Is p16-positive oropharyngeal squamous cell carcinoma associated with favorable prognosis? A systematic review and meta-analysis

Sedghizadeh, Parish P.; Billington, William D.; Paxton, Dain; Ebeed, Rabeh; Mahabady, Susan; Clark, Glenn T.

doi:10.1016/j.oraloncology.2016.01.002

Cited by 99 publications

(72 citation statements)

References 44 publications

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“…38 According to several studies, p16 may be the best single marker for prognosis in OPSCC. 39 Screening molecular HPV assays including PCR based HPV based assays carry the risk of false postive detection of endemic HPV infections not associated with cancer whereas the ISH test carries a low sensitivity. The cervista HPV HR and the Digene Hybrid Capture II (HC2) HR HPV DNA Test are FDA approved for IVD diagnosisand have been used in uterine cervical cancer screening.…”

Section: Demonstration Of Hpv In Tumoursmentioning

confidence: 99%

Human papillomavirus associated head and neck squamous cell carcinoma: Controversies and new concepts

Husain

Neyaz

2017

Journal of Oral Biology and Craniofacial Research

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High-risk human papillomavirus (HR-HPV) is a causative agent for an increasing subset of oropharyngeal squamous cell carcinoma. HPV 16 accounts for 90% of cases. The chance for malignant transformation due to infection with high-risk HPV is proportional to the expression of the viral oncogene products E6 and E7, which inactivate p53 and retinoblastoma (Rb) tumor suppressor functions. P16 is a surrogate marker of HPV associated HNSCC and 2+/3+ expression in more than 75% cells is diagnostic. Molecular demonstration of integrated virus by in situ hybridization is specific but has low sensitivity. HPV associated oropharyngeal carcinomas classically arise in the tonsillar crypts and commonly have basaloid morphology with a prominent lymphocytic repsonse and minimal despmoplastic reaction. In situ vs invasive carcinomas may be difficult to distinguish in histology. The HPV postitivity overrides traditional prognostic indicators such as tumour grade and histological subtype. Small cell morphology carries a poorer prognosis as does marked tumour anaplasia and multinucleation. Lymph node metastasis is extensive and frequently cystic however extranodal extension, laterality or nodal sizes do not carry prognostic implications as in conventional OSCC and OPSCC. Stage IV is reserved for distant metastasis. HPV-16-positive patients had significantly reduced overall and disease-specific mortality rates and an improved 3-year overall survival (OS) and disease-free survival (DFS) compared to patients with HPV negative tumors. Surgical treatment is the main option for primary and secondary HNSCC. Targeted therapies including drugs targeting EGFR and PIK3CA and have shown some promising results. HPV pathway expressing tumors are less aggressive and may receive adequate curative intent therapy from a reduced radiation or chemotherapy dose revision. OSCC however fails to show a distinct difference between HPV associated and tobaccco associated cancer and prognostic differences do not clearly exist.

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Section: Demonstration Of Hpv In Tumoursmentioning

confidence: 99%

Human papillomavirus associated head and neck squamous cell carcinoma: Controversies and new concepts

Husain

Neyaz

2017

Journal of Oral Biology and Craniofacial Research

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“…This binding degrades p53 through ubiquitination. The decrease in p53 may inactivate the protein, leading to cell cycle progression [38][39][40]. Other viral oncoproteins that disrupt the cell cycle include E7, which binds to the retinoblastoma protein (pRB).…”

Section: Discussionmentioning

confidence: 99%

“…However, the E7 viral oncoprotein may bind to pRB, releasing E2F. Absence of the E2F + pRB complex leads to upregulation of p16 and cell cycle progression, even if the DNA is damaged [38][39][40].…”

Section: Discussionmentioning

confidence: 99%

p53 and p16 expression in oral cavity squamous cell and basaloid squamous cell carcinoma

et al. 2018

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Purpose The true aggressive behavior of oral cavity BSCC compared to SCC has been debated, and the study of disturbances in cell cycle proteins may help understand the biological behavior in both variants. The aim of this study was to investigate the p53 and p16 status in 32 SCC and 16 BSCC of oral cavity. Methods Immunohistochemistry was used to assess these proteins' status. The association between p53 and p16 with clinicopathological features and prognostic value were evaluated. Results A high prevalence of p53 disruption was observed in both variants (84.4% of 32-SCC and 81.2% of 16-BSCC; p = 0.78). The BSCC showed a higher prevalence of high p16 expression (86.7% of 15) when compared to SCC (61.3% of 31); however, this difference did not reach statistical significance (p = 0.08). In the SCC variant, cases with high p16 expression showed a lower overall survival. Protein p53 showed association with tobacco use, but with no other clinicopathological features. Conclusions Our results suggest that p53 and p16 cell cycle disruptions are common findings in oral cavity SCC, as well as in BSCC. A higher prevalence of p16 overexpression in oral BSCC cases may be related to carcinogenesis process.

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“…For example, head and neck cancers which are associated with HPV16 have a better prognosis and are more sensitive to radiation therapy than non-HPV cancers. Therefore, accurate detection and knowledge of HPV status is essential for diagnosis, targeted therapeutic approaches, and prognostication, and ultimately improves patient outcomes (47). The main limitation of VirTect is that it depends on a database of all known viruses, which is used to nominate candidate viruses in human cancer tissue.…”

Section: Discussionmentioning

confidence: 99%

VirTect: a computational method for detecting virus species from RNA-Seq and its application in head and neck squamous cell carcinoma

Khan

Chen

et al. 2018

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Next generation sequencing (NGS) provides an opportunity to detect viral species from RNAseq data on human tissues, but existing computational approaches do not perform optimally on clinical samples. We developed a bioinformatics method called VirTect for detecting viruses in neoplastic human tissues using RNA-seq data. Here, we used VirTect to analyze RNA-seq data from 363 HNSCC (head and neck squamous cell carcinoma) patients and identified 22 HPV-induced HNSCCs. These predictions were validated by manual review of pathology reports on histopathologic specimens. Our results suggest that HPV-induced HNSCC involves unique mechanisms of carcinogenesis, so understanding these molecular mechanisms will have a significant impact on therapeutic approaches and outcomes. In summary, VirTect can be an effective solution for the detection of viruses with NGS data, and can facilitate the clinicopathologic characterization of various types of cancers with broad applications for oncology.

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Is p16-positive oropharyngeal squamous cell carcinoma associated with favorable prognosis? A systematic review and meta-analysis

Cited by 99 publications

References 44 publications

Human papillomavirus associated head and neck squamous cell carcinoma: Controversies and new concepts

Human papillomavirus associated head and neck squamous cell carcinoma: Controversies and new concepts

p53 and p16 expression in oral cavity squamous cell and basaloid squamous cell carcinoma

VirTect: a computational method for detecting virus species from RNA-Seq and its application in head and neck squamous cell carcinoma

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