Defining the Prevalence and Prognostic Value of Perineural Invasion and Angiolymphatic Invasion in Human Papillomavirus–Positive Oropharyngeal Carcinoma

Abstract

IMPORTANCE Recently, the American Joint Committee on Cancer (AJCC) updated its staging system for human papillomavirus (HPV)–positive oropharyngeal squamous cell carcinoma (OPSCC). The prognostic significance of perineural invasion (PNI) and angiolymphatic invasion (ALI) within this staging system is unknown. OBJECTIVE To examine the prevalence and prognostic significance of PNI and ALI in HPV-positive OPSCC. DESIGN, SETTING, AND PARTICIPANTS A retrospective review was performed of all patients with HPV-positive OPSCC treated surgically at the University of Pittsburgh Medical Center from January 1, 1980, through December 31, 2015, with at least 1 year of follow-up or death within 1 year. INTERVENTIONS Surgical treatment of HPV-positive OPSCC. MAIN OUTCOMES AND MEASURES The prevalence of PNI and ALI was determined from review of pathologic data, and Kaplan-Meier curves were generated for overall survival and disease-free survival when stratified by the presence of PNI and ALI. Multivariate analysis was performed using a Cox proportional hazards regression model. RESULTS A total of 201 patients met the inclusion criteria (mean [SD] age, 57.4 [9.0] years; 79.6% [3.0%] male, and 20.4% [3.0%] female). Perineural invasion was identified in 32 of 201 primary specimens (15.9%), whereas ALI was identified in 74 of 201 primary specimens (36.8%). Both were significantly associated with increasing T stage. On multivariate analysis, the presence of at least 1 risk factor was significantly associated with overall and disease-free survival (overall hazard ratio, 2.78; 95% CI, 1.15–6.76; disease-free survival hazard ratio, 3.10; 95% CI, 1.17–8.23). Among patients classified as having stage II disease according to the eighth edition of the AJCC manual, the presence of at least 1 risk factor was associated with worse overall survival (hazard ratio, 11.7; 95% CI, 1.2–111.7). CONCLUSIONS AND RELEVANCE Both PNI and ALI were commonly found in HPV-positive OPSCC, with increasing prevalence as T stage increased. The presence of at least 1 risk factor was associated with worse overall and disease-free survival. Specifically, among patients classified as having stage II disease according to the eighth edition of the AJCC manual, the presence of ALI or PNI may suggest a poorer prognosis.

Rate of locoregional recurrence among patients with oropharyngeal squamous cell carcinoma with known HPV status: a systematic review

“…Factors like immune surveillance of virus-specific tumor antigens, like high CD8þ T-cell infiltration, and lack of field cancerization may contribute to the better treatment outcome of HPV-positive OPSCC's overall survival and prognosis [36][37][38][39]. Further, one study found that HPV-positive tumors were not correlated with perineural invasion (PNI) or perivascular invasion (PVI), which have been reported as independent predictors of poor survival [40]. It was also found that HPV-driven tumors display a cohesive invasion pattern at the leading edge of the tumor [41].…”

Primary surgery for human papillomavirus-associated oropharyngeal cancer: Survival outcomes with or without adjuvant treatment

“…Thus, our results should be validated in independent data sets to determine if there is a difference in rates of lo- coregional or distant relapse. Third, there are several unmeasured variables including perineural invasion [28] and previous tobacco smoking history [2], which may be relevant to determining the risk of death in HPV+ OPSCC. Further, factors such as the chemotherapy regimen and quality of RT cannot be assessed.…”

Mouse model of postsurgical primary tumor recurrence and regional lymph node metastasis progression in HPV‐related head and neck cancer

“…Although mechanisms of HPV1 and HPV-negative (HPV2) HNSCC are different, 7 both tumor entities show an invasive phenotype 8,9 and metastasis into the neck lymph nodes (LNs) and distant sites. [10][11][12] Thus, despite their distinct genetic nature 13 and clinico-pathological appearance, 14 treatment approaches of HPV2 and HPV1 HNSCCs are essentially the same and include surgery, radiotherapy, or chemoradiotherapy (cRT) as single or combination modalities, depending on the location and stage of the tumor.…”