Overexpression of p16INK4 is a reliable marker of human papillomavirus–induced oral high-grade squamous dysplasia

Cunningham, Larry L.; Pagano, Giulia; Li, Mengtao; Tandon, Rahul; Holm, Stephen Wilford; White, Daniel; Lele, Subodh M.

doi:10.1016/j.tripleo.2005.11.028

Cited by 53 publications

(59 citation statements)

References 15 publications

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“…The sharp demarcation of the in situ hybridization studies for high-risk HPV subtypes in most cases correlated exactly with the presence of the continuous band for p16 as expected. This pattern was noted in the illustrations in the study by Cunningham et al 25 The frequency of development of invasive carcinoma if such lesions are incompletely excised is unknown. Among cases with follow-up in this study, 3 out of 11 cases (27%) excised with positive margins demonstrated progression of residual disease with 1 developing a carcinoma.…”

Section: Discussionmentioning

confidence: 81%

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: Discussionmentioning

confidence: 81%

Human papillomavirus-associated oral intraepithelial neoplasia

2013

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“…6,36 A HPV-induced SCC demonstrates an absence of pRb and p53 immunostaining with an increase in p16. 10,20 In contrast, a SCC that develops due to chronic UV exposure typically demonstrates p53 and pRb immunostaining without an increase in p16. 8,32 The purpose of the present experiment was to determine whether the presence of PV DNA within a feline cutaneous SCC is associated with a immunohistochemical profile similar to that seen in PV-induced human cancers.…”

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confidence: 99%

Loss of Retinoblastoma Protein, But Not p53, Is Associated With the Presence of Papillomaviral DNA in Feline Viral Plaques, Bowenoid In Situ Carcinomas, and Squamous Cell Carcinomas

Munday

Aberdein

2011

Vet Pathol

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Although papillomaviral (PV) DNA is frequently present in feline cutaneous squamous cell carcinomas (SCCs), a causative association cannot be proven. Oncogenic human PVs cause neoplastic transformation by inhibiting retinoblastoma (pRb) and p53 activity. Therefore, absence of pRb and p53 immunostaining, along with increased p16 immunostaining, indicates a PV cause in some human SCCs. If PVs cause cutaneous feline SCCs, it was hypothesized that a similar immunohistochemistry profile, along with PV DNA, would be detectable. This was investigated using 5 feline viral plaques, 10 Bowenoid in situ carcinomas, 19 SCCs from ultraviolet-exposed (UV-exposed) skin, and 11 SCCs from UV-protected skin. Papillomaviral DNA was amplified by polymerase chain reaction from 30 of 45 lesions. Reduced pRb immunostaining was present in 26 of 45; increased p16 immunostaining was in 30; and p53 immunostaining was in 19. Both reduced pRb immunostaining and increased p16 immunostaining were more frequent in lesions containing PV DNA. In contrast, no association was observed between p53 immunostaining and the presence of PV DNA. SCCs from UV-protected skin more frequently contained PV DNA, reduced pRb, and increased p16 than UV-exposed SCCs. UV exposure was not associated with p53 immunostaining within the SCCs. These results suggest that feline PVs alter cell regulation by degrading pRb. Unlike oncogenic human PVs, there was no evidence that feline PVs degrade p53. These results provide further evidence that PVs may cause feline cutaneous SCCs, especially those in UV-protected skin, and they suggest a possible mechanism of this oncogenic action.

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“…Moreover, the presence of HPV does not necessarily imply its role in carcinogenesis, whereas the evidence of E6/E7 mRNA could better define the biological profile of the lesion. Recently, as a result from the expression of the HR-HPV related protein E7, p16INK4a positivity can be considered as a surrogate of HR-HPV infection [10]; it has been currently established in HNSCC by using different monoclonal antibody clones [12,13,18,19], particularly, E6H4 monoclonal antibody has been employed and its reactivity has been assessed by different cut-off regarding the intensity of the immunoreaction, the staining pattern and the percentage of p16 positive atypical cells [5,8,[19][20][21][22][23]. As a consequence, the reported p16 positivity in HNSCC various significantly: Lassen et al [19] demonstrated p16 expression in 22% of HNSCC tumors whereas, according to a retrospective analysis performed by Ang et al [22], p16 expression was found in 96.1% of tumor samples.…”

Section: Resultsmentioning

confidence: 99%

p16INK4/Ki-67 Dual-Staining Expression as a Prognostic Indicator in Laryngeal Cancer

Carico¹,

Radici²,

Bucci³

et al. 2014

JCPCR

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Among head and neck Squamous cell carcinomas (HNSCCs), the larynx is one of the sites most involved, being traditionally associated with tobacco and alcohol use, especially when in combination [1]. As squamous carcinoma develops throughout a step progression in various stages of dysplasia, many molecular changes have been described [2]. The implication of Human Papilloma Virus (HPV) in HNSCC development [3,4], particularly, the infection with high-risk HPV types (HR-HPV) has also been etiologically linked with a subset of laryngeal carcinoma [5] thus suggesting a different carcinogenetic pathway. Studies regarding HPV induced laryngeal cancers indicate that they are associated with improved outcomes [6], moreover they have more favorable prognosis when treated with surgery alone [7]. At present, the causal role of HR-HPV in laryngeal carcinogenesis is controversial, mainly because no unanimously accepted detection method exists. Commonly used HPV detection methods for formalin fixed paraffin embedded tissue include: HPV consensus PCR method, type specific HPV detection by fluorescence in situ hybridization (FISH) and real-time PCR assays. Alternatively, the role of p16INK4a protein has been reported to identify HPVrelated laryngeal cancers [8]: hypermethylation and underp16INK4/Ki-67 Dual-Staining Expression as a

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Overexpression of p16INK4 is a reliable marker of human papillomavirus–induced oral high-grade squamous dysplasia

Cited by 53 publications

References 15 publications

Human papillomavirus-associated oral intraepithelial neoplasia

Human papillomavirus-associated oral intraepithelial neoplasia

Loss of Retinoblastoma Protein, But Not p53, Is Associated With the Presence of Papillomaviral DNA in Feline Viral Plaques, Bowenoid In Situ Carcinomas, and Squamous Cell Carcinomas

p16INK4/Ki-67 Dual-Staining Expression as a Prognostic Indicator in Laryngeal Cancer

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