Abstract 4848: Penile intraepithelial neoplasia in a multinational cohort of men: the HPV Infection in Men Study.
Authors: Campbell Christine M. Pierce , Lin Hui-Yi , Fulp William , Abrahamsen Martha , Lu Beibei , Villa Luisa L. , Lazcano-Ponce Eduardo , Giuliano Anna R. 
Published: August 2014

The human papillomavirus (HPV) is an established etiologic agent in 50% of penile cancers. While invasive penile cancer is rare in the US, the incidence is nearly 2-fold higher in Hispanics versus non-Hispanics. Recent evidence from Europe suggests that the incidence of penile cancer and its precursor lesion (penile intraepithelial neoplasia [PeIN]) may be on the rise. Little is known about the epidemiology of PeIN and the role of HPV in PeIN lesion development in healthy men. Thus, the purpose of this study was to describe the incidence of PeIN, HPV type distribution within PeIN tissue, and HPV natural history leading to PeIN diagnosis in a cohort of HIV-negative men.

A total of 4,117 men ages 18-70 years living in the US, Brazil, and Mexico were enrolled in the prospective HPV Infection in Men (HIM) Study. Men were examined at baseline and every 6 months over 4 years of follow-up (median: 42 months). At each clinical visit, exfoliated cells of the external genital skin (coronal sulcus/glans penis, shaft, and scrotum) were routinely collected and tested for HPV DNA using Roche Linear Array. Visually identified, HPV-related lesions were biopsied and subjected to pathologic evaluation. The INNO-LiPA genotyping assay was used to detect HPV DNA from within biopsy tissue. Estimates of PeIN incidence included newly diagnosed lesions with person time estimated from study entry to the date of biopsy.

Eleven men in the HIM Study cohort developed pathologically-confirmed, dysplastic penile lesions. Two men exhibited PIN I, 4 had PeIN II, and 4 had PeIN III; one man was diagnosed with invasive penile cancer and was excluded from further analyses. The incidence rate of PeIN was 0.08 per 100 person-years (95% CI: 0.04-0.15). The median age at PeIN diagnosis was 26 years (range: 24-42). Among 9 lesions with adequate specimens for HPV analysis, HPV DNA was detected in the tissues of all PeIN lesions. Most lesions (n=8; 89%) were infected with an oncogenic HPV type, 1 (11%) was infected with only non-oncogenic HPV types, and 4 (44%) were co-infected with multiple HPV types. HPV16 was the most common type detected (5; 56%), followed by oncogenic types HPV51 (2; 22%), HPV18 (1; 11%), and HPV39 (1; 11%), and non-oncogenic types HPV11 (3; 33%) and HPV6 (2; 22%). HPV16 was present in the normal genital skin 12 months prior to lesion detection in 60% (n=3) of men with HPV16+ PeIN, and HPV51 was present in 100% (n=1) of men 12 months prior to detection of HPV51+ PeIN. The mean time from HPV16 detection to the development of HPV16+ PeIN lesions was 16.2 months (SD: 18.9).

This is the first prospective evaluation of the incidence of penile cancer precursor lesions in HIV-negative men over a broad age range. The prevalence of HPV DNA in PeIN was high, particularly for HPV16. Both HPV16 and HPV51 were found to persist at least 12 months before PeIN diagnosis. These data may be useful as baseline measurements to monitor future trends in PeIN lesions.

Citation Format: Christine M. Pierce Campbell, Hui-Yi Lin, William Fulp, Martha Abrahamsen, Beibei Lu, Luisa L. Villa, Eduardo Lazcano-Ponce, Anna R. Giuliano. Penile intraepithelial neoplasia in a multinational cohort of men: the HPV Infection in Men Study. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4848. doi:10.1158/1538-7445.AM2013-4848