Pathologic Markers in Surgically Treated HPV-Associated Oropharyngeal Cancer: Retrospective Study, Systematic Review, and Meta-analysis

Tassone, Patrick; Crawley, Meghan; Bovenzi, Cory D.; Keane, William M.; Cognetti, David M.; Luginbuhl, Adam; Curry, Joseph M.

doi:10.1177/0003489417693014

Cited by 18 publications

(34 citation statements)

References 30 publications

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“…However, there currently is a paucity of evidence showing the benefit postsurgical chemotherapy for HPV + OPSCC specifically. A meta‐analysis of eight studies with a total of 85 HPV + OPSCC patients with 85% receiving adjuvant therapy found T stage, nodal number, lymphovascular invasion, and PNI to be independent risk factors for disease recurrence but not ENE . Another NCDB study analyzing 2,454 HPV‐positive patients with 84% receiving adjuvant therapy found that ENE was associated with worse OS in HPV‐negative OPSCC patients but not HPV‐positive .…”

Section: Discussionmentioning

confidence: 99%

Predictors of Mortality in HPV‐Associated Oropharynx Carcinoma Treated With Surgery Alone

et al. 2019

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Objective Survival outcomes for human papillomavirus‐associated oropharynx squamous cell carcinoma (HPV + OPSCC) treated with surgery alone are unclear. To increase understanding, we assessed overall survival (OS) outcomes using the national cancer database (NCDB). Methods We conducted a retrospective analysis of OS of 736 NCDB HPV + OPSCC patients who underwent surgery alone from 2010 to 2014 using univariate and multivariate analyses and the Kaplan‐Meir method. Results Multivariable analysis found the following independent risk factors for death: American Joint Commission on Cancer (AJCC) 8th edition pathologic stage(p)N2 versus pN0 disease (hazard ratio [HR], 5.5; P = 0.000006), macroscopic extranodal extension (ENE) versus non‐ENE (HR, 4.9; P < 0.02), a positive lymph nodes (LN) percentage of ≥10% (HR, 4.2; P = 0.0002), and five or more positive LNs (HR, 4.9; P = 0.00004). Three‐year OS was significantly worse for AJCC 8th edition pN2 versus pN0 but not for 7th edition pN2 versus pN0 disease. Five‐year OS was significantly worse for positive versus negative surgical margins, AJCC 8th edition stage II versus I, and either microscopic or macroscopic ENE versus non‐ENE positive LNs. For 523 (71%) AJCC 8th edition stage I patients and for 283 (38%) patients who were pT1–T2, with negative margins, pN0–N1, with ≤4 pathologic LNs, without ENE, and with >20 LNs removed during neck dissection, the 3‐year OS rates were 93% and 95%, respectively, and the 5‐year OS rates were 91% and 95%, respectively. Conclusion In the context of the lack of detail and possible inaccuracies found in the NCDB, surgery alone for AJCC 8th edition stage I HPV + OPSCC, particularly pT1–T2, pN0–N1 with ≤4 pathologic LNs, without ENE, and with negative surgical margins has a high OS. Level of Evidence 4 Laryngoscope, 130:E423–E435, 2020

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Section: Discussionmentioning

confidence: 99%

Predictors of Mortality in HPV‐Associated Oropharynx Carcinoma Treated With Surgery Alone

et al. 2019

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“…This is especially true when considering that extracapsular extension, which has been considered as a poor prognostic factor in OPSCC, was not associated with poor outcomes in several HPV-positive cohorts. 8,26,31,32 …”

Section: Discussionmentioning

confidence: 99%

“…A recently published meta-analysis 31 on the pathologic markers in surgically treated HPV-positive patients with OPSCC included only 4 studies that examined PNI and ALI, and these preliminary data reveal no significant negative effect on survival. This same study 31 published prevalence data on PNI and ALI.…”

Section: Discussionmentioning

confidence: 99%

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

Albergotti

Schwarzbach

Abberbock

et al. 2017

JAMA Otolaryngol Head Neck Surg

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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.

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“…HPV detection and genotyping was carried out using the Multiplex HPV Genotyping Kit for Research in Epidemiology (Multimetrix, PROGEN Biotechnik, Heidelberg, Germany), as described previously [9], to apply an analytically sensitive technique that also allows low copy numbers of HPV DNA to be detected. The Luminex bead-based genotyping procedure allows detection of 15 high-risk types (16,18,31,33,35,39,45, 51, 52, 56, 58, 59, 68, 73, and 82), 3 putative high-risk types (26,53, and 66), and 6 low-risk types (6,11,42,43,44, and 70). Sections were evaluated for p16INK4a using immunohistochemistry as previously described [10].…”

Section: Hpv Statusmentioning

confidence: 99%

“…Therefore, the choice between CRT followed by salvage surgery or SRT as definitive primary treatment often depend on institutional biases and patient preferences. Results of pathological markers after SRT in HPV-associated OSCC have recently been published in a review, and T stage, nodal number, perineural invasion, and lymphovascular invasion were shown to have a significant impact on event-free survival [6]. In view of the excellent survival rates of HPV-driven OSCC, there is need for de-escalation of treatments since the toxicity of CRT is a major correlate of reduced quality of life [7], and is reported to be even higher in HPV-driven OSCC [8].…”

Section: Introductionmentioning

confidence: 99%

Risk Factors for Overall Survival Outcome in Surgically Treated Human Papillomavirus-Negative and Positive Patients with Oropharyngeal Cancer

et al. 2017

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Introduction: This study reports the oncological outcome of a non-selected series of patients with human papillomavirus(HPV)-positive and -negative oropharyngeal squamous cell carcinoma (OSCC) preferentially managed with upfront surgery. Methods: Consecutive OSCC cases (n = 378) diagnosed from 2000 to 2010 in our department were evaluated for risk factors, HPV association, therapy and overall survival (OS). HPV status was determined by combined DNA and p16 testing, and treatment was defined as the first course of treatment with any kind of surgery (upfront surgery) or primary chemoradiotherapy. OS of HPV-associated and HPV-negative patients was compared using Kaplan-Meier and multivariable Cox regression analyses. Results: The majority of OSCC patients (215 of 361; 69.5%) received upfront surgery as first-line treatment in curative intent. The 5-year OS rate in patients with HPV-positive and HPV-negative tumors were 81.1 and 39.7%, respectively. Upfront surgery in HPV-negative (p < 0.001) and HPV-positive patients (p = 0.05) resulted in improved OS only in advanced stages. Multivariate analysis for patients revealed age in HPV-associated OSCC as an independent predictor for improved survival, and age, performance, N status and therapy as independent predictors in HPV-negative OSCC. Conclusions: Non-selected OSCC patients amenable to curative therapy show poor 5-year OS. The benefit of upfront surgery remains unclear. A younger patient age was the main factor for a better outcome in patients with HPV-associated OSCC.

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Pathologic Markers in Surgically Treated HPV-Associated Oropharyngeal Cancer: Retrospective Study, Systematic Review, and Meta-analysis

Abstract: While many traditional clinico-pathologic markers of aggressive disease in head and neck cancer also impact survival in surgically treated HPV-associated oropharyngeal cancer, extracapsular extension may be less important.

Cited by 18 publications

References 30 publications

Predictors of Mortality in HPV‐Associated Oropharynx Carcinoma Treated With Surgery Alone

Predictors of Mortality in HPV‐Associated Oropharynx Carcinoma Treated With Surgery Alone

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

Risk Factors for Overall Survival Outcome in Surgically Treated Human Papillomavirus-Negative and Positive Patients with Oropharyngeal Cancer

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