Concurrent cisplatin or cetuximab with radiotherapy for HPV-positive oropharyngeal cancer: Medical resource use, costs, and quality-adjusted survival from the De-ESCALaTE HPV trial

Jones, David A.; Mistry, Pankaj; Dalby, Matthew J.; Fulton-Lieuw, Tessa; Kong, Anthony; Dunn, Janet A.; Mehanna, Hisham; Gray, Alastair

doi:10.1016/j.ejca.2019.10.025

Cited by 14 publications

(12 citation statements)

References 18 publications

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“…Despite the recent approval of two very effective HPV vaccines that prevent primary infection, the impact of vaccination on the incidence of HPV-associated OPC is not expected to become evident until 2060 ( Gillison et al, 2015 ). The morbidity associated with treatment for OPC and the favorable long-term survival demonstrate an ongoing need to develop better prognostic markers for this disease to allow better selection of de-escalation strategies ( Gillison et al, 2019 ; Jones et al, 2020 ; Mehanna et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Profiling HPV-16–specific T cell responses reveals broad antigen reactivities in oropharyngeal cancer patients

Bhatt

Neller

Srihari

et al. 2020

Journal of Experimental Medicine

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Cellular immunotherapeutics targeting the human papillomavirus (HPV)–16 E6 and E7 proteins have achieved limited success in HPV-positive oropharyngeal cancer (OPC). Here we have conducted proteome-wide profiling of HPV-16–specific T cell responses in a cohort of 66 patients with HPV-associated OPC and 22 healthy individuals. Unexpectedly, HPV-specific T cell responses from OPC patients were not constrained to the E6 and E7 antigens; they also recognized E1, E2, E4, E5, and L1 proteins as dominant targets for virus-specific CD8+ and CD4+ T cells. Multivariate analysis incorporating tumor staging, treatment status, and smoking history revealed that treatment status had the most significant impact on HPV-specific CD8+ and CD4+ T cell immunity. Specifically, the breadth and overall strength of HPV-specific T cell responses were significantly higher before the commencement of curative therapy than after therapy. These data provide the first glimpse of the overall human T cell response to HPV in a clinical setting and offer groundbreaking insight into future development of cellular immunotherapies for HPV-associated OPC patients.

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Section: Introductionmentioning

confidence: 99%

Profiling HPV-16–specific T cell responses reveals broad antigen reactivities in oropharyngeal cancer patients

Bhatt

Neller

Srihari

et al. 2020

Journal of Experimental Medicine

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“…age, stage, high CD8 þ tumor infiltrating lymphocyte (TIL) counts, HPV16 E2 mRNA expression, absent/weak CD44, or high LRIG1 or CD98 expression to better select patients for de-escalated therapy [1]. Today there are several ongoing clinical trials including patients with OPSCC based on p16status [17,18]. If the basis of selection, i.e.…”

Section: Discussionmentioning

confidence: 99%

The value of p16 and HPV DNA in non-tonsillar, non-base of tongue oropharyngeal cancer

Hammarstedt

Holzhauser

Zupancic

et al. 2020

Acta Oto-Laryngologica

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Background: Oropharyngeal squamous cell carcinoma (OPSCC) is dominated by tonsillar and tongue base carcinomas (TSCC/BOTSCC), but there are carcinomas at other sites, such as uvula/soft palate/ pharyngeal wall here defined as other OPSCC. Human papillomavirus (HPV) positive TSCC/BOTSCC have favorable outcome, and the TNM-classification separates OPSCC into HPV mediated (p16 INK4a overexpressing, p16þ) and HPV unrelated OPSCC (p16 INK4a non-overexpressing, p16-) cancer, but the prognostic role of p16þ in other OPSCC is unclear. Aims/Objectives: This study therefore aimed to further investigate the prognostic role of p16þ, presence of HPV DNA, or both combined in other OPSCC. Material and methods: 195 other OPSCC, from patients diagnosed 2000-2018 were tested for p16, and/or presence of HPV DNA and the data correlated to outcome. Results: Neither overall survival, nor disease free survival correlated to presence of p16þ or HPV DNA in other OPSCC. p16þ and HPV DNA presence were correlated (p < .0001), but the sensitivity of p16 as a surrogate marker for presence of HPV DNA was low (49%). Conclusions and significance: The data suggest that p16þ (and p16þ/HPV DNA) positive other OPSCC should be analyzed cautiously and possibly separately from the HPV mediated OPSCC staging group.

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“…Two-year overall survival (97.5% vs. 90.0%, HR: 3.268, p = 0·0251) and recurrence rates (6.4% vs. 16.0%, HR: 2.67; p = 0.0024) favored the cisplatin arm. Furthermore, the results of this phase III large trial highlighted that in HPV-positive patients, the standard association of cisplatin-radiotherapy should not be avoided [40].…”

Section: Hpv-related Tumors: Implications In Clinical Practicementioning

confidence: 99%

Management of HPV-Related Squamous Cell Carcinoma of the Head and Neck: Pitfalls and Caveat

Perri

Longo

Caponigro

et al. 2020

Cancers

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Head and neck squamous cell carcinomas (HNSCCs) are a very heterogeneous group of malignancies arising from the upper aerodigestive tract. They show different clinical behaviors depending on their origin site and genetics. Several data support the existence of at least two genetically different types of HNSCC, one virus-related and the other alcohol and/or tobacco and oral trauma-related, which show both clinical and biological opposite features. In fact, human papillomavirus (HPV)-related HNSCCs, which are mainly located in the oropharynx, are characterized by better prognosis and response to therapies when compared to HPV-negative HNSCCs. Interestingly, virus-related HNSCC has shown a better response to conservative (nonsurgical) treatments and immunotherapy, opening questions about the possibility to perform a pretherapy assessment which could totally guide the treatment strategy. In this review, we summarize molecular differences and similarities between HPV-positive and HPV-negative HNSCC, highlighting their impact on clinical behavior and on therapeutic strategies.Cancers 2020, 12, 975 2 of 14 papilloma virus (HPV)-related tumors [1][2][3]. Several lines of evidence support the existence of at least two genetically different types of HNSCC, one virus-related and the other alcohol and/or tobacco and oral trauma-related, characterized by both clinical and biological opposite features [3,4]. Unlike HPV-negative HNSCC, HPV-positive HNSCC often occurs in younger patients with minimal or no tobacco exposure [5,6]. HPV-positive HNSCC, similarly to its HPV-negative counterpart, has a male predominance, with men suffering a three-to-five times higher incidence than women worldwide [7].HPV-positive HNSCC carries a favorable prognosis if compared to HPV-negative tumors. In fact, five-year survival rates for patients with advanced-stage HPV-positive HNSCC are 75-80%, versus values less than 50% in patients with similarly staged HPV-negative tumors [8,9]. The cause of the aforementioned different behavior is the different chemo-and radiosensitivity shown by the HPV-positive and HPV-negative HNSCCs. In fact, several clinical trials have shown that HPV-positive HNSCC patients have a better response to chemotherapy and radiation therapy than HPV-negative cases [10][11][12]. The reasons for this different behavior should be searched in the opposite genetic features which characterize the two types of tumors.In this review, we will analyze the genetics of both HPV-positive and HPV-negative HNSCC, highlighting their impact on the clinical behavior and finally on the therapeutic strategies. Genetics of HPV-Positive HNSCCCarcinogenesis, which is the complex process through which the normal cell is pushed to transform itself into a cancer cell, is very different between HPV-related and non-HPV-related HNSCC. Viral carcinogenesis in HNSCC is partly due to HPV infection, with the oropharynx being the most commonly involved site. HPV-mediated carcinogenesis is driven by a few viral oncoproteins expressed by high-risk HPV genotypes....

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Concurrent cisplatin or cetuximab with radiotherapy for HPV-positive oropharyngeal cancer: Medical resource use, costs, and quality-adjusted survival from the De-ESCALaTE HPV trial

Cited by 14 publications

References 18 publications

Profiling HPV-16–specific T cell responses reveals broad antigen reactivities in oropharyngeal cancer patients

Profiling HPV-16–specific T cell responses reveals broad antigen reactivities in oropharyngeal cancer patients

The value of p16 and HPV DNA in non-tonsillar, non-base of tongue oropharyngeal cancer

Management of HPV-Related Squamous Cell Carcinoma of the Head and Neck: Pitfalls and Caveat

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