Anogenital infection with human papillomavirus (HPV) constitutes a field infection and is the most common sexually transmitted disease worldwide. It is estimated that between 85% and 90% of sexually active individuals will acquire HPV at some point in their lives.1–3 In most cases, these infections are transient and asymptomatic.

HPV is a small DNA virus with tropism for cutaneous and mucosal epithelia. More than 200 genotypes have been identified, of which at least 12 are considered oncogenic.4,5 It is estimated that more than 95% of cervical cancers are related to HPV infection, as well as 90% of anal cancers, 36–40% of penile cancers, 40–64% of vaginal cancers, 40–51% of vulvar cancers, and between 12% and 63% of oropharyngeal cancers.6,7 According to the International Agency for Research on Cancer, in 2018 approximately 69,400 cases of cancer attributable to HPV were estimated in men.8 Similarly, data from the Global Cancer Registries database (GLOBOCAN, Global Cancer Observatory) predict an increase of more than 56% in the incidence rate of penile cancer by 2040.9

On the other hand, HPV is responsible for all cases of genital warts. In Europe, between 379,000 and 510,000 new cases are reported annually in women, and between 377,000 and 428,000 in men. Although these lesions are benign, they affect quality of life and their treatment entails a significant cost for health care systems.10

Historically, HPV research has focused on women and its association with cervical cancer.11 However, in recent years, interest in understanding infection in men has increased, revealing relevant differences between sexes regarding the natural history of the virus and the anatomical sites affected.12 Although this review focuses on the term “men” in a biological sense, some of the clinical signs and risks associated with HPV may be shared by individuals with a penis of diverse genders, such as transgender women or non-binary individuals. In the absence of sufficiently disaggregated studies by gender identity, the data presented here should be interpreted considering this possible population diversity. In addition, genotypes 16, 18, 31, 33, 45, 52, and 58 have been estimated to account for 89% of cancers attributable to HPV in both sexes.13

From a dermatological perspective, HPV is a frequent cause of consultation due to cutaneous and mucocutaneous lesions, particularly condyloma acuminata, which represent one of the main visible clinical manifestations of infection in men. These lesions, in addition to their clinical, functional, and psychosocial impact, may coexist with infections by high-risk genotypes, highlighting the role of the dermatologist in identifying patients at oncological risk. Dermatology plays an essential role not only in the topical or ablative treatment of these lesions but also in health education, vaccination indication, and early referral of cases suspicious for genital or anal malignancy. This multidisciplinary approach is key to optimizing prevention and clinical management of HPV in the male population.

This review aims to further explore these differences and evaluate effective prevention strategies in men to reduce the global burden of HPV-associated cancers.

There are relevant differences in sample collection and anatomical localization of HPV infection between men and women.

In females, cervical sampling for viral DNA detection is well standardized, including established diagnostic and therapeutic pathways according to results. In contrast, in men there is no established clinical protocol nor any FDA-approved screening test for routine use.25

Scientific literature describes multiple anogenital sites susceptible to infection in men, which is explained by the “field infection” nature of HPV, with potential involvement of multiple epithelial surfaces. This anatomical variability complicates both sample collection and interpretation of results.

Nicolau et al. analyzed a total of 55 men with stable HPV-positive partners, using aqueous capture in six different anogenital areas and peniscopy with biopsy of suspicious lesions.25,27 A total of 70% of men were HPV-positive: 32% for high-risk genotypes, 14% for low-risk, and 24% for both groups. The most frequently biopsied site was the inner foreskin (57 of 104 samples). Overall, HPV DNA was detected in 27 of 104 biopsies (26%), although only 14 samples (13.5%) showed histological evidence of infection.

A notable finding was the absence of genotypic correlation between partners, since in 50% of cases in which the woman had high-risk HPV infection, her male partner did not test positive for the same genotypic group. This phenomenon reinforces the complexity of viral transmission and immunological dissociation between sexes.

These data are consistent with those obtained by Anna Giuliano et al. in the HIM study,14 whose objective was to identify optimal sites for HPV detection in heterosexual men. In a cohort of 463 men, HPV DNA presence was evaluated in seven different anatomical sites. In the overall cohort, 65.4% of men were positive in at least one location, a percentage similar to that observed in the subcohort of 186 men with complete anatomical analysis (67.7%).28

Detection was more frequent in the penile shaft (49.9% and 47.9%), followed by the glans and coronal sulcus (35.8% and 32.8%), and the scrotum (34.2% and 32.8%). Other areas such as the perianal region (20.0% and 22.6%), the anal canal (17.6% and 18.3%), the urethra (10.1% and 10.2%), and semen (5.3% and 4.8%) showed lower detection rates. These results support the need to use multiple sampling sites, considering the penile shaft as a priority region for HPV detection in men.

A strong association has been established between HPV and the development of cancers in men, especially penile carcinoma, oropharyngeal carcinoma, and anal carcinoma. The relationship with other tumors such as bladder, urethral, or prostate cancer remains under investigation.

The association between HPV and tumor development was established during the 1970s and 1980s, with the pioneering discoveries of the German virologist Harald zur Hausen, who received the Nobel Prize in Medicine in 2008 for his work on HPV types 16 and 18.29 Globally, HPV is responsible for 4.5% of all cancers in women and men, and in Europe approximately 2.5%, so it is important to highlight that the risk of progression to cancer is associated with the persistence of HPV infection (Table 1).8

HPV infects epithelial cells, and its replication cycle is linked to epithelial differentiation. There are more than 200 genotypes with variable tissue specificity. While most cause benign lesions (such as genital warts or condyloma acuminata, mainly associated with HPV-6 and -11), a subgroup of high-risk HPV (HR-HPV) has oncogenic potential. It should be noted that some condylomas may contain coinfections with HR-HPV genotypes (e.g., HPV-16, -18, -31), which underscores the importance of viral typing in persistent or atypical lesions.30

The E6 and E7 oncoproteins block key cellular functions such as apoptosis and DNA repair, promoting malignant transformation.31

HPV is estimated to be present in 38–40% of cases of penile squamous cell carcinoma,32,33 and its incidence rate is expected to increase by 56% by 2040 according to data from the Global Cancer Observatory (GLOBOCAN).9 HPV-16 is the most widely implicated genotype, responsible for up to 72% of cases.

Mechanistically, HPV contributes to penile carcinogenesis through integration of its viral DNA into the cellular genome, with overexpression of E6 and E7. The p16 protein, whose increase reflects inactivation of Rb by E7, has become a useful prognostic marker.34 A recent meta-analysis demonstrated significantly higher disease-specific survival in HPV-positive men (HR, 0.61) and p16-positive men (HR, 0.45), supporting their clinical value.35

Despite this evidence, there is no established method for early screening of penile cancer, nor is routine HPV detection recommended at this site.36 Treatment is based on conservative surgery when possible, radical lymphadenectomy if there is nodal involvement, and adjuvant chemotherapy in advanced stages.37–39

The association between oropharyngeal squamous cell carcinoma (OPSCC) and HPV, mainly HPV-16, has been confirmed over the last 2 decades; in some countries, these HPV-dependent tumors are already more frequent than HPV-independent ones, traditionally associated with tobacco and alcohol.40 The incidence rate of HPV-positive OPSCC has increased in young men in high-income countries.41 This subtype has a better prognosis and greater sensitivity to radiotherapy, which has been reflected in the eighth edition of the TNM system of the American Joint Committee on Cancer (AJCC).42

The diagnosis of HPV infection is based on immunohistochemistry for p16 combined with in situ hybridization for the detection of oncogenic genotypes (HPV-16 and HPV-18). Although there is no population-based screening method for head and neck cancers, treatment is based on chemoradiotherapy, generally with cisplatin and radiotherapy at 66–70Gy.43

HPV is responsible for >90% of anal carcinoma cases, with HPV-16 being the main implicated genotype.44 The precursor lesion is high-grade squamous intraepithelial lesion (HSIL), equivalent to anal intraepithelial neoplasm (AIN). This progression is more common in high-risk populations, such as MSM and people living with HIV.

In 2022, the ANCHOR (Anal Cancer HSIL Outcomes Research) study was published in The New England Journal of Medicine, evaluating whether treatment of HSIL lesions could prevent anal cancer in people with HIV.45 In a cohort of >4400 HIV-positive patients, treatment reduced the risk of progression to cancer by 57% vs observation. This is the first solid evidence that treating anal precancerous lesions can prevent cancer in high-risk patients. This finding supports the systematic use of anal cytology, high-resolution anoscopy (HRA), and targeted treatment of HSIL, replicating the cervical cancer prevention model.

In MSM with HIV, the prevalence of anal HPV approaches 100%,46,47 and anal cancer rates are up to 80 times higher than in the general population48 Therefore, the use of anal cytology and HRA is recommended in at-risk populations.

Currently, consensus guidelines published by the International Anal Neoplasia Society in 2024 include other high-risk groups in whom anal cancer screening is also indicated—not only MSM with HIV, but also women with a past medical history of high-grade genital intraepithelial neoplasm, immunocompromised individuals, and other patients with HIV.49

Although HPV DNA is not useful as a diagnostic test due to its high prevalence in this population, the combination of cytology and targeted examination has demonstrated high predictive value.

Treatment of anal cancer includes combined chemoradiotherapy, and in early cases, topical or ablative options. However, close follow-up is essential due to the risk of progression and recurrence.

Some studies have identified HPV-16 infection in primary urethral carcinomas, although the evidence is still limited and considered to be in the investigational phase.50,51

Regarding the bladder, a recent meta-analysis including 14 studies showed a significant association between HPV and bladder cancer, with an OR of 4.18 (95%CI, 2.63–6.66), although the evidence is not conclusive due to methodological heterogeneity.52

The relationship between HPV and prostate cancer remains controversial. A meta-analysis including 27 studies (n=1607 tumors; n=1515 controls) found HPV in 25.8% of tumors vs 17.4% in benign prostatic hyperplasia and 9.2% in normal tissue. Although data suggest a possible association, more well-designed studies are required to establish causality.53

Vaccination against human papillomavirus in men has proven to be an effective tool for preventing genital infections, warts, and several types of cancer, in addition to reducing community transmission. However, its implementation and coverage worldwide show notable inequalities.

In North America and Western Europe, countries such as the United States, Canada, the United Kingdom, Germany, and Australia have incorporated male vaccination into their national programs, recommending it from 9–13 years of age. In these contexts, significant reductions in the incidence of HPV infection and genital warts have been observed.1,54

In Latin America, nations such as Argentina, Brazil, Mexico, and Colombia have also introduced male vaccination schemes, although with variable coverage. Argentina, for example, has reported rates>70% in some regions.3

In Asia and Africa, male vaccination is still limited and mainly focused on women. Japan and some Southeast Asian countries have begun to introduce vaccination in men through specific access strategies.7

In low-resource countries, economic, logistical, and awareness barriers continue to hinder implementation, with priority given to the prevention of cervical cancer in women.

In Spain, HPV vaccination is included in the common vaccination schedule throughout life, approved by the Public Health Commission of the Interterritorial Council of the Spanish National Health System. Current funded indications, according to official recommendations from the Spanish Ministry of Health, are:

Systematic vaccination of girls and boys at 12 years of age, with a single-dose schedule.56

Catch-up vaccination up to 18 years of age for unvaccinated adolescents, also with a single dose.55,56

Unvaccinated individuals with certain risk conditions up to 45 years of age, in whom vaccination is recommended if they belong to one of the following groups:

• •

  MSM.

• •

  Individuals engaged in prostitution.

• •

  Immunocompromised individuals: HIV infection, solid organ transplant or hematopoietic stem cell transplant, WHIM syndrome.56

In these cases, the schedule varies according to age:

• •

  From 9 to 25 years: one dose, except in immunocompromised individuals.

• •

  From 26 to 45 years: two doses at least 6 months apart.

• •

  In immunocompromised individuals: 3 doses with a 0, 2, and 6-month schedule, regardless of age.57

• •

  For individuals>45 years, evidence is limited; vaccination may be considered on an individual basis according to risk factors and clinical judgment.

In addition to national recommendations, autonomous communities have implemented their own strategies with differences in coverage, target groups, and catch-up age.58 For example:

• •

  Systematic vaccination at 12 years (common in Andalusia, Castile and León, Castile-La Mancha), with active catch-up up to 18 years in unvaccinated populations.

• •

  Extension to adolescent males:

  • ∘

    Catalonia (up to 18 years, cohorts 2007–2011, from 2025).

  • ∘

    Madrid (13–18 years, from 2024).

• •

  Extended coverage to young adults:

  • ∘

    Galicia: men aged 18–21 years (cohorts 2004–2005), with vaccination starting on May 26, 2025.59

  • ∘

    Murcia: men up to 25 years (cohorts 1999–2000 in phase #1), with progressive implementation from 2024 starting with older cohorts, with the aim of reaching all individuals born between 1999 and 2010 by 2027.60

These territorial differences affect catch-up age, type of vaccine administered, and populations included in funded programs, generating inequalities in access to prevention and highlighting the need to harmonize funding criteria across the national territory.

Male vaccination not only prevents infection in men but also significantly contributes to herd immunity, reduces disease burden, and supports HPV eradication programs. Its inclusion in systematic vaccination schedules should be a priority in global public health policies.

HPV infection in men includes a broad clinical spectrum ranging from asymptomatic carriers to benign signs (warts) or malignant conditions (penile, anal, or oropharyngeal cancers). A practical clinical management algorithm based on individual risk and clinical context is proposed below (Table 2).

HPV infection in men represents a clinical and public health challenge, with direct implications in dermatology, urology, oncology, and infectious diseases. Although research and prevention programs have historically focused on women, there is clear evidence that HPV causes a substantial burden of disease in men, including benign lesions such as condyloma acuminata and malignant anogenital and oropharyngeal neoplasms.

Dermatologists play a key role in the recognition, diagnosis, and treatment of cutaneomucosal signs of HPV, as well as in education, prevention, and timely referral of at-risk patients. Prophylactic vaccination in men, identification of precancerous lesions, and multidisciplinary management of advanced cases are essential pillars of the current strategy.

The approach to HPV in men must be comprehensive, evidence-based, and adapted to the individual risk profile, with special attention to MSM, immunocompromised patients, and individuals with a history of HPV-related lesions. Promoting equity in prevention and expanding access to male vaccination are fundamental steps toward the global control of this infection.

The authors declare that they have no conflict of interest.