Human papillomavirus (HPV) in an Icelandic population: correlation of HPV DNA to cyto- and histopathologic lesions and evaluation of treatment strategies

This study is based on 100 cases with cervical intra-epithelial neoplasia (CIN) smears referred for colposcopy and 200 controls with normal smears. The study analyses (a) the frequency of different grades of CIN and koilocytotic lesions among the cases based on cyto- and histopathologic findings; (b) the frequency of human papillomavirus (HPV) among the cases with Virapap/Viratype (V/V) in biopsies vs swabs and among the controls with V/V and polymerase chain reaction (PCR) in swabs; (c) the frequency of the HPV types according to the grade of CIN. Among the cases koilocytotic lesions were found in 98% of the biopsies and 27% of the smears. High-graded smears and high-risk viruses had at entry a positive predictive value (PPV) of 80% and 88% respectively and a sensitivity of 72% for histologically verified high-graded CIN lesions. Both tests combined increased the sensitivity to 88%. The false-negative rate of colposcopy was 3% and the undergraded rate of CIN I and unclassified CIN smears for histologically verified CIN II–III was 62%. Among the cases the rate of HPV positive tests increased with a higher CIN grade. Cytology and colposcopy are complementary for the diagnosis of CIN and the swabs and biopsies for the diagnosis of HPV. Among the cases the rate of HPV-positive tests with V/V was 62% (97% high-risk viruses) and among the controls 5.5% (78% high-risk viruses). Among the controls the frequency of HPV occurrence with PCR was 11.2% and decreased with older age. The therapeutic conclusions are that the high-graded CIN lesions should receive ablative treatment irrespective of HPV typing, whereas low-graded lesions with high-risk viruses should be treated or observed closely.     

Contribution of human papillomavirus testing by hybrid capture in the triage of women with repeated abnormal pap smears before colposcopy referral

OBJECTIVE: The purpose of this work was to evaluate the ability of testing for high-risk human papillomavirus (HPV) types using the hybrid capture technique to predict the presence of cervical intraepithelial neoplasia (CIN) II,III in patients with repeated atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LGSIL) on Pap smears. METHODS: Hybrid capture testing and tissue biopsy were performed on 503 consecutive women with ASCUS or LGSIL on repeated Pap smears who were referred for colposcopy. RESULTS: A highly significant association (P < 0.0001) was found between a positive test for high-risk HPV types and CIN II,III, with an 87.0% positive predictive value and a 95.7% negative predictive value. In 226 women with ASCUS on repeated Pap smears, a positive test for high-risk HPV types had a 85.7% sensitivity and a 97% specificity for CIN II,III. In 277 patients with LGSIL on repeated Pap smears, a positive test for high-risk HPV types had an 88.2% sensitivity and a 94.7% specificity for CIN I,II. Reserving colposcopy examination for women who were positive for high-risk HPV types would have reduced the number of referrals for colposcopy to 24.6% and maintained a sensitivity of 87.0% for CIN II,III. CONCLUSIONS: A positive hybrid capture test for high-risk HPV types was highly sensitive and specific for the presence of CIN II,III in patients with ASCUS and LGSIL on repeated Pap smears. We believe that improved methodology will eventually enable more selective colposcopy referrals without affecting patient safety among these women.     

Diagnosing human papillomavirus of the female lower genital tract: failure of the Pap smear as a sole screening test

Of 197 patients referred for colposcopy who underwent repeat Pap smears and colposcopic biopsies (when indicated), histologic evidence of human papillomavirus (HPV) infection involving the endocervix, cervix, or vagina or all three sites was documented in 109 biopsies. Sixty-six (61%) had normal Pap smears at the time of colposcopy. Despite a specificity of 92% for detecting HPV, the Pap smear demonstrated a low sensitivity (39%), with a positive and negative predictive test value of 88% and 50%, respectively. In patients with biopsies revealing HPV infection without associated dysplasia, false negative Pap smears were found most often in women with strictly vaginal HPV (74%) (P less than 0.05), followed by those with coexistent cervical and vaginal HPV (65%), and then by those with solely cervical HPV (51%). We question the use of the Pap smear for the detection of lower genital tract HPV, particularly in patients with only vaginal involvement, especially when the smear is repeated at the time of colposcopy. Benefits and disadvantages of other screening tests for HPV are discussed.     

Long term progress of low-grade intraepithelial lesions after a smear and colposcopy, directed biopsies and/or normal endocervical curettage

Low-grade squamous intraepithelial lesions and atypical squamous cells of undetermined significance are the most frequent cytologic abnormalities. Their management is still highly controversial because of the many uncertainties associated with them concerning their histology and their natural history. Cervical smears HPV testing were proposed as an alternative to colposcopy. Neither have a sensitivity equivalent to that of colposcopy. The diagnosis of these abnormalities could be delayed, and a severe lesion may even remain undetected because the cytologic surveillance is frequently omitted, smear sensitivity is far from being perfect and correlation is poor between cytology and histology. The combination of smears with the detection of high risk HPV types increases the triage sensitivity before colposcopy to the detriment of specificity and predictive value, and, therefore, of cost. With colposcopy the histologic diagnosis is rapidly reached and therapeutic management becomes easier because the size and location of the lesion are precisely known. However, the long-term outcome of patients with a normal colposcopy is very poorly known. Our study including 212 patients with a mean follow-up of 79 months, showed an incidence of lesions similar to that found in a control group; 12 CIN (5.7%) were identified, but no cancer. The prevalence of CIN was significantly lower in patients whose initial colposcopy was normal or became normal within the first six months that in patients whose control smear was normal or became normal within six months (1/81 = 1.2% versus 8/143 = 5.6%; P > 0.05). No lesions were observed in patients whose colposcopy and control smear were normal. These results confirm the reliability of colposcopy in patients with minor cytologic abnormalities.     

Human papillomavirus type 16 and 18 detection in the management of mild dyskaryosis.

OBJECTIVE: To determine if semi-quantitative human papillomavirus (HPV) types 16 and 18 detection by polymerase chain reaction can increase the sensitivity and specificity of repeat cytology alone for underlying high grade cervical intraepithelial neoplasia (CIN). DESIGN: Prospective randomised study of immediate treatment and surveillance. SETTING: A dedicated colposcopy clinic serving a regional population. SAMPLE: Three hundred and four women with smears reported as mild dyskaryosis. METHODS: Repeat cytology, HPV 16 and 18 tests, and colposcopy were performed at study entry. Women were randomised to either immediate treatment or surveillance with repeated tests at 6 and 12 months. Unless all study smears were negative, women were treated at study exit by large loop excision of the transformation zone. MAIN OUTCOME MEASURES: Sensitivity and specificity of HPV testing for types 16 and 18 in conjunction with cytology for high grade CIN. RESULTS: Combining repeat cytology with HPV 16 and 18 testing had a sensitivity of 94% and a specificity of 26%, a positive predictive value of 71%, and a negative predictive value of 71%, for underlying high grade CIN. If used to secondary screen in conjunction with repeat cytology for mild dyskaryosis, 88% of women would have been referred for colposcopy on the basis of either test being positive. CONCLUSION: Combining repeat cytology and HPV 16 and 18 detection would result in the majority of women being referred for immediate colposcopy. Taken with an overall default rate of 17%, immediate referral of all women with mild dyskaryosis for colposcopic assessment still appears to be a more effective clinical strategy.     

Human papillomavirus type 16 and 18 detection in the management of mild dyskaryosis

Objective To determine if semi-quantitative human papillomavirus (HPV) types 16 and 18 detection by polymerase chain reaction can increase the sensitivity and specificity of repeat cytology alone for underlying high grade cervical intraepithelial neoplasia (CIN).
Design Prospective randomised study of immediate treatment and surveillance.
Setting A dedicated colposcopy clinic serving a regional population.
Sample Three hundred and four women with smears reported as mild dyskaryosis.
Methods Repeat cytology, HPV 16 and 18 tests, and colposcopy were performed at study entry. Women were randomised to either immediate treatment or surveillance with repeated tests at 6 and 12 months. Unless all study smears were negative, women were treated at study exit by large loop excision of the transformation zone.
Main outcome measures Sensitivity and specificity of HPV testing for types 16 and 18 in conjunction with cytology for high grade CIN.
Results Combining repeat cytology with HPV 16 and 18 testing had a sensitivity of 94% and a specificity of 26%., a positive predictive value of 71%, and a negative predictive value of 71%, for underlying high grade CIN. If used to secondary screen in conjunction with repeat cytology for mild dyskaryosis, 88% of women would have been referred for colposcopy on the basis of either test being positive.
Conclusion Combining repeat cytology and HPV 16 and 18 detection would result in the majority of women being referred for immediate colposcopy. Taken with an overall default rate of 17%, immediate referral of all women with mild dyskaryosis for colposcopic assessment still appears to be a more effective clinical strategy.     

Diagnosis of cervical intraepithelial neoplasia and human papillomavirus infection: punch biopsy versus cervical smear

Summary In 102 patients referred to our colposcopy clinic because of one to three Papanicolaou smears indicating cervical intraepithelial neoplasia (CIN) and/or abnormal colposcopy, routine smears and colposcopically directed punch biopsies were taken simultaneously. For detection and typing of human papillomavirus (HPV)-DNA in situ hybridization was performed in all biopsies and in 46 of the cervical smears. In cases of dysplastic lesions the number of HPV 16/18 (40.5%) and 31/33 (42.9%) was markedly higher than HPV 6/11 (16.6%) infection rate. In cases where simultaneous in situ hybridization in biopsy specimen and cervical smears was performed 21.7% showed a HPV negative smear and a positive biopsy, in 6.5% the results were the other way round. In 34.9% of cases with CIN I and 9.5% of cases with CIN II verified by punch biopsy the cytological smear did not indicate dysplasia. Our data show that mild and moderate CIN lesions of the cervix as well as HPV infection are detected more frequently by a combination of cervical smear and colposcopically directed punch biopsy than by cervical smear alone.     

Prospective follow-up suggests similar risk of subsequent cervical intraepithelial neoplasia grade 2 or 3 among women with cervical intraepithelial neoplasia grade 1 or negative colposcopy and directed biopsy

OBJECTIVE: The purpose of this study was to determine the risk of cumulative cervical intraepithelial neoplasia (CIN) grade 2 or 3 according to initial colposcopy and directed biopsy results among women with low-grade squamous intraepithelial lesions (LSIL) or human papillomavirus (HPV) DNA positive atypical squamous cells of undetermined significance (ASCUS). STUDY DESIGN: A 2-year follow-up of 897 cases of LSIL and 1193 cases of HPV DNA positive ASCUS from the ASCUS/LSIL Triage Study was used to simulate American Society for Colposcopy and Cervical Pathology Consensus Conference recommendations. Women with CIN grade 1 or less were followed up for 2 years by semiannual cytologic examination, with universal exit colposcopy. The clinical end point was a cumulative clinical center histologic diagnosis of CIN grade 2 or 3. RESULTS: The cumulative risk of CIN grade 2 or 3 was equivalent for LSIL (27.6%) and HPV positive ASCUS (26.7%). After excluding the women with a diagnosis of CIN grade 2 or 3 at initial colposcopy and directed biopsy (17.9%), the remaining women were at nearly identical risk for subsequent CIN grade 2 or 3 regardless of initial colposcopy result (completely negative colposcopy-11.3%; negative colposcopically directed biopsy-11.7%; and CIN grade 1 biopsy-13.0%). CONCLUSION: LSIL and HPV positive ASCUS are clinically equivalent. Initial colposcopic detection of obviously prevalent CIN grade 2 or 3 reduces risk. However, for the remaining women who have CIN grade 1 or less on colposcopy and directed biopsy, the risk for subsequent CIN grade 2 or 3 (whether missed, prevalent, or truly incident) is approximately 12% over 2 years. This risk does not vary meaningfully by initial distinction of histologic CIN grade 1 from negative colposcopy and biopsy.     

Analysis of outcome in women with borderline glandular change on cervical cytology

Objective

To review the outcome of women presenting with borderline glandular smear on cervical cytology and to investigate correlation between cytology, colposcopy and histology and subsequent smear history.

Study design

A 5 year retrospective analysis of outcome in all women reported with borderline glandular changes on cytology between 2001 and 2005 at the John Radcliffe Hospital, Oxford, and Cheltenham General Hospital, Gloucestershire, was performed. Cytology, colposcopy, histology and follow-up cytology data at 6, 12 and 24 months after index smear were collated.

Results

Of 92 women with borderline glandular smears, 56 were referred for colposcopy. This accounts for 0.9% of the total referral (6293) to the colposcopy units. A significant rate of abnormal histology was noted, with CIN 1, 2, 3, CGIN or worse in 20 women (36%) and benign pathology in 18 women (32%). Colposcopy had a sensitivity of 82%, specificity of 39%, negative predictive value of 80% and positive predictive value of 49% in predicting abnormal (premalignant/malignant) histology. Only one woman with normal histology at presentation had subsequent abnormal cytology (1/31), whereas abnormal histology at presentation was strongly associated with subsequent abnormality on follow-up cytology over 24 months (8/21) with a p value = 0.0058.

Conclusion

Colposcopic examination and biopsy of colposcopically identified abnormalities is reliable, with negative colposcopy having a high negative predictive value. We also recommend thorough colposcopic examination before any invasive investigation as over treatment may impact on the future reproductive outcome [1].     

Biopsy correlates of abnormal cervical cytology classified using the Bethesda system

OBJECTIVE: The goal of this study was to determine the colposcopic findings underlying cytologic abnormalities classified according to the Bethesda system. METHODS: Women undergoing colposcopy for abnormal cytology at an urban teaching hospital between July 1, 1996 and December 31, 1999 had Papanicolaou smears repeated. Results were compared both with biopsy histology and with the worst histology reported after 8-26 months of follow-up. kappa statistics and Spearman's rho were calculated to determine the degree of agreement. RESULTS: Colposcopy was performed for 2263 (94%) women. Referral and repeat Pap smears were reported identically in 493 (25%) of the 1962 women with results for both. No AGUS (atypical glandular cells of uncertain significance) smears were confirmed on repeat smear, and after excluding AGUS, agreement within one grade was found in 1305 of 1854 (70%). Among the 1842 women with squamous cytologic abnormalities, biopsy revealed a lesion more severe than that suggested by referral cytology in 577 (31%) and a less severe lesion in 648 (35%); exact correspondence was found in only 646 (35%). Of 317 women with ASCUS (atypical squamous cells of uncertain significance) on referral Pap smear, a negative repeat smear, and a specific biopsy result, 95 (30%) had true negative histology, while 148 (47%) had condyloma, 56 (18%) had cervical intraepithelial neoplasia (CIN) 1, 8 (3%) had CIN 2, 10 (3%) had CIN 3, and none had cancer. Comparison of repeat smear and colposcopic biopsy yielded a kappa statistic of 0.16. CONCLUSIONS: Cytology classified according to the Bethesda system does not accurately predict histologic diagnosis.     

Conservative management of the abnormal smear during pregnancy. A long-term follow-up

One hundred and thirty-two pregnant women who had a smear suggestive of cervical intra-epithelial neoplasia (CIN) II or more during the 10th to 12th gestational week, were followed with repeated smears and colposcopy every month and, when indicated, a colposcopically guided biopsy. Post-partum follow-up included cytology, colposcopy, portio biopsies and endocervical curettage. Seventy-nine women with normal findings post partum were checked once a year in a long-term study. A close correlation (71% of CINIII) was found between cytological and histological diagnoses in cases of persistent (three or more) abnormal smears. However, in women with regression of the cytological diagnosis, high frequencies of histologically verified CIN were found. Thus, 37.5% (18/48) of normal or CINI smears were histologically still CINIII. Histologically verified CIN during pregnancy, on the other hand, showed a post partum progression of two degrees or more of CIN in only two cases. Cytology seemed to be inappropriate post partum, with 23.3% smears which were normal or suggestive of CINI, when histology showed CINIII. In a long-term follow-up, 24% of women with a normal post partum follow-up for at least one year had a subsequent recurrence of CIN. It is concluded that follow-up of abnormal smears during pregnancy with repeated smears is not a reliable method. Post-partum follow-up should include at least colposcopy and a biopsy when indicated by the colposcopical examination. Women with a normal post partum follow-up constitute a high risk group for future recurrence of CIN and should be carefully followed for at least 5 years.     

Human papillomavirus screening for women with atypical Papanicolaou smears.

A study was undertaken to evaluate the utility of human papillomavirus (HPV) DNA screening and colposcopy in the management of women whose Papanicolaou smears demonstrated atypia less than dysplasia. Fifty patients whose initial Papanicolaou smears were interpreted as showing atypia less than dysplasia were evaluated for the presence of HPV 16 DNA in exfoliated cervicovaginal cells and for histologic findings on biopsy. Those 50 patients were compared to two groups of patients: one consisting of 124 patients with biopsy-documented cervical intraepithelial neoplasia (CIN) and another of 112 patients with normal Papanicolaou smears. The presence of HPV 16 DNA was confirmed with Southern analysis in 46% of patients with atypical Papanicolaou smears, 46% with confirmed CIN and 11.6% with normal Papanicolaou smears. The 50 patients with atypical smears underwent colposcopically directed cervical biopsies, revealing the following results: 14 (28%) had normal histology, 29 (58%) had koilocytosis without dysplasia, and 7 (14%) had CIN. HPV 16 DNA was present in exfoliated cervicovaginal cells from a large percentage of patients from each category (50% of patients with normal histology, 41.2% with koilocytosis and 57% with CIN). HPV 16 DNA screening did not predict which patients with atypical smears had underlying CIN. Colposcopically directed biopsy remains the evaluation method of choice.     

Managing atypical squamous cells of undetermined significance in Papanicolaou smears

OBJECTIVE: To assess strategies using repeated conventional Pap smear and human papillomavirus (HPV) DNA testing, alone or in combination, for identifying women with concomitant cervical intraepithelial neoplasia 2 and 3 (CIN 2/3) in women with atypical squamous cells of undetermined significance (ASCUS) in their Pap smears. STUDY DESIGN: A total of 360 women cytologically diagnosed with ASCUS were referred for colposcopy and underwent a repeat Pap smear, a biopsy when necessary and HPV testing using three different modes of detection of high-oncogenic-risk HPV types: 1, first-generation Hybrid Capture test (HC-1) (Digene Diagnostics, Gaithersburg, Maryland); 2, second-generation Hybrid Capture test (HC-2); and 3, polymerase chain reaction (PCR). RESULTS: Nineteen patients (5.3%) had histologic CIN 2/3. The sensitivity and specificity of the repeat Pap smear alone for the detection of CIN 2/3 were 73.7% and 62.9%, respectively, when referring all women with a repeat Pap smear using an ASCUS-positive threshold. The proportion of women referred for colposcopy was 39.0%. When HPV testing for high risk was used for identification of women with histologic CIN 2/3, sensitivity and specificity were, respectively, 68.4% and 85.9% for HC-1, 89.5% and 73.9% for HC-2 and 89.5% and 59.0% for PCR. The rate of referral for colposcopy of these three modes of HPV testing was 16.9%, 29.4% and 44.0%, respectively. The sensitivity and specificity for identification of women with concomitant CIN 2/3 using a combination of repeat cytology showing a low grade squamous intraepithelial lesion or high grade squamous intraepithelial lesion and/or a test positive for high-oncogenic-risk HPV group were, respectively, 94.7% and 73.2% when used in combination with HC-2. The referral rate of women for colposcopy of this combined strategy was 30.4%. CONCLUSION: As compared to the strategy using abnormal repeat Pap smear alone, those using high-risk HPV testing with Hybrid Capture showed statistically significantly higher specificities and lower proportions of women with ASCUS referred for colposcopy. In particular, a promising strategy would be to refer for colposcopy only women with repeat Pap smears showing squamous intraepithelial lesion and/or those positive for high-risk HPV detected by Hybrid Capture testing.     

Quantitative detection of oncogenic HPV DNA using hybrid capture to triage borderline and mildly dyskaryotic Papanicolaou smears

OBJECTIVE: To investigate the use of hybrid capture to triage borderline and mildly abnormal PAP smears to either colposcopy or continued cytological surveillance. METHOD: A prospective cross-sectional study of 207 women with either mild or borderline dyskaryosis referred to the colposcopy clinic at the Whittington Hospital, London was done. Quantitative detection of oncogenic human papillomavirus deoxyribose nucleic acid was performed using the solution hybridization technique Hybrid Capture I (Digene Diagnostics). Positive or negative hybrid capture results were compared to colposcopically directed punch biopsy or loop excision of the transformation zone. RESULTS: Hybrid capture correctly predicted 1/1 micro-invasive cancers, 23/24 CIN 3 and 20/24 CIN 2, giving a sensitivity to detect significant disease of CIN 2 or above of 90%. For CIN 1, 37/66 were HPV positive making the sensitivity to detect all grades of CIN 70%. Of women with a normal cervix, 39/92 were HPV positive and in total 58% of the women were HPV positive and would have been referred to colposcopy. CONCLUSIONS: Hybrid capture was a simple solution hybridization method which provided a sensitive method of detecting CIN 2 and above lesions in women with minor PAP smear abnormalities. However, the sensitivity for CIN 1 and the specificity were low, meaning that further improvements in the technique are needed before it can be used as a triage strategy.     

Inflammatory atypia on cervical smears. A diagnostic dilemma for the gynecologist

In light of the current controversy on the significance, follow-up and management of women with cervical smears showing "inflammatory atypia" (IA), a study was conducted to correlate the initial cytologic diagnosis of IA with the follow-up findings in colposcopically directed cervical biopsies and smears. From March 1988 through June 1989, 70 women had two consecutive smears reported as IA; all underwent colposcopy and cervical biopsy. In 58 patients (83%) the biopsies and smears obtained during colposcopy were negative for condyloma and/or cervical intraepithelial neoplasia (CIN). Ten patients (14%) had condylomas, and two (3%) had condylomas with CIN (one CIN I and one II). The initial IA smears from those 12 patients were reviewed retrospectively: 2 showed condylomas (they had been undercalled), 5 were "suggestive of condyloma" (the atypical cells were too few or poorly preserved for a definitive diagnosis), and 5 showed IA. None showed cytologic evidence of CIN, most probably because of sampling error. Our results suggest that colposcopy is warranted after two consecutive diagnoses of IA on cervical smears, considering that 17% of the patients in our study showed underlying intraepithelial lesions of the cervix.     

Cone biopsy: has endocervical sampling a role?

OBJECTIVE: To investigate the sensitivity, specificity and predictive value of endocervical sampling in women with abnormal cervical smears. DESIGN: A randomized study of two methods of endocervical sampling. SETTING: Colposcopy clinic at Aberdeen Royal Infirmary. SUBJECTS: 100 women with abnormal cervical smears selected for cone biopsy according to current colposcopy criteria. INTERVENTIONS: 53 women were randomized to have endocervical sampling with the Kevorkian curette and 47 to have sampling with the Medscand endocervical brush. MAIN OUTCOME MEASURES: Cytology and histology results from endocervical sampling compared with cone biopsy histology. RESULTS: The overall sensitivity of endocervical sampling was 56%, with a false negative rate of 44% and a negative predictive value of 26%. CONCLUSIONS: Endocervical sampling should not influence management when colposcopy is unsatisfactory.     

Human papillomavirus testing improves the accuracy of colposcopy in detection of cervical intraepithelial neoplasia

To assess the performance of human papillomavirus (HPV) testing and colposcopy in detection of cervical pathology. A series of 389 women referred for colposcopy due to an abnormal Pap smear had cervical swabs analyzed for oncogenic (high-risk [HR]) HPV types using Hybrid Capture II (HC2) assay. Loop electrical excision procedure cone biopsy (88%) or colposcopic biopsy (11%) was used as the gold standard. Of the atypical squamous cells of undetermined significance (ASCUS) smears, 48% were positive for HR HPV, as compared to 76.3% of low-grade squamous intraepithelial lesions (LSIL) smears. HR HPV was detected in 66.7% and 90% of patients with cervical intraepithelial neoplasia (CIN) 1 and CIN2 (or higher), respectively. The sensitivity of the Pap smear using an ASCUS threshold in detecting high-grade CIN was 94.5% (95% confidence intervals (CI): 91-97%) and that of colposcopy 98.5% (95% CI: 95-99%). The respective specificities were 30% (95% CI: 17-28%) and 35.6% (CI: 29-42%). HC2 test had comparable sensitivity, 90% (95% CI: 85-93%), but higher specificity, 54.3% (95% CI: 47-61%). Combining HC2 test with Pap increased specificity, 66.7% and 41.3% for ASCUS and LSIL cutoff, respectively. The minor-abnormality threshold together with HC2 increased specificity of colposcopy with no changes in sensitivity. High viral load (>100 relative light unit/positive control) was associated with significant disease. HPV DNA testing improves the accuracy of colposcopy in the detection of high-grade CIN in women with ASCUS or LSIL smears.     

'Abnormal' Papanicolaou smears and colposcopy in pregnancy: ante- and post-partum findings

Abnormal Papanicolaou smears and colposcopic findings suggesting human Papilloma virus (HPV) infection and cervical intraepithelial neoplasia (CIN) may occur during pregnancy. Condylomata acuminata often grow rapidly during pregnancy and may regress spontaneously following delivery. However, the post-partum outcome of the untreated ante-partum abnormal cytologic smear and colposcopy has not been defined clearly. Seventy-three pregnant patients were examined by colposcopy because of genital warts and/or abnormal Papanicolaou smears. Cytologic, colposcopic and histologic re-evaluation was conducted after delivery. Only one of the patients had a normal ante-partum colposcopic examination. This number increased to 15 after delivery. Forty-one patients had normal post-partum cytologic smears, but only 13 had normal histology. Abnormal post-partum cytology was highly predictive of abnormal colposcopy and histology. In contrast, normal post-partum cytology was not very accurate in predicting normal colposcopy and histology. It is concluded that a few pregnant patients may have partial regression of clinical HPV infection and abnormal cytology and colposcopy after delivery. However, the majority will continue to have abnormal findings 4 months following delivery in spite of normal post-partum cytology and even colposcopy.     

Prediction of cervical intraepithelial neoplasia grade 2-3 using risk assessment and human papillomavirus testing in women with atypia on papanicolaou smears

OBJECTIVE: To determine whether human papillomavirus (HPV) DNA testing and risk assessment can predict cervical intraepithelial neoplasia (CIN) 2-3 on biopsies in women with atypia on Papanicolaou smears. METHODS: One hundred ninety-five consenting women were referred for colposcopy because of atypia on Papanicolaou smears between September 1997 and April 1999. Before colposcopy, women completed risk assessments and had cervical swabs collected for HPV testing using the Hybrid Capture-II assay (Digene Corporation, Silver Spring, MD). Associations of demographic and clinical variables were assessed by chi(2) analysis, and logistic regression was used to assess factors associated with CIN 2-3. The cost-effectiveness of routine colposcopy versus reflex HPV testing by either conventional or liquid-based Papanicolaou smear media was compared. RESULTS: Cervical intraepithelial neoplasia was diagnosed in 70 of 195 women (35.9%), 55 (28.2%) with CIN 1 and 15 (7.7%) with CIN 2-3. High-risk HPV types were detected in 31.3% of all subjects, 36.4% of those with CIN 1, and 93.3% of those with CIN 2-3. By logistic regression, CIN 2-3 was associated only with detection of high-risk HPV (odds ratio 110.08, 95% confidence interval 8.35, 999. 00). The sensitivity of high-risk HPV for detecting CIN 2-3 was 93. 3%, specificity 73.9%, positive predictive value 23.0%, and negative predictive value 99.3%. The cost of reflex HPV testing using conventional smear or liquid-based media was less than routine colposcopy ($4809 and $4308, respectively, versus $4875 per case detected). CONCLUSIONS: Triage based on HPV testing would result in referral of approximately 31% of patients to colposcopy and appears to be a sensitive and cost-effective alternative to colposcopy.     

Liquid-based Papanicolaou smears without a transformation zone component: should clinicians worry?

OBJECTIVE: To evaluate whether ThinPrep smears without versus those with a transformation zone component were more likely to have falsely negative cytology findings. METHODS: Women aged 18-50 (N = 4389) attended one of three Planned Parenthood clinics between 1997 and 2001 for screening by ThinPrep Papanicolaou and polymerase chain reaction-based human papillomavirus (HPV) DNA testing. Women with 1) any cytologic abnormality, 2) high-risk HPV types, and 3) a random sample with normal Papanicolaou and negative HPV tests were offered repeat cytology, colposcopy, and biopsy. Cytology and biopsy diagnoses at the colposcopy visit were reviewed according to the presence (n = 3689) or absence (n = 700) of a transformation zone component at screening. RESULTS: Among women with normal cytology at screening, histologic detection of at least cervical intraepithelial neoplasia grade 2 (odds ratio 1.3, 95% confidence interval 0.5, 3.3) at colposcopy did not differ significantly between transformation zone-positive and zone-negative smears. Histologically confirmed cervical intraepithelial neoplasia grade 1 was detected more often among smears lacking a transformation zone component (odds ratio 2.0, confidence interval 1.0, 3.8). Transformation zone-negative smears were more common among older women, current oral contraceptive users, those past the 14th day of their last menstrual period, and those negative for high-risk HPV types. CONCLUSION: Absence of a transformation zone component in a screening ThinPrep Papanicolaou test was not associated with missed high-grade lesions. Based upon our data, we do not recommend repeat screening of reproductive-aged women with negative liquid-based tests and no cytologic evidence of a transformation zone component.