Association of human papillomavirus infection with seminal parameters, anti-sperm antibody, and sperm DNA integrity in Korean men: A preliminary study

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Korean J Fertil Steril. 2026;.cerm.2025.08501

Publication date (electronic) : 2026 March 18

doi : https://doi.org/10.5653/cerm.2025.08501

Gaeun Kim^1,*, Hwahyoung Kang^2,*, Anna Choi³, Ildong Kim¹, Sunghong Joo¹, Jung-won Yoon^,1

¹Department of Obstetrics and Gynecology, National Medical Center, Seoul, Republic of Korea

²Infertility & Fertility Preservation Center, Ewha Womans University Mokdong Hospital, Seoul, Republic of Korea

³Gangwon State Gangneung Medical Center, Gangneung, Republic of Korea

Corresponding author: Jungwon Yoon Department of Obstetrics and Gynecology, National Medical Center, 245 Eulji-ro, Jung-gu, Seoul 04564, Republic of Korea Tel: +82-2-2262-4746 Fax: +82-2-2276-2117 E-mail: erynies4@nmc.or.kr

*These authors contributed equally to this study.

Received 2025 August 1; Revised 2025 November 14; Accepted 2025 November 17.

Abstract

Introduction

Human papillomavirus (HPV) is a virus predominantly transmitted through sexual contact. According to the Centers for Disease Control and Prevention, most sexually active adults contract HPV at some point in their lives [1]. HPV infection can lead to perianogenital lesions and reproductive system cancers in both females and males [1].

Historically, research and prevention strategies for HPV have centered on its oncologic implications, particularly cervical cancer in women. This focus has driven the implementation of female-targeted vaccination programs, including the National HPV Immunization Program in South Korea [2]. In contrast, HPV-related outcomes in men, especially those beyond cancer, have received comparatively limited attention.

Recently, interest in the potential reproductive effects of HPV infection in men has increased. Male factor infertility accounts for 40% to 50% of all infertility cases [3], and previous studies have suggested that HPV infection may contribute to impaired male fertility. Several mechanisms have been proposed, including viral binding to spermatozoa [4,5], induction of anti-sperm antibodies (ASAs) [6,7], and oxidative DNA damage [8]. The prevalence of high-risk HPV types in the semen of infertile men has been reported to exceed that in the general population [9], and HPV infection has been linked to reduced sperm count [10,11], decreased motility [8,10,12], impaired sperm DNA integrity [4,8,12], and increased ASA production [13]. However, the strength and consistency of these associations vary across studies. Although investigations from various countries have examined the effects of HPV infection on semen quality, no study to date has specifically evaluated HPV-related male infertility in Korea. Therefore, this study aimed to determine the detection rate and genotypes of HPV in semen samples from Korean men and to assess their association with semen parameters, ASA, and DNA fragmentation index (DFI).

Methods

Results

A total of 67 samples from 70 subjects were analyzed, with three samples excluded because of insufficient semen volume. None of the participants presented with varicocele, hypogonadism, azoospermia, or leukocytospermia.

The mean age of the participants was 34.7±4.8 years. Mean blood hormone levels were 4.9±2.0 mIU/mL for follicle-stimulating hormone, 5.9±1.8 IU/mL for luteinizing hormone, and 5.0±2.0 ng/mL for testosterone. The overall HPV detection rate was 14.9%, with 10 confirmed cases (Table 1).

Table 1.

Baseline characteristics of the participants (n=67)

Table 2 shows the distribution of HPV genotypes among HPV-positive participants. Detected genotypes included high-risk types 16, 39, 52, 56, 59, 68, 73, and 82, as well as low-risk types 40, 42, 43, 44, 54, 61, and 70. Multiple HPV genotypes were identified in three participants, while the remaining individuals had only a single genotype.

Table 2.

Distribution of HPV genotypes among HPV-positive participants

Age, semen parameters, and blood hormone levels according to HPV detection status are summarized in Table 3. Mean age was 34.5±4.3 years in the HPV-negative group and 35.7±7.2 years in the HPV-positive group, with no statistically significant difference (p>0.05). Blood hormone levels also did not differ significantly between HPV-negative and HPV-positive men. Semen parameters showed no differences in semen volume, total motility, progressive motility, or normal morphology. However, sperm concentration differed significantly between the groups (50.7±31.3×10⁶/mL vs. 31.0±20.2×10⁶/mL, p=0.002). Total sperm number was also significantly different (165.0±119.9×10⁶/ejaculate vs. 76.0±63.2×10⁶/ejaculate, p=0.020). Although statistically significant, both groups had total sperm numbers within the normal range (≥39×10⁶/ejaculate), indicating no clear clinical impact. The percentage of ASA was higher in the HPV-positive group for both ASA IgG (8.6%±6.9% vs. 12.1%±6.8%, p=0.160) and ASA IgA (9.3%±7.1% vs. 12.7%±6.2%, p=0.140), although these differences were not statistically significant. Similarly, the difference in DFI between HPV-positive and HPV-negative groups was not significant (p=0.112).

Table 3.

Comparison of age, blood hormone levels, semen parameters, ASA, and DFI according to HPV detection status

Age, semen analysis, and blood hormone levels were additionally compared among HPV-negative, low-risk HPV-positive, and high-risk HPV-positive groups classified by HPV genotype (Table 4). Although no statistically significant differences were identified among the three groups, total sperm number and DFI showed statistically significant trends.

Table 4.

Comparison of age, blood hormone levels, semen parameters, ASA, and DFI among HPV-negative, low-risk HPV-positive, and high-risk HPV-positive groups

In exploratory subgroup analyses comparing high-risk HPV-positive men (n=6) with HPV-negative men (n=57), only total sperm count remained significantly lower in the high-risk group. Other parameters, including ASA and DFI, showed no additional differences (Welch’s t-test) (Supplementary Table 1).

Discussion

This study investigated the presence of HPV in semen samples and its association with semen parameters, ASA, and sperm DFI in healthy adult men. The HPV detection rate in semen was 14.9%, which was higher than previously reported in Korean studies conducted among fertility-clinic populations [19]. This difference may reflect the inclusion of community-based participants who were interested in sexual health, as well as recent increases in HPV prevalence among men in Korea [20].

HPV genotypes identified in semen were evenly divided between low-risk and high-risk types, with no predominant genotype pattern. This differs from earlier studies reporting a predominance of high-risk types such as HPV 16, 18, 52, and 59 in infertile men [9,10,21], and from research conducted in sexually transmitted disease clinics where low-risk types such as HPV 6 and 11 are more frequently detected [22]. The genotype distribution observed in this study may therefore reflect subclinical or transient infections in the general male population rather than the persistent high-risk infections typically found in infertile cohorts. Larger studies incorporating multiple anatomical sampling sites are needed to clarify genotype-specific site preferences and persistence in semen.

Regarding semen quality, total sperm number and sperm concentration were significantly lower in HPV-positive men, although both measures remained within normal reference limits. Sperm volume, motility, and morphology did not differ significantly between groups, consistent with previous studies reporting modest or minimal effects of HPV on conventional semen parameters [23-25]. Studies showing stronger associations have frequently included infertile men or individuals with higher HPV viral loads [9,10,21]. Thus, in healthy men who likely have lower viral exposure, the effects of HPV on semen quality may be limited.

Several mechanisms may explain how HPV infection could influence sperm function. HPV virions can bind to the equatorial region of the sperm head through interactions between the L1 capsid protein and surface proteoglycans such as syndecan-1, potentially altering membrane integrity and chromatin stability [5,26]. In vitro studies have also shown that exposure to high-risk HPV DNA fragments increases oxidative stress and sperm DNA fragmentation [12,27,28], and clinical meta-analyses have reported higher DFI in HPV-infected men [12]. HPV attachment may additionally facilitate ASA formation by exposing sperm antigens to the immune system [6,7], and previous studies have demonstrated increased ASA positivity in HPV-infected semen that declined after viral clearance [6]. However, in the present study, neither DFI nor ASA differed significantly between groups, suggesting that these biological effects (if present) may be subtle in healthy individuals or may require higher viral loads or persistent infection to be detectable.

Exploratory subgroup analysis comparing high-risk HPV-positive men with HPV-negative men revealed no statistically significant differences in semen parameters except for a lower total sperm count in the high-risk group. Although ASA IgA levels tended to be higher, the difference remained non-significant. Overall, the subgroup results were consistent with the main comparison between all HPV-positive and HPV-negative participants. Nevertheless, the statistical power of this analysis was limited because of the small number of high-risk HPV cases. Although high-risk HPV types have been hypothesized to exert stronger effects through oncogenic viral proteins and oxidative DNA damage [9,10,26], the magnitude of these differences may be too small to detect in a healthy, non-infertile sample.

The mean age of participants in this study (34.7±4.8 years) was higher than that in comparable studies. HPV prevalence in men typically peaks at ages 25 to 29 [29], after which immune clearance and changes in sexual behavior may reduce detectable infection rates. Thus, our sample may represent a population with lower viral activity or individuals in later stages of post-infection recovery, which could contribute to the modest associations observed between HPV detection and semen quality.

This study has several limitations. The sample size was small, and all participants were recruited from a single center. Potential confounders such as smoking, alcohol use, and co-infection with other sexually transmitted pathogens were not controlled for, despite their known associations with semen quality and fertility outcomes [30-32]. Furthermore, HPV load and site-specific localization were not assessed. Despite these limitations, this study provides baseline data on HPV prevalence and genotype distribution in semen among healthy Korean men—a population that has rarely been examined in this context.

In conclusion, HPV was detected in 14.9% of semen samples, with both low- and high-risk genotypes represented. HPV detection correlated with lower total sperm number but was not associated with differences in other semen parameters, ASA, or DFI in this healthy cohort. As global trends increasingly support gender-neutral HPV vaccination programs, similar discussions are emerging in South Korea. This study highlights the need for further research to determine whether HPV vaccination may confer additional benefits for male reproductive health. Larger, multicenter studies incorporating quantitative HPV testing and longitudinal follow-up will be essential to clarify the clinical implications of seminal HPV infection.

Supplementary material

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