Role of histological findings and pathologic diagnosis for detection of human papillomavirus infection in men

Abstract

Early HPV infection in males is difficult to detect clinically and pathologically. This study assessed histopathology in diagnosing male genital HPV. External genital lesions (n = 352) were biopsied, diagnosed by a dermatopathologist, and HPV genotyped. A subset (n = 167) was diagnosed independently by a second dermatopathologist and also re-evaluated in detail, tabulating the presence of a set of histopathologic characteristics related to HPV infection. Cases that received discrepant diagnoses or HPV-related diagnoses were evaluated by a third dermatopathologist (n = 163). Across dermatopathologists, three-way concordance was fair (k = 0.30). Pairwise concordance for condyloma was fair to good (k = 0.30-0.67) and poor to moderate for penile intraepithelial neoplasia (k = -0.05 to 0.42). Diagnoses were 44-47% sensitive and 65-72% specific for HPV 6/11-containing lesions, and 20-37% sensitive and 98-99% specific for HPV 16/18. Presence of HPV 6/11 was 75-79% sensitive and 35% specific for predicting pathologic diagnosis of condyloma. For diagnosis of penile intraepithelial neoplasia, HPV 16/18 was 95-96% specific but only 40-64% sensitive. Rounded papillomatosis, hypergranulosis, and dilated vessels were significantly (P < 0.05) associated with HPV 6/11. Dysplasia was significantly (P = 0.001) associated with HPV 16/18. Dermatopathologists' diagnoses of early male genital HPV-related lesions appear discordant with low sensitivity, while genotyping may overestimate clinically significant HPV-related disease. Rounded papillomatosis, hypergranulosis, and dilated vessels may help establish diagnosis of early condyloma.

Keywords: HPV; PeIN; biopsy; condyloma; histopathology; penile intraepithelial neoplasia.

Figure 1

Common histological findings in condylomas: (A) rounded papillomatosis; (B) parakeratosis; (C) hypergranulosis; (D) dilated vessels; (E) koilocytes and binucleation.

Figure 2

Overview of specimen evaluation. ^aHistopathologic characteristics included rounded papillomatosis (Fig. 1A), parakeratosis (Fig. 1B), hypergranulosis (Fig. 1C), dilated vessels (Fig. 1D), koilocytes and binucleation (Fig. 1E), horn cysts, hyperpigmentation, and dysplasia/atypia. ^bHPV-related diagnoses included condyloma, penile intraepithelial neoplasia I, and penile intraepithelial neoplasia II/III. Note: The lesions evaluated by Pathologist #2 and 3 are not mutually exclusive. Only 155 lesions were utilized for the three-way concordance analysis.

Figure 3

Classic condyloma with well-established features obvious on low power magnification: rounded papillomatosis, hypergranulosis, dilated vessels, koilocytes, horn cysts.

Figure 4

(A and B) Benign squamous keratosis (BSK). These entities have some features of a condyloma: horn cysts, dilated vessels, hypergranulosis, and parakeratosis.