Xuelian Zhao1, Shuang Zhao1, Shangying Hu1, Kevin Zhao2, Qian Zhang1, Xun Zhang3, Qinjing Pan4, Fanghui Zhao1. 1. Department of Epidemiology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. 2. Department of Biology, University of Chicago, Illinois. 3. Department of Pathology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. 4. Department of Cytopathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Abstract
BACKGROUND: Biomarkers highly predictive of cervical cancer are urgently needed for triaging human papillomavirus (HPV)-positive women. METHODS: A total of 1997 women aged 35-45 years in Shanxi, China, were recruited in 1999, and follow-up visits were conducted in 2005, 2010, and 2014. HPV load was measured by the Hybrid Capture 2 assay. Findings were determined by relative light units/cutoff (RLU/CO) and categorized into 4 groups: negative ( <1.0), low (range, 1.0 to <10.0), moderate (range, 10.0 to <100.0), and high (range, 100.0-∞). Cumulative incidence rates (CIRs) and adjusted hazard ratios (aHRs) for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) were calculated for viral load subgroups, using survival analysis. RESULTS: Among 1739 women with normal or CIN1 pathological findings at baseline, 15-year CIRs for CIN2+ for those who were HPV negative and those with low, moderate, and high HPV loads groups were 3.1%, 8.4%, 19.9%, and 22.0%, respectively (Ptrend <.001). Compared with women who were negative for HPV from baseline through follow-up, those who had decreasing, increasing, or stable moderate/high loads had aHRs of 9.1, 38.7, or 379.7, respectively, for CIN2+. There was no significant difference between triage based on cytologic findings (for those with atypical squamous cells of undetermined significance or more-severe findings) and that based on a moderate/high HPV load for HPV primary screening (P = .343). CONCLUSION: A moderate/high HPV load may accelerate the progression of cervical precancers and potentially could be used as a triage indicator for HPV-positive women.
BACKGROUND: Biomarkers highly predictive of cervical cancer are urgently needed for triaging human papillomavirus (HPV)-positive women. METHODS: A total of 1997 women aged 35-45 years in Shanxi, China, were recruited in 1999, and follow-up visits were conducted in 2005, 2010, and 2014. HPV load was measured by the Hybrid Capture 2 assay. Findings were determined by relative light units/cutoff (RLU/CO) and categorized into 4 groups: negative ( <1.0), low (range, 1.0 to <10.0), moderate (range, 10.0 to <100.0), and high (range, 100.0-∞). Cumulative incidence rates (CIRs) and adjusted hazard ratios (aHRs) for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) were calculated for viral load subgroups, using survival analysis. RESULTS: Among 1739 women with normal or CIN1 pathological findings at baseline, 15-year CIRs for CIN2+ for those who were HPV negative and those with low, moderate, and high HPV loads groups were 3.1%, 8.4%, 19.9%, and 22.0%, respectively (Ptrend <.001). Compared with women who were negative for HPV from baseline through follow-up, those who had decreasing, increasing, or stable moderate/high loads had aHRs of 9.1, 38.7, or 379.7, respectively, for CIN2+. There was no significant difference between triage based on cytologic findings (for those with atypical squamous cells of undetermined significance or more-severe findings) and that based on a moderate/high HPV load for HPV primary screening (P = .343). CONCLUSION: A moderate/high HPV load may accelerate the progression of cervical precancers and potentially could be used as a triage indicator for HPV-positive women.