The role of human papillomavirus (HPV)
infections in the development of
verrucous carcinoma, a well-differentiated variant of
squamous cell carcinoma with difficult differential diagnosis, is controversial in the literature. In this study, we analysed
verrucous carcinoma from different origins for the presence and activity of a broad spectrum of HPV types, and carefully reviewed the histopathological features. A random series of 27
formalin-fixed,
paraffin-embedded specimens of
verrucous carcinoma was taken, representing the head and neck region (n=6), anogenital area (n=16) and extragenital skin region (n=5). After review of the histological slides, all samples were subjected to different polymerase chain reaction-based HPV detection techniques, together detecting a total of 83 HPV types, including both mucosal and cutaneous types. Histological revision was carefully performed. Lesions with keratinised papillae, blunt stromal invaginations and minimal cytological atypia were considered
verrucous carcinoma. Condylomatous lesions with viral changes were defined as giant condyloma. Verrucous lesions that did not meet those criteria were classified as verrucous
hyperplasia. Tumours with stromal infiltration were considered as invasive
squamous cell carcinoma. Histological revision revealed that 13 out of 27 cases were
verrucous carcinoma (one showing a double
infection with HPV 35 and 45), 5 invasive
squamous cell carcinomas, 5 verrucous
hyperplasia (one with a double
infection with HPV 4 and 8), 1 pseudoepitheliomatous
hyperplasia and 3 giant condylomas. All three giant condylomas were low-risk HPV positive (HPV 6 and 11) and showed active
mRNA transcription. None of the HPV-positive samples tested positive for diffuse
p16(INK4A) staining. In conclusion, our results do not support a causal role of HPV in the development of
verrucous carcinoma. Testing for LR-HPV, particularly HPV 6 and 11, may help in the differential diagnosis of lesions suspicious of
verrucous carcinoma as those testing positive for LR-HPV most likely represent giant condylomas.