Noninvasive Genotyping Test of Human Papillomavirus in Japanese Male Genital Warts by <scp>PCR</scp> From Scraping Specimens

Genital warts (condyloma acuminatum) are a common sexually transmitted disease, usually caused by low-risk human papillomavirus (LR-HPV) types 6 and 11, which together account for more than 90% of all cases [1]. However, high-risk HPV (HR-HPV), particularly HPV 16, is occasionally detected and associated with penile and cervical cancer [2, 3]. In men, diagnosis typically relies on visual inspection, and confirmation requires biopsy, which imposes an invasive burden. Noninvasive diagnostic methods may help improve patient management and reduce barriers to clinical and epidemiological investigations [1]. We investigated HPV genotypes in male genital warts using a simple swab-based PCR test. Forty-nine Japanese men with suspected genital warts presenting at a community urology clinic were included. Lesions were swabbed at least five times with a sterilized cotton swab by the same experienced urologist, and DNA was extracted using a commercially available kit (Gcube Co. Ltd., Kobe, Japan). Real-time PCR was performed to detect HPV 6, 11, and 16 (The Applied BiosystemsThermo Fisher, QuantStudio 5). HPV genotyping was successfully performed in 46 of 49 patients (93.9%), and the clinical and virological characteristics of these cases are summarized (Table 1). Among them, HPV 6 was found in 23 cases, HPV 11 in 13, and HPV 6 + 11 coinfection in 5. These low-risk types accounted for approximately 89% of positive results. Importantly, HPV 16 was identified in five patients (10.9%), including one mono-infection, three HPV 6 + 16 coinfections, and one triple infection (HPV 6 + 11 + 16). Three patients tested negative, including one seborrheic keratosis and two previously treated with cryotherapy. The detection rate of HPV 16 in our study (10.9%) is consistent with Yuan et al., who reported 13.7% among condyloma patients in Shandong Province, China [1]. Our findings confirm that HPV 16 is frequently codetected with LR-HPV in genital warts, suggesting that clinicians should not regard all condyloma as low-risk disease. The presence of HR-HPV emphasizes the need for careful follow-up, especially considering its strong oncogenic association [3, 4]. Given that HPV 16 is implicated in over two-thirds of penile cancers and is the primary cause of cervical cancer, detection in male patients has important implications for both individual and partner management [4]. This study demonstrates the feasibility of noninvasive scraping combined with PCR for HPV genotyping in clinically diagnosed wart specimens, consistent with prior studies [1]. Traditionally, HPV typing in men has been limited, and biopsy-based sampling discourages routine testing. Invasive procedures for genital warts can be complicated by bleeding [5]. Our study shows that swab-based PCR is feasible, reliable, and suitable for use in outpatient clinics. This approach may help identify high-risk cases requiring closer monitoring, while also supporting public health strategies including male HPV vaccination. Although HPV vaccination programs in Japan have focused mainly on females [6], vaccination in males has likewise been investigated and demonstrated to be effective [7]. Our results highlight the potential benefit of expanding vaccination to men to reduce transmission and cancer risk. First, an internal control such as β-globin was not included to confirm the adequacy of human DNA in all samples; therefore, the true analytical sensitivity of HPV detection could not be fully validated. Second, another limitation of this preliminary study is its small sample size and the restriction to HPV types 6, 11, and 16. Other oncogenic types such as HPV 18, 31, and 45 were not investigated due to the limited detection range of the kit. Third, the persistence of HPV infection and recurrence after treatment were not assessed. Larger and more comprehensive studies are needed to establish the full clinical utility of noninvasive HPV testing in men. In summary, this study demonstrates the clinical feasibility of noninvasive scraping combined with PCR for HPV genotyping in Japanese men with genital warts. The observed distribution of HPV genotypes, including the presence of HPV 16 among successfully genotyped cases, highlights the importance of clinical awareness and supports further discussion regarding male HPV vaccination in Japan. Yu Yoshimura: writing – review and editing, writing – original draft. Mamoru Hashimoto: writing – review and editing. Takahisa Genji: validation. Kenji Nishimura: validation. Masahisa Ikegami: resources. Kazutoshi Fujita: supervision. Approval of the Research Protocol by an Institutional Review Board (IRB): Approved by the Ethics Committee of Kindai University (Approval No. R06-156). Written informed consent was waived due to the retrospective design. Kazutoshi Fujita, an Editorial Board member of the International Journal of Urology and a coauthor of this article, was not involved in any editorial decisions regarding the acceptance of this manuscript in order to minimize potential bias.