Human papillomavirus and oropharyngeal squamous cell carcinoma: a New Zealand cohort study

Ou, Peter; Gear, Kim; Rahnama, Fahimeh; Thomas, Stephen G.; Nagappan, Radhika; Kee, Dennis; Waldvogel-Thurlow, Sharon; Jain, Ravi; McIvor, Nick; Izzard, Mark; Douglas, Richard

doi:10.1111/ans.13759

Cited by 10 publications

(4 citation statements)

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“…In total, 64 articles were included in the analysis, with a total of 11710 patients in these studies. The number of patients varied between 30 and 1474 (mean 202 patients per study) ( Table 1 ) [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] , [43] , [44] , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [53] , [54] , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] , [67] , [68] , [69] , [70] , [71] , [72] , [73] . ...…”

Section: Resultsmentioning

confidence: 99%

Time to change perspectives on HPV in oropharyngeal cancer. A systematic review of HPV prevalence per oropharyngeal sub-site the last 3 years

Haeggblom

Ramqvist

Tommasino

et al. 2017

Papillomavirus Research

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ObjectivesHuman papillomavirus (HPV) as a risk factor in oropharyngeal squamous cell carcinoma (OPSCC) is well established. However, accumulating data imply that the OPSCC concept is too unspecific with regard to HPV prevalence and clinical importance. To further study the role of HPV in OPSCC by sub-site, a systematic review and meta-analysis was performed.Material and methodPubMed was searched and all studies reporting HPV data (p16/HPV DNA/RNA) in both “lymphoepithelial associated” (i.e. tonsillar and base of tongue cancer; TSCC and BOTSCC respectively) and “non-lymphoepithelial” (“other” OPSCC) OPSCC were included. Pooled odds ratios by HPV detection method were analysed using a random effects model.ResultsIn total, 58 unique patient cohorts were identified. Total HPV prevalence in TSCC/BOTSCC was 56%, 95%CI: 55–57% (59%, 95%CI: 58–60% for TSCC only) as compared to 19%, 95%CI: 17–20%, in “other” OPSCC. Significant association of HPV to TSCC/BOTSCC vs. “other” OPSCC was observed no matter HPV detection method used, but statistical homogeneity was only observed when studies using algorithm based HPV detection were pooled.ConclusionHPV prevalence differs markedly between OPSCC sub-sites and while the role of HPV in TSCC/BOTSCC is strong, the role in “other” OPSCC is more uncertain and needs further evaluation.

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Section: Resultsmentioning

confidence: 99%

Time to change perspectives on HPV in oropharyngeal cancer. A systematic review of HPV prevalence per oropharyngeal sub-site the last 3 years

Haeggblom

Ramqvist

Tommasino

et al. 2017

Papillomavirus Research

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“…Ou et al . demonstrated an algorithm consisting of two PCR assays and p16 immunohistochemistry 59 . Prigge et al .…”

Section: Discussionmentioning

confidence: 99%

Meta analysis: HPV and p16 pattern determines survival in patients with HNSCC and identifies potential new biologic subtype

Albers

Qian

Kaufmann

et al. 2017

Sci Rep

103

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Consistent discrepancies in the p16/HPV-positivity have been observed in head and neck squamous cell carcinoma (HNSCC). It is therefore questionable, if all HPV+ and/or p16+ tested cancers are HPV-driven. Patients down-staged according to the HPV-dependant TNM are at risk for undertreatment and data in clinical trials may be skewed due to false patient inclusion. We performed a meta-analysis to classify clinical outcomes of the distinct subgroups with combined p16 and HPV detection. 25 out of 1677 publications fulfilled the inclusion criteria. The proportion of the subgroups was 35.6% for HPV+/p16+, 50.4% for HPV−/p16−, 6.7% for HPV−/p16+ and 7.3% for HPV+/P16−. The HPV+/p16+ subgroup had a significantly improved 5-year overall-survival (OS) and disease-free-survival in comparison to others both for HNSCC and oropharyngeal cancers. The 5-year OS of the HPV−/p16+ HNSCC was intermediate while HPV+/p16− and HPV−/p16− had the shortest survival outcomes. The clearly distinct survival of HPV−/p16+ cancers may characterize a new relevant HPV-independent subtype yet to be biologically characterized. The possibility also exists that in some HPV+/p16+ cancers HPV is an innocent bystander and p16 is independently positive. Therefore, in perspective, HPV-testing should distinguish between bystander HPV and truly HPV-driven cancers to avoid potential undertreatment in HPV+ but non-HPV-driven HNSCC.

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“…The collection of patient tumour specimens for PDX engraftment was approved by the New Zealand Health and Disability Ethics Committee (approval: 14/NTB/122) and the Auckland District Health Board. Tumour specimens from consenting patients undergoing surgery at Auckland City Hospital were histologically confirmed to be HNSCC via tumour biopsy with HPV status inferred by p16 immunohistochemistry, as described previously [55]. For PDX model generation, p16-negative tumours were preferred.…”

Section: Methodsmentioning

confidence: 99%

Impact of Tumour Hypoxia on Evofosfamide Sensitivity in Head and Neck Squamous Cell Carcinoma Patient-Derived Xenograft Models

Harms

Lee

Wang

et al. 2019

Cells

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Tumour hypoxia is a marker of poor prognosis and failure of chemoradiotherapy in head and neck squamous cell carcinoma (HNSCC), providing a strategy for therapeutic intervention in this setting. To evaluate the utility of the hypoxia-activated prodrug evofosfamide (TH-302) in HNSCC, we established ten early passage patient-derived xenograft (PDX) models of HNSCC that were characterised by their histopathology, hypoxia status, gene expression, and sensitivity to evofosfamide. All PDX models closely resembled the histology of the patient tumours they were derived from. Pimonidazole-positive tumour hypoxic fractions ranged from 1.7–7.9% in line with reported HNSCC clinical values, while mRNA expression of the Toustrup hypoxia gene signature showed close correlations between PDX and matched patient tumours, together suggesting the PDX models may accurately model clinical tumour hypoxia. Evofosfamide as a single agent (50 mg/kg IP, qd × 5 for three weeks) demonstrated antitumour efficacy that was variable across the PDX models, ranging from complete regressions in one p16-positive PDX model to lack of significant activity in the three most resistant models. Despite all PDX models showing evidence of tumour hypoxia, and hypoxia being essential for activation of evofosfamide, the antitumour activity of evofosfamide only weakly correlated with tumour hypoxia status determined by pimonidazole immunohistochemistry. Other candidate evofosfamide sensitivity genes—MKI67, POR, and SLFN11—did not strongly influence evofosfamide sensitivity in univariate analyses, although a weak significant relationship with MKI67 was observed, while SLFN11 expression was lost in PDX tumours. Overall, these data confirm that evofosfamide has antitumour activity in clinically-relevant PDX tumour models of HNSCC and support further clinical evaluation of this drug in HNSCC patients. Further research is required to identify those factors that, alongside hypoxia, can influence sensitivity to evofosfamide and could act as predictive biomarkers to support its use in precision medicine therapy of HNSCC.

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Human papillomavirus and oropharyngeal squamous cell carcinoma: a New Zealand cohort study

Abstract: This study highlights the significant role that HPV plays in the aetiology of OPSCC in New Zealand, and confirms the high rate of accuracy of p16 immunostaining.

Cited by 10 publications

References 31 publications

Time to change perspectives on HPV in oropharyngeal cancer. A systematic review of HPV prevalence per oropharyngeal sub-site the last 3 years

Time to change perspectives on HPV in oropharyngeal cancer. A systematic review of HPV prevalence per oropharyngeal sub-site the last 3 years

Meta analysis: HPV and p16 pattern determines survival in patients with HNSCC and identifies potential new biologic subtype

Impact of Tumour Hypoxia on Evofosfamide Sensitivity in Head and Neck Squamous Cell Carcinoma Patient-Derived Xenograft Models

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