HPV42: A Common Low-Risk HPV Type Associated With Distinctive Cervicovaginal and Cutaneous Neoplasia

Seborrheic keratosis-like lesion (SKLL) is an extremely rare, morphologically distinct lesion occurring in the cervix and vagina that differs histologically from other squamous intraepithelial lesions in these sites due to its unique morphology, including close resemblance to cutaneous seborrheic keratosis and lack of viral cytopathic effect (koilocytosis). We report a series of 17 cases, describe in detail the morphology and add to the evidence linking SKLL with low-risk human papillomavirus (LRHPV), specifically HPV42, which was detected in 13 cases; in 3 cases, an additional single HPV type (HPV6, 16, 61) was detected. In 2 of the SKLLs, a component of high-grade morphology and block-type p16 immunoreactivity were observed, prompting speculation as to the oncogenic potential of HPV42. Nineteen cases of papillary immature metaplasia, another distinctive LRHPV-associated lesion with some morphologic overlap with SKLL, were HPV42 negative. Independently, HPV42 has recently been implicated as the cause of a rare, aggressive cutaneous tumour, digital papillary adenocarcinoma (DPA), with experimental molecular data supporting the transforming capacity of this virus. These findings, along with the observation that rare anogenital squamous cell carcinomas are associated with HPV42, demonstrate the rare carcinogenic potential of this LRHPV. The association of HPV42 with these 2 unique and distinctive tumours (SKLL and DPA) also illustrates the incompletely understood diversity of HPV genotype-phenotype associations and virus-host interactions and highlights the importance of HPV typing of novel genital and cutaneous tumours.