Referral Smear Research Articles

Relevance of Human Papillomavirus Screening in Management of Cervical Intraepithelial Neoplasia

Abstract OBJECTIVE: To evaluate the utility of human papillomavirus detection in identifying women with abnormal Papanicolaou smears who can be safely followed up with cytologic study only, we conducted a study to determine the sensitivity, specificity, and negative and positive predictive values of a Food and Drug Administration–approved human papillomavirus test kit for detection of cervical intraepithelial neoplasia in colposcopically directed biopsy specimens. STUDY DESIGN: We enrolled women with abnormal Papanicolaou smears referred to a colposcopy clinic serving indigent patients. All 1128 women had a referral Papanicolaou smear, a clinic Papanicolaou smear, and a sample for human papillomavirus deoxyribonucleic acid test; 1075 underwent colposcopically directed biopsies and endocervical curettage. We used the HPV Profile kit for human papillomavirus testing. RESULTS: Of 486 women with low-grade squamous intraepithelial lesions on Papanicolaou smear, 35.4% had high-risk human papillomavirus deoxyribonucleic acid detected, and of 592 with high-grade lesions, 44.4% had high-risk human papillomavirus detected. Among 527 women with biopsy specimens showing cervical intraepithelial neoplasia and in 267 with cervical intraepithelial neoplasia grades 2 or 3, 38.7% and 56.2% had high-risk human papillomavirus deoxyribonucleic acid detected. However, the sensitivity of human papillomavirus deoxyribonucleic acid detection to identify biopsy-confirmed cervical intraepithelial neoplasia grades 2 or 3 was 55.7%, and the positive predictive value of the test was only 34.9%. CONCLUSION: Human papillomavirus appears to be causally associated with cervical cancer but human papillomavirus screening does not appear to be of value to identify women with abnormal Papanicolaou smears who can be safely followed up with cytologic study alone. (Am J Obstet Gynecol 1997;176:87-92.)

Cervical infection with human papillomaviruses and cervical dysplasia in Norwegian women

SummaryCervical cancer incidence rates have started to increase in Norway and more data are needed on the prevalence of human papillomavirus (HPV) in women with dysplasia and cervical cancer. We attempted to determine the prevalence and types of HPV in women referred for cervical dysplasia. and correlated the HPV status of the cervical smear with the histological findings. We collected follow-up data on progression in a subgroup of women with dysplasias and high-risk HPV-DNA on their referral cytological smear. but with normal histology. One hundred and ninety-four women with an atypical Papanicolaou smear were included. For HPV-DNA detection the Virapap/Viratype method was used. Biopsy was carried out in all patients. HPV was detected in 82 (42·3 per cent) and high risk (16/18 and/or 31/33/35) HPV-DNA in 77 (39·7 per cent) of the patients. High-risk HPV was detected in the cervical cells in 63 152·9 per cent) of 121 women with histological CIN Ill, and in 13 of 73 (17·8 per cent) women with lower grades ...

The Role of Cervical Cytology in the Detection of Adenocarcinoma and Glandular Intraepithelial Neoplasia of the Cervix –A Retrospective Study

SummaryThe predictive accuracies for cervical glandular intraepithelial neoplasia and adenocarcinoma from a cyto-logical finding of endocervical dyskaryosis were examined for 82 patients with endocervical dyskaryosis on a referral cervical smear and for 54 patients with histologically identified adenocarcinoma or cervical glandular intra-epithelial neoplasia.Glandular dyskaryosis on a smear had a positive predictive value for cervical glandular intra-epithelial neoplasia or adenocarcinoma of 60 per cent. If those cases in which the histology showed only cervical intra-epithelial neoplasia grades 2 and 3 were included, the positive predictive value rose to 91 per cent.The finding of glandular abnormality in a cervical smear is therefore highly predictive of significant underlying pathology.

The adequacy of the one-slide cervical smear in the detection of squamous intraepithelial lesions.

This prospective study evaluated the impact of replacing the two-slide cervical smear by a one-slide smear to detect squamous intraepithelial lesions (SIL). The study population consisted of 87 patients with biopsy-proven SILs, a "referral" (precolposcopy) two-slide cervical smear, and a "one-slide repeat" smear done at the time of biopsy. The detection rate of SIL was compared with that of a control group of 85 patients who fulfilled similar criteria; they had a two-slide referral smear, but a "two-slide repeat" smear. Smears nondiagnostic of SIL occurred in 5.7%, 11.8%, 27.6%, and 15.3% in the referral group of the study population, the referral group of the control population, the one-slide repeat smears, and the two-slide repeat smears, respectively. Statistical analysis showed a higher rate of nondiagnostic smears in the one-slide repeat smear (P = .05). Although this may be attributed to the less-than-optimal quality of the preparation, the above findings do not support the use of a one-slide technique for sampling the ectocervix and endocervix.

Large Loop Diathermy of the Transformation Zone: Is ‘See and Treat’ An Acceptable Option for the Management of Women with Abnormal Cervical Smears?

SummaryA total of J 39 women with dyskaryotic cervical smears, in whom the entire lesion could be visualised, were seen in the colposcopy clinic, and large loop diathermy of the transformation zone was performed, resulting in an over-treatment rate of 39 per cent. In 82 per cent of patients, a severely dyskaryotic referral smear resulted in a histologically proved lesion of CIN II or greater. Only 51 per cent of women referred with moderately dyskaryotic cervical smears had histologically proved CIN II or III. The results of further investigations, including repeat cervical smears, helped to improve the identification of high grade abnormalities in this second group, and would have reduced the over-treatment rate in this group. A ‘see and treat’ policy is an acceptable option for the management of women referred with severely dyskaryotic cervical smears, but if a woman is referred for colposcopy with a moderately dyskaryotic cervical smear, the policy of performing further investigations, including a repe...

Value of repeat cervical smears at the time of colposcopic biopsy.

At our institution, gynecologists perform Pap smears not only as an initial screening procedure but also at the time of colposcopy and biopsy. We compared the results of initial Papanicolaou (Pap) smears with those taken at colposcopic biopsy to determine if repeating the Pap smear at the time of colposcopy contributed to patient management. We found that repeat colposcopic smears often agreed with the referral smears and biopsies. When there was disagreement, the colposcopic smear was more often a lower grade than the referral smear and correlated best with the biopsy. Both referral and colposcopic smears underestimated the severity of cervical lesions with the same frequency. We could document only 5/414 (1.2%) colposcopic smears that contributed to patient care.

A retrospective analysis of 94 patients with CIN and false negative cervical smears taken at colposcopy.

This report investigates the reasons for false negative cervical cytology in 94 out of 630 patients (15%) in whom cervical intraepithelial neoplasia (CIN) was diagnosed on colposcopically directed biopsy. Cervical smears were taken immediately before biopsy and the cases with false negative cytology were compared with those whose cytology was abnormal. Patients with false negative cytology were more likely to have been younger (P < 0.01), to have had fewer pregnancies (P < 0.001), to have had a less severe grade of dyskaryosis on their referral smear (P < 0.001), to have had no endocervical cells on the smear (P < 0.05), to have had a less severe grade of CIN on biopsy (P < 0.001), to have had no punctation visible at colposcopy (P < 0.01), and to have had no mosaic pattern seen at colposcopy (P < 0.05). We found no effect attributable to the patient's menstrual history, the interval between referral smear and colposcopy clinic visit, the smear taker or the type of spatula used to take the smear.

Borderline nuclear abnormality in cervical smears: a cytological review of 200 cases with histological correlation.

The cervical cytology and histology specimens from 200 patients referred to colposcopy with borderline nuclear abnormality were reviewed. Human papillomavirus (HPV)-associated changes were identified in 103 of 200 (53%) referral smears and in 139 of 150 (91%) biopsy specimens. Cervical intraepithelial neoplasia (CIN) was less frequently diagnosed on review compared with the original histopathology reports (30.7% vs 45.4%); the discrepancy was largely attributable to a lower incidence of CINI. There was agreement in the grading of borderline nuclear abnormality in 161 of 200 referral smears following review. Twenty-three smears were upgraded to mild dyskaryosis, whereas 16 were reclassified as negative.

Should we report cervical smears lacking endocervical component as unsatisfactory?

The purpose of the study is to correlate the accuracy of diagnosis of cervical smears with the presence/absence of an endocervical component. The referral smears and the smears obtained during colposcopic examination of 84 patients with biopsy-proven squamous lesions were evaluated for the presence of an endocervical component, and the cytologic interpretations were compared with the histologic findings. Of the 136 smears containing an endocervical component, 111 (81.6 percent) had good correlation with histology and 25 (18.4%) showed a discrepancy. Of the 30 smears lacking an endocervical component, 24 (80%) had good histologic correlation and 6 (20%) were discrepant. Our data showed no significant difference in the detection of squamous lesions in those smears with an endocervical component from those without. We conclude that, although the presence or absence of an endocervical component should be documented in the cytology report, its absence should not be an indication to report the cervical smears as unsatisfactory.

Human papillomavirus type 16 DNA in cervical smears as predictor of high-grade cervical cancer

The management of women with mild to moderately dyskaryotic cervical smears would benefit from a non-invasive test that predicts which women have high-grade cervical intraepithelial neoplasia. Detection of human papillomavirus type 16 (HPV16) DNA in cervical smears may be such a test. With the polymerase chain reaction (PCR), we estimated the amount of HPV16 DNA in cervical smears from 85 women referred for colposcopy because of abnormal cytology. An intermediate or high amount of HPV16 DNA predicted the presence of high-grade cervical intraepithelial neoplasia in a subsequent biopsy in almost 90% of patients irrespective of the cytological grade of the referral smear. This technique may allow early identification of those women with low-grade cytological abnormalities who have high-grade underlying cervical disease

The accuracy of repeat cytology in women with mildly dyskaryotic smears

A special colposcopy clinic was established at the Royal Free Hospital to investigate women whose referral smears showed mild dyskaryosis. Of 200 women in the study, 66 (33%) had histologically proven CIN II or CIN III, 59 (29%) had CIN I or human papillomavirus changes, and 54 (27%) were considered normal. These findings demonstrate the importance of adequate diagnosis of this group of women. Of 143 women who had had a single mildly dyskaryotic smear, 45 (31%) had either CIN II or III. Age was not useful for predicting which women were at high risk of significant disease. Careful repeat cervical cytology correlated closely with the histological grade of the lesion. Repeat cytology was associated with an overall 24% false-negative rate, but most missed lesions were of low grade. Repeat cytology correctly identified 82% of all CIN lesions, and 93% of the most significant lesions (CIN II and III). Women who have a mildly dyskaryotic smear followed by a negative smear should not be considered normal, but careful repeat cytology can be considered a reasonably safe practice.

Referral for Colposcopy: Do Our Present Criteria Need Reviewing?

Three hundred and seven women referred to a colposcopy clinic over an 11-year period with mildly atypical cervical cytology had a histological diagnosis established by colposcopically directed biopsy. Of the 256 women who had dyskaryosis on the referral smear, 176 (68.8%) had cervical intraepithelial neoplasia (CIN) grade II or III on histology. One woman had microinvasive carcinoma. Fourteen (27.5%) of the 51 women without dyskaryosis had CIN II or III. Of smears taken at the time of colposcopy, 28.9% had normal cytology, although over one third of these women had CIN II or III diagnosed on histology at that time. This poor correlation of mildly atypical cervical cytology and histology suggests that the common practice of relying on cytology alone for the surveillance of women who have already had an atypical smear should be discouraged.

DOES MILD ATYPIA ON A CERVICAL SMEAR WARRANT FURTHER INVESTIGATION?

228 women referred to a colposcopy clinic over a 10-year period with mildly atypical cervical cytology had a histological diagnosis established by colposcopically directed biopsy. Of the 187 women (82.0%) who had dyskaryosis on the referral smear, 129 (69%) had cervical intraepithelial neoplasia (CIN) grade II or III on histology, as did 12 (29.2%) of the 41 women without dyskaryosis. 27.6% of smears taken at the time of colposcopy had normal cytology, although a third of these women had CIN II or III diagnosed on histology at that time. The poor correlation between mildly atypical cervical cytology and histology suggests that the practice of relying on cytology alone for the surveillance of women who have already had an atypical smear should be discouraged.