Objective: Men who have sex with men (MSM) are at increased risk for Human papillomavirus (HPV) infection compared to women and heterosexual men. We aimed to assess the incidence, clearance and duration of anal human papillomavirus (HPV) infection in HIV-negative MSM and the influencing factors in a 5-year prospective cohort study.Methods: From April 2016 to April 2021, HIV-negative MSM were recruited and followed every 6 months in Urumqi, Xinjiang, China. Questionnaires and anal swabs were collected at baseline and every 6 months. We detected 37 anal HPV genotypes using the HPV Geno Array Diagnostic Kit Test. Incidence and clearance rates of anal HPV infection and the influencing factors were estimated using a two-state Markov model.Results: A total of 585 MSM were included with a median age of 37 years [interquartile range (IQR): 31–43 years] and were followed for a median 2.8 years (IQR: 1.8–3.6 years). Incidence rates for any HPV and high-risk HPV (Hr-HPV) were 53.4 [95% confidence interval (CI): 49.1–58.0] and 39.0 (95% CI: 35.7–42.5)/1,000 person-months. Median duration of infection was 9.67 (95% CI: 8.67–10.86) and 8.51 (95% CI: 7.57–9.50) months, respectively. Clearance rates for any HPV and Hr-HPV were 50.9 (95% CI: 46.7–55.3) and 62.1 (95% CI: 56.8–66.7)/1,000 person-months, respectively. HPV16 and HPV6 had the highest incidence, lowest clearance rate and longest duration of infection among Hr-HPV and low-risk HPV (Lr-HPV) types, respectively. Receptive anal sex is a risk factor for any HPV [hazard ratio (HR) = 1.66, 95% CI: 1.16–2.38] and Hr-HPV infection (HR = 1.99, 95% CI:1.39–2.85). Recent anal sex without condom use was significantly associated with any HPV (HR = 1.80, 95% CI: 1.10–2.94) and Hr-HPV infection (HR = 2.60, 95% CI: 1.42–4.77). Age ≥35 years was significantly associated with Lr-HPV HPV infection only (HR = 1.40, 95% CI: 1.02–1.93). Both inserted and receptive anal sex (HR = 0.60, 95% CI: 0.40–0.89) and anal sex ≥2 times per week (HR = 0.61, 95% CI: 0.43–0.87) were associated with reduced Hr-HPV clearance. Six of the nine-valent vaccine types (HPV6, 11, 16, 18, 52 and 58) occurred most frequently, which indicates the need for high vaccination coverage in MSM.Conclusions: In this cohort study, high incidence and low clearance of any HPV, Hr-HPV and individual HPV infections emphasize the importance of MSM vaccination. Modifiable behavioral factors such as condoms and drug use should be incorporated into HPV prevention strategies.

Objectives: Reinfection of human papillomavirus (HPV) among men who have sex with men (MSM) after clearing the infection of HPV has not been well characterized. To understand the reinfection of HPV among human immunodeficiency virus (HIV) negative MSM without HPV vaccine, we analyzed the reinfection of nine-valent HPV vaccine (9v-HPV) types.Methods: Data were acquired from a prospective cohort study among HIV-negative MSM in Urumqi of Xinjiang from 1 April 2016 to 14 July 2020. Participants were recruited through a local non-government organization using a website advertisement. Self-administered questionnaires and self-collected anal swabs were collected at baseline and every 6 months. The incidence rates of reinfection was calculated based on the number of events divided by person-months of observation of event risk. 95% confidence intervals (CIs) were calculated based on the Poisson distribution.Results: A total of 515 HIV-negative unvaccinated MSM were included with a mean age of 30.93 years (SD 7.85), and 27.68% were reinfected with any 9v-HPV type after clearance. The reinfection incidence rate of any 9v-HPV was 14.47 per 1000 person-months (95% CI: 11.52–17.87). HPV52 was the most common type of reinfection, with a reinfection rate of 17.96 per 1,000 person months (95% CI: 11.58–26.33). Univariate analysis showed that MSM over the age of 30 had a slightly higher risk of reinfection with any 9v-HPV (Hazard ratio (HR): 1.57; 95% CI: 1.01–2.45), but no significant association was observed in multivariate analysis.Conclusions: Our study showed MSM without HPV vaccine will become reinfected following the natural clearance of specific HPV types. It is also suggested that HPV vaccination is recommended not only prior to sexual debut but also after viral clearance for MSM to reduce HPV prevalence.

Background. As a common disease around the world, esophageal cancer (EC) primarily includes two subclasses: esophageal adenocarcinoma and esophageal squamous cell carcinoma. Mortality has been rising over the years; hence, exploring the mechanism of EC development has become critical. Among the alpha protein kinases, alpha protein kinase 2 (ALPK2) presumably has a connection with EC, but it has never been revealed before. Methods. In this study, IHC analysis was used for ALPK2 expression quantification in ES tissues. TE‐1 and Eca‐109, which are both human EC cell lines, were used for in vitro analysis of cell proliferation, migration, apoptosis, and colony formation. Results. ALPK2 was found to have an abundant expression within EC tissues (P < 0.001), as well as in the two selected human EC cell lines (P < 0.05). The data showed that ALPK2 depletion suppressed EC cell proliferation, migration, and colony formation, meanwhile stimulating apoptosis (P < 0.001). The in vivo experiments also displayed inhibitory effects caused by ALPK2 depletion on EC tumorigenesis (P < 0.001). It was further validated that ALPK2 depletion made the phosphorylation of Akt and mTOR, as well as CDK6 and PIK3CA levels downregulated (P < 0.001). Mechanistically, we identified integrin alpha 11 (ITGA11) as a downstream gene of ALPK2 regulating EC. More importantly, we found that ITGA11 elevation promoted cell proliferation and migration and rescued the suppression effects caused by ALPK2 depletion (P < 0.001). Conclusions. ALPK2 promotes esophageal cancer via integrin its downstream gene alpha 11; ALPK2 can potentially act as a target for the treatment of EC.

Background: Men who have sex with men (MSM) are at high risk for anal human papillomavirus (HPV) infection, with HIV-positive MSM bearing the highest disease burden. Longitudinal data on anal HPV infection among HIV-negative and HIV-positive MSM are limited. We assessed and compared the prevalence, incidence, and clearance of anal HPV infection among HIV-negative and HIV-positive MSM in Xinjiang, China. Methods: Sexually active HIV-positive and HIV-negative MSM aged 18 years and older have been enrolled in an ongoing observational cohort study of HPV since 1 September 2016, in Xinjiang, China. Participants were followed up on every 6 months with anal HPV testing and questionnaires regarding sexual behaviors. We compared HPV prevalence, incidence, and clearance between HIV-positive and HIV-negative MSM. Prevalence ratios (PRs), incidence rate ratios (IRRs), and clearance rate ratios (CRRs) for HIV-negative and HIV-positive MSM were calculated. Results: A total of 1425 MSM, including 131 HIV-positive and 1294 HIV-negative individuals, with a median age of 29 years (interquartile range [IQR]: 24 to 36), were included in our analysis. Compared with HIV-negative MSM, HIV-positive MSM demonstrated significantly higher prevalence across both individual and grouped HPV genotypes. Specifically, the prevalence of grouped HPV genotypes (any, high-risk, low-risk, 9v, 4v, HPV16/18, and HPV 6/11) was consistently elevated in HIV-positive individuals. PRs for individual HPV types 31, 45, 34, 44, 53, and 81 were 2.47 (95% CI: 1.16–5.25), 2.47 (1.10–5.54), 4.94 (1.25–19.52), 3.29 (1.08–10.06), 2.02 (1.01–4.04), and 2.66 (1.18–6.01), respectively. Furthermore, the incidence of most individual HPV genotypes were higher, while the clearance rates were lower among HIV-positive MSM. Specifically, IRRs for HPV types 31, 33, 45, 55, and 66 were 2.12 (1.19–3.75), 2.19 (1.24–3.90), 2.32 (1.17–4.59), 3.02 (1.15–7.93), and 2.44 (1.18–5.05), respectively. CRRs for HPV types 51 and 58 were 0.33 (0.21–0.52) and 0.60 (0.45–0.79), respectively. Conclusions: HPV prevalence, incidence, and clearance of anal HPV exhibited heterogeneity between HIV-positive and HIV-negative MSM. HPV vaccination and condom promotion programs should be recommended for HIV-positive MSM to mitigate the burden of HPV infection in this vulnerable population.

Objectives: This study aimed to assess the effects of COVID-19 nonpharmaceutical interventions (NPIs) on the human papillomavirus (HPV) epidemic among men who have sex with men (MSM) in Xinjiang, China.Methods: In our cohort study, we enrolled and followed HIV-negative MSM in Xinjiang, China, between 2016 and 2022. Anal swab samples were collected to test for HPV DNA. We used interrupted time series analysis to characterize the temporal trends in HPV prevalence, incidence, and clearance before (September 01, 2016, to July 16, 2020) and during the implementation of COVID-19 NPIs in Xinjiang (July 17, 2020, to March 31, 2022). We used binomial segmented regression models to estimate the impact of COVID-19 NPIs on HPV prevalence, incidence, and clearance.Results: We recruited 1296 MSM who contributed to a total of 5374 HPV tests in our study. COVID-19 NPIs were associated with a 37.9% decrease in the prevalence (prevalence ratio, 0.621; 95% confidence interval, 0.465-0.830), 52.2% decrease in the incidence (risk ratio, 0.478; 0.377-0.606), and 40.4% increase in the clearance (risk ratio, 1.404; 1.212-1.627) of HPV of any genotype after the implementation of COVID19 NPIs in Xinjiang.Conclusion: COVID-19 NPIs may lead to lower transmission and higher clearance of HPV among MSM. Future studies are needed to clarify the longer-term impact of COVID-19 on the transmission and natural history of HPV among MSM.& COPY; 2023 Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

Studies on the association between syphilis positivity on the natural history of HPV infection among men who have sex with men (MSM) are limited. This study aims to assess the impact of syphilis status on the prevalence, incidence, and clearance of anal HPV in MSM. This study utilized data from a prospective cohort of aged 18 years and older HIV-negative MSM conducted in Xinjiang, China, from May 2016 to November 2025. Self-administered questionnaires collected baseline and every 6 months data on demographics and sexual behaviors. Anal swabs were taken for HPV genotyping, and blood samples for syphilis testing. We compared HPV prevalence, incidence, and clearance rate among syphilis positive and syphilis negative MSM. Poisson regression models were used to calculate prevalence ratios (PRs), incidence rate ratios (IRRs), and clearance rate ratios (CRRs). A total of 743 MSM were included, with a median age of 35 years [IQR: 29-41]. Among them, 186 tested positive for syphilis, while 557 tested negative. The syphilis positive MSM exhibited slightly higher prevalence of any HPV, high-risk HPV, low-risk HPV, and 9v HPV compared to the syphilis negative MSM. During follow-up, after adjustment for age, number of sexual partners in the past six months, and other potential confounders, the syphilis positive MSM exhibited significantly higher incidence of any HPV (IRR=1.37, 95% CI: 1.02-1.84) and low-risk HPV (IRR=1.53, 95% CI: 1.07-2.2). The clearance rate for any HPV (CRR=1.35, 95% CI: 1.01-1.81) and high-risk HPV (CRR=1.71, 95% CI: 1.20-2.43) were also significantly higher among the syphilis positive MSM. Syphilis is a risk factor for HPV prevalence and incidence. Future HPV prevention strategy should adopt an integrated approach that concurrently addresses syphilis and other sexually transmitted infections.