[Prevalence of genotype-specific HPV infection among women in France: implications for screening and vaccination]. / Prévalence des génotypes d'HPV chez les femmes en France : implications pour le dépistage et la vaccination.

OBJECTIVES: To assess human papillomavirus (HPV) prevalence and genotype distribution by age and cervical cytology/histology status among women undergoing routine gynecological examinations, and to discuss the possible impact on preventive strategies. PATIENTS AND METHODS: Liquid-based cytology (LBC) samples were tested for HPV DNA, mRNA, and HPV genotypes. Women with ASC-US+ and/or at least one positive HPV test were referred to colposcopy. Those with normal colposcopy results had biopsies taken at the 6 and 12 o'clock positions of the normal transformation zone. RESULTS: Of the 5002 women, 515 (10.3 %) were less than 25 and 4487 (89.7 %) were 25 years old or more. Overall HPV prevalence was 10.1 % to 16.1 % depending on the assay. HPV prevalence increased with the cytological and histological severity of cervical lesions. Prevalence of HPV 16/18 was 5.2 % and 2.7 % in women less than 25 and 25 years old or more, respectively. HPV 16 was the type most strongly associated with a diagnosis of CIN3+ (odds ratio=11.64 versus HPV 16 absent, P<0.001). A high proportion of high-grade cervical lesions (60.6 % of genotyping assay-positive CIN2+) were associated with HPV types 31, 33, 45, 52, or 58. DISCUSSION ET CONCLUSION: These data indicate that almost all young women could benefit from HPV prophylactic vaccination, but confirm the need for continued cervical screening and highlight the need for future vaccines to target a wider range of HPV types.

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.

[Long-term results of hysteroscopic resection of endometrial polyps in 367 patients. Role of associated endometrial resection]. / Résultats à long terme de la résection des polypes endométriaux chez 367 patientes. Place de l'endométrectomie associée.

OBJECTIVE: To assess the results of hysteroscopic resection of endometrial polyps and the eventual role of associated endometrial resection. PATIENTS AND METHODS: Retrospective study. Between 1998 and 2001, 367 patients had hysteroscopic resection of endometrial polyps, which were initially confirmed by diagnostic hysteroscopy. Fifty-four percent of these had associated endometrial resection. RESULTS: Five intraoperative complications and/or incidents were noted, but there was no major complication. 83% of patients were followed up and the median follow-up period was 40 months (range 17-66 months). The success rate in this study was 96.4%. This is higher in the group of patients that had associated endometrial resection: 98.3 vs 93.7%. DISCUSSION AND CONCLUSION: Hysteroscopic resection is the optimal method for treatment of benign endometrial polyps. Associated endometrial resection in older patients or in patients not desiring to conserve their fertility potential improves the success rate and decreases the rate of recurrences.

Liquid-based cytology for primary cervical cancer screening: a multi-centre study.

The aim of this six-centre, split-sample study was to compare ThinPrep fluid-based cytology to the conventional Papanicolaou smear. Six cytopathology laboratories and 35 gynaecologists participated. 5428 patients met the inclusion criteria (age > 18 years old, intact cervix, informed consent). Each cervical sample was used first to prepare a conventional Pap smear, then the sampling device was rinsed into a PreservCyt vial, and a ThinPrep slide was made. Screening of slide pairs was blinded (n = 5428). All non-negative concordant cases (n = 101), all non-concordant cases (n = 206), and a 5% random sample of concordant negative cases (n = 272) underwent review by one independent pathologist then by the panel of 6 investigators. Initial (blinded) screening results for ThinPrep and conventional smears were correlated. Initial diagnoses were correlated with consensus cytological diagnoses. Differences in disease detection were evaluated using McNemar's test. On initial screening, 29% more ASCUS cases and 39% more low-grade squamous intraepithelial lesions (LSIL) and more severe lesions (LSIL+) were detected on the ThinPrep slides than on the conventional smears (P = 0.001), including 50% more LSIL and 18% more high-grade SIL (HSIL). The ASCUS:SIL ratio was lower for the ThinPrep method (115:132 = 0.87:1) than for the conventional smear method (89:94 = 0.95:1). The same trend was observed for the ASCUS/AGUS:LSIL ratio. Independent and consensus review confirmed 145 LSIL+ diagnoses; of these, 18% more had been detected initially on the ThinPrep slides than on the conventional smears (P = 0.041). The ThinPrep Pap Test is more accurate than the conventional Pap test and has the potential to optimize the effectiveness of primary cervical cancer screening.

[Liquid phase cytology in the primary screening for cervical cancer: a multicenter study]. / Cytologie en phase liquide dans le cadre du dépistage primaire du cancer du col utérin: une étude multicentrique.

The aim of this six-centre, split-sample study was to compare ThinPrep fluid-based cytology to the conventional Papanicolaou smear. Six Cytopathology laboratories and 35 Gynaecologists participated. 5428 patients met the inclusion criteria. Each cervical sample was used first to prepare a conventional Pap smear, then the sampling device was rinsed into a PreservCyt vial, and a ThinPrep slide was made. Screening of slide pairs was blinded. On initial screening, 29% more ASCUS and 39% more low-grade squamous intraepithelial lesions (LSIL) and more severe lesions (LSIL+) were detected on the ThinPrep slides than on the conventional smears (p = 0.001). Independent and consensus review confirmed 145 LSIL + diagnoses; of these, 18% more had been detected initially on the ThinPrep slides than on the conventional smears (p = 0.041). The ThinPrep Pap Test is more accurate than the conventional Pap Test and has the potential to optimize the effectiveness of primary cervical cancer screening.

Analysis of normal breast tissue and of solid breast masses using three-dimensional ultrasound mammography.

OBJECTIVES: To describe the appearance of normal breast tissue and breast masses with three-dimensional ultrasound mammography, and evaluate the contribution of this to the diagnosis of breast masses. MATERIALS AND METHODS: A total of 186 solid hypoechoic breast masses were analyzed with two- and three-dimensional ultrasonography. Three-dimensional planar reformatted sections were reconstructed along planes either orthogonal or parallel to the skin surface. RESULTS: With parallel planar reformatted sections all the masses tended to be round. Margins were clearly demonstrated. In case of carcinomas, circumferential jagging was present in the equatorial planes. In case of fibroadenomas, complete wall continuity of the mass was readily apparent. The hyperechoic bands of fibrous tissue peripheral to the masses appeared either as distinct from the central image (compressive pattern) or converged towards the hypoechoic central core of the mass, producing a stellar pattern (converging pattern). These two patterns were preferentially associated with benign lesions and carcinomas, respectively. Three-dimensional ultrasound mammography had higher specificity, but lower sensitivity, than two-dimensional ultrasound mammography. CONCLUSIONS: Three-dimensional reconstruction, in particular parallel planar reformatted sections, represents a valuable adjunct to the characterization of breast masses using ultrasongraphy. Further studies are necessary to assess the validity of the present findings, particularly with regard to the rarer, more unusual types of carcinoma.

Simultaneous effects of aneuploidy and oncogenic human papillomavirus on histological grade of cervical intraepithelial neoplasia.

OBJECTIVE: To investigate whether ploidy and oncogenic human papillomavirus types can be correlated with the histological grade of cervical intraepithelial neoplasia (CIN) in the same tissue sections. DESIGN: Histological data were obtained from 292 dysplastic lesions of the cervix and classified according to the CIN and the Bethesda terminologies. The samples were analysed using Feulgen-stained image analysis cytometry for ploidy and Human papillomaviruses DNA typing by in situ hybridisation, respectively. SETTING: Colposcopy Clinic at Alfred Fournier Institute, Paris. POPULATION: Three hundred and forty women referred for an abnormal cervical smear. RESULTS: The ploidy data strongly segregate high grade from low grade squamous intraepithelial lesions (aneuploidy 78% versus 21%; P < 0.0001). There was a significant association between aneuploidy and the severity of the lesions (94% for CIN 3, 55% for CIN 2 and 14% for CIN 1; P < 0.0001). Both classifications showed a significant association of histological grade with oncogenic human papillomavirus types (HPV 16-18-33; 20% in low grade and 78% in high grade squamous intraepithelial lesions, 31% and 75% in CIN 1 and CIN 3, respectively; P < 0.0001). The simultaneous effects of these viruses and ploidy demonstrate an association in aneuploid cells between the presence of oncogenic human papillomavirus types and histological grade (76% and 18% in high and low grade squamous intraepithelial lesions, respectively; P < 0.0001). Such an association was not observed in diploid cells (20% in both low and high grade squamous intraepithelial lesions). CONCLUSIONS: High risk human papillomavirus types do not exert and an independent effect on the histological grade of cervical intraepithelial neoplasia.

Genital human papillomavirus infections: correlation of cytological, colposcopic and histological features with viral types in women and their male partners.

To determine the incidence of anogenital papillomavirus infections and to assess the value of available diagnostic methods, we compared the cytological, colposcopic and histological features of anogenital papillomavirus-related lesions with their associated human papillomavirus types (HPV) in 300 women and in their male partners. HPV-type deoxyribonucleic acid was detected by blot hybridization in 398 out of 624 subclinical and clinically defined anogenital lesions. Whatever the site of the lesion, condylomas and low-grade intraepithelial neoplasia (IEN) were found in 84% of lesions associated with HPV 6-11, compared with 32% of lesions containing HPV 16-18 (P < 0.001). Among the HPV 16-18 associated lesions, high-grade cervical, vaginal, vulvar and anal intraepithelial neoplasias represented 45% (P < 0.001) of the lesions. In 65% of 23 cases of squamous anogenital cancer, HPV 16-18 and mixed types were present (P < 0.001). In 54% (161/300) of cases, the lesions were multicentric (161/300). On cytological examination, 27% of the samples gave false negative results. In cervical lesions, there was a good correlation between virological and colposcopic findings, but this was not true for extracervical mucous epithelia in the vagina or on the vulva. With peniscopy in the male partners 220 out of 410 had penile condylomatous lesions and more than half of the 350 male specimens examined by molecular hybridization contained HPV DNA. A correlation was found between the virus types in penile lesions or in cells of the distal urethra and in the cervical lesions of the sexual partner.(ABSTRACT TRUNCATED AT 250 WORDS)

[Role of pathologic anatomy in the diagnosis, prognostic evaluation, and surveillance of bladder tumors]. / Place de l'anatomie pathologique dans le diagnostic, l'évaluation pronostique et la surveillance des tumeurs de vessie.

The usual histological techniques are necessary and sufficient for the routine diagnosis of bladder tumours. Many laboratory tools are designed to determine prognostic factors but require such technical conditions that they cannot be used routinely. The determination of DNA ploidy by flow cytometry of voided urine, fresh, formalin-fixed or paraffin-embedded tumour fragments is a simple, standardised and reproducible technique and the method of choice of pathologists as it allows morphological control of the element analysed. Based on a series of 720 bladder tumours collected by 3 different centres, the authors demonstrate how to use, correlate and integrate into routine practice the data of image analysis flow cytometry in relation to conventional cytology and histology. 5% of grade 1 tumours, 27% of grade 2 tumours, and 92% of grade 3 tumours were DNA aneuploid. 17% of non-invasive tumours (PTa) and 79% of invasive tumours (PT1 and more) were DNA aneuploid. These proportions are in line with the results of various series in the literature. DNA ploidy is therefore an objective and measurable element completing histological grading. The determination of DNA ploidy also helps the cytologist in difficult cases of urine cytology.

DNA content measurement and in situ hybridization in condylomatous cervical lesions.

The present study reports results obtained with DNA ploidy measurement by Feulgen cytophotometry and in situ hybridization (ISH) on the same sections of 36 cervical lesions containing human papillomavirus (HPV) DNA. Fifteen of 16 low grade lesions [11 flat condylomas and five condylomatous with intraepithelial neoplasias (CIN)-1, 1 with condylomatous features] were diploid. "Oncogenic" HPV (types 16 and 33) were detected in three of these cases, while the aneuploid case expressed HPV type 11. By contrast, in the 12 CIN-2 and eight CIN-3 with condylomas, there was a good correlation between presence of an aneuploid DNA pattern and detection of "oncogenic" HPVs. Demonstration of an aneuploid profile and "oncogenic" HPV as found in all our CIN-3, may indicative of a poor prognosis in low grade lesions. Hence, the combination of the two techniques (ISH and Feulgen cytophotometry) may provide significant prognostic information for condylomas and CINs.

Estrogen and progesterone receptors in cervical human papillomavirus related lesions.

According to recent studies showing that human papillomavirus (HPV) infections can be influenced by sex steroid hormones, we performed estrogen (ER) and progesterone (PgR) receptor assays in fresh frozen biopsies of genital-HPV-related lesions. Seventy-three women with normal cervix, condyloma, low- and high-grade CIN and squamous carcinoma were evaluated in comparison with 15 persons with vulvar and 9 with penile papillomavirus-associated lesions. HPV genotypes were determined by dot-blot hybridization. Non-cervical lesions did not express HR. Condyloma on squamous metaplasia of the cervix and high-grade CIN expressed high levels of HR, particularly PgR (mean 4,086 and 4,518 fmoles/g tissue, respectively). Cervical squamous carcinoma expressed very low concentrations of PgR in a limited number of cases. High levels of PgR were correlated with high-grade CIN (p less than 0.05), HPV16-18-associated lesions (p less than 0.01) and ER were correlated to HPV6-11-related lesions (p less than 0.01). The levels were independent of age, cycle stage and oral contraception. Morphological localization of PgR, using an immunocytochemical method using a monoclonal antibody (MAb) (PR-ICA), showed intense homogeneous staining in the nuclei of the stromal fibroblasts underlying dysplastic epithelium and condyloma on squamous metaplasia. These results suggest that, under in vivo conditions, sex steroid hormones, particularly progesterone, may act indirectly on HPV-infected epithelial cells and be implicated as co-factors in HPV-related cervical neoplasia. They could explain the relative predisposition to malignant transformation of the cervix as compared with vulvar and penile mucosa.

[Voided urinary cytodiagnosis. Cyto-histologic comparison]. / Le cytodiagnostic urinaire mictionnel. Confrontation cyto-histologique.

The authors report the results of a 4 year study of voided urinary cytology by cytocentrifugation. The findings were compared with those of histology. The sensitivity of the cytological diagnosis varies with the histological grade of the tumor. Grade 1 papillary tumors are not detectable with classical cytological criteria of malignancy. However they may be evoked if finer criteria are considered. Voided urinary cytology is efficient in the detection of grade 2 and grade 3 papillary tumors as well as dysplasia and in situ carcinoma in flat mucosa. The sensitivity of urinary voided cytology is remarkably improved by repeating the examination 3 successive times. This method detects tumors of the urinary bladder as well as those of the upper urinary tract. False positive results are possible, but may be avoided by knowing the clinical history and by repeated urinary cytology. Protocols are proposed for the diagnosis and follow-up of transitional cell tumors. Systematic screening of high risk subjects is also an important indication for voided urinary cytology, but we lack experience in this domain.