Positive Oropharyngeal Carcinoma Research Articles

Surgical Treatment of Hypopharyngeal Carcinoma, Neck Dissection and Adjuvant Postoperative Therapy of Oropharyngeal and Hypopharyngeal Cancer: Recommendations of the current S3 Guideline - Part II

Part II of the S3 guideline report deals with the surgical treatment of hypopharyngeal carcinoma, neck dissection for oropharyngeal and hypopharyngeal carcinomas and adjuvant therapy options. Primary surgical therapy ± adjuvant radio- or radiochemotherapy and primary radio- or radiochemotherapy are established as primary therapies for local-regional hypopharyngeal carcinomas. Direct randomized comparisons of both basic therapeutic procedures were never conducted. Available registry data show a worse prognosis of hypopharyngeal carcinoma compared to oropharyngeal carcinomas in all locoregional tumor stages, regardless of the treatment method. For T1N0-T2N0 squamous cell carcinoma of the hypopharynx, there are no relevant differences in overall survival and locoregional relapse rate between primary surgical and primary non-surgical treatment. Primary surgical therapy ± adjuvant radiotherapy or radiochemotherapy and primary radiotherapy or radiochemotherapy are established as primary therapies for advanced but locoregionally limited hypopharyngeal carcinomas. Neck dissection is an integral part of the primary surgical treatment of oropharyngeal and hypopharyngeal cancer. There are only a few randomized studies on non-surgical organ preservation for advanced hypopharyngeal cancer as an alternative to pharyngolaryngectomy, but these have led to the recommendation of alternative concepts in the new guideline. The indication and implementation of postoperative adjuvant radiotherapy and radiochemotherapy for hypopharyngeal carcinoma do not differ from those for HPV/p16-negative and -positive oropharyngeal carcinoma.

P16 and HPV status in head and neck sarcomas and sarcomatoid carcinomas

Human papillomavirus (HPV)-positive oropharyngeal carcinoma is a distinct type of head and neck carcinoma with improved prognosis. p16 immunostaining is often used as a surrogate marker for HPV infection in this particular setting. The aim of this study is to estimate the prevalence of p16 staining and HPV infection in head and neck sarcomatoid carcinomas as well as head and neck sarcomas. 21 sarcomatoid carcinomas and 28 head and neck sarcomas were tested for p16 positivity using immunohistochemical staining, and for high-risk HPV infection using In situ hybridization (ISH). 24 % of sarcomatoid carcinomas and 21 % of sarcomas were positive for p16 staining. All 49 cases were negative for HPV ISH. The results confirm that p16 staining is not specific and may not be associated with HPV infection in non-oropharyngeal head and neck sites. They also indicate that non-oropharyngeal head and neck sarcomatoid carcinomas are not likely to be HPV related.

Increasing Patients With HPV-positive Oropharyngeal Squamous Cell Carcinoma and its Oncologic Outcomes in the Rural Region in Northern Japan.

Despite the global rise in the incidence of human papillomavirus (HPV)-positive oropharyngeal carcinoma (OPC) in recent years, its prevalence and oncological outcomes in patients living in rural areas of Northern Japan has not been explored and should be investigated. A total of 105 patients with oropharyngeal squamous cell carcinoma who underwent HPV screening and received first-line treatment were included in this study. The annual changes in the number of patients, survival rates, and clinical factors affecting prognosis were examined. The HPV-positive rate in patients with OPC was low, with the lowest rate of 10.0% in 2013 and the highest rate of 46.7% in 2020. The number of HPV-negative cases remained almost unchanged, whereas the overall number of cases increased with the increasing number of HPV-positive cases. Additionally, HPV-positive cases exhibited a fairly good prognosis. The number of OPC cases increased not only in urban areas, but also in rural areas. HPV-positive cases had better outcomes than HPV-negative cases.

Clinical characteristics and efficacy of oropharyngeal carcinoma with secondary primary tumor

Objective:To analysis the clinical features and prognosis in oropharyngeal carcinoma with secondary primary tumor. Methods:A retrospective analysis was performed on 468 pathologically confirmed oropharyngeal cancer as the primary tumor patients with p16 status, excluded distant metastasis, and admitted to the Chinese Academy of Medical Sciences from January 2010 to December 2020. The clinical features and prognosis of the secondary primary tumor were analyzed. Results:Among 468 patients with oropharyngeal cancer treated at initial diagnosed, 222 cases were P16-negative. With a median follow-up time of 64.3 months, 66 cases developed second primary cancer, with an incidence of 29.3%, among which 63.6%（42/66） were synchronous and 36.4%（24/66） were heterochronous, esophagus was the most commonly involved site. The 5-year OS of p16-negative oropharyngeal carcinoma with synchronous second primary cancer, without second primary cancer and with heterogeneous second primary cancer were 26.3% and 57.3% and 73.2%（P=0.001）; The second primary cancer accounted for 11.2%（12/107） of the deaths in the whole group, among them, the heterochronous second primary accounted for 75.0%（9/12）. There were 246 patients with p16 positive, with a median follow-up time of 52.4 months, 20 patients developed second primary cancer（8.1%）. Among them, 65.0%（13/20） were synchronous and 35.0%（7/20） were heterochronous. Esophagus was the most commonly involved site. The 4-year OS of p16-positive with synchronous, heterochronous and non-second primary cancer group were 51.9%, 80.7% and 83.3%. Secondary primary cancer accounted for 3.8%（2/52） of all deaths in p16 positvie group. Conclusion:The incidence of second primary cancer of p16 positive and negative oropharyngeal carcinoma were different. The esophagus was the most commonly involved site regardless of p16 status. Regardless of p16 status, the survival of patients with synchronous second primary cancer was worse than those without second primary cancer. For p16-negative oropharyngeal carcinoma, the prognosis was better in patients with heterogeneous second primary cancer, the second primary cancer is one of the main causes of death.

Close Margins After Transoral Robotic Surgery for Human Papillomavirus–Positive Oropharyngeal Carcinoma: A Review of the Literature and Practical Recommendations

The purpose of this article is to summarize the literature and practical recommendations from experienced centers for close margins after transoral robotic surgery for human papillomavirus–positive oropharyngeal carcinoma.

New progress in diagnosis and treatment of HPV-positive oropharyngeal carcinoma

In recent years, the incidence of oropharyngeal carcinoma （OPC） is increasing, while the better prognosis of patients with Human papillomavirus （HPV） positive oropharyngeal carcinoma has been confirmed in a number of studies. There are a variety of detection methods for HPV-associated oropharyngeal carcinoma. Including P16 immunohistochemistry, Polymerase Chain Reaction （PCR） or In situ hybridization （ISH） detection of HPV DNA, HPV RNA, Revers transcriptase Polymerase Chain Reaction （RT PCR） was used to detect HPV RNA. The better prognosis of patients with HPV-positive oropharyngeal carcinoma has led to the emergence of a large number of degraded treatment trials. The traditional P16 test has certain limitations in the diagnosis of patients with HPV-positive oropharyngeal carcinoma. It is necessary to combine with other detection methods to accurately screen out patients with HPV-positive oropharyngeal carcinoma and better apply to degraded therapy. In this article, we will briefly introduce the trend of HPV-associated oropharyngeal carcinoma, the detection methods and the new progress of degraded treatment trials.

Use of positron emission tomography/ computed tomography in the initial staging of head and neck squamous cell carcinoma: Accuracy in evaluation of the primary site of the tumor, metastases to cervical lymph nodes, and distant metastases.

Our study aimed to evaluate the use of positron emission tomography/computed tomography (PET/CT) in the initial staging of head and neck squamous cell carcinoma (HNSCC), including assessment of local and distant spread of the disease. We also aimed to compare the accuracy of PET/CT in the evaluation of human papillomavirus (HPV) positive and HPV-negative oropharyngeal carcinoma. This single-center, prospective study was conducted between August 2016 and September 2021. A total of 198 patients with HNSCC who underwent PET/CT within the primary staging were included. We compared PET/CT results with histological findings. We calculated the accuracy, sensitivity, specificity, and positive and negative predictive values to assess the primary tumor, cervical lymph nodes, and distant metastases. PET/CT showed a high success rate (32%) in revealing the primary site of carcinoma of unknown primary (CUP). The accuracy of PET/CT in displaying the primary tumor, cervical lymph node metastases, and distant metastases was 89.4%, 85.4%, and 87.4%, respectively. The method provided high sensitivity but lower specificity in all three areas. Specifically, PET/CT showed low specificity in the assessment of small tumors (75%), metastatic involvement of cervical lymph nodes (69.6%), and HPV-positive oropharyngeal carcinoma (55.6%). The high accuracy of PET/CT to identify distant metastases and whole-body staging in one diagnostic step accelerated primary staging and resulted in earlier commencement of therapy. However, it also led to an overestimation of clinical findings and thus to extensive surgical treatment, especially in patients with small tumors, metastatic involvement of cervical lymph nodes, and HPV- positive oropharyngeal carcinoma. PET/CT is also useful for CUP diagnostics.

Clinical Validity of a Prognostic Gene Expression Cluster-Based Model in Human Papillomavirus-Positive Oropharyngeal Carcinoma.

PURPOSEUnder common therapeutic regimens, the prognosis of human papillomavirus (HPV)–positive squamous oropharyngeal carcinomas (OPCs) is more favorable than HPV-negative OPCs. However, the prognosis of some tumors is dismal, and validated prognostic factors are missing in clinical practice. The present work aimed to validate the prognostic significance of our published three-cluster model and to compare its prognostic value with those of the 8th edition of the tumor-node-metastasis staging system (TNM8) and published signatures and clustering models.METHODSPatients with HPV DNA-positive OPCs with locoregionally advanced nonmetastatic disease treated with curative intent (BD2Decide observational study, NCT02832102) were considered as validation cohort. Patients were treated in seven European centers, with expertise in the multidisciplinary management of patients with head and neck cancer. The median follow-up was 46.2 months (95% CI, 41.2 to 50), and data collection was concluded in September 2019. The primary end point of this study was overall survival (OS). Three-clustering models and seven prognostic signatures were compared with our three-cluster model.RESULTSThe study population consisted of 235 patients. The three-cluster model confirmed its prognostic value. Two-year OS in each cluster was 100% in the low-risk cluster, 96.6% in the intermediate-risk cluster, and 86.3% in the high-risk cluster (P = .00074). For the high-risk cluster, we observed an area under the curve = 0.832 for 2-year OS, significantly outperforming TNM 8th edition (area under the curve = 0.596), and functional and biological differences were identified for each cluster.CONCLUSIONThe rigorous clinical selection of the cases included in this study confirmed the robustness of our three-cluster model in HPV-positive OPCs. The prognostic value was found to be independent and superior compared with TNM8. The next step includes the translation of the three-cluster model in clinical practice. This could open the way to future exploration of already available therapies in HPV-positive OPCs tailoring de-escalation or intensification according to the three-cluster model.

P-71 Incidence of contralateral neck failure (CNF) after long-term follow-up in HPV positive oropharyngeal carcinoma treated with unilateral neck irradiation with or without primary surgery

P-71 Incidence of contralateral neck failure (CNF) after long-term follow-up in HPV positive oropharyngeal carcinoma treated with unilateral neck irradiation with or without primary surgery

De-escalation concepts for chemoradiotherapy of HPV-positive oropharyngeal carcinomas: pros and cons

In contrast to alcohol- and nicotine-induced head and neck tumors, human papillomavirus (HPV)-positive oropharyngeal carcinoma rather affects younger patients, and the incidence of this entity is continuously increasing. Due to the significantly better prognosis of HPV-positive oropharyngeal carcinoma, various treatment de-escalation strategies are currently being investigated, with the aim of reducing toxicity without affecting the good survival rates of these patients. This study aims to evaluate the evidence for treatment de-escalation in HPV-positive oropharyngeal carcinoma. Aliterature search was performed and relevant studies are critically discussed. De-escalation strategies for HPV-associated oropharyngeal carcinoma using induction chemotherapy or radiation dose reduction have demonstrated good oncological results in phaseII trials, with lower toxicity rates compared to historical controls. However, both of the first published phaseIII trials investigating de-escalation of concomitant chemotherapy regimens demonstrated inferior outcomes for the deescalated treatment strategies without improvements in treatment-associated toxicities. Additional phase-III trials investigating other de-escalation strategies have not yet been published. Treatment de-escalation should be performed exclusively in prospective studies and can currently not be recommended in clinical routine.

Pre‐ and Post‐Radiotherapy Radiologic Nodal Features and Oropharyngeal Cancer Outcomes

To assess the prognostic value of pre-/post-radiotherapy (pre-/post-RT) radiologic lymph node (LN) features in human papillomavirus (HPV)-positive and HPV-negative oropharyngeal carcinoma (OPC) patients treated with definitive (chemo-)RT. Clinical node-positive OPCs treated from 2011 to 2015 were reviewed. Nodal features were reviewed by a radiologist on pre-/post-RT computed tomography (CTs). Univariable analysis calculated hazard ratio (HR) for regional failure (RF), distant metastasis (DM), and deaths. Multivariable analysis estimated adjusted HR (aHR) of significant nodal features identified in univariable analysis adjusting for confounders. Pre-RT CT was undertaken in 344 HPV-positive and 94 HPV-negative OPC patients, of whom 242 (70%) HPV-positive and 67 (71%) HPV-negative also had a post-RT CT. Median follow-up was 4.9 years. Pre-RT LN calcification (pre-RT_LN-cal) increased the risk of RF in HPV-negative (aHR: 5.3, P = .007) but not HPV-positive patients (P = .110). Pre-RT radiologic extranodal extension (pre-RT_rENE+) increased the risk of DM and death in both HPV-negative (DM: aHR 6.6, P < .001; death: aHR 2.1, both P = .019) and HPV-positive patients (DM: aHR 4.9; death: aHR 3.0, both P < .001). Increased risk of RF occured with < 20% post-RT LN size reduction in both HPV-negative (HR 6.0, P = .002) and HPV-positive cases (HR 3.0, P = .049). Post-RT_LN-cal did not affect RF, DM, or death regardless of tumor HPV status (all P > .05). Pre-RT_LN-cal is associated with higher RF risk in HPV-negative but not in HPV-positive patients. Pre-RT_rENE increases risk of DM and death regardless of tumor HPV status. Minimal post-RT LN size reduction (< 20%) increases risk of RF in both diseases. Post-RT_LN-cal + has no apparent influence on outcomes in either disease. 4 (a single institution case-control series) Laryngoscope, 131:E1162-E1171, 2021.

The role of surgery and salvage surgery in the era of HPV-associated oropharyngeal carcinomas

The incidence of human papillomavirus (HPV)-positive oropharyngeal carcinomas is increasing worldwide. Due to amarkedly different response to treatment compared to HPV-negative oropharyngeal carcinomas, determining the ideal therapeutic approach can be challenging. Particularly in never-smokers, HPV-positive oropharyngeal carcinomas respond well to primary radiation therapy; at the same time recent studies indicate comparable survival after primary surgery. For stageI tumors according to TNM‑8, retrospective analyses show very good oncologic outcomes after surgery alone, and no added benefit of adjuvant radio- or chemotherapy. Results of prospective treatment deintensification trials are expected in the coming years. Minimally invasive transoral surgical approaches for selected oropharyngeal cancers can improve preservation of postoperative function and quality of life. For both HPV-positive and HPV-negative oropharyngeal carcinomas, salvage surgery is the treatment of choice for resectable recurrent locoregional disease and resectable distant metastases.

Radiotherapy dose and survival outcomes in human papillomavirus positive oropharyngeal cancer.

To evaluate the effect of definitive radiotherapy dose on survival in patients with human papillomavirus positive oropharyngeal carcinoma. Human papillomavirus positive oropharyngeal carcinoma patients staged T1-3 and N0-2c, who received definitive radiotherapy (fraction sizes of 180 cGy to less than 220 cGy), were identified from the National Cancer Database 2010-2014 and stratified by radiation dose (50 Gy to less than 66 Gy, or 66 Gy or more). A total of 2173 patients were included, of whom 124 (6 per cent) received a radiation dose of 50 Gy to less than 66 Gy. With a median follow up of 33.8 months, patients had a 3-year overall survival rate of 88.6 per cent (95 per cent confidence interval = 87.1-90.1 per cent). On multivariate Cox analysis, a radiotherapy dose of 50 Gy to less than 66 Gy (hazard ratio = 0.95, 95 per cent confidence interval = 0.52-1.74, p = 0.86) was not a predictor of increased mortality risk. Human papillomavirus positive oropharyngeal carcinoma patients had excellent outcomes with definitive radiotherapy doses of 50 Gy to less than 66 Gy. These results further support patients enrolling into clinical trials for radiation dose de-escalation.

Current Standard of Care in Squamous Cell Carcinoma of the Head and Neck (SCCHN) - Prevention, diagnostics, prognostication and therapy

The standard of care in squamous cell carcinoma of the head and neck (SCCHN) has recently undergone some major shifts in prevention, diagnostics, staging, prognostication and therapy.Prevention: Subtypes of the human papilloma virus (HPV) have been identified as causative agent for HPV-driven oropharyngeal carcinomas nearly two decades ago. Vaccination against HPV is now recommended for all girls and boys at the age of 9 to 14 years by the Standing Committee on Vaccination at the Robert Koch Institute (STIKO).Diagnostics: 18F-FDG PET/CT allows for a reduction of surgical procedures and is now reimbursed by the german health care system in certain indications. In N2/N3-disease after definitive chemoradiotherapy a FDG PET/CT is indicated to prevent neck dissection in PET negative patients. Moreover, a FDG PET CT is indicated in case of suspected recurrence of laryngeal carcinoma and as staging procedure in patients with cervical manifestation of CUP syndrome.Staging/prognostication: The favorable prognosis of HPV-driven oroparhyngeal carcinomas is now reflected by the 8th edition of the TNM classification. Therapeutic decisions should still be based on the established criteria of the 7thedition.Locally advanced disease: Treatment de-intensification strategies for HPV positive oropharyngeal carcinomas are currently evaluated. So far, the already published trials have reported a disadvantage for less intensive regimens. Therefore, de-intensification should not be practiced in current standard of care.Palliative systemic therapy: Checkpoint inhibitors nivolumab and pembrolizumab are the new standard of care after progression on platinum based therapies. In the Keynote-048 trial, treatment with either pembrolizumab alone (CPS > 1) or its combination with platin+ 5-flourouracil was superior to the current first line standard PFC.

Impact of cisplatin dose and smoking pack-years in human papillomavirus–positive oropharyngeal squamous cell carcinoma treated with chemoradiotherapy

BackgroundTo evaluate the impact of cisplatin cumulative dose (CDDP-D) and smoking pack-years (PYs) on cause-specific survival (CSS) and overall survival (OS) in human papillomavirus–positive (HPV+) oropharyngeal carcinoma (OPSCC) using the eighth edition tumour-node-metastasis (TNM) staging classification (TNM8). Patients and methodsWe reviewed patients with HPV+ OPSCC treated with high-dose CDDP and intensity-modulated radiotherapy between 2005 and 2015 at Princess Margaret Cancer Centre. CSS and OS were compared according to CDDP-D <200/=200/>200 mg/m2 stratified by TNM8. ResultsA total of 482 consecutive patients were evaluated (stage I/II/III: N = 189/174/119; CDDP-D <200/=200/>200 mg/m2: N = 112/220/150). Median follow-up duration was 5.1 years (range: 0.6–12.8). Five-year CSS and OS differed by stages I/II/III: 96%/85%/88% (p=0.005) and 93%/84%/78% (p = 0.001), respectively. Five-year CSS by CDDP-D <200/=200/>200 mg/m2 was similar in stage I (98%/95%/95%, p = 0.74) and stage II (88%/84%/84%, p = 0.86) but different in stage III (76%/98%/84%, p = 0.02). Five-year OS by CDDP-D <200/=200/>200 mg/m2 did not differ significantly among stages. In the multivariable analysis, CDDP-D <200 mg/m2 did not influence CSS in the whole cohort versus = 200/>200 mg/m2 (p=0.53/0.79, respectively) but was associated with reduced CSS in stage III subgroup versus =200 mg/m2 (=200 mg/m2 versus < 200 mg/m2 hazard ratio [HR] = 0.08; 95% confidence interval [CI]: 0.01–0.67; p = 0.02). Higher smoking PYs had no effect on CSS (p = 0.34) but reduced OS in the whole cohort (HR = 1.14 [95% CI: 1.02–1.27], p=0.01). ConclusionCDDP-D correlated with neither survival nor disease-specific outcomes in this large and homogeneous HPV+ cohort, although reduced CSS was observed in stageIII HPV+ OPSCC receiving CDDP-D <200 mg/m2. Smoking PYs were negatively associated with OS but not with CSS.

Abstract CT123: IMvoke010: Randomized Phase III study of atezolizumab as adjuvant monotherapy after definitive therapy of squamous cell carcinoma of the head and neck (SCCHN)

Abstract Background: Locally advanced SCCHN is associated with a high risk for local recurrence and distant metastases. Current treatment options include a combination of surgery, radiation therapy and chemotherapy to optimize the chances for long-term disease control and improved survival. As standard of care, patients are monitored after definitive local therapy for local recurrence and/or distant metastases. No effective systemic adjuvant treatment has been identified. Atezolizumab (atezo) is an anti-programmed death-ligand 1 (PD-L1) monoclonal antibody that restores anti-tumor immunity by preventing PD-L1 from binding to its receptors. Efficacy results from a cohort of 32 patients with recurrent/metastatic SCCHN in the Phase I PCD4989g study suggested that atezo offers promising clinical benefit in SCCHN. The objective of IMvoke010 (NCT03452137) is to evaluate the efficacy and safety of adjuvant treatment with atezo in comparison to placebo in patients with locally advanced SCCHN who are at high risk for disease recurrence or progression following definitive curative therapy. Trial design: IMvoke010 is a global, double-blind, placebo-controlled, randomized Phase III trial currently enrolling patients who have completed definitive local/regional therapy for Stage III human papillomavirus (HPV)-positive oropharyngeal carcinoma or Stage IVA or IVB HPV-negative SCCHN involving the oral cavity, oropharynx, larynx or hypopharynx and are at high risk for disease recurrence or progression. Approximately 400 patients will be randomized 1:1 to receive placebo or atezo 1200 mg every 3 weeks for up to a year (≤ 16 cycles) or until unacceptable toxicity, disease recurrence or progression. Patients with nasopharyngeal carcinoma, metastatic disease or progressive disease during or at completion of definitive local therapy will be excluded. Primary endpoints are independent review facility-assessed event-free survival (EFS) and overall survival. Key secondary endpoints include investigator-assessed EFS, safety and patient reported outcomes. Exploratory biomarkers will also be assessed. Citation Format: Deborah J. Wong, Jerome Fayette, Ye Guo, Matthew Kowgier, Ezra Cohen, Ricard Mesia Nin, Arunee Dechaphunkul, Kumar Prabhash, Jessica Geiger, Sarwan Bishnoi, Henning Schafer, Christina Matheny, Fairooz Kabbinavar, Alan Sandler, David Raben, Robert Haddad. IMvoke010: Randomized Phase III study of atezolizumab as adjuvant monotherapy after definitive therapy of squamous cell carcinoma of the head and neck (SCCHN) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT123.

EP-2026 Diffusion weighted textural differences between p16 positive and negative oropharyngeal carcinoma

EP-2026 Diffusion weighted textural differences between p16 positive and negative oropharyngeal carcinoma

Human papillomavirus 16 and p16 positive nasal cutaneous squamous cell carcinoma in immunocompetent men in their twenties

Cutaneous squamous cell carcinoma is usually associated with long-term ultraviolet light exposure. Human papillomavirus 16 is a high-risk mucosal human papillomavirus type, usually associated with anogenital and oropharyngeal cancer. This paper describes the first two cases of human papillomavirus 16 and p16 related nasal cutaneous squamous cell carcinoma. Prospective case series from December 2015. Two young, male, fair-skinned patients had large (greater than 20 mm), rapidly growing, ulcerated lesions of the nasal tip. The tumours were excised, with at least a 6 mm margin, and the patients' noses were subsequently reconstructed. Neither patient had cervical lymphadenopathy or underwent adjuvant radiotherapy. Both patients were registered at the same general practice. The tumours were human papillomavirus 16 and p16 positive; the latter indicated that the virus was driving the disease process. Except for superficial burns, neither patient had other risk factors. Changes in sexual practices have led to an increase in human papillomavirus positive oropharyngeal carcinoma and there may be an associated increase in human papillomavirus type 16 positive nasal cutaneous squamous cell carcinoma.

An evaluation of the significance of surgical margin in p16 positive oropharyngeal carcinoma

An evaluation of the significance of surgical margin in p16 positive oropharyngeal carcinoma

Impact of Smoking on Outcomes of HPV-related Oropharyngeal Cancer Treated with Primary Radiation or Surgery

Tobacco exposure is known to affect the biological behavior of human papilloma virus (HPV)-positive oropharyngeal carcinoma (OPC) with intermediate outcomes relative to tumors that are HPV associated with no smoking exposure and smoking-related HPV-negative tumors. We aim to evaluate the impact of smoking on the outcomes of patients with HPV-associated locally advanced OPC when stratified by treatment modality. A retrospective chart review was undertaken for 352 patients with known p16-overexpressing locally advanced OPC who were managed with curative-intent therapy from 2006 to 2015. The impact of smoking status on overall survival (OS) and recurrence-free survival were compared using the Kaplan-Meier method. Of the 352 patients, 67.6% (n=238) were managed with primary chemoradiation therapy (CRT) and 32.4% (n=114) with primary surgery±adjuvant therapy. The median smoking pack-year was 15. Twenty-seven percent of patients were active smokers at the time of presentation, with 40.3% identifying as former smokers and 32.7% having never smoked. Median follow-up for surviving patients was 4.2years. Current smokers had a significantly worse relapse-free survival and OS compared with never and former smokers (P=.03 and P=.0001, respectively), with outcomes significantly worsening with increasing smoking exposure. The 5-year OS for more than 10, 20, and 30 pack-year smoking history was 73.2%, 64.7%, and 59.1%, respectively. Current smokers managed with CRT had a 5-year OS of 64.2% compared with former and never smokers (93.1% and 78.2%, respectively). For current smokers managed primarily by surgery the 5-year OS was 57.6% compared with former and never smokers (69.6% and 73.5%, respectively). Current smokers and those with higher smoking exposure had poorer outcomes irrespective of their primary modality of treatment. Although not the specific focus of the study, definitive CRT appeared to at least be equivalent to surgery with respect to disease outcomes for patients with HPV-associated oropharyngeal cancer, regardless of smoking status.