| BackgroundPersistent infection of high-risk human papillomavirus(hrHPV)is the necessary factor of cervical cancer.Human immunodeficiency virus(HIV)infected women is the high-risk group to having cervical cancer.Compared with HIV-negative women,the prevalence of HPV among HIV-positive women was higher;the process of elimination of HPV was slower;the persistence of HPV infection was longer,the process of developing to cervical cancer and precancerous lesions was faster and worse prognosis.The AIDS epidemic in Yunnan province,Guangxi Zhuang Autonomous Region and Xinjiang Uygur Autonomous Region emerged earlier and is more serious than other areas in China.It was estimated there were 165,000 HIV-infected women,who were mainly distributed in those 3 provinces.Free antiretroviral therapy(ART)were provided in China since 2002.It was reported that the death risk of people living with HIV reduced 73%-82%,and the life expectancy was longer.Research has showed that with the universal ART coverage,the risk of cervical cancer would increase if HIV-infected women didn’t receive cervical cancer screening.HIV-infected women were tended to conceal their HIV-infected status,and were afraid of disclosing their HIV-infected status to others due to stigma and discrimination.Hence,there were barriers to utilize cervical cancer screening service for HIV-positive women.Currently,the reproductive health services aimed at HIV-positive women mainly focuses on prevention mother-to-child transmission of HIV.Services on prevention of sexual transmitted diseases and cervical cancer are limited.The coverage and screening rate of the national program on cervical cancer screening for rural women is still limited and relatively low.Compared with other women,HIV-infected women were more likely to have less chance to obtain the free cervical cancer screening.The needs of cervical cancer prevention and control among HIV-positive women have not been met and need to be concerned about.Currently,there are few studies on hrHPV infection status and persistence of hrHPV infection and their influencing factors among HIV-infected women.There is rare research on cervical squamous intraepithelial lesion(SIL),cervical cancer and precancerous lesions among HIV-infected women in China.Especially,there is no reported on the incidence of hrHPV infection and SIL and their influencing factors among HIV-infected women in China.There is little known on the status of hrHPV infection and the influencing factors,the persistence,elimination,and incidence of hrHPV infection and their influencing factors.There is also little known on the relations between different hrHPV infectious status and SIL,cervical cancer and precancerous lesions,and their influencing factors.Hence,it is necessary to carry out research on the persistence,elimination of hrHPV infection,the incidence of hrHPV infection and SIL,and the influencing factors on cervical cancer and precancerous lesions among HIV-positive women,in order to provide evidence to carry out appropriated cervical cancer screening services to HIV-positive women in China in the future.Objective1.To study the infection status of hrHPV and influencing factors among HIV-positive women.2.To follow up the HIV-positive women and observe the persistence,elimination,and incidence of hrHPV infection,and to analyze the relation between HIV-infection related factors and other factors and the persistence of hrHPV infection and the incidence of hrHPV infection.3.To study the status of cervical lesions caused by different hrHPV infection status in HIV-infected women and its influencing factors.And to analyze the incidence of cervical lesions caused by different status of hrHPV infection and its influencing factors among HIV-positive women.MethodsThis study was a prospective follow-up study.The study sites were Babu district of Hezhou city from Guangxi Zhuang Autonomous Region,Ruili city and Longchuan county from Yunnan province,Yining city and Huocheng county from Xinjiang Uygur Autonomous Region.In the study sites,the cluster random sampling method was applied.During May to August in 2015,695 HIV-infected women aged 18-49 years old were recruited and participated the baseline survey.The information was collected through questionnaire,medical records,laboratory tests and cervical cancer screening.1.The information of basic characteristics of HIV-positive women was collected through structured questionnaire.The information included social demographic characteristics,behavior characteristics,fertility history.2.From the medical records,the information on the use of ART,previous CD4+T lymphocytes count testing and HIV viral load detection testing was collected.3.Applying gynecological examination,vaginal secretions detection,syphilis serological tests,hepatitis B surface antigen detection,HIV viral load detection(HIV-1 nucleic acid quantitative detection),CD4+T lymphocyte count detection(flow cytometry),and HPV testing(Roche cobas 4800),we collected:1)infectious status of reproductive tract infection and sexual transmitted infections,including cervicitis,vaginitis,Hepatitis B virus infection,and syphilis infection;2)CD4+T lymphocytes count and HIV viral load,3)hrHPV infectious status and type distribution.4.through the cervical cytology(Thin layer liquid-based cytology),colposcopy and histopathological examination,we collected cervical intraepithelial lesions,cervical cancer and precancerous lesions among HIV-positive women.The HIV-positive women,who participated the baseline survey,were followed up and received the follow-up survey between August and November in 2016.The general information and status of ART,pervious CD4+T lymphocytes count test and HIV viral load test.By applying the same laboratory tests as the baseline survey,the information on infectious status of RTIs and STDs,CD4+T lymphocytes counts and HIV viral loads,and the infectious status of hrHPV among HIV-positive women was collected.By applying the cervical cytology,colposcopy and histopathological examination,the occurrence of cervical intraepithelial lesions,cervical cancer and precancerous lesions in HIV-positive women was collected.The field staff were trained to unified the methods.The blood samples,cervical exfoliative cells,cervical pathology samples were collected,preserved,transported and tested according to relative standards and operation guideline.Every step of cervical cancer screening was under the quality control.Epidata 3.0 software was applied to set up the database.The information was double entered by two persons followed by the consistency test and logic error correction.Multivariate analysis was used to control the confounding factors.The rate or percentage were used for descriptive analysis.Univariate and multivariate analysis were performed using Personχ2(Fisher exact probability)and unconditional logisitic regression analysis.Frist,described the prevalence of hrHPV and distribution of 14 genotypes of hrHPV,analyzed the relationship between hrHPV infection and the different status of ART,CD4+T lymphocyties counts,HIV viral loads,and other factors.Second,described the persistence and elimination of hrHPV infection of HIV-positive women during the follow-up period.Analyzed the relationship between hrHPV persistence infection and ART status,level of CD4+T lymphocyties counts and HIV viral loads at baseline survey and follow-up survey and their changes and other factors.Third,described the occurrence of hrHPV infection during the follow-up period,and analyzed the relationship between cervical cancer and precancerous lesion and the different hrHPV infectious status and genotypes,factors associated with HIV infection,sexual behaviors,and RTIs/STDs.Main resultsAmong 695 HIV-positive women participated the baseline survey,25 women were detected with precancerous lesions(CIN2 and CIN3),and other 670 were followed up continuously.The follow-up survey was conducted 12-16 months later after the baseline survey.Among 670 women were followed-up,108 women were lost contact,16 women could not receive the investigation due to health problems,and 5 were died.Finally,541 HIV-positive women participated the follow-up survey.The follow-up rate was 80.75%(541/670).1.In the research,among 695 HIV-positive women,180 were infected with hrHPV and the prevalence of hrHPV in HIV-positive women was 25.90%.The most common types of hrHPV was HPV16,52,58 and 51,and the prevaleneces were 6.76%,5.47%,5.04%,and 2.45%respectively.The hrHPV prevalence among HIV-positive women who were receiving ART was lower than those who didn’t have ART(x2=7.256,P=0.007).The higher the CD4+T lymphocytes counts were,the lower prevalence of hrHPV was(trendx2=9.883,P=0.002).The lower the level of HIV viral loads,the higher prevalence of hrHPV was(trendχ2=17.547,P<0.001).Multivariate analysis showed that the women with CD4+T lymphocytes counts<350 cell/μl were more likely to be infected with hrHPV than those with CD4+T lymphocytes counts≥500cell/μl(aOR=2.07,95%CI:1.35-3.17,P=0.001).The women with HIV Ⅵ≥1000 copies/mlw were more likely to be infected with hrHPV than those with HIV VL<50 copies/ml(aOR=2.09,95%CI:1.28-3.40,P=0.003).2.After an average of 14 months follow up,the persistence rate of hrHPV infection among HIV-positive women with hrHPV infection at baseline survey was 38.02%(46/121).The persistence rates of hrHPV infection were different in different research sites.HIV-positive women from research sites in Guangxi and Yunnan had more risk to have persistant hrHPV infection than those in Xinjiang(aOR=4.19,95%CI:1.48-11.82,P=0.007;aOR=4.35,95%CI:1.39-13.64,P=0.012).3.After an average of 14 months follow up,the incidence of hrHPV infection among HIV-psotive women was 8.33%(35/420).The multivariate analysis showed that the risk of newly infecting hrHPV among floating women was 4.86 times that of local women(95%CI:1.78-13.29,P=0.002).The risk of newly infecting hrHPV among HIV-positive women from Xinjiang sites was 6.83 times that of HIV-positive women from Yunnan sites(95%CI:2.51-18.58,P<0.001).The HIV-positive women with HBV infection had higher risk to be infected with hrHPV than those without HBV infection(aOR=3.67,95%CI:1.17-11.51,P=0.026).4.The detection rates of cytology abnormalities in HIV-positive women at baseline survey and follow-up survey were 12.66%and 14.88%respectively.And the detection rates of precancerous lesions were 4.05%and 0.43%.The percentages of infected with hrHPV increased from 19.24%of normal cytology to 100%of HSIL(trend χ2=129.290,P<0.001).The percentages of infected with hrHPV increased from 17.60%of normal to 100.00%of CIN3(trend χ2=58.460,P<0.001).Multivariate analysis showed that the risk factors of precancerous lesions included multiple hrHPV infection(aOR=74.56,95%CI:14.44-385.13,P<0.001),single hrHPV infection(aOR=38.64,95%CI:8.35-178.89,P<0.001),infection with HPV16/18(aOR=169.06,95%CI:34.21-835.34,P<0.001),infection with other 12 types hrHPV(aOR=18.31,95%CI:3.65-91.95,P<0.001),early age at sexual exposure(less than 18 years old)(aOR=3.32,95%CI:1.11-9.96,P=0.032),infected with syphilis(aOR=4.28,95%CI:0.99-18.59,P=0.023).5.In this study,among 479 HIV-positive women with normal or ASC-US of cytology at the baseline survey,after an average of 14-month follow-up,18 women developed SIL.The incidence of SIL was 3.76%.The HIV-positive women with multiple hrHPV infection or single hrHPV infection were more likely to develop SIL than women without hrHPV infection(aOR=14.90,95%CI:3.83-57.95,P<0.001 and aOR=3.41,95%CI:0.96-12.18,P=0.058).The risk of developing SIL in women who were infected with HPV16/18 or other type of hrHPV was associated with 7.81 times(95%CI:1.84-33.15,P=0.005)and 5.05 times(95%CI:1.53-16.65,P=0.008)respectively,for women who were not infected with hrHPV.Compared with other ethnic women,Uygur women had higher risk to develop SIL(aOR=3.67,95%CI:1.19-11.35,P=0.024).ASC-US at baseline survey was also associated with risk of SIL(aOR=11.43,95%CI:3.19-40.99,P<0.001).Conclusion1.Among HIV-positive women in research sites,the hrHPV prevalence was 25.90%.With ART,the suppression of HIV and improving immunization level,the risk of being infected with hrHPV will be reduced.2.After an average of 14 months follow up,the persistence rate and the incidence of hrHPV infection among HIV-psotive women was 38.02%and 8.33%respectively.The persistent rates and incidence of hrHPV infection were various from different research sites.HIV-positive women who were floating population,infected with HBV were more likely to be newly infected with hrHPV during the period of follow-up.3.HIV-positive women were high risk group to cervical lesions.Infected with hrHPV,sexual onset less than 18 years old,infected with syphilis was the risk factors to have cervical lesion.Women with multiple hrHPV infection or infected with HPV16/18 were at the greater risk to have cervical precancerous lesions.4.The incidence of SIL(TCT)among HIV-positive women was 3.76%after an average of 14-month follow-up.Infected with hrHPV,with abnormal result of TCT at the baseline,and infected with syphilis were the risk factor of developing SIL.Women with multiple hrHPV infection and HPV16/18 infection had more risk to develop SIL during the follow-up.5.Due to the limited time of follow-up in this research,the information on persistence and incidence of hrHPV infection,the incidence of SIL was limited.It is necessary to follow up HIV-positive women continuously in order to investigate persistence and incidence of hrHPV infection,the incidence of precancerous lesions,and their impact factors.With the time and resource permitted,it needs to establish the control of HIV negative women to in-depth study the differences on the prevalence,persistent infection and incidence of hrHPV infection between HIV-positive women and HIV-negative women.Currently,there is little known about RTIs and STDs among HIV-positive women in China.It necessary to conduct study on RTIs/STDs among HIV-positive women in the future. |
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