Mengfei Liu

Oral Human Papillomavirus Infection and Its Risk Factors among 5,410 Healthy Adults in China, 2009–2011

Background: Despite the established link between oral human papillomavirus (HPV) infection and a subset of oropharyngeal squamous cell carcinoma (OSCC), little is known about the epidemiology of oral HPV infection among healthy adults in China. Methods: Oral swab specimens and questionnaires were collected from 5,410 individuals (ages 25–65 years). HPV DNA in oral exfoliated cells was tested by general primer-mediated (SPF1/GP6+) PCR and sequencing. Univariate and multivariate analyses were performed to assess the associations between exposure factors and oral infection. Results: Alpha mucosal HPV types were detected in 0.67% [95% confidence interval (CI), 0.47%–0.93%] of 5,351 β-globin–positive specimens, and cutaneous HPV in 5.46% (95% CI, 4.86%–6.10%). HPV 16 and 3 were the most prevalent types of α mucosal (0.43%; 95% CI, 0.27%–0.64%) and cutaneous HPV (4.17%; 95% CI, 3.65%–4.74%), respectively. The prevalence of α mucosal HPV decreased with increasing age (25–65 years) from 0.93% to 0.36% (Ptrend = 0.033), and was associated with self-reported history of oral disease [adjusted odds ratio (OR), 4.78; 95% CI, 1.07–21.41]. In 1,614 heterosexual couples, cutaneous HPV in one partner was found to increase the other partners risk of cutaneous HPV infection (adjusted OR, 2.33; 95% CI, 1.22–4.48). Conclusions: Oral HPV infection, particularly with α mucosal types, is rare among healthy adults in China. A younger age and a history of oral disease imply higher risk of α mucosal HPV infection. Impact: This study addresses the paucity of epidemiological data on oral HPV infection among healthy population in China. Cancer Epidemiol Biomarkers Prev; 23(10); 2101–10. ©2014 AACR.

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.

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.

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.

Multiregional Sequencing Reveals Genomic Alterations and Clonal Dynamics in Primary Malignant Melanoma of the Esophagus

Primary malignant melanoma of the esophagus (PMME) is a rare and aggressive disease with high tendency of metastasis. To characterize the genetic basis and intratumor heterogeneity of PMME, we performed multiregion exome sequencing and whole genome SNP array genotyping of 12 samples obtained from a patient with PMME. High intratumor heterogeneity was observed in both somatic mutation and copy-number alteration levels. Nine geographically separate samples including two normal samples were clonally related and followed a branched evolution model. Most putative oncogenic drivers such as BRAF and KRAS mutations as well as CDKN2A biallelic inactivation were observed in trunk clones, whereas clinically actionable mutations such as PIK3CA and JAK1 mutations were detected in branch clones. Ancestor tumor clones evolved into three subclonal clades: clade1 fostered metastatic subclones that carried metastatic features of PIK3CA and ARHGAP26 point mutations as well as chr13 arm-level deletion, clade2 owned branch-specific JAK1 mutations and PTEN deletion, and clade3 was found in two vertical distribution samples below the primary tumor area, highlighting the fact that it is possible for PMME to disseminate by the submucosal longitudinal lymphatic route at an early stage of metastasis. These findings facilitate interpretation of the genetic essence of this rare melanoma subtype as well as the pattern of cancer evolution, thus reinforcing the therapeutic challenges associated with PMME.Significance: This study highlights the use of multiregion exome sequencing and whole genome SNP array genotyping to comprehensively characterize the genetic landscape of a rare type of esophogeal melanoma. Cancer Res; 78(2); 338-47. ©2017 AACR.

The distribution and common amino acid polymorphisms of human papillomavirus (HPV)-31 variants in 2700 women from Northern China.

To investigate the distribution of Human papillomavirus (HPV)-31 A, B and C variants as well as the common amino acid polymorphisms in Chinese women, all 14 HPV-31 positive cervical exfoliated cell specimens identified from a descriptive study including ∼2700 women from Northern China were analyzed. HPV-31 positive specimens were identified by Mass Spectrometry and the fragments of partial Long Control Region, E6 and E7 were amplified and directly sequenced or cloned into vector and then sequenced to confirm the variant information. HPV-31 prevalence in Northern Chinese female population was 0.52%. Six different sequences represented all 14 isolates, and these isolates were subsequently classified into variant lineage A (9), B (0) and C (5) by phylogenetic analysis. Five common amino acid polymorphism sites (2 in E6 and 3 in E7) and a novel non-synonymous mutation were detected in the current study. Our investigation suggested that HPV-31 was much less detected in Chinese women population than that in western countries. A and C variants were commonly detected while B variants were rarely detected in this population.

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.

Epidemiology of self-rated health in rural China: a population-based cross-sectional study.

Self-rated health (SRH) has been shown to be a good predictor of mortality. Data on SRH and its associated factors in the Chinese general population are limited. This study aims to assess the epidemiology of SRH in rural Anyang, China. SRH (categorized as “healthy”, “fair” or “unhealthy”) was measured in a population-based study of 2,814 adults (including 697 couples) aged 25 to 69 who were recruited from rural Anyang in 2014. Of 2,814 subjects, 63.1% rated their health as “healthy”, whereas 28.1% and 8.8% rated their health as “fair” and “unhealthy”. Compared to males, females had a higher likelihood of reporting a better SRH. Health ratings declined with increasing age, unmarried status, lower education levels. Poor SRH was positively correlated with medical history as well as high levels of fasting plasma glucose and total cholesterol, but not with unhealthy lifestyle indicators including smoking, drinking, and obesity. High household income was predictive of better SRH in men but not in women. Among couples, a positive spousal SRH concordance was observed, although the strength of this concordance was low. These findings will be useful for formulation of appropriate strategies for improving risk perception and promoting general health in economically developing regions.

Incidence and clearance of oral human papillomavirus infection: A population-based cohort study in rural China

The natural history of oral human papillomavirus (HPV) infection which is linked with the increased incidence of oropharyngeal squamous cell cancer (OPSCC) has been incompletely studied. Oral swab specimens and questionnaire data were obtained bi-annually for up to 6 visits from 4314 healthy adults aged 25-69 in rural Anyang, China. HPV infection status was evaluated with PCR-based sequencing. Participants with at least two consecutive valid HPV results within the study period were included in the incidence and clearance analysis. Among 3289 participants included in this analysis (median follow-up time 18.3 months), incidence rates of mucosal HPV, oncogenic mucosal HPV and cutaneous HPV were 0.53 (95% CI: 0.39-0.73), 0.30 (95% CI: 0.20-0.46), and 4.17 (95% CI: 3.70-4.70) per 1,000 person-months respectively. Most newly acquired infections were cleared within one year. Recent practice of oral sex increased the risk of incident infection with mucosal HPV (Adjusted HR, 5.03; 95% CI, 1.16-21.73) and oncogenic mucosal HPV (Adjusted HR, 10.13; 95% CI, 2.14-48.06). Newly acquired oral mucosal HPV infections are rare and most are cleared within one year in rural Chinese. This study expands understanding of the natural history of oral HPV in countries with a lower incidence of HPV-OPSCC.The natural history of oral human papillomavirus (HPV) infection which is linked with the increased incidence of oropharyngeal squamous cell cancer (OPSCC) has been incompletely studied. Oral swab specimens and questionnaire data were obtained bi-annually for up to 6 visits from 4314 healthy adults aged 25-69 in rural Anyang, China. HPV infection status was evaluated with PCR-based sequencing. Participants with at least two consecutive valid HPV results within the study period were included in the incidence and clearance analysis. Among 3289 participants included in this analysis (median follow-up time 18.3 months), incidence rates of mucosal HPV, oncogenic mucosal HPV and cutaneous HPV were 0.53 (95% CI: 0.39-0.73), 0.30 (95% CI: 0.20-0.46), and 4.17 (95% CI: 3.70-4.70) per 1,000 person-months respectively. Most newly acquired infections were cleared within one year. Recent practice of oral sex increased the risk of incident infection with mucosal HPV (Adjusted HR, 5.03; 95% CI, 1.16-21.73) and oncogenic mucosal HPV (Adjusted HR, 10.13; 95% CI, 2.14-48.06). Newly acquired oral mucosal HPV infections are rare and most are cleared within one year in rural Chinese. This study expands understanding of the natural history of oral HPV in countries with a lower incidence of HPV-OPSCC.