Urine sample for HPV detection in men: is it a valid and non-invasive diagnostic alternative?

ABSTRACT Human papillomavirus (HPV) represents the most prevalent sexually transmitted infection worldwide, often presenting as asymptomatic or subclinical in males. There is still uncertainty about the most suitable biological specimen for an accurate HPV diagnosis in males since the sampling site influences the performance of the diagnosis. Conventional diagnostic strategies rely on uncomfortable specimens for patients, such as urethral swabs. This study aimed to evaluate the diagnostic performance of using non-invasive, self-collected urine samples as an alternative to urethral swabs for detecting HPV infections in men. A total of 110 men provided a genital swab, a urethral swab, and a urine sample for analysis. HPV DNA was detected in 74.5% of the total samples, with 89.0% of HPV-positive samples harboring at least one oncogenic genotype. The most frequently detected genotypes were HPV53, HPV66, and HPV16. Of the individual specimens examined, genital swabs demonstrated the highest HPV positivity rate (68.2%), significantly outperforming urethral swabs and urine samples ( P < 0.05). No significant difference was observed between urethral swabs and urine samples. However, the urine specimen alone demonstrated high specificity (100%), but limited sensitivity (53.7%), and moderate accuracy (65.5%). Receiver operating characteristic (ROC) analysis revealed that combining genital swabs with urine samples achieved excellent diagnostic performance (area under the ROC curve/AUC = 0.994), raising sensitivity to 98.8%, specificity to 100%, and accuracy to 99.1%. Overall, the results suggest that the combination of genital swabs and urine samples represents a reliable, non-invasive, and patient-acceptable alternative to conventional urethral sampling for HPV detection in men. IMPORTANCE This study is important because it addresses a major unmet need in the diagnosis of HPV infection in men, namely, the lack of a standardized, reliable, and well-tolerated biological specimen. Using urine as a diagnostic sample, particularly in conjunction with genital swabs, has the potential to improve diagnostic efficacy while minimizing patient discomfort. A more acceptable diagnostic approach could enhance patient compliance, enable earlier detection of HPV infection, and improve clinical management. Furthermore, standardizing sampling strategies in men would help to close a critical gap in HPV prevention and control, with potential benefits for public health and reducing viral transmission.