p16 Immunohistochemistry Can Be Used to Detect Human Papillomavirus in Oral Cavity Squamous Cell Carcinoma

Duncan, Lisa; Winkler, Marcus; Carlson, Eric R.; Heidel, R. Eric; Kang, Ellen S.; Webb, David V.

doi:10.1016/j.joms.2013.02.019

Cited by 57 publications

(55 citation statements)

References 39 publications

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“…28 There is a wide range in the reported frequencies of strong and diffuse p16 INK4a overexpression in oral cavity squamous cell carcinoma. [29][30][31][32][33][34][35][36][37][38] Here, in studying a large cohort of patients with oral cavity squamous cell carcinoma, we confirm that p16 INK4a overexpression is uncommon (15.5%). Furthermore, we demonstrate that p16 INK4a overexpression has a protective effect with respect to disease progression (hazard ratio 0.11, 95% CI 0.02-0.63).…”

Section: Discussionsupporting

confidence: 65%

The protective effect of p16INK4a in oral cavity carcinomas: p16Ink4A dampens tumor invasion—integrated analysis of expression and kinomics pathways

Isayeva

Ragin

et al. 2015

Modern Pathology

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A large body of evidence shows that p16 INK4a overexpression predicts improved survival and increased radiosensitivity in HPV-mediated oropharyngeal squamous cell carcinomas.(OPSCC). Here we demonstrate that the presence of transcriptionally active HPV16 in oral cavity squamous cell carcinomas does not correlate with p16 INK4a overexpression, enhanced local tumor immunity, or improved outcome. It is interesting that HPVmediated oropharyngeal squamous cell carcinomas can be categorized as having a 'nonaggressive' invasion phenotype, whereas aggressive invasion phenotypes are more common in HPV-negative squamous cell carcinomas. We have developed primary cancer cell lines from resections with known pattern of invasion as determined by our validated risk model. Given that cell lines derived from HPV-mediated oropharyngeal squamous cell carcinomas are less invasive than their HPV-negative counterparts, we tested the hypothesis that viral oncoproteins E6, E7, and p16 INK4a can affect tumor invasion. Here we demonstrate that p16 INK4a overexpression in two cancer cell lines (UAB-3 and UAB-4), derived from oral cavity squamous cell carcinomas with the most aggressive invasive phenotype (worst pattern of invasion type 5 (WPOI-5)), dramatically decreases tumor invasiveness by altering expression of extracellular matrix remodeling genes. Pathway analysis integrating changes in RNA expression and kinase activities reveals different potential p16 INK4a -sensitive pathways. Overexpressing p16 INK4a in UAB-3 increases EGFR activity and increases MMP1 and MMP3 expression, possibly through STAT3 activation. Overexpressing p16 INK4a in UAB-4 decreases PDGFR gene expression and reduces MMP1 and MMP3, possibly through STAT3 inactivation. Alternatively, ZAP70/Syk might increase MUC1 phosphorylation, leading to the observed decreased MMP1 expression.

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Section: Discussionsupporting

confidence: 65%

The protective effect of p16INK4a in oral cavity carcinomas: p16Ink4A dampens tumor invasion—integrated analysis of expression and kinomics pathways

Isayeva

Ragin

et al. 2015

Modern Pathology

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“…Although, tumors showing the above microscopic description are considered as a synonym for BSCC by some [8], others consider it as 2 different tumor entities [34,35]. In support of the latter theory, there is evidence that suggests HPV-associated OSCCs as a distinct clinicopathologic entity with a younger age at onset, association with oral sexual behavior, and better prognosis than HPV-negative SCCs [18,34,35]. Furthermore, we were unable to include the tumors analyzed by Duncan et al [18], because they have used the word nonkeratinized carcinoma instead of BSCC.…”

Section: Discussionmentioning

confidence: 99%

“…Basaloid squamous cell carcinoma is considered as a tumor that predominantly arises in elderly men. In addition, these tumors have been identified in numerous head and neck sites including oral cavity [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18], oropharynx [1,6,[19][20][21][22][23], hypopharynx [16,[24][25][26], esophagus [27][28][29], and sinonasal region [30]. Basaloid squamous cell carcinomas are also considered as more aggressive tumors showing a poorer survival compared with squamous cell carcinoma by some authors [15,21,31], whereas others disagree with this observation [12,16,18,27].…”

Section: Introductionmentioning

confidence: 99%

A literature review on oral basaloid squamous cell carcinomas, with special emphasis on etiology

Jayasooriya

Tilakaratne

Mendis

et al. 2013

Annals of Diagnostic Pathology

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a b s t r a c t a r t i c l e i n f o Keywords: Basaloid squamous cell carcinoma Human papillomavirus Etiology PrognosisIn the recent years, basaloid squamous cell carcinomas (BSCCs) have gained attention because of (1) observation of a relative increase in the number of tumors arising particularly in head and neck sites, (2) identification of human papillomavirus (HPV) in BSCCs arising predominantly in the oropharynx, and (3) controversies that exist regarding the biological aggressiveness of the tumor. The objective of the present review was to address the issues mentioned above by focusing primarily on oral BSCCs, using literature that has been published in the English language up to 2013. According to the literature review, oral BSCCs were found to be relatively more common in elderly patients with a mean age of 64 years. A male predominance with a male/female ratio of 3:1 was observed. The predominant site was the tongue, with almost half of the reported cases occurring at this site, followed by the floor of the mouth and palate. With reference to habit history, majority were found to be tobacco and alcohol users. However, only 3 studies revealed data on HPV status of purely oral BSCC, and according to the results of these studies, of the 17 tumors tested, 4 had harbored high-risk HPV. Furthermore, most oral BSCCs were in an advanced clinical stage, namely, stage III or IV with T3 or T4 lesions and cervical lymph node metastasis at initial presentation, whereas 41% of patients had presented with local recurrences and 45% had died of the disease. In conclusion, although, the present literature review found enough evidence to consider tobacco and alcohol as risk factors for the development of oral BSCC, steps should be taken to fill the gap in our knowledge that exist with reference to contribution of oncoviruses, particularly HPV in the etiology of oral BSCC.

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“…There is evidence that HPV also infects the gingival tissue with periodontal pocket; the only location that is exposed to the external environment [33][34][35]. Wide-ranging studies analyzing large number of patients and describing anatomic subsites, as well HPV DNA frequency per site, indicate that HPV can be found in any of the subsites [8,10,22,[36][37][38][39][40]. Subsite frequencies are varying between studies, but floor of mouth (9-42 %) and the tongue (8-25 %) seem to be predominantly infected by HPV.…”

Section: Discussionmentioning

confidence: 99%

Human Papilloma Virus in Oral Cavity Cancer and Relation to Change in Quality of Life Following Treatment—a Pilot Study from Northern India

Singh

Kushwaha

Anand

et al. 2016

Indian J Surg Oncol

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Human papilloma virus (HPV)-associated head and neck cancer (HNC) has generated significant amount of research interest in recent times with focus shifted to oral cavity squamous cell cancer (OCSCC) after oropharyngeal cancer. Due to high incidence of OCSCC and anecdotal reports on association of HPV infection from northern region of India, this study was conceived to investigate HPV infection and establish its association with lifestyle habits such as tobacco, alcohol consumption, oro-genital sex, number of sexual contacts, and change in quality of life posttreatment. A total of 43 primary OCSCC biopsy specimens were collected. These samples were analyzed for HPV DNA genotyping which was done by using 13 high-risk HPV real-time PCR kits. Quality of life was assessed using University of Washington questionnaire for HNC patients, which was administered pretreatment and 3-months posttreatment. HPV presence was confirmed in only three patients (7.0 %). HPV positivity did not find any statistical correlation with age, gender, residence, addiction habit, stage, tumor size, nodal status, tumor grade, and number of sexual contacts. There was no significant (p > 0.05) difference in the average percent change in QOL parameters from pretreatment to posttreatment when correlated with HPV status.

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p16 Immunohistochemistry Can Be Used to Detect Human Papillomavirus in Oral Cavity Squamous Cell Carcinoma

Cited by 57 publications

References 39 publications

The protective effect of p16INK4a in oral cavity carcinomas: p16Ink4A dampens tumor invasion—integrated analysis of expression and kinomics pathways

The protective effect of p16INK4a in oral cavity carcinomas: p16Ink4A dampens tumor invasion—integrated analysis of expression and kinomics pathways

A literature review on oral basaloid squamous cell carcinomas, with special emphasis on etiology

Human Papilloma Virus in Oral Cavity Cancer and Relation to Change in Quality of Life Following Treatment—a Pilot Study from Northern India

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