Skip to main content

Semen human papillomavirus (HPV) shedding in males: frequency, clinical significance, and reproductive outcomes—literature review



The interest in the HPV status of the male has risen after the discovery of HPV shedding in the semen. To date, there is no consensus on the true prevalence of male HPV infection, yet there is a rising body of evidence suggesting that male HPV infection might negatively affect the sperm parameters.

Main body

The concern that HPV can lead to a couple’s infertility and affect reproductive outcomes had increased after the multiple publications of semen criteria perturbations specifically the asthenospermia associated with HPV infection. An extensive literature review was performed to define the actual frequency of male HPV infection as well as the true extent of sperm analysis perturbations related to the HPV illness. We also intended to define the impact of these infections on reproductive outcomes and to highlight any treatment plans for affected couples.


HPV is a prevalent disease with a rising concern among the male populations given the suggested impact on sperm motility as well as the pregnancy and miscarriage rates post-ART treatment. Vaccines are being studied now as a possible infertility adjunct treatment for males who are already infected.


Human papillomavirus (HPV) is a small non-enveloped icosahedral virus with a double-stranded circular DNA, which multiplies in the basal layer of the stratified epithelium [1, 2]. More than 150 types of HPV have been identified, sequenced, and divided into high and low-risk types depending on their association with cancerous or benign lesions [3]. Although studies have shown a 40% prevalence worldwide in males and females, the true prevalence awaits to be determined since the gold standard diagnostic test for detecting subclinical infections is lacking [4, 5].

Extensive research revealed the presence of HPV DNA in the male genital tract as well as in the seminal fluid and sperm cells [6, 7]. Although the influence of viral shedding on sperm parameters remains poorly understood, there is a growing body of evidence suggesting a negative effect on sperm motility and male fertility overall [8, 9]. Also, based on assisted reproductive technique (ART) studies, it is speculated that when HPV-infected sperm is used in intracytoplasmic sperm injection (ICSI), fertilization, implantation, and embryo development is negatively affected [8, 10]. Hence, suspected semen infection may lead to female partner inoculation, unexplained male infertility, fertilization failure, post-implantation failure, and increased miscarriage rates. Given the rising interest in male HPV infection and the growing concern about the potential negative impact on the reproductive outcomes of the affected couple, this review of the literature was performed. The aims of this review were to define the actual prevalence of male HPV infection, highlight the possible implications of the infection on the sperm parameters, and characterize the effect of that infection on reproductive outcomes whether through natural conception or through ART. We also aimed at drawing attention to the possible safety measures as well as treatments that can be implemented in case of male HPV infection to optimize treatment results.


HPV infects both males and females. Even though the bulk of the research done earlier focused on the female population, the interest in the male HPV status has risen after the discovery of HPV shedding in the semen. HPV DNA is believed to be generally bound to the equatorial region of the sperm head surface with approximately 25% of the sperm population can be found infected in one semen sample [7, 11]. There is no consensus on the true prevalence of male HPV infection as different studies used different HPV DNA detection techniques as well as sampled different male populations. One meta-analysis has shown that the method used to detect HPV DNA does affect the rate of positive results significantly especially in the infertile male population. It has been found that using type-specific primers in conjunction with the PCR techniques provided a higher detection rate when compared with the consensus type primers [12]. The numbers vary widely between the high-risk population with unsafe sexual practices where the average prevalence was found to be almost 31% and the general population with an average frequency of 7.8–12.4% [13, 14]. Other reports demonstrated that the infertile male population has a higher prevalence of HPV infection when compared to the general fertile population with a frequency of approximately 10.2–16% versus 2.2–10%, respectively [8, 15, 16]. It was noted that in the general male population, the frequency of high- and low-risk HPV infections was almost the same, contrary to the infertile male population where high-risk HPV infections were more prevalent. The highest prevalence of HPV infection in the general population was noted among European males (15.2%), while in the infertile male population, the highest frequency was noted among Latin American males (38.2%) [12] The prevalence of such infections has been found to be independent of the age of the male as the incidence of HPV infection remained stable above the age of 24 years [17]. Table 1 summarizes the articles included in this review.

Table 1 Summary of the articles included in the review

HPV-positive status and semen parameters

Given that HPV was found to be more prevalent in the infertile population as already discussed in paragraph 3, a negative effect on the semen parameters could be anticipated. In that sense, a study performed by Schillaci et al. found no association between the HPV status of the male and the different abnormalities of the semen parameters [13]. Luttmer et al. supported the former’s findings [16]. On the other hand, Damke et al. in a more recent study reported that HPV infections reflect negatively on the parameters of the semen analysis. The authors found that HPV-infected samples had a higher incidence of hypospermia and increased seminal viscosity (p = 0.01 and 0.0002, respectively); however, the sperm motility was found to be unaffected (p = 0.5) [19]. Nevertheless, multiple recent metanalyses did document an increased rate of asthenospermia in HPV-infected males especially in the infertile male population. Foresta et al. conducted a review on 1920 patients which showed that males suffering from idiopathic infertility not only had a higher incidence of HPV infection but also a significant deterioration of sperm motility [9]. In another metanalysis, Weinberg et al. recently revealed a significantly increased incidence of asthenospermia, supporting the findings of Foresta et al. [9, 22]. As per Muscianisi et al. in the most recent systematic review, 11 out of the 14 studies included in the analysis concluded that HPV male infection was associated with an impairment in sperm parameters whether it is oligospermia, asthenospermia, teratozoospermia, or a combination of the three [21]. In addition, Boeri et al. found an increased DNA fragmentation index in HPV-infected semen contradicting the previously published reports [23,24,25]. Given the published data, there is a growing concern regarding the reproductive outcomes of ART treatment cycles especially since a meta-analysis by Lyu et al. in recent years suggested a strong association between a positive male HPV status and male infertility (OR = 2.93, 95% CI = 2.03–4.24) [12]. HPV infection however was not shown to eliminate the fertilization capacity of the sperm, and thus, the risk of transmission of HPV virions or DNA into the oocyte remains a possible risk [26].

HPV-positive status and reproduction/ART outcomes

Other than affecting semen parameters and potentially causing male infertility, the main concern is whether infected sperm can transfect oocytes upon fertilization, negatively affecting the reproductive potential of embryos and thus jeopardizing pregnancy outcomes. Despite that the debate is still ongoing on whether the incorporation of viral DNA takes place early on during spermatogenesis or later during the maturation stages of the sperm, there is an agreement that HPV-positive males can harbor the DNA material in the sperm. Thus, the apprehension that infected male gametes might transmit viral DNA to oocytes upon penetration at fertilization still exists. The repercussions on the embryos resulting from oocyte fertilization with infected sperm remain to be elucidated [27, 28]. In an attempt to highlight the effects of HPV DNA on embryos, scientists have cultured murine embryos in HPV DNA-containing media. A study published a while ago by Henneberg et al. showed that embryonic exposure to HPV DNA during the early stages of embryonic development (2 cells stage embryos) resulted in embryonic demise. The authors also reported that the blastulation rate decreased by a quarter when the embryos were cultured with HPV 16 and/or 18 DNA fragments [29]. Hong et al. cultured murine embryos in HPV-16-rich media. In comparison with the control group, the exposed murine embryos were found to form less adhesions, affecting the trophoblast function thus possibly preventing normal implantation without affecting the embryonic development per se [30]. The presumed decreased implantation potential is thought to be due to the accelerated HPV transfection-induced apoptosis in infected cells when compared to non-infected cells [10, 31]. The question that arises here is whether the findings with murine embryos could be extended to the human race. In humans, Perino et al. showed that when the male is HPV positive, while pregnancy rates were equal with the controls, the chances of miscarriage of the IVF-treated couple were higher (66.7% vs 15%) [32]. Garolla et al. demonstrated that HPV-positive semen samples were associated with a significant decline in the success rates of both intra-uterine insemination (IUI) and ICSI cycles which were reduced by half. It was also noted that cumulative pregnancy rates whether spontaneous or with ART were decreased as well. The authors hypothesized that the isolated presence of HPV DNA in the semen in the setting of unexplained infertility might be the hindering factor [33]. This could be explained in part by the anti-sperm antibodies (ASA) as multiple reports highlighted a relationship between HPV infection and ASA in infected infertile males [21]. In the most recent metanalysis published by Weinberg et al., the results also supported the negative impact of male HPV infection on fertility treatment outcomes leading to lower pregnancy rates and higher miscarriage rates [22]. The exact mechanism leading to the reduced reproductive potential of human blastocysts resulting from HPV-infected sperm remains to be fully understood. It is worth mentioning that at this point, the life-long risks of fetal exposure to HPV infection whether in utero or upon delivery remain to be elucidated.

HPV status and partner/recipient safety

On another level, concern with seminal HPV infection is increasing especially in case the female partner of the infertile couple is HPV naive or when using donor semen for intra-uterine insemination. This poses health risks to the recipient patient other than fertility treatment failure particularly if the donor carries infectious agents that are contagious such as HIV, hepatitis B virus, CMV, and possibly HPV. As per the societies’ recommendations, it is necessary to screen all donor semen samples for dangerous contagious agents. HPV, which can be harbored in the semen of clinically asymptomatic donors, is notorious for inducing a well-known range of medical conditions from benign warts to anogenital cancers. Given the presence of such theoretical risks screening for HPV in donors of semen might be valid and attempts at its eradication then should be implemented [15]. The previously suggested method that has been found to eradicate the viral DNA from the sperm was the modified swim-up technique at the expense of the decline of the sample quality [34]. Newer approaches with the addition of hyaluronidase enzyme to the modified swim-up technique have been evaluated. This method was shown to eliminate the HPV virions completely from an infected sperm without negatively affecting the quality of the sperm [18].

HPV prevention/management

In a trial to decrease the burden of HPV infections, Foresta et al. documented that introducing the quadrivalent HPV vaccine to males including those who already had HPV DNA in their semen had promising results. They demonstrated that the prophylactic HPV vaccination reduced the mean time for viral clearance which provides a new therapeutic approach for infertile HPV-infected males or donors who are already carriers of HPV infections [35]. Garolla et al. reported in a retrospective study, the improvement of the sperm parameters of HPV-infected males who received the vaccine in comparison with those who did not (79 vs 71). An improvement in the reproductive outcomes concerning the pregnancy and the miscarriage rates was also noted [36]. It is believed that in men, as in women, the active HPV infection is cleared from the system where the mean clearance time is estimated to be about 6 months; however, the new data suggests that HPV vaccine administration accelerated the rate of clearance [35]. Muscianisi et al. suggested using it as part of HPV-infected males’ treatment to increase the chances of natural conception [21].

Limitations and recommendations

One of the main limitations of the findings of this review was that the studies that were included lacked standardized HPV detection methods. This might have contributed to the discrepancies between the different studies concerning the sperm parameters as well as the reproductive outcomes. Without standardization, screening of asymptomatic males would not be efficient due to the lack of sensitivity. The other point to keep in mind was the actual impact of these infections on reproductive outcomes as there was no consensus among the studies. Until we have more consistent evidence, we would assume that the application of standardized HPV testing in males who are at risk might be cost-effective. This category would include males with a history of unprotected sexual intercourse with multiple partners, males whose female partners were diagnosed with HPV, being a partner in a couple suffering from unexplained infertility, or if the male were found to have asthenospermia.


HPV is a prevalent disease with a rising concern among the male populations given the suggested impact on sperm motility as well as the pregnancy and miscarriage rates post-ART treatment. Vaccines are being studied now as a possible infertility adjunct treatment for males who are already infected.

Availability of data and materials

Not applicable.



Assisted reproductive techniques


Anti-sperm antibodies


Deoxyribonucleic acid


Human papillomavirus


Intra-cytoplasmic sperm injection


Intrauterine insemination


  1. Quint WGV et al (2006) Results of the first World Health Organization international collaborative study of detection of human papillomavirus DNA. J Clin Microbiol 44(2):571–579

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Schiller JT, Day PM, Kines RC (2010) Current understanding of the mechanism of HPV infection. Gynecol Oncol 118(1):S12–S17

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Ochsendorf FR (2008) Sexually transmitted infections: impact on male fertility. Andrologia 40(2):72–75

    Article  CAS  PubMed  Google Scholar 

  4. Barzon L, Militello V, Pagni S, Franchin E, Dal Bello F, Mengoli C, Palù G (2010) Distribution of human papillomavirus types in the anogenital tract of females and males. J Med Virol 82(8):1424–1430

    Article  PubMed  Google Scholar 

  5. Nasseri S, Monavari SH, Keyvani H, Nikkhoo B, Roudsari RV, Khazeni M (2015) The prevalence of human papilloma virus (HPV) infection in the oligospermic and azoospermic men. Med J Islam Repub Iran 29:272

    PubMed  PubMed Central  Google Scholar 

  6. Švec A, Mikyšková I, Hes O, Tachezy R (2003) Human papillomavirus infection of the epididymis and ductus deferens: an evaluation by nested polymerase chain reaction. Arch Pathol Lab Med 127(11):1471–1474

    Article  PubMed  Google Scholar 

  7. Foresta C, Pizzol D, Moretti A, Barzon L, Palù G, Garolla A (2010) Clinical and prognostic significance of human papillomavirus DNA in the sperm or exfoliated cells of infertile patients and subjects with risk factors. Fertil Steril 94(5):1723–1727

    Article  CAS  PubMed  Google Scholar 

  8. Garolla A, Pizzol D, Foresta C (2011) The role of human papillomavirus on sperm function. Curr Opin Obstet Gynecol 23(4):232–237

    Article  PubMed  Google Scholar 

  9. Foresta C, Noventa M, De Toni L, Gizzo S, Garolla A (2015) HPV-DNA sperm infection and infertility: from a systematic literature review to a possible clinical management proposal. Andrology 3(2):163–173

    Article  CAS  PubMed  Google Scholar 

  10. Gomez LM, Ma Y, Ho C, McGrath CM, Nelson DB, Parry S (2008) Placental infection with human papillomavirus is associated with spontaneous preterm delivery. Hum Reprod 23(3):709–715

    Article  CAS  PubMed  Google Scholar 

  11. Foresta C, Patassini C, Bertoldo A, Menegazzo M, Francavilla F, Barzon L, Ferlin A (2011) Mechanism of human papillomavirus binding to human spermatozoa and fertilizing ability of infected spermatozoa. PLoS ONE 6(3):e15036

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Lyu Z, Feng X, Li N, Zhao W, Wei L, Chen Y, Yang W, Ma H, Yao B, Zhang K, Hu Z (2017) Human papillomavirus in semen and the risk for male infertility: a systematic review and meta-analysis. BMC Infect Dis 17(1):1–9

    Article  Google Scholar 

  13. Schillaci R, Capra G, Bellavia C, Ruvolo G, Scazzone C, Venezia R, Perino A (2013) Detection of oncogenic human papillomavirus genotypes on spermatozoa from male partners of infertile couples. Fertil Steril 100(5):1236–1240

    Article  CAS  PubMed  Google Scholar 

  14. Hebnes JB, Olesen TB, Duun-Henriksen AK, Munk C, Norrild B, Kjaer SK (2014) Prevalence of genital human papillomavirus among men in Europe: systematic review and meta-analysis. J Sex Med 11(11):2630–2644

    Article  PubMed  Google Scholar 

  15. Laprise C, Trottier H, Monnier P, Coutlee F, Mayrand MH (2014) Prevalence of human papillomaviruses in semen: a systematic review and meta-analysis. Hum Reprod 29(4):640–651

    Article  PubMed  Google Scholar 

  16. Luttmer R, Dijkstra MG, Snijders PJ, Hompes PG, Pronk DT, Hubeek I, Berkhof J, Heideman DA, Meijer CJ (2016) Presence of human papillomavirus in semen in relation to semen quality. Hum Reprod 31(2):280–286

    PubMed  Google Scholar 

  17. Desai S, Chapman R, Jit M, Nichols T, Borrow R, Wilding M, Linford C, Lowndes CM, Nardone A, Pebody R, Soldan K (2011) Prevalence of human papillomavirus antibodies in males and females in England. Sex Transm Dis 38(7):622–629

    Article  CAS  PubMed  Google Scholar 

  18. Garolla A, Engl B, Pizzol D, Ghezzi M, Bertoldo A, Bottacin A, Noventa M, Foresta C (2016) Spontaneous fertility and in vitro fertilization outcome: new evidence of human papillomavirus sperm infection. Fertil Steril 105(1):65–72

    Article  PubMed  Google Scholar 

  19. Damke E, Kurscheidt FA, Balani VA, Takeda KI, Irie MM, Gimenes F, Consolaro ME (2017) Male partners of infertile couples with seminal infections of human papillomavirus have impaired fertility parameters. Biomed Res Int. 2017:4684629

    Article  PubMed  PubMed Central  Google Scholar 

  20. Xiong YQ, Chen YX, Cheng MJ, He WQ, Chen Q (2018) The risk of human papillomavirus infection for male fertility abnormality: a meta-analysis. Asian J Androl. 20(5):493

    Article  PubMed  PubMed Central  Google Scholar 

  21. Weinberg M, Nahshon CSS, Feferkorn I, Bornstein J (2020) Evaluation of human papilloma virus in semen as a risk factor for low sperm quality and poor in vitro fertilization outcomes: a systematic review and meta-analysis. Fertil Steril 113(5):955–969

    Article  CAS  PubMed  Google Scholar 

  22. Lai YM, Lee JF, Huang HY, Soong YK, Yang FP, Pao CC (1997) The effect of human papillomavirus infection on sperm cell motility. Fertil Steril 67(6):1152–1155

    Article  CAS  PubMed  Google Scholar 

  23. Muscianisi F, De Toni L, Giorato G, Carosso A, Foresta C, Garolla A (2021) Is HPV the novel target in male idiopathic infertility? A systematic review of the literature. Front Endocrinol 12:643539

    Article  Google Scholar 

  24. Lee CA, Huang CT, King A, Chan PJ (2002) Differential effects of human papillomavirus DNA types on p53 tumor-suppressor gene apoptosis in sperm. Gynecol Oncol 85(3):511–516

    Article  CAS  PubMed  Google Scholar 

  25. Boeri L, Capogrosso P, Ventimiglia E, Pederzoli F, Cazzaniga W, Chierigo F, Pozzi E, Clementi M, Viganò P, Montanari E, Montorsi F (2019) High-risk human papillomavirus in semen is associated with poor sperm progressive motility and a high sperm DNA fragmentation index in infertile men. Hum Reprod 34(2):209–217

    Article  CAS  PubMed  Google Scholar 

  26. Kaspersen MD, Bungum M, Fedder J, Bonde J, Larsen PB, Ingerslev J, H. and Höllsberg, P. (2013) No increased sperm DNA fragmentation index in semen containing human papillomavirus or herpesvirus. Andrology 1(3):361–364

    Article  CAS  PubMed  Google Scholar 

  27. Cortés-Gutiérrez EI, Dávila-Rodríguez MI, Fernández JL, de la O-Pérez, L.O., Garza-Flores, M.E., Eguren-Garza, R. and Gosálvez, J. (2017) The presence of human papillomavirus in semen does not affect the integrity of sperm DNA. Andrologia 49(10):e12774

    Article  Google Scholar 

  28. Lai YM, Yang FP, Pao CC (1996) Human papillomavirus deoxyribonucleic acid and ribonucleic acid in seminal plasma and sperm cells. Fertil Steril 65(5):1026–1030

    Article  CAS  PubMed  Google Scholar 

  29. Kadze R, Chan PJ, Jacobson JD, Corselli JU, King A (2002) Temperature variable and the efficiency of sperm mediated transfection of HPV16 DNA into cells. Asian journal of andrology 4(3):169–174

    CAS  PubMed  Google Scholar 

  30. Hong LJ, Oshiro BT, Chan PJ (2013) HPV-16 exposed mouse embryos: a potential model for pregnancy wastage. Arch Gynecol Obstet 287(6):1093–1097

    Article  PubMed  Google Scholar 

  31. Boulenouar S, Weyn C, Van Noppen M, Moussa Ali M, Favre M, Delvenne PO, Bex F, Noël A, Englert Y, Fontaine V (2010) Effects of HPV-16 E5, E6 and E7 proteins on survival, adhesion, migration, and invasion of trophoblastic cells. Carcinogenesis 31(3):473–480

    Article  CAS  PubMed  Google Scholar 

  32. Henneberg AA, Patton WC, Jacobson JD, Chan PJ (2006) Human papilloma virus DNA exposure and embryo survival is stage specific. J Assist Reprod Genet 23(6):255–259

    Article  PubMed  PubMed Central  Google Scholar 

  33. Spandorfer SD, Bongiovanni AM, Fasioulotis S, Rosenwaks Z, Ledger WJ, Witkin SS (2006) Prevalence of cervical human papillomavirus in women undergoing in vitro fertilization and association with outcome. Fertil Steril 86(3):765–767

    Article  PubMed  Google Scholar 

  34. Perino A, Giovannelli L, Schillaci R, Ruvolo G, Fiorentino FP, Alimondi P, Cefalù E, Ammatuna P (2011) Human papillomavirus infection in couples undergoing in vitro fertilization procedures: impact on reproductive outcomes. Fertil Steril 95(5):1845–1848

    Article  PubMed  Google Scholar 

  35. Depuydt CE, Donders GGG, Verstraete L, Broeck DV, Beert JFA, Salembier G, Bosmans E, Ombelet W (2019) Infectious human papillomavirus virions in semen reduce clinical pregnancy rates in women undergoing intrauterine insemination. Fertil Steril 111(6):1135–1144

    Article  PubMed  Google Scholar 

  36. Gizzo S, Ferrari B, Noventa M, Ferrari E, Patrelli TS, Gangemi M, Nardelli GB (2014) Male and couple fertility impairment due to HPV-DNA sperm infection: update on molecular mechanism and clinical impact—systematic review. Biomed Res Int. 2014

    Article  PubMed  PubMed Central  Google Scholar 

Download references




Not applicable.

Author information

Authors and Affiliations



AS did the literature review and wrote the manuscript. MZ helped write the manuscript. The authors read and approved the final manuscript.

Corresponding author

Correspondence to Anastasia Salame.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhaffal, M., Salame, A. Semen human papillomavirus (HPV) shedding in males: frequency, clinical significance, and reproductive outcomes—literature review. Middle East Fertil Soc J 28, 6 (2023).

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: