Human papillomavirus-associated oral intraepithelial neoplasia

Abstract

This study evaluated an unusual subset of oral epithelial dysplasia for the presence of transcriptionally active high-risk HPV subtypes and to further characterize the histological criteria for this condition. There were 20 cases diagnosed as epithelial dysplasia with marked apoptosis of the anterior oral cavity. Clinical and followup data were collected and histopathological features were documented. Immunoperoxidase studies were performed for p16 and in situ hybridization studies were performed for low-and high-risk HPV sub-types. Gender-and site-matched controls of conventional moderate-to-severe oral epithelial dysplasia were similarly evaluated using immunoperoxidase studies for p16 and in situ hybridization; the number of apoptotic cells for study and control cases was counted at two different tissue sites. There were 17 men and 3 women with a median age of 56 years. Seventeen lesions were described as white and five were described as rough or papillary. Thirteen were located on the lateral or ventral tongue, some extending onto the floor of the mouth. Epithelial hyperplasia with marked karyorrhexis and apoptosis were present in all the cases, along with features of conventional oral epithelial dysplasia. A statistically significant number of apoptotic cells were identified in the study cases when compared with controls (P40.0001). Twenty cases were positive for high-risk HPV by in situ hybridization and all 19 nineteen cases evaluated for p16 demonstrated overexpression. Two patients were diagnosed with squamous cell carcinomas and one patient developed recurrent disease. We report a subset of oral epithelial dysplasia that occurs mostly in adult men on the ventral or lateral tongue and is positive for high-risk HPV and for p16. We propose use of the term 'HPV-associated Oral Intraepithelial Neoplasia' to characterize these lesions of the oral cavity for consistency in nomenclature with HPV-associated lesions of the lower anogenital tract. One case recurred and one developed invasive cancer. Keywords: HPV apoptotic oral epithelial dysplasia; koilocytic dysplasiaIn the United States, smoking frequency has decreased by 16% and the overall number of cases of cancer of the oral cavity and pharynx has fallen by 18% since 1975. 1 However, rates of cancers of the oral tongue, base of tongue, and palatine tonsils have continued to rise by 2-4% among younger men. 2,3 This may, in part, be explained by the increased prevalence of a subset of oropharyngeal carcinoma associated with human papillomavirus (HPV), mostly HPV-16. 4-7 Importantly, p16 overexpression is noted in almost all HPV-associated head and neck cancers and indicates that the virus is transcriptionally active. Patients with HPV-positive, p16-positive oropharyngeal carcinomas are slightly younger than those with tumors not associated with HPV and show improved survival. 8,9 It is generally believed that HPV has only a minor role in squamous cell carcinoma of the anterior oral cavity, because it has been identified in only 2.9-5.9% of cases and the beha...

Extensive HPV-Related Carcinoma In Situ of the Upper Aerodigestive Tract with ‘Nonkeratinizing’ Histologic Features

“…This description is similar to the bowenoid dysplasia described by Daley et al [11]. Another recent study by Woo et al [13] examined only oral cavity high grade dysplasias with 'marked apoptosis' and found all 20 cases to harbor high risk HPV DNA by ISH. Focal, but not diffuse, koilocytes were noted in all of these HPV-related cases and all tested cases showed strong and continuous p16 positivity, as well.…”

“…The morphology of the case presented here has features that are similar to those described by Daley et al, McCord et al, and Woo et al [11][12][13] in that it has full-thickness loss of maturation and a high mitotic rate, but it is not identical. The present case is more akin to HPV-related 'nonkeratinizing' squamous cell carcinoma of the tonsillar crypts in that it had oval to spindled nuclei and indistinct borders-features that were not described or presented in the previous studies [11][12][13].…”

“…The present case is more akin to HPV-related 'nonkeratinizing' squamous cell carcinoma of the tonsillar crypts in that it had oval to spindled nuclei and indistinct borders-features that were not described or presented in the previous studies [11][12][13]. Nonetheless, it appears that HPV-related premalignant lesions may have histologic features that are distinct from HPV-unrelated lesions.…”

“…Matched control cases of conventional dysplasia were all HPV negative. The described bowenoid histology of the HPVrelated dysplasias in these studies is nearly identical and suggests that there may be a subset of HPV-related oral cavity dysplasias with unique histologic features [11][12][13].…”

“…Recent evidence suggests that a subset of oral cavity severe dysplasia cases may be HPV-related and have unique morphologic features that resemble Bowen's disease of the skin [11][12][13]. Here, we present an unusual case of extensive HPV-related carcinoma in situ of the upper aerodigestive tract that occurred in a tobacco user and had 'nonkeratinizing' histologic features.…”