Prevalence Of Human Papillomavirus Infection, Cervical Cytology Abnormality And Gene Methylation Status In Qujing Of Yunnan Province

Background Cervical cancer is the second most common tumor of women. Human papillomavirus infection is one of the causes of cervical cancer. This study was undertaken to determine the prevalence of HPV infection, cytological abnormality and risk factors, as well as the related gene methylation status in general female population of Qujing in Yunnan province.Methods The cross-sectional study was conducted in5936resident women aged18to65years in Qujing city. Participants were asked to complete a questionnaire, which designed to elicit socio-demographic status, sexual behavior and other probable risk factors for cervical cancer. Cervical specimens were obtained for both cytology diagnose and HPV DNA detection using HPV GenoArray Test kit. In case-control study, methylation status of MGMT,RAR,DAPK1genes in abnormal cytology samples were compared with randomly selected normal controls using methylation-specific PCR accompanied with denaturing high performance liquid chromatography (DHPLC). Frequencies were compared by χ2tests and logistic regression was utilized to evaluate risk factors.Results A total of5936women participated in the study. The overall HR-HPV prevalence was8.3%with two peaks of age-specific infection. The first was11.5%in women aged18-24and the second was11.2%in women aged55-59. In412HR-HPV genotyping positive samples, the five most prevalent types were HPV-16(3.4%), HPV-56(1.7%), HPV-58(1.4%), HPV-33(1.2%) and HPV-52(0.88%). The prevalence of multiple HPV infections was3.5%with the most common combination of HPV-16and HPV-56. Multivariate logistic regression model indicates that age of50-65, being married are protective factors of HPV infection.The overall prevalence of cytological abnormality was5.8%, with a maximum of7.3%at age35-39. The OR for LSIL and HSIL is the highest for HPV-33(OR60.64, CI18.40-199.87; OR381.06, CI68.88-2108.02), followed by HPV-58. Among multiple HPV infection, the OR for HSIL (OR699.11, CI190.30-2568.32) is two times higher than that for HSIL with single HPV infection (OR196.35, CI59.00-653.33). Multivariate logistic regression model indicates that HPV infection, age of50-54, smoke and trichomoniasis infection are risk factors, and age of35-39is a protective factor of cytological abnormality. In case-control study on related genes methylation status analysis, methylation frequencies of MGMT,RARβ2,DAPK1genes were36.9%,42.0%and46.7%in women with normal cytology, respectively. The age-specific methylation frequency of any gene was significantly different. The frequency of MGMT and RARβ2gene methylation was significantly different in negative, ASCUS, LSIL and HSIL. There was a trend of an increasing number of methylated genes with increasing severity of cervical cytology. The methylation of each gene and any of the genes were risk factors of cytological abnormality. There is no relationship with HPV infection and methylation of three genes. The methylation frequency of DAPK1within pathologyically confirmed normal specimen was significantly higher than in CIN1. The sensitivity and specificity of methylation in MGMT gene to diagnose CIN2+was75%and60%, respectively.Conclusions HR-HPV prevalence was8.3%in Qujing. There were two peaks of HPV infection in18-24and55-59age groups. The most prevalent type was HPV-16and the prevalence of multiple HPV infection accounted for50.5%of genotyping positive sample. Age of50-65, being married was protective factors of HPV infection.The overall prevalence of cytological abnormality was5.8%. HPV infection was the strongest risk factor for cytological abnormality. The infection of HPV-33and HPV-58play an important role in cytological abnormality. It deserved to attach importance to multiple HPV infection and cervical cytology screening for perimenopausal women has more important clinical value in screening program of cervical cancer.There was a trend of an increasing number of methylated genes with increasing severity of cervical cytology. There is no relationship between HPV infection and methylation of MGMT,RARβ2,DAPK1genes. The methylation frequency of DAPK1in normal specimen is higher than CIN1in LSIL. The sensitivity and specificity of methylation in MGMT gene to diagnose CIN2+was relatively high.This study described the prevalence of HPV infection and cytological abnormality in Qujing of Yunnan province, providing comprehensive baseline data for HPV vaccine research.