Human papillomavirus (HPV) is one of the most common sexually transmitted infections. Among the more than 170 identified HPV subtypes, over 40 are associated with genital infections. These subtypes are either classified as high-risk (HR-HPV) or non-high risk (non-HR-HPV) based on their oncogenic potential (Graham, 2017; Galeshi et al., 2022). Non-HR-HPV typically causes benign lesions, such as genital and cutaneous warts (Foresta et al., 2015). In contrast, HR-HPV is associated with malignant lesions, including cervical, anal, and oropharyngeal cancers (Soheili et al., 2021). It is estimated that approximately 570,000 women and 60,000 men are infected each year worldwide, with a lifetime probability of infection being 80% for women and 90% for men (Hirth, 2019; Szymonowicz and Chen, 2020). While significant progress has been made in HPV research among women, data on men’s HPV infections remain limited (Lieblong et al., 2019; Tang et al., 2023).

Although HPV-related disease research has historically focused on women, interest in male HPV infection has recently increased. In recent years, several reviews have summarized the related topics of HPV infection in male sperm and sperm quality as well as male infertility (Cao et al., 2020; Garolla et al., 2024). At present, most studies suggest that HPV infection in semen could affect sperm quality and male fertility, but there are still some studies that suggest that HPV infection in semen has no relation to semen quality (Golob et al., 2014; Lyu et al., 2017). This difference might be related to the limitations of various research investigations (including differences in the study population, semen microenvironment, co-infection with other specific pathogenic microorganisms, or other factors).

Ejaculation dysfunction is a relatively serious problem in male infertility, accounting for 14% to 18% of infertile men (Álvarez et al., 2024). For certain men who struggle to obtain semen smoothly, sampling from the genital tract becomes especially crucial. Despite the potential for contamination, the impact of HPV on the genital tract has been investigated much less in men than in women. This might be due to the fact that men do not have specific symptoms and the limitations of methods for assessing HPV infection in the male genital tract. Therefore, there is relatively little data on the prevalence of HPV in the male genital tract. Literature reports indicate that the detection rate of HPV in semen and the genital tract is consistent (Olivera et al., 2024). However, there are few literatures that statistically analyze the series of impacts caused by HPV infection in the male genital at present.

The series of effects of HPV infection in male genital tract remain an area of active investigation. This study aimed to evaluate the prevalence of genital HPV infection in men, assess the distribution of HPV subtypes, and investigate the association between HPV infection including co-infection with other pathogens and semen parameters. Meanwhile, analyze the consistency of HPV infection in the male genital tract and that in the spouse. These findings may help elucidate the potential adverse effects of HPV on male genital health.

HPV infection is a major public health concern, particularly among women, for whom extensive evidence exists regarding its epidemiology and associated health impacts. However, our understanding of HPV epidemiology in men remains limited (Lieblong et al., 2019). In recent decades, there has been increasing interest in male HPV infections and their potential effects on sperm quality and fertility (Cao et al., 2020; Rivero et al., 2023; Garolla et al., 2024). In this retrospective study involving 624 males from Sichuan, China, we evaluated the prevalence and genotype distribution of genital HPV infections, concordance of HPV genotypes between couples, and associations between HPV infection status and semen parameters.

As one of the most common sexually transmitted pathogens, HPV prevalence in men worldwide ranges from 1.3% to 72.9% (Dunne et al., 2006). In our cohort, the overall prevalence was 43.8% (273/624), slightly higher than the 31% male infection rate reported in a 2023 study across 35 countries (Bruni et al., 2023). Single-genotype HPV infection was the most common pattern in our study population, accounting for 59.3% (162/273), compared to dual (27.8%) and multiple (≥ three genotypes, 13.6%) infections. This result aligns with findings from other regions (Abbasi et al., 2024; Liu et al., 2024), suggesting that HPV infection in men in Sichuan predominantly presents as a single-type infection. A total of 23 HPV genotypes were identified, with HPV52 (20.50%) and HPV16 (16.50%) being the most common HR-HPV types—findings largely consistent with previous reports (Huang et al., 2024; Wen et al., 2025). HPV42 was the most prevalent non-HR-HPV genotype in our cohort, whereas other studies more commonly report HPV6 or HPV11 as dominant (Szymonowicz and Chen, 2020). Non-HR-HPV genotypes may cause genital or cutaneous warts. In particular, HPV42 has been associated with low-grade cervical intraepithelial lesions in women. (28–30). The fact suggests that the different genotypes of prevalence vary from one geographic area to another. The HPV genotypes included in the Gardasil 9 vaccine (6, 11, 16, 18, 31, 33, 45, 52, and 58) represent 65.2% of those detected in our cohort. We findings indicate that male genital HPV positivity increases the risk of HPV infection in their female partners, particularly for HR-HPV genotypes.

Although the types of infections between partners may be similar. The Benevolent team’s study has confirmed that male HPV positivity is more common in HPV-positive female sexual partners. Males may be an important source of HPV transmission between sexual partners (Benevolo et al., 2008). Thus, the vaccination of males against HPV might be a prevention option. Our study offers preliminary insights into HPV prevalence and genotype distribution among reproductive-age men in Sichuan.

HPV may persist in the genital tract, including semen, male external genitalia, perianal skin, urethra, vas deferens, epididymis, and testes, and continue to infect the host (Dunne et al., 2006). Reports assessed the relationship between male fertility and HPV infection in semen. It showed that HPV infection in semen impairs male fertility to a certain extent and that HPV in semen alters some parameters of spermatozoa, especially sperm motility (Xiong et al., 2018; Santos et al., 2023). Our research found that genital tract HPV-positive men demonstrated significantly lower sperm motility and a reduced proportion of morphologically normal sperm. HPV infection could affect every cell in the body, including sperm count, motility, genome integrity, morphology, and concentration (Schillaci et al., 2013). Although the specific mechanism of HPV infection in semen is currently unclear, and the role of infected cells in virus transmission is also vague, but it can be confirmed that HPV virus can bind to the equatorial end of sperm head through the interaction between L1 viral capsid protein and proteoglycan Syndecan-1, thereby affecting sperm motility (Foresta et al., 2011; Schillaci et al., 2013). However, some studies have reported no association between HPV infection in semen and impaired sperm function (Bezold et al., 2007; Foresta et al., 2015; Luttmer et al., 2016). Such discrepancies in findings may stem from differences in study populations, semen microenvironments, or other factors.

Roosmarijn et al. found that 85% of men had consistent HPV infections in their genital and semen specimens. This was determined by taking scrapings from the penis and three semen samples, with each sample taken one week apart (Luttmer et al., 2015). The presence of HPV in semen was associated with the presence of HPV in the penile scrape also on a genotype-specific level. The researchers studied 213 cases of HPV infection in men, both on the penis and in the sperm. They found that men who tested positive for HPV in penile scrapings were more likely to test positive for HPV in semen than those who tested negative. At the same time, it was found that the semi-quantitative HPV viral load in penile scratches was statistically positively correlated with the semi-quantitative viral load in semen (Luttmer et al., 2015). We suspect that the process of sperm infection with HPV might be a downward infection through the male urogenital tract and sexual behavior. Our research indicates that HPV infection in the genital tract may have a negative impact on semen, there is no statistical difference between HR-HPV and non-HR-HPV infections and sperm. This is similar to the research results of Carolina et al (Olivera et al., 2024). However, there are contrary studies suggesting that we should focus on the specific types of HPV infection in the male genital tract. Though neither HR-HPV nor non-HR -HPV were associated with significant alterations in routine sperm quality parameters. HR-HPV+ individuals showed significantly higher levels of sperm necrosis and exhibited increased proportions of ROS+ spermatozoa compared to non-HR-HPV+ or control individuals (Olivera et al., 2024). Despite this, the impact of HR or non-high-risk on sperm remains unclear. Some reports suggest that HR-HPV is more likely to have adverse effects on sperm, as sperm DNA fragmentation is more likely to lead to an increase in sperm necrosis (Boeri et al., 2019; Capra et al., 2022).

HPV infection may have adverse effects on sperm and, by extension, negatively impact male fertility. For instance, HPV16 and HPV31 have been shown to impair embryo development, while HPV11, HPV16, HPV18, and HPV31 reduce implantation rates (Zacharis et al., 2018). In contrast, Tangal et al. reported no significant differences in implantation or clinical pregnancy rates between individuals with HPV-infected and uninfected sperm undergoing in vitro fertilization (IVF). However, the miscarriage rate in IVF procedures involving HPV-infected spermatozoa was reported to be 33%, compared to 10% in uninfected individuals (Tangal et al., 2019). In our study, although the associations between HPV infection and either infertility or miscarriage were not statistically significant, HPV-positive men still had numerically higher rates of both outcomes than HPV-negative men. Prior studies have also reported reduced pregnancy rates and increased miscarriage rates in both male and female HPV-infected individuals (Garolla et al., 2016). Depuydt et al. found that pregnancy rates following intrauterine insemination declined when sperm DFI exceeded 26%, and that sperm samples containing HPV had significantly higher DFI values than HPV-negative samples (Depuydt et al., 2021). Other studies have also demonstrated that HR-HPV infection is associated with decreased semen viscosity, reduced sperm motility, and increased sperm DNA fragmentation (Damke et al., 2017; Boeri et al., 2019). Our results show that male urogenital infection by either HR-HPV or non-HR-HPV does not impair most sperm parameters. This is consistent with the viewpoint of Canarella et al (Cannarella et al., 2022). This difference might be due to deviations in our analytical methods. Because our high-risk type infection is defined as any infection type that includes any high-risk genotype. Therefore, the high-risk HPV infections we included in the analysis may also include other non-high-risk types. Subsequently, we analyzed single-type HPV infection and multi-type HPV infection in the male genital tract, and the results showed that there was no difference in their sperm parameters. Nonetheless, the overall impact of HPV infection on male fertility and reproductive outcomes remains controversial. However, further studies will be needed to assess the infectiousness of genital HPV and its impact on reproductive health.

Interestingly, in the semen microenvironment, it is worthwhile to pay attention to co-infections with other pathogenic microorganisms, and in this paper, we analyzed the effect of HPV co-infections with the most common pathogenic microorganisms, UU and CT, on semen in men, in order to exclude the potential effect of other concurrent infections. We found that coinfection with HPV significantly lowered total sperm number when the above-mentioned common infections were present. In addition, total sperm number were significantly reduced in men with HPV mixed UU infection. Evidence suggests that semen biota play an important role in determining reproductive health and pregnancy outcomes. However, unlike other studies, we did not find that UU and CT infections were associated with sperm viability. This may stem from the diversity of the semen microenvironment and the in vivo balance of microorganisms, and perhaps studies with larger samples are needed to clarify the effect of HPV coinfection on semen.

Our study has several strengths. First, we collected extensive clinical data to maximize the exclusion of confounding factors that may interact with HPV infection. Second, our sampling was focused primarily on the external genitalia, particularly the urethra. Most existing studies have concentrated on detecting HPV in semen and examining its effects on semen parameters and male fertility. However, few have explored the series of impacts of genital HPV infection on men. At present, there is no gold standard for sampling. Differences in sampling techniques across studies may partially explain the variability in reported infection rates. Nonetheless, genital sampling in me should be promoted, as it is quick, painless, and minimally invasive.

This study also had some limitations. First, we did not analyze the correlation between HPV infection of the external genitalia and HPV presence in semen. Prior research has shown that HPV prevalence and viral load can vary depending on the anatomical sampling site (Hernandez et al., 2008). Genital epithelial scraping specimens are more likely to be HPV-positive than semen samples (Luttmer et al., 2015), which may have contributed to a slightly higher positivity rate in our male cohort. Furthermore, all participants were first-time testers, and it is possible that some had recently cleared transient HPV infections, thereby introducing potential bias into our statistical analysis. Finally, for patients whose partners experienced infertility or miscarriage, we could not fully rule out female-related causes, which may have confounded our evaluation of the relationship between HPV infection and fertility outcomes.

We indicated that HPV genital tract infection in men is a widespread phenomenon, and it is also a serious social problem. Male infection with HPV not only increases the risk of transmission to partners but also affects semen quality and harms fertility. Given its simplicity and speed, genital tract HPV screening could be integrated into routine health assessments for men, providing valuable insights into male reproductive health and contributing to broader HPV surveillance efforts.