Le-Ni Kang

The Natural History of Cervical Cancer in Chinese Women: Results from an 11-Year Follow-Up Study in China Using a Multistate Model

Background: It is important to understand the natural history of cervical cancer, which has implications for cancer prevention and management. However, a dearth of studies on the long-term development of cervical cancer exists in China. Methods: We investigated the natural history of cervical cancer in Chinese women by creating a multistate model using 11 years of follow-up data from the Shanxi Province Cervical Cancer Screening Study I conducted from 1999 to 2010. In 1999, a total of 1,997 eligible women, ages 35 to 45 years, were enrolled in Xiangyuan County, Shanxi Province. Participants were followed up in 2005 and 2010, respectively. Results: The average time a subject spent in CIN1 before transiting into another state was 1.4693 years [95% confidence interval (CI): 1.1215–1.9251] and the average time a subject spent in CIN2 was 2.9822 years (95% CI: 1.9790–4.4938). A subjects transition probability from CIN1 to normal increased with time. However, the transition probability from CIN1 to CIN2 was relatively lower, with 3-, 5-, and 10-year transition probabilities of 0.1415, 0.1066, and 0.0437. Comparison of 5-year transition probabilities between CIN2 to normal/CIN1 and CIN2 to CIN3+ yielded a ratio of 2.74. Conclusions: Women with CIN1 had a substantial tendency for regression. Similarly, women with CIN2 had a higher probability of regression to normal/CIN1 than progression to CIN3+. Findings in this study may have significant implications for the development and evaluation of formal cervical cancer preventive strategies in China. Impact: This study may serve as a valuable reference to future research on other multistate cancer processes. Cancer Epidemiol Biomarkers Prev; 23(7); 1298–305. ©2014 AACR.

Elevated Expression of Human Papillomavirus-16/18 E6 Oncoprotein Associates with Persistence of Viral Infection: A 3-Year Prospective Study in China

Background: An association between high-risk human papillomavirus (HR-HPV) oncoprotein expression and viral persistence has been suggested by the outcome of etiology studies, but there are no epidemiologic studies evaluating that link. Methods: We performed a 3-year prospective study in which 2,498 Chinese women ages 25 to 65 years were screened by six screening tests, including the OncoE6 Cervical Test (Arbor Vita Corporation) in 2011 (baseline). Six-hundred and ninety women who were positive for any of the tests and a random sample of 164 women with all negative results received colposcopy, and cervical specimens for the cobas 4800 HPV test (“cobas,” Roche Molecular Systems) were collected before colposcopy; of this group, 737 cervical specimens were collected to perform cobas and OncoE6 Cervical Test in 2014 (follow-up). Twenty-four cases of HPV16/18 E6 positives and 204 selected controls at baseline, 13 cases of HPV16/18 E6 positive and another 204 selected controls at follow-up were analyzed separately using unconditional logistical regression models to estimate ORs and 95% confidence intervals (CI). Results: Compared with women who were HPV16 E6 oncoprotein negative at baseline, women in the E6-positive group had a much higher risk of HPV persistence (adjusted OR, 54.64; 95% CI, 7.19–415.09) at 3-year follow-up; a statistically strong association was also found between HPV16/18 HPV persistence and E6 oncoprotein expression detected at follow-up (adjusted OR, 360.57; 95% CI, 28.30–4,593.55). Conclusions: A single detection of HPV16/18 E6 oncoprotein expression was strongly associated with viral persistence. Impact: HPV16/18 E6 oncoprotein constitutes a marker for risk of HPV persistence. Cancer Epidemiol Biomarkers Prev; 25(7); 1167–74. ©2016 AACR.

p16/Ki-67 co-expression associates high risk human papillomavirus persistence and cervical histopathology: a 3-year cohort study in China

Purpose To evaluate the association of p16/Ki-67 co-expression and persistence of high-risk human papillomavirus (HR-HPV) infection as well as cervical abnormalities. Methods We performed a 3-year cohort study among which 2498 Chinese women aged 25 to 65 years were screened by different HPV tests in 2011. 690 women who were positive at any of the tests and a random sample of 164 women with all negative results received colposcopy, cervical specimens for cobas HPV test (Roche diagnostics) were collected before colposcopy; of this group, 737 cervical specimens were collected to perform cobas, Liquid-based cytology, HPV E6 test (Arbor Vita Corporation) and p16/Ki-67 dual staining (Roche diagnostics) in 2014. Colposcopy and biopsies was performed on women with any abnormal result. Results Compared to women without HR-HPV persistent infection, women in the HR-HPV persistence group had a higher risk of p16/Ki-67 positive, with an adjusted Odds Ratio(OR) and 95% confidence interval (CI) of 6.29 (4.07-9.72); moreover, adjusted odds ratio for women who had HPV16/18 persistent infection was nearly 4-folder higher than women with other 12 HR-HPV persistent infection (adjusted OR = 17.15, 95% CI: 7.11-41.33 vs adjusted OR = 4.68, 95% CI: 2.89-7.58). Additionally, p16/Ki-67 positivity rate significantly increased with the severity of the cytological and histological abnormalities, and resulted strongly associated with a CIN2+ diagnosis (OR = 16.03, 95% CI: 4.46-57.59). Conclusions p16/Ki-67 co-expressions associated strongly with HR-HPV persistence, especially with HPV16/18, and the presence of a CIN2+ lesion. Therefore, p16/Ki-67 could be considered as a suitable biomarker for cervical cancer screening, particularly in HPV-based screening programs.