Atypical glandular cells and adenocarcinoma in situ according to the Bethesda 2001 classification: cytohistological correlation and clinical implications

BACKGROUND: The objective of this study was to evaluate the correlation between the 2001 Bethesda classification of endocervical glandular abnormalities and histological diagnosis. STUDY DESIGN: A series of 155 women with endocervical glandular abnormalities on cervical smears were included: 91 with atypical glandular cells (AGC) not otherwise specified (NOS), 15 with AGC-favor neoplastic (FN); 35 with AGC associated with high-grade squamous intraepithelial lesion (HSIL) as combined diagnosis and 14 with adenocarcinoma in situ (AIS). RESULTS: Histological outcome of squamous neoplasias (CIN 2 or worse) and adenocarcinoma were significantly associated with AGC-FN and AIS, taking as reference AGC-NOS, and more associated with AIS than AGC-FN. Similar associations were observed for histological outcome of adenocarcinoma, but no association was observed for only squamous neoplasia. Histological outcome of CIN2 or worse was strongly associated with AGC when HSIL was also present, but no association was observed with only for adenocarcinoma histological outcome. CONCLUSIONS: AGC-NOS, AGC-FN and AIS cytological diagnosis represent a progressively increasing association with neoplastic diagnosis, due to progressively increasing association with adenocarcinoma. Histological outcome of squamous neoplasia is frequent but does not differ with these cytological interpretations. The presence of HSIL associated with AGC represents greater probability of squamous neoplasia but not adenocarcinoma.     

Prediction of high-grade cervical disease with human papillomavirus detection in women with glandular and squamous cytologic abnormalities

The objective of this study was to assess whether human papillomavirus (HPV) detection with hybrid capture II (HC II) can help predict the presence and the nature, glandular or squamous, of histologic cervical lesions in women referred due to atypical glandular cells (AGC) or high-grade squamous intraepithelial lesion (HSIL). A total of 247 women were included. Referral Pap smears comprised AGC (51 cases), AGC plus HSIL (28 cases), adenocarcinoma in situ (10 cases), and HSIL (158 cases). All patients were tested for high-risk HPV with HC II and had a histologic assessment of their cervix. Histologic analysis showed 38 women with (15.3%) cervicitis, 194 with (75.5%) squamous lesions, and 15 with (9.2%) glandular neoplasia. The overall rate of high-risk HPV detection was 77%. Almost 70% of AGC-HPV-negative patients did not have a pathologically proven cervical neoplasia, whereas 76% of women with AGC-HPV-positive result were diagnosed with a squamous or glandular neoplasia. Most (95%) of the lesions in patients with AGC-HSIL were of squamous nature, and HPV detection did not contribute to their differentiation from glandular lesions. We conclude that in women with AGC, HPV positivity strongly correlated with the presence of glandular or squamous cervical lesion but did not help distinguishing women with squamous from those with glandular neoplasia.     

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.     

The effect of time interval between referral and colposcopy on detection of human papillomavirus DNA and on outcome of biopsy

OBJECTIVE: This study was undertaken to assess the effect of the time interval between referral cytology and the outcome of colposcopically directed biopsy in relation to human papillomavirus (HPV) DNA detected by polymerase chain reaction in women referred after abnormal Papanicolaou (Pap) smears. STUDY DESIGN: The study enrolled 453 women who were referred for colposcopic examination after two Pap smears were reported as atypical squamous cells of undetermined significance (ASCUS) or low-grade intraepithelial lesions (LSIL) and 553 women who were referred with a single smear reported as high-grade squamous intraepithelial lesions (HSIL). RESULTS: The results in both patient groups were evaluated in time intervals of 60 days or more, 61 to 120 days, and more than 120 days between referral and colposcopy. A higher proportion of white women than African American women and Hispanic women were seen within 60 days after referral in both referral groups. Women of all race/ethnic backgrounds referred with HSIL were seen within 60 days in a significantly larger proportion than women referred with ASCUS/LSIL. Women referred with ASCUS/LSIL had an increasing frequency of negative HPV findings with the prolonged time intervals. In women referred with a single smear of HSIL, there was a significantly decreasing trend over time in detection of low-risk and unidentified types of HPV and an increasing trend of HPV DNA negative results. CONCLUSION: The frequency of high-risk HPV DNA was similar in patients referred with ASCUS/LSIL or HSIL. In both referral groups, there was a time-dependent increase of negative biopsy results and a decreased frequency of low-risk HPV or of unidentified HPV types. This suggests that the initial abnormality on the Pap smear associated with other than high-risk HPV types may regress over time. The presence of high-risk HPV DNA does not predict the actual histologically verifiable tissue changes but indicates a lower probability of negative biopsy results in all time intervals between referral and biopsy.     

Prevalence of high-risk human papillomavirus (HR-HPV) types 16 and 18 in healthy women with cytologically negative Pap smear

OBJECTIVE: To study the prevalence of high-risk human papillomavirus (HR-HPV) types 16 and 18 in healthy women with negative Pap smears in identifying women with underlying cervical squamous intra-epithelial (SIL) lesions. METHODS: A total of 3300 women who were attending the Gynecology OPD of Lok Nayak Hospital, one of the major government tertiary hospitals in New Delhi, were screened during a 1-year study period, and 2079 (63%) of them were found to have cytologically negative Pap smear with inflammation and the rest (37%) also had negative Pap report but without inflammation. Hundred and sixty of these sexually active women aged between 20 and 60 years were randomly selected, and were investigated by colposcopy and a guided biopsy was done wherever required. HPV types 16 and 18 DNA was detected in scraped cervical cells from all women using type-specific primers in polymerase chain reaction (PCR). RESULTS: The high-risk HPV (type 16 and 18) prevalence by PCR was found to be 10% (16/160). Histopathological findings were obtained in 123 women, out of which 15 had LSIL and four had HSIL. High-risk HPV types 16/18 could be detected in nine out of these 19 (47.3%) squamous intra-epithelial lesions (p < 0.00008) which includes two out of the four women (50%) having HSIL, while only seven out of 104 (6.7%) of the subjects with normal (negative) Pap reports (p = 0.03) had infection of high-risk HPV. CONCLUSION: The results indicate that about 10% of women who show a negative Pap smear, but have inflammation are positive for high-risk HPV types 16/18 and about 15% harbor squamous intra-epithelial lesions. It is suggested that high-risk HPV detection can be utilized as an adjunct to routine cytology screening programs to identify 'high risk' women who have concurrently negative Pap smears but may harbor oncogenic HPV infection and/or more likely to develop CIN lesions.     

High-risk HPV DNA detection by Hybrid Capture II. An adjunctive test for mildly abnormal cytologic smears in women > or = 50 years of age

OBJECTIVE: To determine whether high-risk human papillomavirus (HPV) DNA testing could improve the detection of cervical intraepithelial neoplasia (CIN) and cancer in older women (> or = 50 years old) with mildly abnormal results on conventional cytology. STUDY DESIGN: The study was based on 119 patients aged over 50 (median, 62; range, 50-78) referred for colposcopy with Pap smears reported as atypical squamous cells of undetermined significance (ASCUS) or low grade squamous intraepithelial lesion (LSIL) from February 1997 to September 1998. The presence of high-risk HPV DNA (including HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68) was determined with the Hybrid Capture II (Digene, Inc., Silver Spring, Maryland) microplate method. Cytologic examination by Pap smear was based on the Bethesda System and, cervical biopsy was done via colposcopy. RESULTS: High-risk HPV DNA was demonstrated in 75.6% (34/45) of patients with LSIL and 52.7% (39/74) with ASCUS. Those who were HPV positive were significantly more likely to have CIN or cancer (odds ratio, 33.40; 95% confidence interval, 11.89-93.97; P < .0001). The sensitivity of HPV assay for detection of lesions more severe than CIN 2 was 100%, specificity 64.8%, positive predictive value 66.7% and negative predictive value 100%. CONCLUSION: The addition of a high-risk HPV DNA assay to cytologic examination appears to provide excellent sensitivity and negative predictive value for early detection of high grade CIN or cancer in older women with minimally abnormal Pap smears.     

Clinical and histological significance of atypical glandular cell on Pap smear

BACKGROUND: Atypical glandular cell (AGC) on Pap smear is uncommon but may represent a variety of benign and malignant lesions. AIM: The aim of this study was to evaluate the association between AGC on Pap smear and significant pathological finding to tailor management protocols. METHODS: Between 2002 and 2005, 60 women with AGC on Pap smears were referred to our colposcopy clinic. Forty-one women underwent colposcopy-directed biopsy, endocervical curettage, endometrial sampling and cervical conisation to determine the cytological and histological correlations of AGC on Pap smears. RESULTS: The mean age of the patients was 46.9 +/- 11.5 years (range, 23-80 years). Of these patients 13 patients (31.7%) were postmenopause and 28 patients (68.2%) were in reproductive age. We found eight (19.5%) significant pathological findings including four (9.7%) high-grade squamous intraepithelial lesion, one (2.4%) adenocarcinoma of uterus, one (2.4%) adenocarcinoma of cervix, one (2.4%) squamous cell carcinoma of cervix and one (2.4%) papillary serous tumour of ovary. CONCLUSION: AGC on Pap smear was associated with a clinically significant diagnosis in approximately 20% of our cases. The women with a diagnosis of AGC on cervicovaginal smear are needed to be evaluated at least with colposcopy, endocervical and endometrial curettage. Clinicians should be careful about the significance of AGC on Pap smears.     

Human Papillomavirus Typing in Patients with Papanicolaou Smears Showing Squamous Atypia

Three hundred sixty consecutive patients followed at the Massachusetts General Hospital Colposcopy Clinic had HPV typing performed from exfoliated cervical cells by a commercially available dot blot hybridization assay. This assay tests for three groups of HPV types: 6/11, 16/18, and 31/33/35. Of this group, 171 patients were referred because of a Papanicolaou (Pap) smear showing squamous atypia. Of the 171 patients referred for squamous atypia, 17 (10%) had histologic evidence of CIN. Thirty-three of the 171 (19%) had detectable HPV DNA, and 28 of the 33 had high-risk HPV types (16/18, 31/33/35). Of the 17 women with CIN, only 6 (35%) had high-risk types and 11 (65%) had no HPV DNA detected. Of the 28 women with atypia and high-risk HPV types, only 6 (21%) had CIN. This study demonstrates that commercially available HPV typing when used in patients with Pap smears showing squamous atypia is not clinically useful in identifying patients for colposcopic referral.     

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.     

Comparison of three management strategies for patients with atypical squamous cells of undetermined significance, after six months delay: A three-year experience in an Iranian university hospital

Background: A Pap test result of atypical squamous cells of undetermined significance (ASCUS) presents a clinical challenge. Only 5–10% of women with ASCUS harbour serious cervical disease.
Methods: We screened 3619 women, who attended to Mirza Koochak Khan Hospital at Tehran University of Medical Sciences with Pap smears, of whom 100 returned with ASCUS. After six months, each subject underwent a standard cytology (conventional Pap smear), human papillomavirus (HPV) DNA testing (identifying high-risk HPV types with polymerase chain reaction) and colposcopy with multiple cervical biopsies.
Results: Mean age was 44.09 ± 8.6 years. The estimated prevalence of cervical intraepithelial neoplasia (CIN) II or higher was 4%. When histologically verified high-grade lesions (≥ CIN II) were observed, the relative sensitivity of HPV DNA testing was 100% compared with conventional Pap smear, which performed 75% versus 100% relative sensitivity, respectively, using cytological diagnosis high-grade squamous intraepithelial lesion, or low-grade squamous intraepithelial lesion (LSIL) as the cut-off. Negative and positive predictive values (NPV and PPV) of Pap test were 98.9% and 100%. The NPV and PPV of HPV DNA testing were 100%.
Conclusions: Although less complicated than colposcopy, the repeat Pap smear triage algorithm for ASCUS may underdiagnose some women with high-grade CIN, when compared with colposcopy. Considering the high sensitivity of HPV testing, it may be useful as an alternative to the current policy of six-month repeat cytology for women with ASCUS results.     

Human Papillomavirus DNA Detection in Cervical Specimens by Hybrid Capture: Correlation with Cytologic and Histologic Diagnoses of Squamous Intraepithelial Lesions of the Cervix

Human papillomavirus (HPV) DNA detection in cervical specimens was correlated with cytologic and histologic diagnoses for 151 women who were referred to the Johns Hopkins Hospital colposcopy clinic for evaluation of an abnormal Pap smear. HPVs were identified as “high-risk” or “low-risk” by Hybrid Capture. The final disease status was categorized as high-grade squamous intraepithelial lesion (HSIL) by histology (n= 26), low-grade squamous intraepithelial lesion (LSIL) by histology (n= 43), equivocal [histology negative, cytology atypical squamous cells of undetermined significance (ASCUS) or higher,n= 42], and negative (both histology and cytology negative,n= 40). Thirty-five percent of disease-negative women and 84% of the women with biopsy-proven or equivocal disease were HPV-positive. Ninety-two percent of the HPV-positive women harbored high-risk HPVs, either high-risk HPVs alone (77%) or high-risk HPVs along with low-risk HPVs (15%). High-risk HPVs predominated in disease-negative as well as disease-positive women. Collection of specimens with a cytobrush was more efficient for HPV DNA detection than collection by cervicovaginal lavage. Large amounts of HPV DNA correlated with presence of HSIL or LSIL. For detection of HSIL, considering only brush samples, the sensitivities of abnormal cytology (ASCUS or higher), of high-risk HPVs, and of the two combined were, respectively, 87, 93, and 100%; the corresponding specificities were 30, 30, and 20%. HPV DNA detection may be most beneficial in populations with low HPV prevalence.     

Cervical Pap screening among Israeli women, 2005–2010

Purpose

This study describes the distribution and the trends of cervical abnormalities in Israel, based on Pap smear results.

Methods

A retrospective analysis of cervical smears received by the Central Pathology Laboratory of Maccabi Healthcare Services between January 2005 and December 2010.

Results

In total, 711,541 Pap smears were screened in the study period. Cytological abnormalities were observed in 4.78 % of the total smears screened. An increase was observed in the rate of positive results from 2.63 % in 2005 to 6.78 % in 2010 (p = 0.0026). The cervical abnormalities in the study period distributed as follows: atypical squamous cell (ASC)—2.72 %, low-grade squamous intraepithelial lesion (LSIL)—1.54 %, high-grade squamous intraepithelial lesion (HSIL)—0.34 %, squamous cell carcinoma—0.01 %, atypical glandular cells (AGC)—0.10 %, adenocarcinoma in situ (AIS)—0.06 % and invasive adenocarcinoma—0.01 %. The increase was statistically significant for ASC (p = 0.0028), LSIL (p = 0.0069) and for HSIL (p = 0.0260). The mean ages at diagnosis of women with ASCUS, LSIL, HSIL, squamous cell carcinoma, AGC, AIS and adenocarcinoma were 37.8, 33.2, 38.6, 55.4, 41.1, 49.9 and 57.1 years, respectively.

Conclusions

The increase in the rate of squamous cell abnormalities demonstrated in this study emphasizes the need of implementing an education and a screening program among Israeli women. HPV vaccine, sexual behavior, cytology performance and HPV test are primary and secondary prevention tools which may reduce morbidity and mortality in the future. In addition, based on the age at diagnosis of the different pathologies, the age group in which Pap test is performed in Israel should be expanded from 35–54 to 25–65 years.     

Comparison of HPV test versus conventional and automation-assisted Pap screening as potential screening tools for preventing cervical cancer

OBJECTIVE: To evaluate new techniques in primary cervical cancer screening programmes. DESIGN: Cross sectional pilot study. SETTING: Department of Obstetrics and Gynaecology, Helsinki University Hospital. POPULATION: Consecutive 2032 human papillomavirus (HPV) DNA and Pap smear samples were taken. Histological diagnoses were obtained from 460 patients. METHODS: We compared the validity of the high risk (HR) HPV DNA detection test to automation-assisted and conventional Pap smear screening. MAIN OUTCOME MEASURES: Specificity and sensitivity of screening methods. RESULTS: Twenty-three percent of women were HPV positive. Forty-five of 46 had high grade lesions and cancers were HR HPV DNA positive, whereas 72/93 of low grade and more severe lesions were HR HPV DNA positive. When histologically verified high grade lesions were observed, the relative sensitivity of HR Hybrid Capture 2 (HR HC2) test was 98% compared with conventional Pap smear and Papnet tests, which performed 54%versus 58%, 83%versus 86% and 93%versus 98% relative sensitivity respectively, using cytological diagnoses HSIL (high grade squamous intraepithelial lesion), LSIL (low grade squamous intraepithelial lesion) or ASCUS (atypical squamous cells of undetermined significance) as the cutoff. The specificity of HC2 test (77-79%) was comparable with the ASCUS+ (ASCUS and more severe) cytology (68-79%), but lower when compared with LSIL+ (91-95%) or especially HSIL+ (97-99%) Pap smear results. CONCLUSION: Pap smear, as a screening test, is very different from HPV DNA detecting test HR HC 2. If cutoff LSIL or more severe lesions is used, primary Pap smear is clearly more specific than HR HC2, but markedly less sensitive. Due to high relative sensitivity of the HPV, only very few histologically confirmed high grade lesions would be detected among HPV negatives using simultaneous cytology. On the other hand, using HPV DNA test alone would lead to multifold amounts of referrals for colposcopy. A posterior Pap smear assessment among HPV positives might be helpful in increasing sensitivity and specificity of screening and defining those who need an immediate referral or treatment. We plan to incorporate primary HR HPV DNA test with posterior Pap smear reading of HPV positives into our ongoing randomised prospective multiarm trial evaluating new techniques in organised screening for cervical cancer in Finland.     

Performance of Pap smear and human papilloma virus testing in the follow-up of women with cervical intraepithelial neoplasia grade 1 managed conservatively

BACKGROUND: Conservative management (follow-up) of cervical intraepithelial neoplasia grade 1 (CIN1) is acceptable, but evidence on performance of follow-up tools, such as Pap smear and human papilloma virus (HPV) test, is still needed. METHODS: A cohort of 78 women with histologically confirmed CIN1, referred because of atypical squamous cell or low-grade squamous intraepithelial lesion in their Pap smear, was enrolled between August 2000 and September 2002 and was prospectively followed-up at 6 and 12 months, until September 2003. Follow-up examinations included Pap test and Hybrid Capture II (HCII) with high-risk HPV, colposcopy, and cervical biopsies in patients with persistent abnormalities. Odds ratios and performance indicators (with 95% confidence interval) were calculated for HPV and Pap test results in detecting biopsy-confirmed CIN during the follow-up. RESULTS: Thirty-seven (47%) of the women were HPV-positive at baseline. At first follow-up visit, 30 women had persistent CIN1 and one woman progressed to CIN2; 15 patients had CIN1 and one patient CIN2 at the second follow-up visit. Women with persistent CIN1 (or progression) during follow-up had a significantly higher HPV detection rate and abnormal Pap tests, compared to women with regressive disease. Cytology had a far better sensitivity in detecting CIN than HCII at the first follow-up visit (81 versus 52%, respectively), whereas both examinations had equivalent sensitivities at the second follow-up visit (69 and 56%, respectively). Cytology had a superior negative predictive value at the first follow-up visit and better positive predictive value, in addition, at the second visit. CONCLUSIONS: Because cytological abnormalities correlated generally better with the persistence of biopsy-confirmed CIN1 in this follow-up protocol, HCII test is the second-hand option to Pap test, but the use of both Pap and HCII together seems an unnecessary waste of resources.     

A Study of Cervical Intraepithelial Neoplasia in Pregnancy

Objective

To find the incidence of human papillomavirus (HPV) infection and cervical intraepithelial neoplasia (CIN) in pregnant women and compare Pap smear with the HPV DNA test in detecting HPV infection.

Materials and Methods

Hundred antenatal women, irrespective of gestational age, were enrolled as subjects in this prospective pilot study for blood investigations, wet mount examination of cervical discharge, Pap smear, and high-risk HPV DNA detection of cervical scrape by PCR. Women showing abnormality in Pap smear and/or those who were high-risk HPV DNA positive were subjected to colposcopy.

Results

The incidence of HPV-positive pregnant women was 18 %. Koilocytosis on Pap smear was observed in six women. Three high-risk HPV DNA-positive women showed changes consistent with CIN 1 on colposcopy.

Conclusions

The HPV DNA test is the most sensitive and reliable in detecting HPV infection as compared to Pap smear, but considering the cost of PCR, Pap smear screening of all antenatal women was recommended.     

Expanded cytological referral criteria for colposcopy in cervical screening: comparison with human papillomavirus testing

OBJECTIVE: The goal of this study was to investigate whether expanded cytologic referral criteria for colposcopy or the addition of human papillomavirus (HPV) testing on cervical screening could improve the rates of detection of cervical intraepithelial neoplasia (CIN). METHODS: HPV testing by semiquantitative polymerase chain reaction/ELISA was performed in 1000 women who were self-referred for routine Pap smear. They underwent colposcopy following an abnormal smear result or a positive HPV test. As abnormal smear results were considered reports of low- or high-grade squamous intraepithelial lesion, atypical squamous cells of undetermined significance, and even HPV-associated reactive cellular changes (mild koilocytosis, mild dyskeratocytosis, hyperchromatic nuclei, bimultinucleation, and cleared cytoplasm). Loop excision of the transformation zone was performed in women with cytology and colposcopy indicative of CIN, as well as in women with normal cytology but positive HPV test and colposcopic impression of CIN. RESULTS: The Pap test was abnormal in 89% of the cases of CIN 1 (34/38) and 96% of CIN 2/3 (27/28) diagnosed in our population. HPV testing picked up four additional cases of CIN 1 (11%) and one case of CIN 2/3 (4%). Overall the HPV test detected 95% of the cases of CIN 1 (36/38) and 89% of the cases of CIN 2/3 (25/28). CONCLUSION: HPV testing does not appear to add significantly to cytology in terms of positive predictive value or detection rate, if extended cytologic indications for colposcopy are used.     

Human papillomavirus (HPV) testing in the management of women with abnormal Pap smears. Experience of a colposcopy referral clinic

BACKGROUND AND OBJECTIVES: Several detailed algorithms for the appropriate use of human papillomavirus (HPV) testing in the management of women with abnormal Pap (Papanicolaou) smears have been launched, but their direct country-to-country adoption is difficult. This necessitates their testing in individual settings, which is ongoing in our colposcopy referral clinic. METHODS: A series of 224 consecutive women attending the clinic with the usual referral indications (ASC-US or higher in Pap) were examined by the conventional diagnostic tools (PAP smear, colposcopy, punch biopsy) and subjected to HPV testing and viral typing for both low-risk (L-R) and high-risk (H-R) types by nested PCR-based techniques. Predictors of the high-grade diagnostic categories were analysed using both univariate- and multivariate modelling, and the performance characteristics (sensitivity, specificity, NPV, PPV) of all tests in detecting high-grade CIN were calculated. RESULTS: In the PAP test, ASC-US smears were most common (37.9%), followed by low-grade squamous intraepithelial lesions (LSIL) (26.3%) and high-grade SIL (HSIL) (4.9%). Colposcopy was performed for 180 women, of whom 48.3% had a normal transformation zone (TZ), 40.6% had ATZ1 (abnormal TZ grade 1), and 5.6% had ATZ2. In biopsy (n = 71), 49.3% had CIN1, 5.6% CIN2, and 16.9% CIN3. The HPV test was positive in 64 (28.8%) women, more often in those aged < 35 years (p = 0.025). High-grade colposcopy (ATZ2) was significantly associated with HSIL in the Pap test (OR 20.5; 95% CI: 4.34-96.47), and with HPV test positivity (OR 6.37; 95% CI: 1.58-25.73). The most significant predictors of CIN3 were HSIL in the PAP, HPV test positivity, and high-grade colposcopy. HSIL and HPV test (for H-R types), but not colposcopy, retained their significance as independent predictors of CIN3 also in adjusted multivariate models: OR 88.27; 95% CI 4.17-1867.04, and OR 19.46; 95% CI 2.01-187.75, for the HSIL and H-R HPV test, respectively. Changing the cut-off level of the Pap test from ASC-US to HSIL increased the specificity of the test up to 96.4%, with the loss in sensitivity from 87.5% to 43.8%. Colposcopy (ATZ2) had 92% specificity, and NPV competing with that of the Pap test. The sensitivity of HPV test exceeds that of the Pap test at HSIL cut-off level, but the specificity of the PAP test is clearly superior. CONCLUSIONS: Accurate predictors of significant cervical pathology (CIN3) are well defined, but the problem is the different performance of the diagnostic tools in clinical practice. A proficient combination of the tests is likely to result in the most satisfactory clinical practice in the management of women with abnormal Pap tests (MAPS).     

CIN in pregnancy: antepartum and postpartum cytology and histology

OBJECTIVE: To determine the rates of antepartum and postpartum cervical intraepithelial neoplasia (CIN) 2 or worse in pregnant women with abnormal cervical cytology. STUDY DESIGN: A prospective, cohort study of 283 pregnant women referred for colposcopy between 1992 and 1999 for the evaluation of abnormal Pap smears. In this analysis, the population was stratified by severity of referral cytology (atypical squamous cells of undetermined significance [ASCUS] or low grade squamous intraepithelial lesion [LSIL] versus high grade squamous intraepithelial lesion [HSIL] and atypical glandular cells of undetermined significance [AGUS]). RESULTS: Sixty-seven women (24%) had ASCUS, 147 (52%) LSIL, 67 (24%) HSIL and 2 (0.7%) AGUS. As compared to women with HSIL or AGUS, women with ASCUS or LSIL were less likely to undergo antepartum biopsy (relative risk [RR] .34, 95% CI .23-.51) and if biopsied, less likely to have CIN 2 or worse (OR .49, 95% CI .24-.99). Women with antepartum ASCUS or LSIL were less likely to have postpartum HSIL (OR .29, 95% CI, .17-.52) and tended to have fewer histologically severe biopsies as compared to women with antepartum HSIL (OR .55, 95% CI .31-1.05). CONCLUSION: Among those biopsied, pregnant women with mildly abnormal cytology (ASCUS or LSIL), as compared to pregnant women with HSIL, were less likely to have either antepartum or postpartum CIN 2 or worse.     

Correlation of cervical cytology and human papillomavirus DNA detection in postmenopausal women.

This study correlated the cytological features of cervical swabs from postmenopausal women with the histological findings and the detection of human papillomavirus (HPV) using filter hybridization analysis. Of 17 postmenopausal women seen at colposcopy for an abnormal Papanicolaou (Pap) smear, most often squamous atypia, HPV DNA was detected in one (6%) cervical swab. Biopsy-proven cervical squamous intraepithelial lesions (SILs) were noted in two of the 17 (12%). The HPV DNA detection rate was equivalent to that found in 47 postmenopausal women who had hysterectomies for noncervical disease. The rates of HPV detection and biopsy-proven SIL in premenopausal women seen at colposcopy was 55% and 66%, respectively. The HPV DNA detection rate for postmenopausal women with biopsy-proven SILs as determined by in situ hybridization was 19/26 (73%), which is equivalent to the rate in premenopausal women. It is concluded that squamous atypia in postmenopausal women is rarely associated with either biopsy-proven SIL or HPV DNA detection and thus, in many cases, may represent atrophic changes.     

宫颈巴氏涂片与LCT在低收入妇女妇科普查中的应用

目的探讨宫颈巴氏涂片与液基细胞学（LCT）在低收入已婚妇女宫颈癌筛查中的应用价值。方法2008年1月至6月上海市浦东新区妇幼保健院对所在社区6416例低收入已婚妇女（低收入组）采用宫颈巴氏涂片进行了宫颈癌筛查,其中322例同期行LCT,并与同期来上海市浦东新区妇幼保健院做宫颈癌筛查行LCT的294名妇女进行对照（对照组）。结果①宫颈刮片巴氏异常者（≥Ⅱb级）低收入组中22例（0．34％）,其中Ⅱb级12例（0．19％）,Ⅲ级10例（0．16％）,无Ⅳ级及Ⅴ级。15例（Ⅱb5例,其余Ⅲ级）行阴道镜下活检,病理结果CIN8例,其中CIN12例,CIN2和CIN3各3例;②低收入组同期行LCT的322例妇女中,细胞学≥ASCUS共41／322例（12．73％）,其中ASCUS15例,HSIL 1例,行阴道镜下活检病理结果CIN5例（CIN1和CIN2各2例,CIN31例）;HSIL1例为子宫颈鳞状细胞癌。对照组：细胞学≥ASCUS 22／294例（7．48％）。其中ASCUS 11例行阴道镜下活检。病理结果仅CIN 21例;2例LSIL;1例为CIN2。两组AGC各1例经阴道镜下活检均无异常;③低收入组中322例行宫颈刮片和LCT做自身对照：315例巴氏均为Ⅰ级,LCT正常;巴氏Ⅱb级2例,LCT均为ASCUS,病理分别为CIN1和CIN2;巴氏Ⅲ级3例,LCT检查,其中2例为ASCUS,阴道镜活检仅1例病理为CIN2。结论宫颈细胞学是筛查宫颈病变的有效手段,巴氏涂片法在基层对低收入人群仍可为主要筛查方法。有条件者可采用LCT,以提高宫颈疾病筛查的敏感性。