High-risk HPV detection and associated cervical lesions in a population of French menopausal women.

BACKGROUND: With population ageing, post-menopausal women represent a new group to be considered in cervical cancer screening strategies, including the significance of High Risk (HR)-HPV detection. OBJECTIVES: A retrospective analysis was conducted in a cohort of 406 menopausal women attending routine gynaecological consultation at the Hospital of Montpellier (France). STUDY DESIGN: All women benefited from a cervical smear and HR-HPV detection using Hybrid Capture 2 (HC2) test. The prevalence of cytological abnormalities, HR-HPV detection and risk factors associated with HR-HPV detection were analyzed. Evolution of both tests was evaluated in a sub-group of women with adequate follow-up. RESULTS: Five women (1.2%) had an abnormal cervical smear at baseline. HR-HPV was detected in 40 women (9.9%), including 36 women with normal cytology (9%). Risk factors associated with HR-HPV detection at enrolment were a previous history of Cervical Intraepithelial Neoplasia and a high socio-economic level, but not hormone replacement therapy. When cytology and HR-HPV detection were negative at enrolment, both remained negative for 95% (230/241) of women during follow-up (median duration of follow-up: 60 months). HR-HPV persistence was observed for 55% (18/33) of women with normal cytology and positive HR-HPV test. Finally, all women with a final diagnosis of high-grade (CIN2+) cervical lesion (N = 7) had a positive HR-HPV test with or without abnormal cytology. CONCLUSIONS: HR-HPV was detected in 9.9% of menopausal women. HR-HPV detection was a better predictor of CIN2+ lesions than cytology in this population. Women with previous CIN history should benefit from HR-HPV testing and need long term follow-up.

Diagnostic value of human papillomavirus (HPV) 16 and HPV18 viral loads for the detection of high-grade cervical intraepithelial neoplasia (CIN2+) in a cohort of African women living with HIV.

BACKGROUND: African women living with HIV (WLHIV) are at high risk of cervical cancer but rarely adequately screened. Better strategies enabling identification of WLHIV with high-grade cervical intraepithelial lesions (CIN2+) are required. OBJECTIVES: To investigate the diagnostic value of HPV16 and HPV18 viral loads in a cohort of African WLHIV. DESIGN: HPV16 and HPV18 viral loads were determined by quantitation of the E6 gene DNA by real-time PCR in cervical specimens collected at baseline and endline (16 months) from 245 African WLHIV positive for HPV16 or/and HPV18. Cervical biopsies were graded using the histopathological CIN classification. RESULTS: Women with CIN2+ had higher viral load for HPV16 (p < 0.0001) or HPV18 (p = 0.03) than those without CIN2+. HPV16 viral load ≥3.59 log copies/1000 cells detected CIN2+ with sensitivity and specificity of 93.5% (95%CI: 81.7-98.3%) and 74.1% (95%CI: 66.3-80.6%), respectively, whereas HPV18 viral load ≥1.63 log copies/1000 cells detected CIN2+ with sensitivity and specificity of 59.1% (95%CI: 38.7-76.7%) and 66.9% (95%CI: 58.8-74.1%), respectively. A high baseline HPV16 viral load was significantly associated with persistence of, or progression to CIN2+ at endline; these findings were not observed for HPV18. CONCLUSIONS: HPV16 viral load is a powerful marker of CIN2+ in African WLHIV. HPV18 viral load is of lower diagnostic value in this population.

Cervical intraepithelial neoplasia (CIN) in African women living with HIV: role and effect of rigorous histopathological review by a panel of pathologists in the HARP study endpoint determination.

AIMS: To analyse the effect of the expert end-point committee (EPC) review on histological endpoint classification of cervical intraepithelial neoplasia (CIN). METHODS: A cohort of women living with HIV were recruited in Burkina Faso (BF) and South Africa (SA) and followed over 18 months. Four-quadrant cervical biopsies were obtained in women with abnormalities detected by at least one screening test. A central review by a panel of five pathologists was organised at baseline and at endline. RESULTS: At baseline the prevalence of high-grade CIN (CIN2+) was 5.1% (28/554) in BF and 23.3% (134/574) in SA by local diagnosis, and 5.8% (32/554) in BF and 22.5% (129/574) in SA by the EPC. At endline the prevalence of CIN2+ was 2.3% (11/483) in BF and 9.4% (47/501) in SA by local diagnosis, and 1.4% (7/483) in BF and 10.2% (51/501) in SA by EPC. The prevalence of borderline CIN1/2 cases was 2.8% (32/1128) and 0.8% (8/984) at baseline and endline. Overall agreement between local diagnosis and final diagnosis for distinguishing CIN2+ from ≤CIN1 was 91.2% (κ=0.82) and 88.9% (κ=0.71) for BF at baseline and endline, and 92.7% (κ=0.79) and 98.7% (κ=0.97) for SA at baseline and endline. Among the CIN1/2 cases, 12 (37.5%) were graded up to CIN2 and 20 (62.5%) were graded down to CIN1 at baseline, and 3 (37.5%) were graded up to CIN2 and 5 (62.5%) were graded down to CIN1 at endline. CONCLUSIONS: This study highlights the importance of a centralised rigorous re-reading with exchange of experiences among pathologists from different settings.

Associations of Human Papillomavirus (HPV) genotypes with high-grade cervical neoplasia (CIN2+) in a cohort of women living with HIV in Burkina Faso and South Africa.

OBJECTIVE: To describe associations of high-risk human papillomavirus (HR-HPV) with high-grade cervical intraepithelial neoplasia (CIN2+) in women living with HIV (WLHIV) in Burkina Faso (BF) and South Africa (SA). METHODS: Prospective cohort of WLHIV attending HIV outpatient clinics and treatment centres. Recruitment was stratified by ART status. Cervical HPV genotyping using INNO-LiPA and histological assessment of 4-quadrant cervical biopsies at enrolment and 16 months later. RESULTS: Among women with CIN2+ at baseline, the prevalence of any HR-HPV genotypes included in the bi/quadrivalent (HPV16/18) or nonavalent (HPV16/18/31/35/45/52/58) HPV vaccines ranged from 37% to 90%. HPV58 was most strongly associated with CIN2+ (aOR = 5.40, 95%CI: 2.77-10.53). At 16-months follow-up, persistence of any HR-HPV was strongly associated with incident CIN2+ (aOR = 7.90, 95%CI: 3.11-20.07), as was persistence of HPV16/18 (aOR = 5.25, 95%CI: 2.14-12.91) and the additional HR types in the nonavalent vaccine (aOR = 3.23, 95%CI: 1.23-8.54). CONCLUSION: HR-HPV persistence is very common among African WLHIV and is linked to incident CIN2+. HPV vaccines could prevent between 37-90% of CIN2+ among African WLHIV.

Performance of careHPV for detecting high-grade cervical intraepithelial neoplasia among women living with HIV-1 in Burkina Faso and South Africa: HARP study.

BACKGROUND: The careHPV assay is a test for high-risk (HR) human papillomaviruses (HPV) detection designed to be affordable in resource-poor settings. We evaluated the performance of careHPV screening among 1052 women living with HIV/AIDS included in the HARP (HPV in Africa Research Partnership) study in Burkina Faso (BF) and South Africa (SA). METHODS: Cervical samples were tested for HR-HPV by the careHPV and the INNO-LiPA HPV genotyping Extra assays. All women had Pap smear testing, visual inspection with acetic acid/Lugol's iodine (VIA/VILI) and colposcopy. Cervical biopsies were obtained for participants who were HR-HPV DNA positive by careHPV or who had abnormalities detected on cytology, VIA/VILI or colposcopy. RESULTS: Overall, 45.1% of women had a positive careHPV test (46.5% in BF, 43.8% in SA). The careHPV positivity rate increased with the grade of cytological lesions. Sensitivity and specificity of careHPV for the diagnosis of CIN2+ (n=60, both countries combined) were 93.3% (95% confidence interval (CI): 83.8-98.2) and 57.9% (95% CI: 54.5-61.2), respectively. Specificity increased with CD4 count. careHPV had a similar clinical sensitivity but higher specificity than the INNO-LiPA assay for detection of CIN2+. CONCLUSIONS: Our results suggest that careHPV testing is a reliable tool for cervical cancer screening in HIV-1-infected women in sub-Saharan Africa.

Comparison of analytical and clinical performances of the digene HC2 HPV DNA assay and the INNO-LiPA HPV genotyping assay for detecting high-risk HPV infection and cervical neoplasia among HIV-positive African women.

OBJECTIVES: To compare the Hybrid Capture 2 human papillomaviruses (HPV) DNA assay (HC2) and the INNO-LiPA HPV Genotyping Extra assay (INNO-LiPA) for cervical cancer screening in HIV-1-infected African women. DESIGN: The tests were compared for agreement in detecting high-risk HPV (hr-HPV) and performance to detect squamous intraepithelial lesions (SIL), by cytology, and cervical intraepithelial neoplasia, by histology, in cervical samples from 1224 women in Burkina Faso (N = 604) and South Africa (N = 620). RESULTS: When considering the 13 hr-HPV types detected by HC2, 634 (51.8%) and 849 (69.4%) samples were positive by HC2 and INNO-LiPA, respectively. Agreement between assays was 73.9% [adjusted kappa coefficient value, 0.44 (95% confidence interval: 0.43 to 0.53)]. Agreement improved with analysis restricted to women with high-grade cervical lesions [adjusted kappa coefficient value, 0.83 (95% confidence interval: 0.74 to 0.91)]. The prevalence of hr-HPV, as determined by HC2 and INNO-LiPA, was 34.5% and 54.5%, respectively, in samples with normal cytology, 48.0% and 68.0%, respectively, in samples with atypical squamous cells of undetermined significance, 51.8% and 75.2%, respectively, in samples with low-grade SIL, and 86.3% and 89.8%, respectively, in samples with high-grade SIL/atypical squamous cells that cannot exclude HSIL. Sensitivity, specificity, positive, and negative predictive values for the diagnosis of histological high-grade lesions (CIN2+) were 88.8%, 55.2%, 24.7% and 96.7%, and 92.5%, 35.1%, 19.1% and 96.6% for HC2 and INNO-LiPA, respectively. CONCLUSIONS: HC2 has lower analytical sensitivity but higher specificity than INNO-LiPA for diagnosing high-grade lesions; the 2 tests presented a comparable clinical sensitivity. HC2 might be suitable for cervical cancer screening in HIV-1-infected African women, but its use in resource-limited settings merits to be further evaluated in comparison with other prevention strategies.

Cervical cancer screening by cytology and human papillomavirus testing during pregnancy in French women with poor adhesion to regular cervical screening.

In France, cervical screening is opportunistic and approximately 40% of women do not attend regular screening programs. The aim of this study was (1) to assess the prevalence of human papillomavirus (HPV) cervical infection and of cytological abnormalities in a population of young pregnant women with poor adherence to cervical cancer screening and (2) to evaluate the adherence to a screening strategy combining HPV testing and cytology during pregnancy. For this purpose, pregnant women benefited from a cervical smear associated with HPV DNA detection. High-risk HPV types were detected and identified using the HC2 assay and the INNO-LiPA HPV genotyping Extra assay. Two hundred forty-seven women (mean age 26.6 ± 5.1 years) were enrolled. Among them, 76.8% did not attend regular cervical cancer screening programs. High-risk HPV types were detected in 50 (20.2%) samples, HPV 16 being the most frequent (N = 12; 14.5%), with multiple HPV infection in 17 samples (27%). Nine (3.6%) abnormal cervical smears were diagnosed. Follow-up of women with abnormal cytology and/or infection with high-risk HPV was obtained in 29 cases (55.8%), showing 12 persistent high-risk HPV infections. Nine women had colposcopy with a final diagnosis of four normal cervixes, three cervical intraepithelial neoplasia grade 1 and two cervical intraepithelial neoplasia grade 2. Overall, women adherence to the free post-partum follow-up visit was 53.5%. This study suggests that a screening program combining HPV testing with cervical cytology during pregnancy may be one option to target young women with poor adhesion to regular cervical cancer screening.