Increased radiosensitivity of HPV-positive head and neck cancers: Molecular basis and therapeutic perspectives

Mirghani, Haïtham; Amen, Furrat; Tao, Yungan; Deutsch, Éric; Lévy, Antonin

doi:10.1016/j.ctrv.2015.10.001

Cited by 122 publications

(104 citation statements)

References 79 publications

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“…HPV status of the tumor could determine the molecular profile of the cancer, which consequently influence the subsequent response to therapy. HPV‐positive vulvar cancers might have a higher sensitivity to radiotherapy, which has also been suggested for head‐and‐neck cancers . Different biological factors are thought to explain the improved response to radiotherapy in HPV‐positive head‐and‐neck tumors.…”

Section: Discussionmentioning

confidence: 85%

“…Different biological factors are thought to explain the improved response to radiotherapy in HPV‐positive head‐and‐neck tumors. These include impaired DNA repair, decreased repopulation signaling pathways, downregulation of cell cycle control mechanisms, rapid resolution of cell hypoxia, and an enhanced immune response . Specifically, it has been suggested that the TP53‐mediated apoptosis following radiation is increased in HPV‐positive head and neck SCC .…”

Section: Discussionmentioning

confidence: 99%

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Does HPV status influence survival after vulvar cancer?

Rasmussen

Sand

Frederiksen

et al. 2017

Intl Journal of Cancer

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High-risk human papillomavirus (HPV) infection is essential in the carcinogenesis of a substantial part of anogenital and oropharyngeal cancers and has additionally been shown to be a possible predictive marker for survival, especially in oropharyngeal cancer. Studies examining the influence of HPV status on survival after vulvar cancer have been conflicting and limited by small study populations. Therefore, the aim of this review and meta-analysis was to examine whether HPV status influences survival after vulvar cancer, which, to our knowledge, has not been done before. We conducted a systematic search of PubMed, Cochrane Library and Embase to identify studies examining survival after histologically verified and HPV tested vulvar cancer. A total of 18 studies were eligible for inclusion. Study-specific and pooled HRs of the 5-year OS and DFS were calculated using a fixed effects model. The I statistic was used to describe heterogeneity. The studies included a total of 1,638 women with HPV tested vulvar cancers of which 541 and 1,097 were HPV-positive and HPV-negative, respectively. Fifteen studies included only squamous cell carcinomas. We found a pooled HR of 0.61 (95% CI: 0.48-0.77) and 0.75 (95% CI: 0.57-1.00) for 5-year OS and DFS, respectively. Across study heterogeneity was moderate to high (OS: I = 51%; DFS: I = 73%). In conclusion, women with HPV-positive vulvar cancers have a superior survival compared to women with HPV-negative, which could be of great clinical interest and provides insight into the differences in the natural history of HPV-positive and negative vulvar cancers.

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Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Does HPV status influence survival after vulvar cancer?

Rasmussen

Sand

Frederiksen

et al. 2017

Intl Journal of Cancer

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“…HPV-positive oropharyngeal tumors tend to present decreased EGFR expression [50, 60, 63, 64, 67, 105], and increased EGFR gene copy number is restricted to HPV-negative cancer [3, 65]. Although the rationale underlying those findings has not been fully elucidated yet, it is widely accepted that HPV-positive tumors have a different genetic profile compared with HPV-negative counterparts, thus contributing to the different clinical behavior and to the higher chemo- and radiosensitivity [68, 105, 106]. Therefore, the greater impact of EGFR deregulation in HPV negative tumors should be analyzed within the context of this different genetic pattern, and the “combined” effect of HPV status and EGFR expression on prognosis both of HPV-positive and negative or only of HPV-negative patients remains to be defined.…”

Section: Resultsmentioning

confidence: 99%

Prognostic and predictive value of EGFR in head and neck squamous cell carcinoma

et al. 2016

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EGFR is an extensively studied biomarker in head and neck squamous cell carcinoma (HNSCC). In this review, we discuss the prognostic and predictive role of EGFR in HNSCC, focusing on the different molecular alterations in specific treatment modalities such as radiotherapy alone (RT), combination of surgery, RT and chemotherapy (CT), EGFR inhibitors. We considered EGFR at different molecular levels: protein expression, protein activation, gene copy number, polymorphisms, mutation, EGFRvIII expression and EGFR ligand expression.Considering RT alone, evidence supports the predictive and prognostic role of high EGFR expression only when evaluated by quantitative assays: this may help select the patients who can mostly benefit from accelerated treatment. Conversely, no predictive biomarkers are available when treatment is a combination of surgery, CT and RT. For this combined treatment, several studies indicate that EGFR expression represents a good prognostic parameter only when measured by a “quantitative” or at least semi-quantitative method. With respect to EGFR inhibitors, neither EGFR expression nor increased gene copy number represent prognostic/predictive factors.If validated, nuclear EGFR, TGFα levels, EGFR phopshorylation and polymorphisms could represent additional prognostic factors in relation to combination of surgery, CT and RT, while EGFR polymorphisms and high amphiregulin levels could have prognostic value in patients treated with EGFR inhibitors.

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“…Indeed, a recent study by Lee and colleagues indicates that patients with p16‐positive, HPV‐associated vulvar cancers have decreased recurrence and improved survival after radiation therapy . Multiple biological explanations have been put forth to explain the improved radiation response of HPV‐positive oropharyngeal SCC, including decreased DNA repair, rapid resolution of hypoxia, differential activation of signal transduction pathways and enhanced immune response . Recent genome sequencing efforts have helped elucidate the genetic and epigenetic differences between HPV‐associated and HPV‐independent HNSCC that may explain these biological differences .…”

Section: Discussionmentioning

confidence: 99%