Clinical vs Microscopic Extranodal Extension and Survival in Oropharyngeal Carcinoma in the Human Papillomavirus Era

Objective Extranodal extension (ENE) is known to be associated with poor outcomes in head and neck squamous cell carcinoma. The objective of this study is to examine the impact of extent of ENE on survival in oropharyngeal carcinoma in the human papillomavirus (HPV) era. Study Design Retrospective database review. Setting Review of the National Cancer Database. Subjects and Methods The National Cancer Database was used to examine surgically treated head and neck squamous cell carcinoma of the tonsil and base of tongue from 2010 to 2015. Nodes available for pathologic examination were classified as ENE negative (–), ENE clinically (+), or ENE (+) on pathology only. The primary outcome was overall survival. Cox regression modeling was used to examine the effect of ENE on survival while controlling for patient demographics, HPV status, stage, adjuvant radiation, and chemotherapy. Results Of the 66,106 patients identified, 16,845 were treated with surgery ± adjuvant therapy, 8780 of whom were known HPV+. Overall 5-year survival for this group was 86%. Documented ENE was associated with over a 60% decrease in survival for clinical (hazard ratio [HR], 1.63) and pathologic (HR, 1.62) ENE compared to negative ENE, after adjustment for stage, adjuvant radiation ± chemotherapy, HPV, and other variables. No significant differences were found between clinical and pathologic ENE (HR, 1.001). Conclusion While both surgically resected clinical and pathologic ENE are associated with decreased survival, no significant differences are observed between the two. The impact of these observations on potential de-escalation therapeutic strategies requires further study.

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Prognostic relevance of human papillomavirus infection in anal squamous cell carcinoma: Analysis of the National Cancer Database.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.735 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. 735-735

Author(s):

Jaymin Jhaveri ◽

Lael Rayfield ◽

Yuan Liu ◽

Mudit Chowdhary ◽

Richard John Cassidy ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Human Papillomavirus ◽

Cell Carcinoma ◽

Squamous Cell ◽

Hpv Infection ◽

National Cancer Database ◽

Anal Squamous Cell Carcinoma ◽

Prognostic Relevance ◽

Hpv Status ◽

The Impact

735 Background: To examine the prognostic relevance of human papillomavirus (HPV) infection for anal squamous cell carcinoma (ASCC) patients treated with chemoradiation in the National Cancer Database (NCDB). Methods: The 2014 NCDB was queried for non-metastatic, histologically confirmed, ASCC patients diagnosed between 2004 and 2013. Patients were required to have HPV status documented in order to be eligible. Patients were then stratified into two groups: HPV+ and HPV-. Univariate analysis was performed using the χ2 test for categorical covariates and ANOVA for numerical covariates. Multivariable analysis (MVA) was performed using Cox proportional hazard model for overall survival (OS). Hazard ratios (HR) and 95% confidence intervals (CI) were generated for each covariate. To minimize selection bias, propensity score (PS) weighting was implemented to balance OS related variables between the groups including: age, education level, stage, diagnosis year, insurance type, and agent of chemotherapy. Results: A total of 1,063 patients were eligible. Patients were stratified into HPV+ (n = 498, 46.8%) and HPV- (n = 565, 53.2%). After PS weighting, MVA for OS showed that for men, HPV infection was associated with better OS (HR 0.60, CI 0.38-0.96; p = 0.034). However, for women, HPV infection did not significantly influence survival (HR 1.47, CI 0.96-2.25; p = 0.074). Conclusions: To our knowledge, this is the largest patient series evaluating the impact of HPV infection on OS in patients with anal cancer. We found that HPV infection is associated with a statistically significant better survival for men with ASCC. In contrast, for women, HPV infection did not significantly influence survival.

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Metabolic Plasticity and Combinatorial Radiosensitisation Strategies in Human Papillomavirus-Positive Squamous Cell Carcinoma of the Head and Neck Cell Lines

Cancers ◽

10.3390/cancers13194836 ◽

2021 ◽

Vol 13 (19) ◽

pp. 4836

Author(s):

Mark D. Wilkie ◽

Emad A. Anaam ◽

Andrew S. Lau ◽

Carlos P. Rubbi ◽

Nikolina Vlatkovic ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Human Papillomavirus ◽

Cell Carcinoma ◽

Head And Neck ◽

Cell Lines ◽

Squamous Cell ◽

Metabolic Profile ◽

Metabolic Phenotype ◽

The Impact

Background: A major objective in the management of human papillomavirus (HPV)-positive squamous cell carcinoma of the head and neck (SCCHN) is to reduce long-term functional ramifications while maintaining oncological outcomes. This study examined the metabolic profile of HPV-positive SCCHN and the potential role of anti-metabolic therapeutics to achieve radiosensitisation as a potential means to de-escalate radiation therapy. Methods: Three established HPV-positive SCCHN cell lines were studied (UM-SCC-104, UPCI:SCC154, and VU-SCC-147), together with a typical TP53 mutant HPV-negative SCCHN cell line (UM-SCC-81B) for comparison. Metabolic profiling was performed using extracellular flux analysis during specifically designed mitochondrial and glycolytic stress tests. Sensitivity to ionising radiation (IR) was evaluated using clonogenic assays following no treatment, or treatment with: 25 mM 2-deoxy-D-glucose (glycolytic inhibitor) alone; 20 mM metformin (electron transport chain inhibitor) alone; or 25 mM 2-deoxy-D-glucose and 20 mM metformin combined. Expression levels of p53 and reporters of p53 function (MDM2, p53, Phospho-p53 [Ser15], TIGAR and p21 [CDKN1A]) were examined by western blotting. Results: HPV-positive SCCHN cell lines exhibited a diverse metabolic phenotype, displaying robust mitochondrial and glycolytic reserve capacities. This metabolic profile, in turn, correlated with IR response following administration of anti-metabolic agents, in that both 2-deoxy-D-glucose and metformin were required to significantly potentiate the effects of IR in these cell lines. Conclusions: In contrast to our recently published data on HPV-negative SCCHN cells, which display relative glycolytic dependence, HPV-positive SCCHN cells can only be sensitised to IR using a complex anti-metabolic approach targeting both mitochondrial respiration and glycolysis, reflecting their metabolically diverse phenotype. Notionally, this may provide an attractive platform for treatment de-intensification in the clinical setting by facilitating IR dose reduction to minimise the impact of treatment on long-term function.

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Human Papillomavirus Testing in Head and Neck Squamous Cell Carcinoma: Impact of the 2018 College of American Pathologists Guideline Among Referral Cases at a Large Academic Institution

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2020-0220-oa ◽

2020 ◽

Author(s):

Donna C Ferguson ◽

Mitra Mehrad ◽

Kim A Ely ◽

Justin R Shinn ◽

James S. Lewis

Keyword(s):

Squamous Cell Carcinoma ◽

Human Papillomavirus ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Oropharyngeal Squamous Cell Carcinoma ◽

Neck Squamous Cell Carcinoma ◽

Human Papillomavirus Testing ◽

P16 Immunohistochemistry ◽

The Impact

Context.— Given the growing clinical significance of human papillomavirus status in oropharyngeal squamous cell carcinoma, the College of American Pathologists established a set of evidence-based recommendations for high-risk human papillomavirus testing. Objective.— To evaluate the impact of the recommendations on human papillomavirus ancillary test ordering habits by comparing compliance before and after the guideline was published. Design.— We retrospectively reviewed head and neck squamous cell carcinoma biopsy or resection specimens from outside institutions during a 2.5-year period around guideline publication for whether or not human papillomavirus testing was performed in accordance with the guideline. Results.— Human papillomavirus testing deviated from the guideline in 45 of 107 cases (42.1%) before and 93 of 258 cases (36.0%) after their publication (P = .29). This included 6 of 26 cases of oropharyngeal squamous cell carcinoma (23.1%) before and 5 of 55 cases (9.1%) after (P = .16), with 5 of 5 (100.0%) after due to not performing p16 immunohistochemistry. This also included 30 of 68 cases of nonoropharyngeal carcinoma (44.1%) before and 69 of 163 (42.3%) after the guideline was published (P = .88), with 29 of 30 (96.7%) before and 67 of 69 (97.1%) after due to unnecessary use of p16 immunohistochemistry. Nodal metastasis testing deviated in 9 of 13 cases (69.2%) before and 19 of 40 cases (47.5%) after (P = .21) with marked variability in testing, including 3 of 9 (33.3%) before and 8 of 19 (42.1%) after, for not confirming certain p16 immunohistochemistry–positive tumors with human papillomavirus–specific testing. Conclusions.— Pathologists continue to deviate from the testing guideline significantly in everyday practice. Further education and discussion about the appropriate handling of head and neck cancer specimens may be needed.

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