposcopic and histologic evidence of cervical condylomata. The purpose of this study was to identify a novel cytologic diagnostic criterion, spindled nuclei, to predict the presence of human papillomavirus (HPV) infection of the cervical epithelium. Review of the hospital records of 100 consecutive cases with spindled nuclei on Papanicolaou smear identified 36 patients in whom a colposcopic examination and/or cervical biopsy had been performed between January 1, 1988, and March 31, 1989. Ninety-seven percent of these 36 cases were positive by colposcopy and 89% of the cases were positive by cervical biopsy for changes of condyloma or intraepithelial neoplasia. HPV DNA hybridization in situ was positive in 16 of 36 patients, and the probe for types 31/33/35 most often stained histologic sections showing condylomatous change without concurrent dysplasia. Electron microscopy of spindled nuclei showed evidence of HPV-type viral particles in the five cases examined.

Reporting cervical intra‐epithelial neoplasia (CIN): Intra‐ and interpathologist variation and factors associated with disagreement

Eight histopathologists, based at different hospitals, who had previously examined 100 consecutive colposcopic cervical biopsies were circulated with the results of the initial study. The slides were then 'reblinded' and re-examined by the pathologists who, as before, assigned them into one of six diagnostic categories. The degree of interpathologist agreement for the seven observers who returned usable responses was characterized by kappa statistics and compared to the corresponding figures for the same observers from the previous study. Although some of the observers showed significant alterations in their diagnostic practices there was persistent poor agreement for CIN 1 and 2, mediocre agreement for CIN 3 and excellent agreement for invasive carcinoma. Intra-observer agreement was consistently better than inter-observer agreement for each of the diagnostic categories. Significant differences were found among observers in the degree of intra-observer variability. The 20 cases in which there was most disagreement were re-examined by one of the authors who compared these with 20 biopsies which caused little disagreement. Disagreement was considered to be associated with florid papilloma-virus changes, basal cell hyperplasia and severe inflammation in varying combinations. On the basis of these findings we suggest changes in the terminology of CIN lesions.

Observer variation in histopathological diagnosis and grading of cervical intraepithelial neoplasia.

To assess the variability among histopathologists in diagnosing and grading cervical intraepithelial neoplasia eight experienced histopathologists based at different hospitals examined the same set of 100 consecutive colposcopic cervical biopsy specimens and assigned them into one of six diagnostic categories. These were normal squamous epithelium, non-neoplastic squamous proliferations, cervical intraepithelial neoplasia grades I, II, and III, and other. The histopathologists were given currently accepted criteria for diagnosing and grading cervical intraepithelial neoplasia and asked to mark their degree of confidence about their decision on a visual linear analogue scale provided. The degree of agreement between the histopathologists was characterised by kappa statistics, which showed an overall poor agreement (unweighted kappa 0.358). Agreement between observers was excellent for invasive lesions, moderately good for cervical intraepithelial neoplasia grade III, and poor for cervical intraepithelial neoplasia grades I and II (unweighted kappa 0.832, 0.496, 0.172, and 0.175, respectively); the kappa value for all grades of cervical intraepithelial neoplasia taken together was 0.660. The most important source of disagreement lay in the distinction of reactive squamous proliferations from cervical intraepithelial neoplasia grade I. The histopathologists were confident in diagnosing cervical intraepithelial neoplasia grade III and invasive carcinoma (other) but not as confident in diagnosing cervical intraepithelial neoplasia grades I and II and glandular atypia (other). Experienced histopathologists show considerable interobserver variability in grading cervical intraepithelial neoplasia and more importantly in distinguishing between reactive squamous proliferations and cervical intraepithelial neoplasia grade I. It is suggested that the three grade division of cervical intraepithelial neoplasia should be abandoned and a borderline category introduced that entails follow up without treatment.

Genito‐urinary approach to the management of colposcopic abnormalities of the cervix

SummaryOne hundred and fifty nine patients with abnormal cervical cytology were studied by colposcopy and histologically. Fifty six were attending the Department of Genito‐Urinary Medicine, 103 were referred from elsewhere. The STD clinic patients were younger (73 per cent under the age of 29 years) and 89 per cent had a satisfactory colposcopy. The incidence of cervical intra‐epithelial neoplasia (C1N) for both groups was 87 per cent. This was associated with human papilloma virus in 35 per cent of cases. Treatment by laser vaporisation for CIN with koilocytic change was 100 per cent successful, probably due to the screening and treatment of sexual partners. A distinct genitourinary approach to these patients is suggested. Patients with an unsatisfactory colposcopy (with evidence of CIN) should be referred to the gynaecologist for cone biopsy and treatment without any further investigations such as colposcopic cervical biopsies in the STD clinic. Patients with a satisfactory colposcopy may be investigated, treated and followed‐up in the STD clinic.