Analysis And Treatment Of HPV Infection In HIV-positive MSM Population In Shenyang

Objective: Men who have sexual activity with other men(MSM)are at a heightened risk for anal cancer and high-grade squamous intraepithelial lesions(HSIL),compared to the male population at large.In the United States,the incidence of anal cancer among HIV-negative MSM is reported to be as high as 37/100,000,and this risk is significantly amplified amongst HIV-positive MSM,with an incidence rate of 131/100,000.Despite the availability of antiretroviral therapy(ARV),such treatment has yet to reduce the occurrence of anal cancer amongst HIV-positive populations in the US,with some studies suggesting that the incidence of anal cancer remains high even in the presence of ARV.Analogous to cervical cancer,human papillomavirus(HPV)is the pathogen chiefly responsible for most instances of anal cancer.HIV-positive MSM are also more prone to anal HPV infection than their HIV-negative counterparts.The effective prevention of HPV transmission and appropriate management of genital warts in HIV-positive MSM represent significant clinical hurdles.Notably,local hyperthermia therapy has exhibited high cure rates,as well as features such as painlessness,low recurrence rates,lack of specific contraindications,and the ability to provide multi-site treatment,thus establishing it as an efficacious treatment plan for HPV infection.This study examines the feasibility and underlying mechanisms of local hyperthermia therapy for the prevention and treatment of HPV infection based on the sexual behavior and general characteristics of HIV-positive MSM,thus generating new ideas for the further exploration of the effectiveness of hyperthermia therapy for HPV infection.Methods: This study collected clinical data from a total of 150 participants,including118 clinically diagnosed HIV-positive MSM and 32 HIV-negative MSM patients who visited the First Hospital of China Medical University and the Sixth People’s Hospital of Shenyang from September 2020 to May 2022.Demographic information was utilized to determine the typing of 21 common HPV viruses,including HPV16,18,31,33,35,39,45,51,52,56,58,59,66,68,and a suspected high-risk type HPV53,with precise classification being performed using the human papillomavirus typing test kit developed by Guangdong Kaipu Company in China.Genital warts tissue from HIV-positive MSM patients were subjected to in vitro 44 ℃ hyperthermia therapy,with a control group undergoing 37 ℃ normal temperature stimulation.Subsequently,second-generation high-throughput sequencing was conducted to obtain genomic data,and the physiological functions of differentially expressed genes were analyzed based on these results.The genital warts tissue from HIV-positive MSM patients was also subjected to simulated clinical hyperthermia therapy in a 44 ℃ water bath to explore the effects of hyperthermia therapy on HPV infection and potential mechanisms in HIV-positive MSM after pathological diagnosis.Furthermore,a stable CaSki-HIV1-tat human cervical cancer epithelial cell line was constructed,and the effect of 44 ℃ hyperthermia therapy on the proliferation of CaSki-HIV1-tat cells was investigated using CCK8,plate cloning,and EdU experiments.Additionally,the study explored whether 44 ℃ hyperthermia therapy could regulate the apoptosis of CaSki-HIV1-tat cells using TUNEL experiments.Results: 1.A total of 118 MSM diagnosed as HIV positive and 32 MSM diagnosed as HIV negative were included in this study.Among HIV positive MSM,50 people(42.4%)were between the ages of 30 and 39,and 77 people(65.3%)received education at university or above;92 people(78.0%)have full-time or part-time jobs;71 people(60.2%)are unmarried.83(70.3%)participants had incomes ranging from 1000 to 5000 RMB,of which 75(63.6%)reported high-risk behaviors such as never using condoms and experiencing commercial sexual activity in the past six months;In addition,26people(22.0%)reported having never received voluntary HIV counseling and testing before,87 people(73.7%)had never undergone circumcision,94 people(80.0%)had never tested for HPV,and 102 HIV positive MSMs(86.4%)had tested positive for HPV,all of which are clear characteristics of high-risk behavior.Among these individuals,64(54.2%)were infected with HPV16,with the five most common HPV types being HPV16,HPV 18,HPV6,HPV 51,and HPV 11.Among HIV negative MSM,22(68.8%)tested positive for HPV,and 5(15.6%)tested positive for high-risk HPV.17 people(53.1%)are over 40 years old,14 people(43.8%)have received university education or above,25 people(78.1%)have full-time or part-time jobs,16 people(50.0%)are unmarried,and the majority of people(28 people,87.5%)earn less than 5000 RMB.2.The second generation high-throughput sequencing was performed on HIV positive MSM condyloma acuminatum tissues after warm stimulation,and 20323 expressed genes were identified,including 247 differential genes,48 up-regulated genes and 199down-regulated genes.We found that the Pearson correlation coefficient between all samples is approximately 1,indicating a strong positive correlation between them.After enrichment analysis of Gene Ontology(GO),compared with the control group condyloma acuminatum tissue,warm treatment also significantly changed the immune response,cell migration pathway and other biological processes of the experimental group.After enrichment analysis by the Kyoto Encyclopedia of Genes and Genomes(KEGG),we found that compared with the control group of condyloma acuminatum tissue,hyperthermia therapy significantly altered signal transduction pathways such as IL-17,TNF,MAPK,and apoptosis in the experimental group,which may improve the treatment response of condyloma acuminatum tissue.A search was conducted on 48 upregulated differentially expressed genes,and 10 genes have not yet been reported in genital warts.So as an alternative differential gene for further research.3.We investigated the therapeutic effect of 44 ℃ hyperthermia therapy on genital warts in HIV positive MSM and found that 6 cases of anal genital warts in HIV positive MSM were cured.Warm stimulation was performed on CaSki-HIV1-tat human cervical cancer epithelial cell line,and it was found that hyperthermia therapy can effectively inhibit the proliferation ability of CaSki-HIV1-tat cells,and hyperthermia therapy inhibits CaSki-HIV1-tat human cervical cancer epithelial cell line through apoptosis pathway.Conclusions: This study presents a comprehensive survey of HPV infection prevalence and genotypes among HIV-positive MSM in Shenyang,China.Additionally,we conducted transcriptome analysis of genital wart tissues obtained from HIV-positive MSM before and after hyperthermia therapy,which has not been reported previously.Our clinical data demonstrate that 44℃ hyperthermia therapy is highly effective in treating genital warts in HIV-positive MSM,with lower recurrence rates and no specific contraindications compared to traditional treatment modalities.In vitro experiments further shed light on the underlying mechanisms,showing that hyperthermia therapy induces apoptosis and inhibits cell proliferation of CaSki-HIV1-tat human cervical cancer epithelial cells.These results offer novel avenues for developing therapeutic interventions against HPV-related diseases in HIV-positive MSM and may have implications for better understanding the pathogenesis and prevention of HPV in this population.