Prevalence of type-specific human papillomavirus infection among women in France: Implications for screening, vaccination, and a future generation of multivalent HPV vaccines.

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. Liquid-based cytology (LBC) samples were tested for HPV DNA, mRNA, and HPV genotypes. Women with atypical squamous cells of undetermined significance or greater (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. Of the 5002 women, 515 (10.3%) were <25 and 4487 (89.7%) were ≥25years old. Overall HPV prevalence varied between 10.1% and 16.1% depending on the assay. Risk factors for HPV infection included greater number of recent sexual partners, history of abnormal cervical pathology, age <25years, and smoking. 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 <25 and ≥25years old, respectively. HPV 16 was the type most strongly associated with a diagnosis of cervical intraepithelial neoplasia grade 3 or higher (CIN3+) (odds ratio=11.64 vs. 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. 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 potential benefit of future vaccines targeting a wider range of HPV types.

Risk assessment and clinical impact of liquid-based cytology, oncogenic human papillomavirus (HPV) DNA and mRNA testing in primary cervical cancer screening (the FASE study).

OBJECTIVE: New commercial HPV RNA assays require further validation studies in population-based cervical cancer screening settings. To assess the performance of (FDA-approved) APTIMA® HPV Assay (AHPV), Hybrid Capture 2 (HC2), in-house PCR genotyping, and ThinPrep LBC in population-based screening, stratified by three histological gold standards. STUDY DESIGN: A multi-center trial in 5006 women undergoing routine screening in France was designed to compare the absolute and relative risks of diagnosing CIN3+ and CIN2+ lesions by different diagnostic tests. RESULTS: Reproducibility between the primary and second pathology reading was excellent for CIN3+ and CIN2+ endpoints (Cohen's kappa 0.948 and 0.854). Absolute risks (PPV) of different tests (AHPV, HC2, PCR genotyping, LBC) in diagnosing CIN2+ (15-20%) and CIN3+ (4-6%) were similar for the first, second, and consensus pathology readings. The relative risks of diagnosing these lesions by the four tests were also similar when the first, second or third pathology readings were employed. AHPV had the highest absolute risk of both histological endpoints, and detects 5% to 15% more CIN3+ and CIN2+ lesions, respectively, than LBC. Compared with HC2 assay, the relative risk of AHPV is 24% to 29% higher, with a significant difference in CIN2+ detection. With LBC as reference, AHPV had the best sensitivity/specificity balance measured by AUC (area under ROC curve) comparison test (significant for CIN2+), and the colposcopy referral rate (9.2%) comparable to that of LBC (8.7%). CONCLUSIONS: These data corroborate the suitability of AHPV for the primary cervical cancer screening.

Evaluation of oncogenic human papillomavirus RNA and DNA tests with liquid-based cytology in primary cervical cancer screening: the FASE study.

The APTIMA 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 2; HC2) and liquid-based cytology (LBC; using PreservCyt ThinPrep liquid Pap) in a screening setting (French APTIMA screening evaluation [FASE] study). Women (N = 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-US+ 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 CIN2+ (92.0% and 96.7%) and CIN3+ (95.7% and 95.3%) detection and much more sensitive than LBC (69.1% for CIN2+ and 73.3% for CIN3+). 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.