A novel algorithm for reliable detection of human papillomavirus in paraffin embedded head and neck cancer specimen.
Serge J. Smeets,Albertus T. Hesselink,Ernst-Jan M. Speel,Annick Haesevoets,Peter J.F. Snijders,Michael Pawlita,Chris J.L.M. Meijer,Boudewijn J.M. Braakhuis,C. René Leemans,Ruud H. Brakenhoff +9 more
TLDR
It is shown that clinically meaningful viral HPV infections can be more reliably measured in FFPE H NSCC samples in a standard and high throughput manner, paving the way for prognostic and experimental vaccination studies, regarding not only HNSCC, but possibly also cancer types with HPV involvement in subgroups such as penile and anal cancer.Abstract:
Human papillomavirus type 16 (HPV16) plays a role in the development of a subgroup of head and neck squamous cell carcinomas (HNSCC). However, uncertainty exists about the true impact of HPV in this tumor type as conflicting reports have been published with prevalence rates from 0 to 100%. We aimed to find a detection algorithm of a biologically and thus clinically meaningful infection, applicable for high-throughput screening of frozen and formalin-fixed paraffin embedded (FFPE) specimens. By considering detection of HPV E6 oncogene expression in frozen biopsies as gold standard for a meaningful HPV infection, the value of several assays was evaluated on FFPE tumor specimens and sera of 48 HNSCC patients. The following assays were evaluated on FFPE tissue samples: HPV DNA general primer (GP)5+/6+ PCR, viral load analysis, HPV16 DNA FISH detection, HPV16 E6 mRNA RT-PCR, p16 immunostaining, and on corresponding serum samples detection of antibodies against the HPV16 proteins L1, E6 and E7. Comparing single assays on FFPE tissue samples detection of E6 expression by RT-PCR was superior, but application remains at present limited to HPV16 detection. Most suitable algorithm with 100% sensitivity and specificity appeared p16 immunostaining followed by GP5+/6+ PCR on the p16-positive cases. We show that clinically meaningful viral HPV infections can be more reliably measured in FFPE HNSCC samples in a standard and high throughput manner, paving the way for prognostic and experimental vaccination studies, regarding not only HNSCC, but possibly also cancer types with HPV involvement in subgroups such as penile and anal cancer.read more
Citations
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Human Papillomavirus and Survival of Patients with Oropharyngeal Cancer
K. Kian Ang,Jonathan Harris,Richard H. Wheeler,Randal S. Weber,David I. Rosenthal,Phuc Felix Nguyen-Tân,William H. Westra,Christine H. Chung,Richard C.K. Jordan,Charles Lu,Harold Kim,Rita Axelrod,C Craig Silverman,Kevin P. Redmond,Maura L. Gillison +14 more
TL;DR: Tumor HPV status is a strong and independent prognostic factor for survival among patients with oropharyngeal cancer and the risk of death significantly increased with each additional pack-year of tobacco smoking.
Journal ArticleDOI
The molecular biology of head and neck cancer
TL;DR: The recent literature on tumour heterogeneity, field cancerization, molecular pathogenesis and the underlying causative cancer genes that can be exploited for novel and personalized treatments of patients with HNSCC are discussed.
Journal ArticleDOI
HPV-associated head and neck cancer: a virus-related cancer epidemic
TL;DR: In this paper, the authors highlight current understanding of the epidemiology, biology, detection, and management of HPV-related oropharyngeal head and neck squamous cell carcinoma, and describe unresolved issues.
Journal ArticleDOI
The molecular landscape of head and neck cancer
TL;DR: It became apparent that HNSCC is a disease characterized by frequent mutations that create neoantigens, indicating that immunotherapies might be effective and that immunotherapy trials with immune checkpoint inhibitors were published, and these may be considered as a paradigm shift in head and neck oncology.
Journal ArticleDOI
Head and Neck Squamous Cell Carcinoma: Update on Epidemiology, Diagnosis, and Treatment.
TL;DR: The changing epidemiology, advances in diagnosis, and treatment options for squamous cell cancers of the head and neck, along with data on risk stratification specific to oropharyngeal cancer are focused on, and the direction of current trials is highlighted.
References
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Practical statistics for medical research
TL;DR: Practical Statistics for Medical Research is a problem-based text for medical researchers, medical students, and others in the medical arena who need to use statistics but have no specialized mathematics background.
Journal ArticleDOI
Human papillomavirus is a necessary cause of invasive cervical cancer worldwide.
Jan M. M. Walboomers,M. V. Jacobs,M. M. Manos,Franz X. Bosch,J. A. Kummer,Keerti V. Shah,Peter J.F. Snijders,Julian Peto,Chris J.L.M. Meijer,Nubia Muñoz +9 more
TL;DR: The presence of HPV in virtually all cervical cancers implies the highest worldwide attributable fraction so far reported for a specific cause of any major human cancer, and the rationale for HPV testing in addition to, or even instead of, cervical cytology in routine cervical screening.
Journal ArticleDOI
Epidemiologic Classification of Human Papillomavirus Types Associated with Cervical Cancer
Nubia Muñoz,F. Xavier Bosch,Silvia de Sanjosé,Rolando Herrero,Xavier Castellsagué,Keerti V. Shah,Peter J.F. Snijders,Chris J.L.M. Meijer +7 more
TL;DR: In addition to HPV types 16 and 18, types 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82Should be considered carcinogenic, or high-risk, types, and types 26, 53, and 66 should be considered probably carcinogenic.
Journal ArticleDOI
Papillomaviruses and cancer: from basic studies to clinical application
TL;DR: Links between human papillomaviruses (HPVs) and cervical cancer were first suspected almost 30 years ago and DNA of specific HPV types has since been found in almost all cervical cancer biopsies.
Journal ArticleDOI
Evidence for a Causal Association Between Human Papillomavirus and a Subset of Head and Neck Cancers
Maura L. Gillison,Wayne M. Koch,Randolph B. Capone,Michael Spafford,William H. Westra,Li Wu,Marianna Zahurak,Richard W. Daniel,Michael P. Viglione,David Eric Symer,Keerti V. Shah,David Sidransky +11 more
TL;DR: It is suggested that HPV-positive oropharyngeal cancers comprise a distinct molecular, clinical, and pathologic disease entity that is likely causally associated with HPV infection and that has a markedly improved prognosis.