Interaction Between Polycyclic Aromatic Hydrocarbons And HPV Infection In Cervical Intraepithelial Neoplasia

Objective The occurrence and development of cervical intraepithelial neoplasia depends on many factors besides HPV infection type, HPV-DNA content, and the duration of infection. Among them, the relationship between polycyclic aromatic hydrocarbons exposure and cervical intraepithelial neoplasia is increasingly attracting the attention of researchers all over the world. Studies have shown that environmental pollutants polycyclic aromatic hydrocarbons exposure may increase the risk of cervical dysplasia. Experimental study of cytology also shown that the representative of polycyclic aromatic hydrocarbons benzo(a) pyrene could induce HPV persistent infection by changing the HPV life cycle. However, there were no report about the relationship between polycyclic aromatic hydrocarbons and cervical lesions and the relationship between polycyclic aromatic hydrocarbons and HPV infection in the occurrence and development of cervical intraepithelial neoplasia. This study selected different cervical lesion women as the research object in community population. The 1-hydroxypyrene in urine and the HPV infection status were detected and the correlation between the above biological events was observed, which was used to evaluate the relationship between HPV infection and polycyclic aromatic hydrocarbons and the effect in the occurrence and development of cervical intraepithelial neoplasia. This will provide a theoretical basis for the study of the etiology and pathogenesis of cervical intraepithelial neoplasia, and provide a new idea for the prevention and intervention of cervical intraepithelial neoplasia.Methods All the research objects were selected from Thinprep Cytologic Test(TCT), colposcopy uterus of neck and pathological diagnosis from Shanxi Yangqu County cervical lesion cohort during June 2014 to December 2014. Total 486 patients with 208 normal cervical(NC), 154 cervical intraepithelial neoplasia Ⅰ(CIN Ⅰ), and 124 cervical intraepithelial neoplasiaⅡ/Ⅲ(CINⅡ/Ⅲ) were included in this study. Relevant information of general demographic characteristics and factors associated with cervical intraepithelial neoplasia was collected with structural questionnaire, and collected cervical cells and urine by operating specifications. HPV infection status and 1-hydroxypyrene in urine were detected by flow-through hybridization technology and high performance liquid chromatography respectively. The database was established by Epi Data(version 3.1) software and the data was analyzed by SPSS(version 20.0). Differences among groups were assessed by chi-square test, the correlation relationship between variables was analyzed by spearman rank correlation, strength of the correlation between disease and factors was evaluated by OR and OR95%CI, logistic regression model was adopted by multivariate analysis. Additive effect model and interaction indices relative excess risk(RERI), attribution hazard ratio(API) and interaction index(S) was used to qualitative and quantitative evaluation of interaction effects.Results 1. HPV infection status in different cervical lesions: The age group of the highest HPV infection rate in different cervical lesion groups was less than 35 years old group(52.4%), 35 to 44 years old group(59.4%), 45 to 54 years old group(69.8%), respectively. With increasing of the degree of cervical lesions, the age of the highest HPV infection rate was gradually increased. The top three HPV genotypes were 16, 58 and 52 in different cervical lesions. HPV infection was mainly dominated by a single infection. 2. Relationship between HPV infection, HR-HPV infection, HPV16 infection and cervical intraepithelial neoplasia: HPV infection rates were 30.3%, 39.0% and 58.9% respectively in different cervical lesions, and the overall distribution of the difference was statistically significant(c2(28)26.55, P(27)0.001). With increasing of the degree of cervical lesions, HPV infection rate was gradually increased(c2trend(28)25.15, P(27)0.001). HR-HPV infection rates were 29.8%, 37.7% and 58.9% respectively in different cervical lesions, and the overall distribution of the difference was statistically significant(c2(28)27.80, P(27)0.001). With increasing of the degree of cervical lesions, HR-HPV infection rate was gradually increased(c2trend(28)25.83, P(27)0.001). The infection rate of HPV16 was 8.7%, 10.4% and 37.9% respectively, and the difference was statistically significant(c2(28)54.25, P(27)0.001). The infection rate of HPV16 increased gradually along with the severity of cervical lesions(c2trend(28)41.85, P(27)0.001). 3. Relationship between polycyclic aromatic hydrocarbons and cervical intraepithelial neoplasia: The concentrations of 1-hydroxypyrene were 0.07±0.09mmol/mol Cr, 0.11±0.10mmol/mol Cr and 0.17±0.15mmol/mol Cr respectively in different cervical lesions, and the overall distribution of the difference was statistically significant(H(28)76.36, P(27)0.001). The difference between any two groups was statistically significant(P(27)0.001). Compared with 50% 1-hydroxypyrene concentration of NC group, with increasing of the degree of cervical lesions, 1-hydroxypyrene high exposure rate was gradually increased(c2trend(28)27.94, P(27)0.001). 4. Relationship between polycyclic aromatic hydrocarbons and HPV infection in cervical intraepithelial neoplasia: HPV infection, HR-HPV infection, HPV16 infection and 1-hydroxypyrene exposure were positively correlated(r(28)0.615, P(27)0.001; r(28)0.615, P(27)0.001; r(28)0.357, P(27)0.001). There was a positive additive interaction between HPV infection and 1-hydroxypyrene in CINⅡ/Ⅲ group but not in CINⅠgroup. 5. Analysis of factors related cervical intraepithelial neoplasia: Significant factors was put into the unconditional logistic regression model, such as age structure, passive smoking, bathing frequency, washing vagina frequency, underwear washing frequency, menstrual menarche age, menopause, age of first sexual intercourse, gravidity, parity, IUD, HPV infection, PAHs exposure. Factors which enter the model in CINⅠgroup were passive smoking, underwear washing frequency, age of first sexual intercourse, and factors which enter the model in CINⅡ/Ⅲ group were passive smoking, frequency of washing vagina, menopause, age of first sexual intercourse, parity, IUD, HPV infection, PAHs exposure.Conclusion 1. The main subtypes of HPV infection in this area were 16, 58, 52. This study reports inconsistent with other regions, which indicated that the distribution of subtypes of high-risk HPV in different areas was different. Therefore, to study the distribution of HR-HPV subtypes in different regions is helpful to research and develop the HPV vaccine with different valence, which has important value in the prevention of cervical cancer and precancerous lesions. 2. HPV infection, HR-HPV infection and HPV16 infection can increase the risk of CINⅠand CINⅡ/Ⅲ. Childbearing age women should not only carry out TCT screening regularly, but also carry out the classification of HPV screening at the same time. Early detection of abnormal changes of cervical cells, and prevention and control HPV infection can nip it in the bud. 3. PAHs exposure may lead to an increased risk of CIN. There was a positive correlation between PAHs exposure and HPV infection. PAHs exposure and HPV infection present positive interaction in CINⅡ/Ⅲ group. These suggested that PAHs and HPV infection simultaneously exist may increase the risk of CIN. The relevant departments should not only prevent and control HPV infection but also increase efforts to control environmental pollution, and reduce the risk of PAHs exposure to childbearing age women. 4. The common risk factors of CINⅠand CINⅡ/Ⅲ included passive smoking and too small age of first sexual intercourse. High frequency of washing underwear was a protective factor of CINⅠ. Washing the vagina high frequency and menopause were protective factors of CINⅡ/Ⅲ. Having IUD and multiparity were risk factors of CINⅡ/Ⅲ. Therefore, strengthening sexual and reproductive health education among childbearing age women, raising health awareness of childbearing age women, promoting healthy sexual life and avoiding exposure to cigarette smoke have a significant role in the prevention and control of cervical cancer and precancerous lesions.