Relationships between p53 mutation, HPV status and outcome in oropharyngeal squamous cell carcinoma

Hong, Angela; Zhang, Xiaoying; Jones, D. Brian; Veillard, Anne-Sophie; Zhang, Mei; Martin, Andrew; Lyons, J. Guy; Lee, C. Soon; Rose, Barbara

doi:10.1016/j.radonc.2016.02.009

Cited by 43 publications

(44 citation statements)

References 28 publications

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“…Smoking-related cancers demonstrated loss-of-function p53 mutations and CDKN2A inactivation. We previously showed that HPV-positive OSCC were significantly less likely to have a p53 mutation than HPV-negative OSCC (25.8% vs 46.7%, p = 0.0021) [25]. The underlying difference in mutation load between HPV-positive and HPV-negative OSCC may account for the difference in PD-L1 expression.…”

Section: Discussionmentioning

confidence: 99%

PD-L1 expression in tonsillar cancer is associated with human papillomavirus positivity and improved survival: implications for anti-PD1 clinical trials

et al. 2016

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In this study, we examined PD-L1 expression by immunohistochemistry in 99 patients with tonsillar cancer and known human papillomavirus (HPV) status to assess its clinical significance. We showed that the pattern of PD-L1 expression is strongly related to HPV status. The PD-L1 positivity rate was 83.3% in HPV-positive cases and 56.9% in HPV-negative cases (p < 0.05). Patients with HPV-positive/PD-L1-positive cancer had significantly better event free survival and overall survival compared with patients with HPV-negative/PD-L1-negative cancer. Relative to those patients with HPV-negative/PD-L1-negative disease who had the highest risk of death, patients with HPV-positive/PD-L1-positive cancers had a 2.85 fold lower risk of developing an event (HR 0.35, 95% CI: 0.16–0.79) and a 4.5 fold lower risk of death (HR =0.22, 95% CI: 0.09–0.53). Our findings will help to guide future clinical trial design in immunotherapy based on PD-L1 expression in tonsillar cancer.

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Section: Discussionmentioning

confidence: 99%

PD-L1 expression in tonsillar cancer is associated with human papillomavirus positivity and improved survival: implications for anti-PD1 clinical trials

et al. 2016

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“…Although chemically induced OPSCCs bear disruptive mutations in the TP53 gene leading to the loss of tumor suppression activity, in hrHPV‐driven carcinomas, the E6 oncoprotein drives cell proliferation by stimulating ubiquitination and proteasome‐dependent degradation of the p53 protein . Thus, hrHPV‐driven OPSCC are considered to contain sufficient intact p53 to preserve a radiosensitive phenotype . Several trials are ongoing to test if less intensive treatment regimens may achieve similar efficacy, while decreasing the toxicity in patients with hrHPV‐driven OPSCC …”

Section: Introductionmentioning

confidence: 99%

Absence of disruptive TP53 mutations in high‐risk human papillomavirus‐driven neck squamous cell carcinoma of unknown primary

et al. 2019

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Background To enforce the evidence for causality between high‐risk human papillomavirus (hrHPV) infections and neck squamous cell carcinoma from unknown primary (NSCCUP) and provide biological basis for treatment de‐intensification, we searched for TP53 mutations in association with HPV status. Methods TP53 mutations were searched for by amplification of exons 4 to 10. Results Of the 70 NSCCUP, 27 (39%) harbored HPV infection. TP53 sequencing resulted in the identification of 19 patients harboring single mutations including 16 disruptive alterations (84%). The association of TP53 mutations and HPV could be evaluated in 48 NSCCUP including those with disruptive mutation in any exon (n = 16) and those without mutations but with complete sequence of exons 4 to 9 (n = 32): no disruptive mutations were found in the 17 HPV‐driven NSCCUP but in 16 of the 31 non‐HPV‐driven NSCCUP (P = .0002). Conclusion In a fraction of cases, NSCCUP is an HPV‐driven entity harboring wild‐type TP53 gene or nondisruptive TP53 mutations. HPV‐driven NSCCUP might benefit from treatment de‐intensification.

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“…Both P53 mutation and overexpression of MDM2 can disrupt this loop (31). Hong et al (32) confirmed exon 5–8 mutations of the P53 gene in oropharyngeal cancer and suggested that P53 mutation is not a significant predictor of outcome. Our result showed that OSCC patients with high P53 expression levels have a short survival time and a poor prognosis (Fig.…”

Section: Discussionmentioning

confidence: 99%

Expression and prognostic significance of the P53‐related DNA damage repair proteins checkpoint kinase 1 (CHK1) and growth arrest and DNA‐damage‐inducible 45 alpha (GADD45A) in human oral squamous cell carcinoma

Xie

Jia

et al. 2020

European J Oral Sciences

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DNA damage repair is a key factor in the maintenance of cell genome stability, plays an important role in the regulation of tumour evolution, and can affect the prognosis of cancer patients. This study aimed to detect the protein expression of the DNA damage repair protein P53 and its upstream and downstream regulators, CHK1, GADD45A, and MDM2, in oral squamous cell carcinoma (OSCC), in order to analyse the association between the expression of these proteins and overall survival, and to assess their prognostic implications for OSCC patients. The expression of the above proteins was detected by immunohistochemistry in 80 human OSCC tissue samples and in non‐cancerous tissue samples. Compared to that in the non‐cancerous tissue, the expression of CHK1, GADD45A, and MDM2 in OSCC tissue was significantly increased. The protein expression of the tumour suppressor gene P53 was also increased. Patients with high CHK1 and MDM2 expression levels had a reduced survival time and a poor prognosis, whereas patients with high GADD45A expression levels had a good prognosis. Our results indicate that high CHK1 expression is an independent risk factor for poor OSCC prognosis, and that CHK1 may be a potential target for OSCC clinical treatment.

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Relationships between p53 mutation, HPV status and outcome in oropharyngeal squamous cell carcinoma

Cited by 43 publications

References 28 publications

PD-L1 expression in tonsillar cancer is associated with human papillomavirus positivity and improved survival: implications for anti-PD1 clinical trials

PD-L1 expression in tonsillar cancer is associated with human papillomavirus positivity and improved survival: implications for anti-PD1 clinical trials

Absence of disruptive TP53 mutations in high‐risk human papillomavirus‐driven neck squamous cell carcinoma of unknown primary

Expression and prognostic significance of the P53‐related DNA damage repair proteins checkpoint kinase 1 (CHK1) and growth arrest and DNA‐damage‐inducible 45 alpha (GADD45A) in human oral squamous cell carcinoma

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