Oropharyngeal Squamous Cell Carcinoma in 390 Patients: Analysis of Clinical and Histological Criteria Which Significantly Impact Outcome

Abstract

This study evaluates the prognostic impact of several factors in oropharyngeal squamous cell carcinoma (OPSCC), controlling for human papillomavirus (HPV)-associated tumors and stage (American Joint Committee on Cancer 8th edition). All patients in Southern California Permanente Medical Group diagnosed with OPSCC between 2006 and 2012 tested for p16 immunohistochemistry were included. Review of all pathology materials was combined with central p16 testing. Multivariable analyses were performed. The cohort of 390 patients included 342 p16-positive and 48 p16-negative tumors. For all-comers, on univariate analysis, the following factors, when present, were associated with improved patient survival: p16-positive tumor (n = 324, p < 0.001); crypt versus surface tumor location (n = 312, p = 0.004); nonkeratinizing type (n = 309, p < 0.0001); nonkeratinizing with maturation type (n = 37, p < 0.0001); basaloid pattern (n = 284, p = 0.005); and a broad, pushing border of infiltration (n = 282, p = 0.004). Inferior survival outcomes were observed with: age ≥ 55 years (p < 0.0001); ≥ 10 pack-year smoking history (n = 183, p = 0.003); increasing tumor stage (p < 0.0001); overt radiographic extranodal extension (ORENE) (n = 58, p < 0.0001); low level IV/Vb lymph node involvement (n = 45, p = 0.0002); a jagged pattern of infiltration (n = 76, p = 0.0004); tumor ulceration (n = 76, p = 0.0004); absent lymphocytic infiltrate (p < 0.0001); and concurrent dysplasia (n = 125, p = 0.009). On multivariable analysis, accounting for patient age, smoking history ≥ 10 pack-years, and TNM stage, for patients with p16-positive disease, advanced TNM stage (p = 0.007), the presence of ORENE (p = 0.0002), and low-neck lymphadenopathy (p = 0.0001) were independent negative prognostic factors for disease free survival (DFS). Older age (p < 0.0001), smoking history ≥ 10 pack-years (p = 0.02), advanced TNM stage (p = 0.0002), ORENE (p = 0.004), and low-neck lymphadenopathy (p = 0.002) were independent negative prognostic factors for OS. Among patients with p16-positive OPSCC, older age, smoking history, advanced stage, ORENE, and low-neck lymphadenopathy were significant negative prognostic factors for DFS and/or OS. Further refinement of staging to incorporate additional lymph node findings may be warranted.

Prognostic Significance of Extranodal Extension in HPV‐Mediated Oropharyngeal Carcinoma: A Systematic Review and Meta‐analysis

“…In total, 18 studies met inclusion criteria and were included in our meta-analysis. 12-14,25,26,37-49…”

p16 in highly malignant esophageal carcinomas: the correlation with clinicopathological factors and human papillomavirus infection

“…Consequently, an inactivation of Rb1 protein results in the overexpression of p16 [9,12]. HPV-associated oropharyngeal squamous cell carcinomas were pathologically and clinically different from the non-HPV-associated counterparts [19]. These tumors had a lower metastatic rate and TNM stages than HPV-negative squamous cell carcinomas [19], resulting in better clinical outcome and response to chemotherapy, radiotherapy, or chemoradiotherapy than those with HPV-negative squamous cell carcinomas [20][21][22][23].…”

Macrophages expressing TREM-1 are involved in the progression of HPV16-related oropharyngeal squamous cell carcinoma

“…Routine histology has demonstrated that HPVrelated carcinomas show peculiar findings, for instance, non-keratinizing, basaloid, papillary and lymphoepithelial patterns [3][4][5][6].…”

“…Moreover, much interest has been devoted to the cellular components of the tumoral microenvironment (TME) and their functional implications: for instance, the presence of an intense lymphocytic infiltration is associated with a better prognosis [6]; the qualitative analysis, made by lymphocytic immunophenotyping, has demonstrated that high amounts of peritumoral and intratumoral CD8 þ cells correspond to a significant-good prognosis in HPV-related tumours [7][8][9]; CD4 þ lymphocytes are also significantly more numerous in HPV-tumours, while T regulatory lymphocytes CD4 þ FoxP3 þ are not differently represented in HPV and non-HPV tumours [10]. Independently from the HPV association, natural killer CD56 þ lymphocytes are consistently more represented in cases with better outcomes.…”