Human papillomaviruses in oral carcinoma and oral potentially malignant disorders: a systematic review

Syrjänen, Stina; Lodi, Giovanni; Bültzingslöwen, Inger von; Aliko, Ardita; Arduino, Paolo Giacomo; Campisi, Giuseppina; Challacombe, Stephen; Ficarra, Giuseppe; Flaitz, Catherine M.; Zhou, Hongmei; Maeda, Hideaki; Miller, Craig S.; Jontell, Mats

doi:10.1111/j.1601-0825.2011.01792.x

Cited by 303 publications

(332 citation statements)

References 80 publications

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“…The primary antibody for p16 was a mouse monoclonal antibody clone E6H4TM directed against human P16INK4a and a standard twostep immunohistochemical staining procedure was used for formalin-fixed, paraffin-embedded tissue using horseradish peroxidase and goat anti-mouse antibody (CINtecTM Histology Kit, MTM Laboratories, Westborough, MA, USA). In situ hybridization studies were performed using a cocktail of biotinylated probes against low-risk HPV genotypes 6 and 11 and high-risk HPV genotypes 16,18,31,33,35,39,45, 51, 52, 56, 58, and 66 on the Ventana Benchmark XT automated platform (Ventana Medical Systems, Tucson, AZ, USA).…”

Section: Methodsmentioning

confidence: 99%

Human papillomavirus-associated oral intraepithelial neoplasia

2013

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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...

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Section: Methodsmentioning

confidence: 99%

Human papillomavirus-associated oral intraepithelial neoplasia

2013

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“…Seven years later, in 1983, we published the first evidence suggesting that a subgroup (some 20 %) of oral cancers is associated with HPV, based on detection of HPV structural proteins in these lesions using an antibody prepared against pooled HPV types [39]. We subsequently identified HPV types 11, 16 and 18 in these samples [40][41][42][43][44][45][46][47][48][49]. This concept has now been well accepted, and a growing body of evidence is supporting that approximately 20 % of oral cancers and 60-80 % of oropharyngeal cancers are caused by HPV [41][42][43][44].…”

Section: Hpv and Head And Neck Cancer (Hnscc)mentioning

confidence: 99%

“…We subsequently identified HPV types 11, 16 and 18 in these samples [40][41][42][43][44][45][46][47][48][49]. This concept has now been well accepted, and a growing body of evidence is supporting that approximately 20 % of oral cancers and 60-80 % of oropharyngeal cancers are caused by HPV [41][42][43][44]. In 2011, the International Agency of Research of Cancer (IARC), classifying both chemical and biological carcinogens to humans, declared that there is sufficient evidence that HPV-16 is causally associated with oral cancer [45].…”

Section: Hpv and Head And Neck Cancer (Hnscc)mentioning

confidence: 99%

Biology of Human Papillomavirus Infections in Head and Neck Carcinogenesis

Rautava

Syrjänen

2012

Head and Neck Pathol

121

133

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“…Despite these limitations, a recent meta-analysis by Syrjanen et al [19] did find an increased risk of HPV detection in oral cavity potential premalignant lesions and dysplasia relative to controls in biopsies (odds ratio of 3.87, 95 % CI 2.22-6.13 and 5.10, 95 % CI 2.03-12.80, respectively). Another meta-analysis including 15 studies of oral cavity dysplastic lesions found an HPV prevalence of 25.3 % [18].…”

Section: Discussionmentioning

confidence: 98%

“…For these reasons, some consider all HPV-related neoplasia of the tonsillar crypts as potentially malignant regardless of whether or not there is clear-cut histologic evidence of stromal invasion [17]. Numerous studies have also evaluated squamous dysplasia/carcinoma in situ of the surface mucosa of the upper aerodigestive tract (mainly oral cavity but also larynx) for the presence of HPV [18][19][20][21][22][23][24][25]. However, the rates of HPV detection are widely variable between studies.…”

Section: Discussionmentioning

confidence: 99%

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

Chernock¹,

Nussenbaum²,

Thorstad³

et al. 2013

Head and Neck Pathol

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Over the past several decades, it has become clear that human papillomavirus (HPV) is important for the development and progression of many head and neck squamous cell carcinomas, particularly those arising in the oropharyngeal tonsillar crypts. Yet, our understanding of HPV's role in premalignant squamous lesions remains relatively poor. This is in part because premalignant lesions of the oropharyngeal tonsillar crypt tissue, where most HPV-related carcinomas arise, are difficult if not impossible to identify. Recent evidence does suggest a role for HPV in a subset of premalignant lesions of the surface epithelium, especially the oral cavity, despite the rarity of HPV-related invasive squamous cell carcinomas at this site. Furthermore, these HPV-related oral cavity dysplasias appear to have unique, bowenoid histologic features described as 'basaloid' with full-thickness loss of squamous maturation, mitotic figures and apoptosis throughout. Here, we present a unique case of an HPV-related premalignant lesion (squamous cell carcinoma in situ) extensively involving the surface epithelium of the oral cavity, oropharynx and larynx that had 'nonkeratinizing' histologic features typical of HPVrelated invasive squamous cell carcinoma. This case was strongly p16 positive by immunohistochemistry and harbored transcriptionally active HPV as demonstrated by E6/E7 RNA in situ hybridization. Furthermore, the patient had an excellent response to radiation treatment.

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Human papillomaviruses in oral carcinoma and oral potentially malignant disorders: a systematic review

Cited by 303 publications

References 80 publications

Human papillomavirus-associated oral intraepithelial neoplasia

Human papillomavirus-associated oral intraepithelial neoplasia

Biology of Human Papillomavirus Infections in Head and Neck Carcinogenesis

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

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