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immune cells and prognosis in hpv-associated oropharyngeal squamous cell carcinomas

S Wagner, H Böckmann, S Gattenlöhner, J P Klussmann, C Wittekindt
Based on clinical and experimental data, oropharyngeal squamous cell carcinomas (OPSCC) associated with human papillomavirus (HPV) have been recognized as a distinct entity of head and neck cancers. However, outside of clinical trials, HPV status currently has no impact on treatment. The natural replication cycle of HPV takes place in epithelial cells, and is thus spatially separated from cytotoxic immune cells in the epidermis. Dendritic cells (Langerhans cells, LC), however, are frequent in this upper dermal layer...
February 15, 2018: HNO
Ye Tao, Erich M Sturgis, Zhigang Huang, Ying Wang, Peng Wei, Jennifer Rui Wang, Qingyi Wei, Guojun Li
Purpose: TGFβ1 plays a critical role in inflammation and immune responses and treatment response and survival. TGFβ1 variants may affect its expression level or functional efficiency, thus modifying tumor status and survival in human papillomavirus (HPV)-positive squamous cell carcinoma of the oropharynx (SCCOP). Experimental Design: We determined tumor HPV16 status and genotyped three TGFβ1 polymorphisms in 564 incident SCCOP patients treated with radiotherapy or chemoradiation. Univariate and multivariable Cox models were used to evaluate the associations between the three polymorphisms and survival...
February 20, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Priscila Lie Tobouti, Robert Bolt, Raghu Radhakrishnan, Suzana Cantanhede Orsini Machado de Sousa, Keith D Hunter
Toll-like receptors (TLRs) have been widely investigated due to their importance in the inflammatory response and possible links to tumor promotion/regression and prognosis. In cancers with an infective etiology, such as human papillomavirus (HPV)-associated Oropharyngeal Squamous Cell Carcinoma (OPSCC), TLR responses may be activated and play a role in tumorigenesis. Our aim was to assess the expression of all TLRs in OPSCC cell lines (both HPV+ and HPV-) by qPCR, Western Blot and flow cytometry and assess their response to TLR ligands lipopolysaccharide (LPS), LPS ultra-pure (LPS-UP) and peptidoglycan (PGN) by analyzing IL-8 and IL-6 production...
January 2, 2018: Oncotarget
Trisha Wise-Draper, Arun Sendilnathan, Sarah Palackdharry, Nicholas Pease, Julianne Qualtieri, Randall Butler, Nooshin Hashemi Sadraei, John C Morris, Yash Patil, Keith Wilson, Jonathan Mark, Keith Casper, Vinita Takiar, Adam Lane, Lisa Privette Vinnedge
Head and neck cancer (HNC) remains the sixth most common malignancy worldwide and survival upon recurrence and/or metastasis remains poor. HNSCC has traditionally been associated with alcohol and nicotine use, but more recently the Human Papilloma Virus (HPV) has emerged as a favorable prognostic risk factor for oropharyngeal HNSCC. However, further stratification with additional biomarkers to predict patient outcome continues to be essential. One candidate biomarker is the DEK oncogenic protein, which was previously detected in the urine of patients with bladder cancer and is known to be secreted by immune cells such as macrophages...
February 2018: Translational Oncology
Lauri Jouhi, Hesham Mohamed, Antti Mäkitie, Satu Maria Remes, Caj Haglund, Timo Atula, Jaana Hagström
A large subset of oropharyngeal squamous cell carcinomas (OPSCCs) is associated with HPV infection and has better outcome than non-viral-related tumors. Various malignancies also carry a role for TLRs, key activators of inflammation and innate immunity. We examined the expression of TLRs in OPSCC, and their association with HPV status and treatment outcome. TLR 5, 7, 9, and p16 were studied by immunohistochemistry and HPV status was detected with in situ hybridization in 202 tumors of consecutively treated OPSCC patients using tissue microarray method...
December 2017: Cancer Immunology, Immunotherapy: CII
Priscila Lie Tobouti, Robert Bolt, Raghu Radhakrishnan, Suzana Cantanhede Orsini Machado Sousa, Keith D Hunter
Toll-like receptors (TLRs) have been widely investigated due to their importance in the inflammatory response and possible links to tumor promotion/regression and prognosis. In cancers with an infective etiology, such as human papillomavirus (HPV)-associated Oropharyngeal Squamous Cell Carcinoma (OPSCC), TLR responses may be activated and play a role in tumorigenesis. Our aim was to assess the expression of all TLRs in OPSCC cell lines (both HPV+ and HPV-) by qPCR, Western Blot and flow cytometry and assess their response to TLR ligands lipopolysaccharide (LPS), LPS ultra-pure (LPS-UP) and peptidoglycan (PGN) by analyzing IL-8 and IL-6 production...
July 4, 2017: Oncotarget
Ankur Chakravarthy, Stephen Henderson, Stephen M Thirdborough, Christian H Ottensmeier, Xiaoping Su, Matt Lechner, Andrew Feber, Gareth J Thomas, Tim R Fenton
Purpose In squamous cell carcinomas of the head and neck (HNSCC), the increasing incidence of oropharyngeal squamous cell carcinomas (OPSCCs) is attributable to human papillomavirus (HPV) infection. Despite commonly presenting at late stage, HPV-driven OPSCCs are associated with improved prognosis compared with HPV-negative disease. HPV DNA is also detectable in nonoropharyngeal (non-OPSCC), but its pathogenic role and clinical significance are unclear. The objectives of this study were to determine whether HPV plays a causal role in non-OPSCC and to investigate whether HPV confers a survival benefit in these tumors...
December 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Camelia Nami Saber, Christian Grønhøj Larsen, Tina Dalianis, Christian von Buchwald
Currently, oropharyngeal squamous cell carcinomas (OPSCC) are treated based on the traditional TNM-classification, although this scheme might be inadequate for the subgroup of human papillomavirus (HPV)-associated OPSCCs. It remains debatable whether this subgroup of patients with favorable prognosis should be offered altered treatment. Besides the well-known biomarkers of HPV and p16, new promising immune cells and markers might nuance the prognosis and treatment for patients with HPV+ OPSCC. We systematically reviewed the literature on immunological features of HPV-associated OPSCCs, and report that a high number of cytotoxic T cells (CD8s) and a low number of CD98 positive cells is associated with better outcome, while an increased CD4/CD8 ratio and a high human leukocyte antigen 1 (HLA1) intensity is most likely associated with worse outcome...
July 2016: Oral Oncology
Pauline M W van Kempen, Rob Noorlag, Justin E Swartz, Niels Bovenschen, Weibel W Braunius, Jeroen F Vermeulen, Ellen M Van Cann, Wilko Grolman, Stefan M Willems
OBJECTIVES: Patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinomas (OPSCCs) have an improved prognosis compared to HPV-negative OPSCCs. Several theories have been proposed to explain this relatively good prognosis. One hypothesis is a difference in immune response. In this study, we compared tumor-infiltrating CD3+, CD4+, CD8+ T-cells, and granzyme inhibitors (SERPINB1, SERPINB4, and SERPINB9) between HPV-positive and HPV-negative tumors and the relation with survival...
May 2016: Cancer Immunology, Immunotherapy: CII
Steffen Wagner, Claus Wittekindt, Miriam Reuschenbach, Ben Hennig, Mauran Thevarajah, Nora Würdemann, Elena-Sophie Prigge, Magnus von Knebel Doeberitz, Thomas Dreyer, Stefan Gattenlöhner, Jens Peter Klussmann
Human papillomavirus (HPV)-related squamous cell carcinoma of the oropharynx (OSCC) are clinical and biological distinct from their HPV-unrelated counterparts. Patients with HPV-related OSCC display improved prognosis and therefore we investigated possible immune cell infiltrations associated with this tumor phenotype. We retrospectively analyzed a randomly selected cohort of 140 OSCC for presence of immune cells and HPV by immunohistochemistry and PCR followed by bead-based hybridization (Luminex technology)...
May 1, 2016: International Journal of Cancer. Journal International du Cancer
S Partlová, J Bouček, K Kloudová, M Zábrodský, R Špíšek, A Fialová
The insight into the biological nature of head and neck squamous cell carcinoma has evolved significantly in the last few years. Tobacco use and alcohol consumption are proven risk factors of head and neck squamous cell carcinoma. Cancer patients possessing such a tumor are generally elderly, mostly in fifth or sixth decade of life. In addition, significant association of head and neck squamous cell carcinoma with infection by human papillomavirus (HPV) was proven. HPV is now considered to be one of the most important risk factors, particularly for oropharyngeal carcinoma...
2015: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
Tina Dalianis
Numerous reports in recent decades have shown that, in addition to smoking and alcohol, human papillomavirus (HPV) is also associated with the development of oropharyngeal squamous cell carcinoma (OPSCC), predominantly in the tonsils and base of the tongue. In 2007, the International Agency on Research against Cancer (IARC) therefore declared HPV to be a risk factor for OPSCC and noted that 80% of those affected are men. In addition, patients with HPV-positive OPSCC, in particular never-smokers, have a much better clinical response to therapy than patients with HPV-negative OPSCC and other head and neck cancers...
December 2014: La Presse Médicale
Gregory T Wolf, Douglas B Chepeha, Emily Bellile, Ariane Nguyen, Daffyd Thomas, Jonathan McHugh
OBJECTIVES: Tumor infiltrating lymphocytes (TILs) in the microenvironment reflect may tumor biology and predict outcome. We previously demonstrated that infiltrates of CD4, CD8, and FoxP3 positive lymphocytes were associated with HPV-status and survival in oropharyngeal cancers. To determine if TILs were of prognostic importance in oral cancer, TIL levels were evaluated retrospectively in 52 oral cancer patients treated with surgery and correlations with outcome determined. METHODS: Complete TIL and clinical data were available for 39 patients...
January 2015: Oral Oncology
Nicole G Chau, Guilherme Rabinowits, Robert I Haddad
Human papillomavirus-associated oropharynx cancer (HPV-OPC) is growing in incidence and has distinct clinical, pathologic, molecular, and epidemiologic features. However, the management of HPV-OPC does not presently differ from HPV-negative OPC based on the current evidence and requires complex multidisciplinary approaches. The superior prognosis of HPV-OPC and the toxicities of current multimodality treatment in a young population serve as the impetus to evaluate de-intensification treatment regimens aimed at reducing toxicity while maintaining therapeutic efficacy...
December 2014: Current Treatment Options in Oncology
E Lukesova, J Boucek, E Rotnaglova, M Salakova, E Koslabova, M Grega, T Eckschlager, B Rihova, B Prochazka, J Klozar, R Tachezy
BACKGROUND: Human papillomaviruses (HPVs) have been proved as one of the etiological factors of oropharyngeal squamous cell carcinoma (OPSCC). Patients with tumors of viral etiology have a lower recurrence rate and better prognosis. OPSCC is linked to an alteration in the immune system. Only a limited number of studies have correlated both the immunological parameters and HPV status with patient prognosis. The aim of this study was to determine whether HPV infection and the immunological status influence patient prognosis individually or in concurrence...
2014: BioMed Research International
B Kofler, S Laban, C J Busch, B Lörincz, R Knecht
Epidemiological studies show an increasing incidence of human papilloma virus-associated oropharyngeal cancer. HPV-positive head and neck squamous cell carcinoma (HNSCC) is recognized as a special subgroup of HNSCC. Because HPV-positive patients are often younger and have an outstanding prognosis, long-term toxicities of therapy have become an important issue. Current clinical trials focus on a reduction of treatment-related toxicity and the development of HPV-specific therapies. New treatment strategies include a dose reduction of radiotherapy, the use of cetuximab instead of cisplatin for chemoradiation and transoral robotic surgery (TORS)...
July 2014: European Archives of Oto-rhino-laryngology
Anne Skou Andersen, Anne Sophie Koldjaer Sølling, Therese Ovesen, Maria Rusan
Persistent infection with human papillomavirus (HPV) type 16 is a major risk factor for the development of head and neck squamous cell carcinoma (HNSCC), in particular oropharyngeal squamous cell carcinoma (OPSCC). The oropharyngeal epithelium differs from the mucosal epithelium at other commonly HPV16-infected sites (i.e., cervix and anogenital region) in that it is juxtaposed with the underlying lymphatic tissue, serving a key immunologic function in the surveillance of inhaled and ingested pathogens. Therefore, the natural history of infection and immune response to HPV at this site may differ from that at other anatomic locations...
June 15, 2014: International Journal of Cancer. Journal International du Cancer
Massimo Rittà, Vincenzo Landolfo, Jasenka Mazibrada, Marco De Andrea, Valentina Dell'Oste, Valeria Caneparo, Alberto Peretti, Carlo Giordano, Giancarlo Pecorari, Massimiliano Garzaro, Santo Landolfo
The association between human papillomavirus (HPV) DNA positivity, p53 codon 72 polymorphisms, and the type of leukocyte infiltration in head and neck squamous cell carcinomas (HNSCC) and their combined impact upon patient survival is poorly investigated. For this reason, leukocyte infiltration profile and p53 codon 72 polymorphisms were assessed in freshly removed HNSCC specimens (N=71 patients). HPV detection was performed by nested-PCR followed by DNA sequencing. Viral loads were determined by quantitative RT-PCR...
April 2013: New Microbiologica
Giuseppe Pannone, Angela Santoro, Silvana Papagerakis, Lorenzo Lo Muzio, Gaetano De Rosa, Pantaleo Bufo
Cancer statistics report an increased incidence of OSCC and OPSCC around the world. Though improvements in screening and early diagnosis have dramatically reduced the incidence of this neoplasm in recent years, the 5-year-disease-free survival, is still poor, specially for oropharyngeal cancer, despite the great scientific and financial efforts. Recently, several papers showed that HPV may be involved at least in the pathogenesis of a subgroup of oral and cervical SCC, leading to distinct molecular characteristics compared with HPV-negative ones...
March 29, 2011: Infectious Agents and Cancer
Derrick Wansom, Emily Light, Frank Worden, Mark Prince, Susan Urba, Douglas B Chepeha, Kitrina Cordell, Avraham Eisbruch, Jeremy Taylor, Nisha D'Silva, Jeffrey Moyer, Carol R Bradford, David Kurnit, Bhavna Kumar, Thomas E Carey, Gregory T Wolf
OBJECTIVE: to determine whether the favorable outcome associated with human papillomavirus (HPV) 16-positive oropharyngeal cancer is related to a patient's adaptive immunity. SETTING: academic medical center. PATIENTS: forty-seven of 66 previously untreated patients (6 of 20 patients with stage III and 41 of 46 with stage IV cancer) in a prospective clinical trial of chemoradiotherapy. INTERVENTION: all patients were treated with a single course of neoadjuvant chemotherapy followed by either surgery (for nonresponders) or chemoradiotherapy...
December 2010: Archives of Otolaryngology—Head & Neck Surgery
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