HPV16 viral load and physical state measurement as a potential immediate triage strategy for HR-HPV-infected women: a study in 644 women with single HPV16 infections

American Journal of Cancer Research

Frank Stubenrauch¹  Anna Manawapat-Klopfer²  Lisa Wang³  Juliane Haedicke-Jarboui⁴ 

[1] Department of Obstetrics and Gynecology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark;Division of Experimental Virology, Institute for Medical Virology, University Hospital, Tbingen, Elfriede-Aulhorn Str. 6, 72076, Tbingen, Germany;Institute for Clinical Epidemiology and Applied Biometry, Silcherstrae 5, 72076, Tbingen, Germany;Unit of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Strandboulevarden 49, DK-2100 Copenhagen, Denmark

关键词: HPV;    cervical lesions;    viral load;    physical state;    triage marker;   

DOI  :  

学科分类：肿瘤学

来源: e-Century Publishing Corporation

【 摘 要 】

High genome copy number (viral load) of human papillomavirus (HPV) is being discussed as a risk factor for high-grade cervical lesions. However, conflicting data about the integration status or viral load of the virus as risk factors for prevalent high-grade squamous intraepithelial lesions (HSIL) are found in the literature. To investigate whether viral load and/or integration status are indicative for prevalent ASCUS/LSIL or HSIL, we determined the HPV16 viral load and the physical state of the genome in 644 women with single HPV16 infections stratified by their cytology results from a large Danish population-based cohort consisting of 40,399 women. Cervical smear samples were tested using a multiplex quantitative real-time PCR (qPCR) with primers specific for HPV16 E2, E6 and beta actin, allowing simultaneous determination of the genome’s physical state and the viral copy number per cell. The associations of viral load and physical state with cervical abnormalities were assessed using multinomial logistic regression. We found that a 10-fold increase in viral load was significantly associated with the presence of ASCUS/LSIL (OR=3.91; 95% CI, 2.49-6.13) and HSIL (OR=4.1; 95% CI, 2.45-6.68). A significant association with HSIL was observed for primarily integrated genomes (OR=6.68; 95% CI, 1.45-30.8). Among women with integrated viral genomes, we observed a trend towards increased risk of ASCUS/LSIL (OR=1.32; 95% CI -2.90-3.44) and HSIL (OR=5.10; 95% CI -0.67-38.9) per 10-fold increase in viral load, although not statistically significant. In conclusion, increasing viral load and integrated viral genomes were significantly associated with prevalent HSIL, thus indicating that viral load and physical state may potentially be useful triage markers for HPV16-positive women during cervical screening.

【 授权许可】

CC BY-NC