The APTIMA V R HPV Assay (AHPV) allows detection of 14 high-risk human papillomavirus (HPV) RNA types in cervical specimens. Until present, the assay has been compared to HPV DNA tests only in triage settings. Herein, we compare AHPV with a DNA assay (Hybrid Capture V R 2; HC2) and liquid-based cytology (LBC; using PreservCyt V R ThinPrep liquid Pap) in a screening setting (French APTIMA screening evaluation [FASE] study). Women (N 5 5,006) aged 20-65 were screened by gynecologists in 17 private practices in Paris, France. One cervical specimen was collected and tested with LBC, AHPV and HC2 assays. Women were referred to colposcopy if they were ASC-US1 in LBC or HPV positive in either HPV assay. To control for verification bias, a random group (14%) with normal LBC and dually HPV negative tests underwent colposcopy. Data from 4,429 women were analyzed. Sensitivity, specificity and predictive values were calculated for the three tests. AHPV and HC2 were highly sensitive for CIN21 (92.0% and 96.7%) and CIN31 (95.7% and 95.3%) detection and much more sensitive than LBC (69.1% for CIN21 and 73.3% for CIN31). Specificity of AHPV was higher than that of HC2, but similar to that of LBC (p < 0.001). Combining LBC with either HPV test slightly increased sensitivity but compromised specificity. AHPV assay is both specific and sensitive for the detection of high-grade precancerous lesions and may be considered as an option for routine cervical cancer screening for women over 20 years of age.Invasive cervical cancer (ICC) is the second most frequent female cancer worldwide, 1 with an estimation of 493,000 cases annually. ICC incidence and mortality rates have dramatically declined over the past five decades in developed countries, largely due to screening programs based on conventional cervical Papanicolaou (Pap) smears. 2,3 Conventional Pap smear screening, however, has limited sensitivity, positive predictive value (PPV) and reproducibility, which limits its use for primary screening. 3,4-7 Liquid-based cytology (LBC) has been shown to be more sensitive than conventional

SummaryThe 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 = 0.041 360-366 © 2001 Cancer Research Campaign doi: 10.1054/ bjoc.2000.1588, available online at http://www.idealibrary.com on http://www.bjcancer.com Linder and Zahniser, 1997;Roberts et al, 1997; Bolick and Heuman, 1998;Corkill et al, 1998;Dupree et al, 1998;Papillo et al, 1998; Carpenter and Daveu, 1999;Diaz-Rosario and Kabawat, 1999;Guidos and Selvaggi, 1999;Wang et al, 1999; Yeoh et al, 1999; Weintraub and Morabia, 2000).This study, conducted in France, is the first formal multilaboratory, large-scale evaluation of the ThinPrep Pap Test in the European setting. METHODS Study organization6 laboratories in France participated in the study, each laboratory obtaining cervical samples from 5 to 8 participating gynaecologists and their patients. A total of 35 gynaecologists participated in the study.Before the study commenced, the 6 laboratory directors (4 cytopathologists and 2 cytologists) and their participating staff were trained to interpret ThinPrep slides, and also to use the Bethesda System for reporting the screening results (Kurman and Solomon, 1994). The study protocols and forms were reviewed and approved by the local Ethics Committee.Patients were recruited sequentially in the participating gynaecologists' practices, from March 1998 to September 1998. According to the inclusion criteria, female patients aged 18 and older, attending regular cervical cancer screening, and who voluntarily gave their informed consen...

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.

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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.