Human Papillomavirus—Associated Oropharyngeal Squamous Cell Carcinomas: Primary Tumor Burden and Survival in Surgical Patients

Ukpo, Odey C.; Pritchett, Cedric V.; Lewis, Jean E.; Weaver, Amy L.; Smith, Jeremy C.; Moore, Eric J.

doi:10.1177/000348940911800509

Cited by 26 publications

(23 citation statements)

References 15 publications

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“…These virally mediated cancers tend to present with smaller primary tumor volume and more advanced nodal disease. 21,26,27 This changing pattern of the disease with fewer locally advanced tumors may then be more amenable to surgical resection without rendering patients functionally disabled from high-volume resections. Indeed, of the 364 patients (88.8%) in this study treated for oropharyngeal primary tumors, 314 had pathologic stage T2 or lower disease.…”

Section: Discussionmentioning

confidence: 99%

Oncologic Outcomes After Transoral Robotic Surgery

Almeida

Magnuson

et al. 2015

JAMA Otolaryngol Head Neck Surg

250

234

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IMPORTANCE Large patient cohorts are necessary to validate the efficacy of transoral robotic surgery (TORS) in the management of head and neck cancer. OBJECTIVES To review oncologic outcomes of TORS from a large multi-institutional collaboration and to identify predictors of disease recurrence and disease-specific mortality. DESIGN, SETTING, AND PARTICIPANTS A retrospective review of records from 410 patients undergoing TORS for laryngeal and pharyngeal cancers from January 1, 2007, through December 31, 2012, was performed. Pertinent data were obtained from 11 participating medical institutions. INTERVENTIONS Select patients received radiation therapy and/or chemotherapy before or after TORS. MAIN OUTCOMES AND MEASURES Locoregional control, disease-specific survival, and overall survival were calculated. We used Kaplan-Meier survival analysis with log-rank testing to evaluate individual variable association with these outcomes, followed by multivariate analysis with Cox proportional hazards regression modeling to identify independent predictors. RESULTS Of the 410 patients treated with TORS in this study, 364 (88.8%) had oropharyngeal cancer. Of these 364 patients, information about post-operative adjuvant therapy was known about 338: 106 (31.3) received radiation therapy alone, and 72 (21.3%) received radiation therapy with concurrent chemotherapy. Neck dissection was performed in 323 patients (78.8%). Mean follow-up time was 20 months. Local, regional, and distant recurrence occurred in 18 (4.4%), 15 (3.7%), and 10 (2.4%) of 410 patients, respectively. Seventeen (4.1%) died of disease, and 13 (3.2%) died of other causes. The 2-year locoregional control rate was 91.8% (95% CI, 87.6%-94.7%), disease-specific survival 94.5% (95% CI, 90.6%-96.8%), and overall survival 91% (95% CI, 86.5%-94.0%). Multivariate analysis identified improved survival among women (P = .05) and for patients with tumors arising in tonsil (P = .01). Smoking was associated with worse overall all-cause mortality (P = .01). Although advanced age and tobacco use were associated with locoregional recurrence and disease-specific survival, they, as well as tumor stage and other adverse histopathologic features, did not remain significant on multivariate analysis. CONCLUSIONS AND RELEVANCE This large, multi-institutional study supports the role of TORS within the multidisciplinary treatment paradigm for the treatment of head and neck cancer, especially for patients with oropharyngeal cancer. Favorable oncologic outcomes have been found across institutions. Ongoing comparative clinical trials funded by the National Cancer Institute will further evaluate the role of robotic surgery for patients with head and neck cancers.

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Section: Discussionmentioning

confidence: 99%

Oncologic Outcomes After Transoral Robotic Surgery

Almeida

Magnuson

et al. 2015

JAMA Otolaryngol Head Neck Surg

250

234

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“…This is in contrary to the common misconception that HPV and smokingrelated carcinogenesis pathways are either partially or totally exclusive of each other. The larger literature also shows most HPV-related OSCC patients to be current or former smokers [2,8,[35][36][37][38][39], although it is clear that there are less overall smokers amongst the HPV-related cases and their amounts of exposure are less. Dysplastic changes secondary to tobacco smoke could be accompanied by aberrant expression of B7-H1.…”

Section: Discussionmentioning

confidence: 99%

“…The younger age of patients with HPV-related tumors, the lower smoke and alcohol exposure rates, and increased rates of sexual exposure suggest that HPV has a central role in carcinogenesis [1][2][3][4]. The prevalence of HPV in OSCC is between 60 % and 80 %, and rates are steadily increasing, with the mechanism believed to be chronic persistent infection leading to carcinogenesis [5][6][7][8]. Studies have demonstrated that oral infection by HPV is not uncommon [3,9].…”

Section: Introductionmentioning

confidence: 99%

B7-H1 Expression Model for Immune Evasion in Human Papillomavirus-Related Oropharyngeal Squamous Cell Carcinoma

Ukpo

Thorstad

Lewis

2012

Head and Neck Pathol

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122

104

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Human papillomavirus (HPV) is associated with oropharyngeal squamous cell carcinomas. Persistent viral infection is postulated to lead to carcinogenesis, although infection of benign adjacent epithelium is not typically observed. It is known that immune evasive tumor cells can provide an ideal niche for a virus. The B7-H1/ PD-1 cosignaling pathway plays an important role in viral immune evasion by rendering CD8? cytotoxic T cells anergic. We hypothesized that HPV-related oropharyngeal squamous cell carcinomas express B7-H1 as a mechanism for immune evasion. A tissue microarray was utilized, for which HPV E6/E7 mRNA by in situ hybridization was previously performed. Immunohistochemistry was performed to detect B7-H1 and staining was characterized by pattern, distribution, and intensity. B7-H1 was expressed by 84 of the 181 (46.4 %) cases. Both tumor cell membranous and cytoplasmic expression were present and cytoplasmic expression was identified in some peritumoral lymphocytes. Expression was analyzed in several different ways and then considered binarily as positive versus negative. Tumors expressing B7-H1 were more likely to be HPV positive (49.2 vs. 34.1 %, p = 0.08). B7-H1 expression showed no correlation with disease recurrence in the entire cohort (OR = 1.09, p = 0.66), HPV positive cohort (OR = 0.80, p = 0.69) or HPV negative cohort (OR = 2.02, p = 0.22). However, B7-H1 expression intensity did correlate with the development of distant metastasis (p = 0.03), and B7-H1 intensity of 3? (versus all other staining) showed a strong trend towards distant metastasis in the HPV positive (OR = 6.67, p = 0.13) and HPV negative (OR = 9.0, p = 0.13) cohorts. There was no correlation between B7-H1 expression and patient survival for any of the different ways in which staining was characterized, whether binarily, by distribution, intensity, or combined scores. B7-H1 is expressed in the majority of oropharyngeal squamous cell carcinomas with transcriptionally-active HPV. This suggests that B7-H1 expression by tumor cells may play a role in harboring persistent HPV infection.

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“…Two studies found that HPV status also conferred a favorable prognosis in surgically treated oropharyngeal cancer patients (31, 40). However, a recent study from the Mayo Clinic showed that HPV status did not impact prognosis in patients presenting with surgically resectable cancers of the oropharynx (41). In this latter study, the association between HPV status and overall survival had a hazard ratio of 1.02 (the 95% CI: 0.53–1.99).…”

Section: Discussionmentioning

confidence: 99%

Novel biomarker panel predicts prognosis in human papillomavirus‐negative oropharyngeal cancer

Posner

Schumaker

et al. 2011

Cancer

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Purpose New treatment strategies for locally-advanced HNSCC combine induction chemotherapy and chemoradiation. Identifying predictors of outcome for sequentially-treated patients is critical for focusing therapeutic research. In this analysis, we evaluated HPV-16 status as well as expression of a defined set of biomarkers to identify predictors of response to this treatment modality. Experimental Design 114 oropharyngeal cancer (OPC) patients treated on the TAX 324 trial had pretreatment biopsy specimens that were evaluable for HPV-16 DNA and immunohistochemical expression of the following biomarkers: beta-tubulin II (βT-II), glutathione S-transferase (GST-π), p53, and Bcl-2. Patients were categorized into risk groups based on their HPV status and biomarkers’ expression level. Results High risk OPC patients were defined by HPV (−) status and elevated expression of βT-II or at least 2 out of 3 of the other adverse markers (GST-π, p53, and low Bcl-2). All other HPV (−) patients were considered moderate risk. 55 patients were HPV (+); 59 patients were HPV (−). Of these, 34 were high risk and 25 were moderate risk. Median survival for HPV (+) patients was not reached. Median survival time for moderate risk patients was 44.2 (the 95% CI: 20.9-NR) months and was 12.1 (the 95% CI: 7.5–19.7) months for high risk patients. The 24-month survival rate was 89% for HPV (+) patients, 67% for moderate risk patients, and 29% for high risk patients (P < 0.0001). Conclusions Our molecular data set readily differentiates between 2 distinct groups of patients with locally-advanced, HPV (−) OPC. This risk stratification strategy may serve as a guide for treatment selection.

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Human Papillomavirus—Associated Oropharyngeal Squamous Cell Carcinomas: Primary Tumor Burden and Survival in Surgical Patients

Abstract: Primary tumor burden was not associated with HPV status. Patients with HPV-positive oropharyngeal squamous cell carcinomas had a higher prevalence of neck nodal metastases and high-grade lesions.

Cited by 26 publications

References 15 publications

Oncologic Outcomes After Transoral Robotic Surgery

Oncologic Outcomes After Transoral Robotic Surgery

B7-H1 Expression Model for Immune Evasion in Human Papillomavirus-Related Oropharyngeal Squamous Cell Carcinoma

Novel biomarker panel predicts prognosis in human papillomavirus‐negative oropharyngeal cancer

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