Chanyuan Zhang

Nine Complete Genome Sequences of Cutaneous Human Papillomavirus Genotypes Isolated from Healthy Skin of Individuals Living in Rural He Nan Province, China

ABSTRACT Nine novel human papillomavirus (HPV) types were isolated from healthy skin of individuals in rural Anyang, China. All of these isolates belong to the genus Gammapapillomavirus. These data will provide us with useful information for a better understanding of PV evolution and the relationship of PV with the host.

Seroprevalence of Merkel cell polyomavirus in the general rural population of Anyang, China.

Background Despite the probably causal link between Merkel cell polyomavirus (MCPyV) infection and Merkel cell carcinoma (MCC), a rare but aggressive skin malignancy, little is known about the seroepidemiology of MCPyV among healthy adults in China. Methods Serum antibodies against MCPyV were evaluated by multiplex serology in a population-based study of 5548 adults (including 1587 heterosexual couples) aged 25–65 years who were enrolled from rural Anyang, China in 2007–2009. Univariate and multivariate logistic regression analyses were performed to assess the risk factors for the seropositivity of MCPyV. Results The seroprevalence for MCPyV was 61.0%. MCPyV seropositivity was significantly higher in males than in females (64.5% vs. 57.7%, P<0.001), and for both genders, showed a trend of increase with age (Male: P trend<0.001; Female: P trend<0.001). Furthermore, among antibody positives, antibody levels of MCPyV increased with advancing age (P trend = 0.017). MCPyV seropositivity of one spouse was significantly associated with that of the other partner (Adjusted OR = 1.32, 95% CI: 1.07–1.62). However, there was no association between sexual behaviors and the seropositivity of MCPyV. Conclusions High seroprevalence of MCPyV was observed in healthy Chinese individuals. Serological evidence suggests that nonsexual horizontal spread of MCPyV can occur among family members, and further research in this regard is needed.

Improved detection of human papillomavirus harbored in healthy skin with FAP6085/64 primers

FAP59/64, FAP6085/6319, and CUT primer sets were designed for detecting cutaneous HPV and have been used in many clinical and epidemiology studies. The FAP6085/64 primer set was first evaluated in this study and the FAP6085/64 combination was found to be much more sensitive than all three original primer sets by using HPV plasmids as a template. To confirm further the effectiveness of the FAP6085/64 primer set in human DNA templates, 90 palmar exfoliated cell DNA samples were used to detect the cutaneous HPV by both the FAP59/64 and FAP6085/64 primer sets. The overall proportion of HPV detection in those skin samples was 77.8% (70/90) using FAP6085/64, as compared to 55.6% (50/90) using FAP59/64. The FAP6085/64 primer set was also applied in a population based study. The proportion of HPV detection was 73.96% (2076/2807) in skin samples collected from healthy individuals, and a total of 336 different PV types were found. Sixty (17.9%) of them were fully characterized HPV types, 127 (37.8%) were putative HPV types which had been described previously, 149 (44.3%) were novel putative HPV types, and two animal PVs were also detected. These results suggest that the FAP6085/64 primer set was sensitive and effective for detection of cutaneous HPV in healthy skin samples.

Prevalence, Incidence, Clearance, and Associated Factors of Genital Human Papillomavirus Infection among Men: A Population-Based Cohort Study in Rural China

Background: The natural history of human papillomavirus (HPV) infection in men on a population base has rarely been studied in general, particularly among Chinese men. Methods: A total of 1,286 men ages 25 to 65 years from rural China were enrolled during 2009–2010 and their genital HPV infection status was assessed biannually for up to seven visits using PCR and sequencing methods. Prevalence analysis was performed among men with at least one valid HPV result (N = 1,279) and men with at least two consecutive HPV results (N = 1,059) were included in incidence and clearance analyses (median follow-up time, 31.8 months; interquartile range, 15.4–37.9 months). Results: The prevalence and incidence of any HPV type, oncogenic, and nononcogenic HPV were 17.8%, 6.4%, 12.4%, and 14.6, 4.9, 10.8 per 1,000 person months, respectively. The median duration of infection with any HPV type, oncogenic, and nononcogenic HPV was 11.5, 6.8, and 11.5 months, respectively. The number of lifetime sexual partners was consistently associated with increased risk of prevalent and incident infection of HPV. Men ages 25 to 50 years had a higher incidence and longer duration of HPV infection than older men (51–65 years). Conclusions and Impact: This epidemiologic investigation provides basic information of genital HPV infection among the Chinese male population; these data are crucial for the consideration of primary strategies against HPV-related carcinoma in the Chinese male and female population. Cancer Epidemiol Biomarkers Prev; 23(12); 2857–65. ©2014 AACR.

Seroprevalence of 10 human papillomavirus types in the general rural population of Anyang, China: a cross-sectional study

Objectives Data on the seroprevalence of human papillomavirus (HPV) in China are limited. The objective of this study was to characterise the serological profiles of HPV infection in a rural Chinese population and help establish effective vaccine policy. Methods Serum antibodies against the major capsid protein L1 of 10 HPV types (HPV-3, 6, 11, 16, 18, 45, 52, 57, 58 and 75) were evaluated with Luminex-based multiplex serology in a population-based study of 5548 adults (including 1587 couples) aged 25–65 years enrolled from rural Anyang, China, in 2007–2009. Results The seroprevalence for any HPV type and any of the types HPV-6/11/16/18 was 64.8% and 34.4%, respectively. 30.3% of adults were seropositive for any mucosal high-risk (HR) HPV, and HPV-58 (10.6%), HPV-16 (9.7%) and HPV-18 (9.3%) were the three most common types. 24.8% of seropositive individuals were positive for multiple mucosal HR-HPV serotypes. Seroprevalence for most HPV types was similar among men and women. While mucosal low-risk HPV seropositivity was found to significantly decrease with age, the prevalence of antibodies to mucosal HR antigens showed a general trend of increase with age. The lifetime number of sex partners was independently associated with mucosal HR-HPV seropositivity. Positive correlation of spousal seropositivity was observed for mucosal HPV but not for cutaneous HPV. Conclusions HPV infection was common in both men and women in rural China. HPV seroprevalence differed significantly with age, sexual behaviour and spousal infection status. These findings will be useful for evaluating and establishing HPV vaccination programmes.

Transmission of genital human papillomavirus infection in couples: a population-based cohort study in rural China

HPV transmission dynamics have rarely been studied in the general population, especially in China. We followed the genital HPV infection status of both partners in 874 couples aged 25-65 years from rural China for up to 7 bi-annual visits during 2009-2013. The positive HPV concordance and transmission rate for partners in a couple were evaluated and relevant risk factors were assessed. The concordance of any, oncogenic, and non-oncogenic HPV was 15.52%, 16.18% and 10.41%, respectively. Male-to-female transmission rate was 7.11, 12.13 and 4.77/1000 person months for any, oncogenic and non-oncogenic HPV respectively. The female-to-male transmission rate was 5.56, 2.37, and 17.01/1000 person months for any, oncogenic and non-oncogenic HPV respectively. The risk of male-to-female transmission was significantly higher than that of female-to-male transmission for oncogenic types. However, for non-oncogenic types, the risk of male-to-female transmission was significantly lower than that of female-to-male transmission. Younger couples, persistent infection with HPV, higher numbers of sexual partners and higher frequency of sexual intercourse were positively associated with HPV transmission in couples. Our results indicate that men in rural China play a more important role than men in western populations as a source of cervical oncogenic HPV infection in women.

A Model To Identify Individuals at High Risk for Esophageal Squamous Cell Carcinoma and Precancerous Lesions in Regions of High Prevalence in China

BACKGROUND & AIMS: We aimed to develop a population‐based model to identify individuals at high risk for esophageal squamous cell carcinoma (ESCC) in regions of China with a high prevalence of this cancer. METHODS: We collected findings from 15,073 permanent residents (45–69 years old) of 334 randomly selected villages in Hua County, Henan Province, China who underwent endoscopic screening (with iodine staining) for ESCC from January 2012 through September 2015. The entire esophagus and stomach were examined; biopsies were collected from all focal lesions (or from standard sites in the esophagus if no abnormalities were found) and analyzed histologically. Squamous dysplasia, carcinoma in situ, and ESCC were independently confirmed by 2 pathologists. Before endoscopy, subjects completed a questionnaire on ESCC risk factors. Variables were evaluated with unconditional univariate logistic regression analysis; variables found to be significantly associated with ESCC were then analyzed by multivariate logistic regression modeling. We used the Akaike information criterion to develop our final model structure and the coding form of variables with multiple measures. We developed 2 groups of models, separately defining severe dysplasia and above (SDA) (lesions including severe dysplasia and higher‐grade lesions) and moderate dysplasia and above (lesions including moderate dysplasia and higher‐grade lesions) as outcome events. Age‐stratified and whole‐age models were developed; their discriminative ability in the full multivariate model and the simple age model was compared. We performed area under the receiver operating characteristic curve (AUC) and the DeLong test to evaluate model performance. RESULTS: Our age‐stratified prediction models identified individuals 60 years of age or younger with SDA with an AUC value of 0.795 (95% confidence interval, 0.736–0.854) and individuals older than 60 years with SDA with an AUC value of 0.681 (95% confidence interval, 0.618–0.743). Factors associated with SDA in individuals 60 years or younger included age closer to 60 years, use of coal or wood as a main source of cooking fuel, body mass index of 22 kg/m2 or less, unexplained epigastric pain, and rapid ingestion of meals. In subjects older than 60 years, SDA associated with age, family history of ESCC, cigarette smoking, body mass index of 22 kg/m2 or less, pesticide exposure, irregular eating habits, intake of high temperature foods, rapid ingestion of meals, and ingestion of leftover food in summer months. Use of our model in screening could have allowed 27% of subjects 60 years or younger and 9% of subjects older than 60 years to avoid endoscopy without missing SDAs. This means that approximately 2500 of endoscopies in total (16.6%) could have been avoided. CONCLUSIONS: We developed a low‐cost, easy‐to‐use model to identify individuals at risk for severe dysplasia or cancer of the esophagus living in a region of China with a high risk of ESCC. This model might be used to select individuals and groups of persons who should undergo endoscopy analysis for esophageal cancer.

Viral Load in the Natural History of Human Papillomavirus Infection Among Men in Rural China: A Population-based Prospective Study

Background High-risk human papillomavirus (HR-HPV) load is predictive of HR-HPV persistence and subsequent carcinogenesis in women. However, in men, data on genital HPV load and its effect on the natural history of HPV infection are limited. Methods The subjects included 1532 men aged 25-65 years with up to 7 biannual visits for evaluation of genital HPV load in rural China during 2009-2013 who were positive for ≥1 of the 18 selected HPV types (including 10 HR-HPV types) detected by general primer-mediated polymerase chain reaction (PCR) and sequencing. Type-specific HPV load was quantified with real-time PCR and dichotomized based on median values. Results Men with multiple lifetime sex partners were more likely to have higher overall levels of HR-HPV load across visits (adjusted odds ratio, 2.42; 95% confidence interval [CI], 1.12-5.24; 2 partners vs 0-1 partner). Higher levels of HR-HPV load at the time of the first HPV diagnosis conferred an increased probability of the subject remaining type-specific HPV-positive up to 12 months and an increased probability of persistent/intermittent infection (virus detected repeatedly with or without a period of intercurrent negativity) versus transient infections (single-time positive). Higher overall HR-HPV levels were predictive of reduced HR-HPV clearance rates (adjusted hazard ratio, 0.47; 95% CI, .27-.83). Conclusions Having multiple lifetime sex partners is associated with increased male genital HR-HPV load. Higher HR-HPV load predicts persistence of HR-HPV in men from rural China.

Human papillomavirus DNA positivity and seropositivity in rural Chinese men and women: a population-based cross-sectional study

Data on simultaneous analysis of human papillomavirus (HPV) DNA and serology and the correlations within a single general population are limited. Among 1603 men and 2187 women enrolled from rural China, serum antibodies against bacterially derived GST-L1 fusion proteins of HPV were assessed with multiplexed serology and HPV DNA was evaluated with PCR-based sequencing. Few subjects were dually positive to HPV DNA and serum antibodies for any HPV (6.6% of men and 3.1% of women). The proportion of men ever having been infected with any HPV (DNA and/or antibody positive) was higher than that of women (71.0% vs. 65.2%, P < 0.001). Type-specific association was observed for genital HPV infection and HPV seropositivity among women but not among men. A positive correlation between the number of lifetime sexual partners and positivity for oncogenic HPV DNA and/or antibodies was found in men but was absent in women. Among 762 couples, the presence of HPV DNA and/or antibodies in one partner was positively associated with the identical HPV type in the other partner. These findings may reflect a site-specific natural course of HPV infection and further understanding of the epidemiology of HPV.

The Willingness to Change Risky Health Behaviors among Chinese Rural Residents: What We Learned from a Population-Based Esophageal Cancer Cohort Study

Background The effectiveness of health interventions can be impaired by low socio-economic status and poor living conditions of the target population. However, the specifics of this problem in rural China are still unclear, and appropriate strategies should be explored. Methods In 2013, we conducted a questionnaire-based investigation among 410 participants from a population-based esophageal cancer cohort study in rural Anyang, China. Information regarding their demographic characteristics, levels of exposure to four health-risk behaviors, including smoking, alcohol consumption, risky dietary behaviors and poor hygiene, as well as willingness to change these behaviors, and data on potential predictors of willingness to change behaviors were collected. Results In this study, 33.3% (23/69), 25.0% (13/52), 60.7% (68/112) and 62.2% (237/381) of respondents reported that they were willing to change smoking, alcohol consumption, risky dietary behaviors and poor hygiene, respectively. Older people had higher exposure levels and less willingness to change these four health-risk behaviors. The levels of these four health-risk behaviors were negatively associated with willingness to change, while faith in people and behavioral change in surrounding people increased willingness to change risky behaviors. Conclusions In behavior-intervention-based health-promotion programs in rural China, the elderly and highly exposed populations should be the most difficult part and community- or household-based intervention would be more efficient.