The Optimal Anatomic Sites for Sampling Heterosexual Men for Human Papillomavirus (HPV) Detection: The HPV Detection in Men Study

Human papillomavirus (HPV) infection is the necessary etiologic agent for cervical carcinogenesis, with HPV infection in men significantly contributing to infection and subsequent cervical disease in women as well as to disease in men [1–4]. Case-control studies of women with cervical cancer and their husbands have demonstrated that men’s sexual behavior affects women’s risk of cervical neoplasia, even when controlling for female sexual activity. In areas with a high incidence of cervical cancer, men’s sexual behavior is a risk factor for cervical neoplasia [5]. Available information regarding penile HPV infection is primarily derived from 3 sources: (1) studies of husbands of women with cervical cancer [6–9]; (2) cross-sectional studies of select populations, such as patients with sexually transmitted diseases (STDs) and military recruits [10, 11]; and (3) small prospective studies [12, 13] (see [14] for a recent review of the literature). The reported prevalence of HPV infection in men varies widely. Early studies used acetowhitening of the penis as a diagnostic marker for HPV infection and examined men for epithelial lesions [15]. Although HPV is significantly associated with acetowhite penile lesions [16], many other genital conditions are also associated with these lesions [17, 18], resulting in poor specificity for HPV detection. To accurately assess HPV infection in men, molecular techniques must be used. Recent studies using polymerase chain reaction (PCR), a method sensitive enough to detect 10–100 copies of viral DNA, have found HPV detection in men to be as high as in their female counterparts [19]. Most studies of HPV infection in men have sampled penile skin—specifically, the coronal sulcus and glans penis—and the urethra [6–9, 11–13, 20–23]. Many studies combined specimens from the skin and urethra to report HPV DNA prevalence. In 2 studies, urine was collected [21, 24]; however, neither reported HPV DNA results. There is some consensus that sampling the coronal sulcus and glans penis is necessary for assessing HPV status in men because of direct contact with the cervix [14]. There is less consensus regarding urethral sampling, particularly among asymptomatic men. In addition to potentially not yielding informative data, urethral sampling may decrease study participation, particularly in prospective studies that require repetitive sampling of anatomic sites. Several studies have evaluated the scrotum and semen for the presence of HPV DNA [25–38]; however, the majority did not also evaluate the presence of HPV at other anatomic sites [25, 27, 29–31, 34, 36]. As a result, it is unclear whether sampling the scrotum and semen contribute meaningful information to the estimation of HPV prevalence. Twelve studies have attempted to evaluate HPV sampling at multiple anatomic sites [12, 21, 26, 28, 33, 37, 39–44]. The purpose of the present study was to determine the optimal anatomic site(s) for the detection of HPV infection among heterosexual men by assessing HPV DNA in urethral, glans penis/coronal sulcus, penile shaft/prepuce, scrotal, perianal, anal canal, semen, and urine samples.