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Oropharyngeal Cancer

3 sections of the pharnx The oropharynx is the middle part of the pharynx (throat) behind the mouth. It is important for speach and swallowing. The oropharynx includes the soft palate, base of the tongue, side walls of the throat and the posterior pharyngeal wall. Oropharyngeal cancer occurs when the cells of the oropharynx become abnormal and start growing in an uncontrolled way. The majority of oropharyngeal cancers are squamous cell carcinomas (squamous cells are the thin, flat cells in the lining of the oropharynx), but there are a number of other different types.

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Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Megwalu UC, Ma Y
Racial Disparities in Oropharyngeal Cancer Stage at Diagnosis.
Anticancer Res. 2017; 37(2):835-839 [PubMed] Related Publications
AIM: To evaluate the impact of race on disease stage at diagnosis in patients with oropharyngeal cancer.
PATIENTS AND METHODS: The cohort included 18,791 adult patients diagnosed with oropharyngeal squamous cell carcinoma between 2004 and 2012, from the Surveillance, Epidemiology, and End Results 18 Database.
RESULTS: After adjusting for age, sex, marital status, tumor site, and year of diagnosis, black race was associated with increased risk of presenting with Stage III or IV disease (OR 1.24, p=0.016), T3 or T4 tumors (OR 2.16, <0.001), distant metastasis (OR 2, p<0.001), and unresectable tumors (OR 1.65, p<0.001). Race was not associated with risk of presenting with nodal metastasis diagnosis (OR 0.93, p=0.241).
CONCLUSION: Black race is associated with increased risk of advanced disease presentation in oropharyngeal cancer.

Hoch S, Thelen K, Vorwerk H, et al.
Impact of Different Treatment Concepts on Regional Failure in Advanced Oropharyngeal Cancer.
Anticancer Res. 2017; 37(2):727-734 [PubMed] Related Publications
BACKGROUND: The management of patients with advanced oropharyngeal cancer is complex and mostly requires a multidisciplinary treatment approach. In general, organ preservation by primary concurrent radiochemotherapy (RCT), or surgery completed by adjuvant radiotherapy are established treatment strategies for these patients. However, it is unclear if primary treatment has an effect on regional tumor control. The purpose of the present study was to evaluate the regional control after different treatment concepts.
PATIENTS AND METHODS: Clinical data, including histological and radiological results, of 82 patients with T2-T3 oropharyngeal cancer and N2 neck were retrospectively analyzed. They underwent either RCT with salvage neck dissection (ND) (n=45), or primary transoral surgery with ND and adjuvant RCT (n=37). In all cases, the primary tumor was successfully treated, without evidence of local failure in the follow-up.
RESULTS: Overall, 11 (13.4%) patients developed regional failure during the follow-up. There were no significant differences in frequency of regional failure (p=0.75), distant metastasis (p=0.35) and overall survival (p=0.22) between treatment groups. However, 5-year disease-free survival was significantly worse (39.0% vs. 57.0%) for patients treated by RCT, with more frequent regional failure detected compared to surgically-treated patients in univariate analysis (p=0.04).
CONCLUSION: Treatment concept does not seem to affect regional tumor control in advanced oropharyngeal cancer after successful treatment of the primary tumor.

Sera T, Kashiwagi S, Takashima T, et al.
Multiple metastatic malignant phyllodes tumor of the breast with tonsillar metastasis: a case report.
BMC Res Notes. 2017; 10(1):55 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Tonsillar metastasis is very rare and accounts for only 0.8% of tonsillar tumors. And phyllodes tumor of the breast with tonsillar metastasis is very rare.
CASE PRESENTATION: A 57-year-old Japanese woman received surgery (partial mastectomy) of malignant phyllodes tumor. Seven months after initial surgery, pharyngeal pain, swelling, and a feeling of dyspnea developed, and tumor was found in the left palatine tonsil. Computed tomography for further evaluation showed a tonsillar lesion with contrast enhancement, and tonsillar metastasis was suspected. The metastatic lung tumors had not progressed. Laryngoscopic biopsy showed a tonsillar metastasis from the malignant phyllodes tumor. Despite the diagnosis of malignant phyllodes tumor with tonsillar and pulmonary metastases, the patient refused further treatment and died about 1 month later.
CONCLUSIONS: A patient with a malignant phyllodes tumor of the breast and tonsillar metastasis was reported, along with a discussion of the relevant literature of this very rare pattern of metastasis.

Howard J, Masterson L, Dwivedi RC, et al.
Minimally invasive surgery versus radiotherapy/chemoradiotherapy for small-volume primary oropharyngeal carcinoma.
Cochrane Database Syst Rev. 2016; 12:CD010963 [PubMed] Related Publications
BACKGROUND: More than 400,000 cases of oropharyngeal squamous cell carcinoma (OPSCC) are diagnosed each year worldwide and the incidence is rising, partly as a result of human papillomavirus. Human papillomavirus-associated OPSCC affects younger patients and often presents at a higher stage; however, it is associated with a better prognosis.Until recently, first-line management of OPSCC involved chemoradiotherapy, as research had demonstrated comparable survival outcomes when compared with open surgery, with significantly decreased morbidity. However, interventions have now evolved with computerised planning and intensity-modulated radiotherapy, and the advent of endoscopic head and neck surgery, which provide the potential for decreased treatment-associated morbidity.The oropharynx plays an essential role in swallowing, speech and protecting the airway as it is situated at the bifurcation of the respiratory and digestive tracts. Treatment modality recommendations are based on survival outcomes. Given the younger patient demographic, establishing the safety of modalities that potentially have better functional outcome is becoming increasingly important.
OBJECTIVES: To assess the efficacy of endoscopic head and neck surgery (transoral robotic surgery or transoral laser microsurgery) for small-volume, primary (T1-2, N0-2) oropharyngeal squamous cell carcinoma (OPSCC) in comparison to radiotherapy/chemoradiotherapy.
SEARCH METHODS: The Cochrane ENT Information Specialist searched the ENT Trials Register; Central Register of Controlled Trials (CENTRAL 2016, Issue 10); PubMed; EMBASE; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 8 November 2016.
SELECTION CRITERIA: Randomised controlled trials in patients with carcinoma in the oropharynx subsite (as defined by the World Health Organization classification C09, C10). Cancers included were primary squamous cell carcinomas arising from the oropharyngeal mucosa. The tumours were classified as T1-T2 with or without nodal disease and with no evidence of distant metastatic spread. The intervention was transoral, minimally invasive surgery with or without adjuvant radiotherapy or adjuvant chemoradiotherapy. The comparator was primary radiotherapy with or without induction or concurrent chemotherapy for the tumour. The treatments received and compared were of curative intent and patients had not undergone prior intervention, other than diagnostic biopsy.
DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. Our primary outcomes were overall survival (disease-related mortality was to be studied where possible), locoregional control, disease-free survival and progression-free survival or time to recurrence. All outcomes were to be measured at two, three and five years after diagnosis. Our secondary outcomes included quality of life, harms associated with treatment, patient satisfaction and xerostomia score.
MAIN RESULTS: No completed studies met the inclusion criteria for the review. Two ongoing trials fulfilled the selection criteria, however neither are complete.'Early-stage squamous cell carcinoma of the oropharynx: radiotherapy versus trans-oral robotic surgery (ORATOR)' is a phase II randomised controlled trial comparing primary radiation therapy with primary transoral robotic surgery for small-volume primary (T1-2, N0-2) OPSCC. It is currently in progress with an estimated completion date of June 2021.'European Organisation for Research and Treatment of Cancer 1420 (EORTC 1420-HNCG-ROG)' is a phase III, randomised study assessing the "best of" radiotherapy compared to transoral robotic surgery/transoral laser microsurgery in patients with T1-T2, N0 squamous cell carcinoma of the oropharynx and base of tongue. It was due to start accrual mid-2016.
AUTHORS' CONCLUSIONS: The role of endoscopic head and neck surgery in the management of OPSCC is clearly expanding as evidenced by its more overt incorporation into the current National Comprehensive Cancer Network guidelines. Data are mounting regarding its outcomes both in terms of survival and lower morbidity. As confidence increases, it is being used in the management of more advanced OPSCC.Based on this review, there is currently no high-quality evidence from randomised controlled trials regarding clinical outcomes for patients with oropharyngeal cancer receiving endoscopic head and neck surgery compared with primary chemoradiotherapy.

DE Felice F, Abate G, Galdieri A, et al.
Impact of Induction Chemotherapy in Locally Advanced HPV-negative Oropharyngeal Cancer. A Propensity Score-matched analysis.
Anticancer Res. 2016; 36(12):6667-6672 [PubMed] Related Publications
AIM: To estimate the clinical outcomes of induction chemotherapy (IC) followed by standard chemoradiotherapy (CRT) and CRT alone in patients with locally advanced human papilloma virus (HPV)-negative oropharyngeal squamous cell carcinoma.
PATIENTS AND METHODS: Consecutive patients with histologically-proven HPV-negative squamous cell carcinoma of the oropharynx were included and treated with IC-CRT or CRT alone. In order to compare treatment outcomes and toxicity between groups, patients were matched by primary tumor site and clinical disease stage. Overall survival (OS), disease-free survival (DFS) and metastasis-free survival (MFS) curves were calculated with the Kaplan-Meier method.
RESULTS: Nine IC patients and 18 CRT patients were included. All patients completed the programmed treatment. The median follow-up was 38 months. There were no statistically significant differences in OS and DFS between groups. The 5-year MFS was 88.9% and 50.8% in the IC-CRT group, respectively. There was no meaningful difference in toxicity between patients.
CONCLUSION: In HPV-negative patients with locally advanced oropharyngeal cancer, adding IC to standard CRT may increase the MFS rate. However no significant differences in OS and DFS were observed. More studies are needed to better elucidate the role of IC in this setting.

Toman J, Von Larson S, Umeno H, et al.
HPV-Positive Oropharyngeal Cancer Via p16 Immunohistochemistry in Japan.
Ann Otol Rhinol Laryngol. 2017; 126(2):152-158 [PubMed] Related Publications
OBJECTIVES: Human papillomavirus (HPV) has emerged as a driving cause of head and neck cancer, but investigations outside the West are limited. A p16 immunohistochemistry is a commonly used biomarker for HPV cancers. We sought to investigate the pathology and rates of HPV head and neck oropharyngeal cancer in Japan via p16 immunohistochemistry at 2 institutions in Japan.
METHODS: Fifty-nine oropharyngeal specimens from 2 university hospitals in Japan were examined for morphology and p16 immunohistochemistry. The rate of p16 positivity was then determined, and the 2 groups were compared for differences in age, smoking history, gender, and stage of presentation and mortality.
RESULTS: The rate of p16 positivity among the oropharyngeal specimens was 29.5%. There were important differences in the pathology compared to morphology usually seen in the US. The patients with p16+ cancer tended to be younger. There was no significant difference in smoking status. Patients with p16+ cancers trended toward better survival.
CONCLUSION: There appears to be a geographical difference in HPV rates of oropharyngeal cancers with persistently lower rates in Asian countries when compared to Western Europe and the US. Conclusions about HPV head and neck squamous cell carcinoma (HNSCC) in Western countries may not be generalizable across the globe at this time.

Shimura E, Hama T, Suda T, et al.
The Presence of HPV DNA in Neck Lymph Node Metastasis Correlates with Improved Overall Survival of Patients with Oropharyngeal Cancer Undergoing Surgical Treatment.
Oncology. 2017; 92(2):87-93 [PubMed] Related Publications
BACKGROUND: Few studies have addressed how human papilloma virus (HPV) infection in oropharyngeal squamous cell carcinoma (OPSCC) affects the outcome of surgical therapy; furthermore, the relationship between the presence of HPV DNA and neck lymph node (LN) metastasis has not been well established.
METHODS: A total of 65 patients who underwent surgery as a first-line therapy for OPSCC were enrolled in this study. In HPV-positive patients, the presence of HPV DNA in metastatic neck LN lesions was evaluated.
RESULTS: The HPV-positive patients had significantly better overall survival than the HPV-negative patients (log-rank test, p = 0.04), whereas HPV infection status did not significantly affect disease-free survival (log-rank test, p = 0.65). In all of the HPV-positive OPSCC patients who developed cervical LN metastasis, the same HPV DNA type was found in both the primary tumour and the metastases.
CONCLUSIONS: The present results suggest that HPV infection is a determining factor for good prognosis in patients undergoing first-line surgical therapy for OPSCC.

Hamilton D, Khan MK, O'hara J, Paleri V
The changing landscape of oropharyngeal cancer management.
J Laryngol Otol. 2017; 131(1):3-7 [PubMed] Related Publications
BACKGROUND: Oropharyngeal cancer is increasing in prevalence in the UK and this is thought to be due to the emergence of disease related to human papilloma virus.
METHOD: A literature review was conducted on the diagnosis and latest management of oropharyngeal cancer.
RESULTS: In non-smokers, human papilloma virus related disease is thought to have better outcomes, but this casts doubt on previous research which did not stratify patients according to human papilloma virus status. However, this theory provides a route for researchers to risk stratify and de-escalate treatments, and hence reduce treatment burden. In addition, the emergence of minimally invasive transoral techniques allows surgeons to remove large tumours without many of the side effects associated with radical (chemo)radiotherapy.
CONCLUSION: The emergence of human papilloma virus related disease and minimally invasive techniques have led the clinical and academic community to reconsider how oropharyngeal cancer is managed. Comparative and risk-stratification trials are urgently required and ongoing.

Mehanna H, Evans M, Beasley M, et al.
Oropharyngeal cancer: United Kingdom National Multidisciplinary Guidelines.
J Laryngol Otol. 2016; 130(S2):S90-S96 [PubMed] Free Access to Full Article Related Publications
This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. There has been significant debate in the management of oropharyngeal cancer in the last decade, especially in light of the increased incidence, clarity on the role of the human papilloma virus in this disease and the treatment responsiveness of the human papilloma virus positive cancers. This paper discusses the evidence base pertaining to the management of oropharyngeal cancer and provides recommendations on management for this group of patients receiving cancer care. Recommendations • Cross-sectional imaging is required in all cases to complete assessment and staging. (R) • Magnetic resonance imaging is recommended for primary site and computed tomography scan for neck and chest. (R) • Positron emission tomography combined with computed tomography scanning is recommended for the assessment of response after chemoradiotherapy, and has a role in assessing recurrence. (R) • Examination under anaesthetic is strongly recommended, but not mandatory. (R) • Histological diagnosis is mandatory in most cases, especially for patients receiving treatment with curative intent. (R) • Oropharyngeal carcinoma histopathology reports should be prepared according to The Royal College of Pathologists Guidelines. (G) • Human papilloma virus (HPV) testing should be carried out for all oropharyngeal squamous cell carcinomas as recommended in The Royal College of Pathologists Guidelines. (R) • Human papilloma virus testing for oropharyngeal cancer should be performed within a diagnostic service where the laboratory procedures and reporting standards are quality assured. (G) • Treatment options for T1-T2 N0 oropharyngeal squamous cell carcinoma include radical radiotherapy or transoral surgery and neck dissection (with post-operative (chemo)radiotherapy if there are adverse pathological features on histological examination). (R) • Transoral surgery is preferable to open techniques and is associated with good functional outcomes in retrospective series. (R) • If treated surgically, neck dissection should include levels II-IV and possibly level I. Level IIb can be omitted if there is no disease in level IIa. (R) • If treated with radiotherapy, levels II-IV should be included, and possibly level Ib in selected cases. (R) • Altering the modalities of treatment according to HPV status is currently controversial and should be undertaken only in clinical trials. (R) • Where possible, patients should be offered the opportunity to enrol in clinical trials in the field. (G).

Dale OT, Sood S, Shah KA, et al.
Long-term survival outcomes in patients with surgically treated oropharyngeal cancer and defined human papilloma virus status.
J Laryngol Otol. 2016; 130(11):1048-1053 [PubMed] Related Publications
OBJECTIVE: This study investigated long-term survival outcomes in surgically treated oropharyngeal cancer patients with known human papilloma virus status.
METHODS: A case note review was performed of all patients undergoing primary surgery for oropharyngeal cancer in a single centre over a 10-year period. Human papilloma virus status was determined via dual modality testing. Associations between clinicopathological variables and survival were identified using a log-rank test.
RESULTS: Of the 107 cases in the study, 40 per cent (n = 41) were human papilloma virus positive. The positive and negative predictive values of p16 immunohistochemistry for human papilloma virus status were 57 per cent and 100 per cent, respectively. At a mean follow up of 59.5 months, 5-year overall and disease-specific survival estimates were 78 per cent and 69 per cent, respectively. Human papilloma virus status (p = 0.014), smoking status (p = 0.021) and tumour stage (p = 0.03) were significant prognostic indicators.
CONCLUSION: The long-term survival rates in surgically treated oropharyngeal cancer patients were comparable to other studies. Variables including human papilloma virus status and tumour stage were associated with survival in patients treated with primary surgery; however, nodal stage and presence of extracapsular spread were non-prognostic.

Nico L, Cester G, Viaro F, et al.
Endovascular recanalization of the common carotid artery in a patient with radio induced chronic occlusion.
BMJ Case Rep. 2016; 2016 [PubMed] Related Publications
Recanalization of chronic occlusion of the common carotid artery (CCA) in patients with a history of neck irradiation is challenging, both for vascular surgeons and interventional neuroradiologists. We describe a case of successful stenting of radio induced chronic occlusion of the right CCA in a 41-year-old patient with neurological deterioration and minor stroke due to cerebral hypoperfusion caused by concomitant bilateral arterial occlusions. Direct surgery and surgical bypass were considered contraindicated. The endovascular approach was successful and required multiple precautions during the procedure. We describe particular solutions, not used in day to day practice, that allowed us to carry out the endovascular treatment in this unusual situation.

Megwalu UC
Exploring the Use of Oropharyngeal Cancer Histology to Account for HPV Status in Population-based Studies.
Anticancer Res. 2016; 36(10):5515-5518 [PubMed] Related Publications
AIM: To assess whether poorly differentiated tumors and non-keratinizing tumors have similar demographic and clinical characteristics as human papilloma virus (HPV)-positive tumors in patients with oropharyngeal cancer.
PATIENTS AND METHODS: The study cohort included patients diagnosed with oropharyngeal squamous cell carcinoma between 2004 and 2012 identified in the Surveillance, Epidemiology, and End Results 18 Database.
RESULTS: Poorly differentiated tumors were associated with early T stage (odds ratio (OR)=1.23), nodal metastasis (OR=1.66) and tonsil fossa origin (OR=1.22). Non-keratinizing tumors were associated with early T stage (OR=1.23), nodal metastasis (OR=1.66) and tonsil fossa origin (OR=1.22). Poorly differentiated tumors were associated with improved overall survival (OS) (hazard ratio (HR)=0.78, p<0.001). Non-keratinizing tumors were associated with improved OS (HR=0.71, p<0.001).
CONCLUSION: Histological grade and keratinization may be useful surrogates to adjust for the effects of HPV status in oropharyngeal cancer studies utilizing population-based cancer databases.

Okano Y, Satoh T, Horiguchi K, et al.
Nivolumab-induced hypophysitis in a patient with advanced malignant melanoma.
Endocr J. 2016; 63(10):905-912 [PubMed] Related Publications
The anti-programmed cell death-1 monoclonal antibody (mab), nivolumab has recently been approved for the treatment of unresectable or metastatic malignant melanoma and non-small-cell lung cancers in Japan. Ipilimumab, an anti-cytotoxic T lymphocyte antigen-4 mab for malignant melanoma that was approved earlier than nivolumab in Western countries, is known to frequently cause endocrine immune-related adverse events such as hypophysitis and thyroid dysfunction. We herein report a patient with advanced melanoma who appeared to develop hypophysitis as a consequence of the inhibition of PD-1 by nivolumab. One week after the 6(th) administration of nivolumab, the patient developed progressive fatigue and appetite loss. Laboratory data on admission for the 7(th) administration of nivolumab showed eosinophilia and hyponatremia. Since ACTH and cortisol levels were low, nivolumab was discontinued and a large dose of hydrocortisone (100 mg/d) was promptly administered intravenously. A magnetic resonance imaging scan revealed the mild enlargement of the anterior pituitary gland and thickening of the stalk with homogenous contrast. A detailed assessment of anterior pituitary functions with hypothalamic hormone challenges showed that hormonal secretions other than ACTH and TSH were normal. With a replacement dose of hydrocortisone (20 mg/d), the 7(th) administration of nivolumab was completed without exacerbating the patient's general condition. The present report provides the first detailed endocrinological presentation of nivolumab-induced hypophysitis showing the enlargement of the pituitary gland and stalk in a malignant melanoma patient in Japan. Oncologists and endocrinologists need to be familiar with potentially life-threatening hypophysitis induced by immune-checkpoint inhibitors.

Mehanna H
Update on De-intensification and Intensification Studies in HPV.
Recent Results Cancer Res. 2017; 206:251-256 [PubMed] Related Publications
In this chapter, we discuss de-esclation of treatment for patients with HPV-positive disease. We discuss the rationale for de-escalation (why de-escalate?), patient selection criteria (who to de-esclate?) and what the treatment options for de-esclation are and the studies that are currently being run in those areas (how to de-escalate?). We stress the importance of clinicians NOT changing the management of oropharyngeal cancer patients outside clinical trials, and encourage them to recruit to the ongoing studies.

Gross ND, Hanna EY
The Role of Surgery in the Management of Recurrent Oropharyngeal Cancer.
Recent Results Cancer Res. 2017; 206:197-205 [PubMed] Related Publications
The incidence of oropharyngeal squamous cell carcinoma (OPSCC) continues to rise worldwide at a dramatic pace, buoyed by the predominance of human papilloma virus (HPV) driven disease (Panwar et al. 2014). While the outcomes of patients with HPV-positive OPSCC are dramatically improved compared to HPV-negative OPSCC, treatment failures do occur. The result is an inevitable rise in the incidence of recurrent OPSCC. Since the majority of incident OPSCC cases are treated with some form of radiation therapy (primary or adjuvant), surgery remains the backbone of treatment for recurrent OPSCC. This section will focus on options for surgical management of recurrent OPSCC.

Golusinski W
The Role of Conventional Surgery in Oropharyngeal Cancer.
Recent Results Cancer Res. 2017; 206:185-195 [PubMed] Related Publications
Anatomically, the oropharynx can be divided into four subsites: the soft palate, pharyngeal wall, base of tongue, and the tonsillar complex. Surgical access to these tumours is often challenging due to the anatomic localization. For this reason, such tumours were traditionally managed with open surgical techniques, usually involving a mandibulotomy, to provide better visualization and access to the oropharynx, followed by free-flap reconstruction of the oropharyngeal defect. However, the invasiveness of this approach could lead to significant morbidity, including speech, swallowing, and airway dysfunction, in addition to poor cosmetic outcomes. In response, less invasive approaches (Mercante et al. 2013) have been developed including minimally invasive surgical approaches (chiefly transoral surgery) as well as non-surgical methods, primarily radiotherapy, and chemotherapy (Mercante et al. 2013).

Dietz A, Wichmann G, Wiegand S
Should We De-escalate the Treatment for HPV-Positive Tumors?
Recent Results Cancer Res. 2017; 206:173-181 [PubMed] Related Publications
De-escalation or de-intensification of therapy is discussed since many retrospective analyses of former trials demonstrated significantly better outcome for patients suffering from p16/HPV16-positive oropharyngeal squamous cell carcinoma of head and neck (OHNSCC). These observations are comprehensively addressed, but the reader has to keep in mind that none of the currently discussed data result from prospective controlled trials addressing the HPV-discrimination in the primary endpoint design. Identification of the true HPV16-related tumors is still challenging and in addition with different clinical reports and lack of data of prospective trials not mature for routine clinical decision making in 2016. Independent of the currently lacking evidence for HPV-dependent treatment de-escalation, there are some relevant arguments to address this question in ongoing and future trials.

Langendijk JA, Steenbakkers RJ
Optimizing Radiotherapy in HPV-Associated Oropharyngeal Cancer Patients.
Recent Results Cancer Res. 2017; 206:161-171 [PubMed] Related Publications
Concurrent chemoradiation is considered the golden standard in the treatment of locally advanced OPC. However, given the very high survival rates in favorable HPV-positive OPC and the high rates of acute and late treatment-related side effects, de-escalation strategies have to be considered. In this chapter, the potential benefit of a number of de-escalation strategies is described, including of replacement of concurrent chemotherapy by cetuximab, radiation dose de-escalation based on response to induction chemotherapy, radiotherapy alone without systemic treatment, and limiting elective nodal target volumes for radiation. In addition to de-escalation, modern radiation technologies like protons will offer increasing opportunities to decrease the dose to normal tissues in order to prevent radiation-induced toxicities. Initial analysis showed that radiation dose de-escalation based on response to induction chemotherapy in combination with intensity-modulated proton therapy (IMPT) has the highest potential to decrease acute and late toxicities.

Wittekindt C, Klussmann JP
Tumor Staging and HPV-Related Oropharyngeal Cancer.
Recent Results Cancer Res. 2017; 206:123-133 [PubMed] Related Publications
The current TNM staging for oropharyngeal cancer (OSCC) was designed empirically for non-HPV-related disease. Emerging evidence suggests it is unsuited for Human papillomavirus (HPV)-related OSCC. Patients with HPV-positive tumors have improved prognosis, despite presenting at advanced stages. These shortcomings of the current staging system have been identified in single- and multi-institutional trials. Patients with HPV related OSCC typically present with advanced N-stages leading to higher stage groupings. A rarity of stages I and II therefore represents the nature of HPV-related OSCC. Concerning prognosis of the patients, N-category and extracapsular spread seem to be of minor importance, whereas advanced T-stages result in unfavourable outcome. Anatomical staging therefore has been implied into different proposals to prognostic risk classifications in HPV-related disease as an additive compound. Prognostic risk groupings are further enhanced by incorporating non-anatomical factors. To summarize, it can be suggested that the current TNM system alone has little prognostic value in HPV-related OSCC.

Golusinski P
Risk Factors for Oral Infection with Human Papillomavirus.
Recent Results Cancer Res. 2017; 206:73-85 [PubMed] Related Publications
Human papillomavirus has been identified as a causative factor for a subset of head and neck carcinomas (HNSCC). The majority of the HPV-positive tumors arises in the oropharyngeal region, and at present, the infection of the human papilloma type 16 is the major cause of the oropharyngeal cancer development. Patients with HPV DNA-positive tumors have been shown to be younger in age and are less likely to have a history of tobacco smoking or alcohol use. The tumors referred to the HPV positivity have been proven to more likely confer better prognosis. Seven percent of the population between ages of 14 and 69 are infected by HPV at any given time within the oral mucosa. However, only about 1 % of those infections is associated with the high-risk cancerogenous types of the virus. Up to date few risk factors of HPV infection have been identified including age, gender and the sexual behavior. Tobacco smoking and immunosuppression have also been reported to play a role in HPV infection.

Chen F, Chen C, Qu Y, et al.
Selenium-binding protein 1 in head and neck cancer is low-expression and associates with the prognosis of nasopharyngeal carcinoma.
Medicine (Baltimore). 2016; 95(35):e4592 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Selenium-binding protein 1 (SELENBP1) expression is reduced markedly in many types of cancers and low SELENBP1 expression levels are associated with poor patient prognosis.
METHODS: SELENBP1 gene expression in head and neck squamous cell carcinoma (HNSCC) was analyzed with GEO dataset and characteristics of SELENBP1 expression in paraffin embedded tissue were summarized. Expression of SELENBP1 in nasopharyngeal carcinoma (NPC), laryngeal cancer, oral cancer, tonsil cancer, hypopharyngeal cancer and normal tissues were detected using immunohistochemistry, at last, 99 NPC patients were followed up more than 5 years and were analyzed the prognostic significance of SELENBP1.
RESULTS: Analysis of GEO dataset concluded that SELENBP1 gene expression in HNSCC was lower than that in normal tissue (P < 0.01), but there was no significant difference of SELENBP1 gene expression in different T-stage and N-stage (P > 0.05). Analysis of pathological section concluded that SELENBP1 in the majority of HNSCC is low expression and in cancer nests is lower expression than surrounding normal tissue, even associated with the malignant degree of tumor. Further study indicated the low SELENBP1 expression group of patients with NPC accompanied by poor overall survival and has significantly different comparing with the high expression group.
CONCLUSION: SELENBP1 expression was down-regulated in HNSCC, but has no associated with T-stage and N-stage of tumor. Low expression of SELENBP1 in patients with NPC has poor over survival, so SELENBP1 could be a novel biomarker for predicting prognosis.

Lybak S, Ljøkjel B, Haave H, et al.
Primary surgery results in no survival benefit compared to primary radiation for oropharyngeal cancer patients stratified by high-risk human papilloma virus status.
Eur Arch Otorhinolaryngol. 2017; 274(1):477-487 [PubMed] Related Publications
We changed the primary oropharynx squamous cell carcinoma (OPSCC) treatment recommendation from primary radiation therapy (RT) to tumor surgery and neck dissection, followed by RT around the year 2000 with apparently improved survival. However, high-risk human papilloma virus (hr-HPV)-16-caused OPSCCs have increased during this period. Furthermore, hr-HPV+ OPSCC carry a better prognosis than hr-HPV-negative patients. We have, therefore, evaluated the 5-year survival in the period from 1992 to 1999 versus 2000 to 2008 stratified by hr-HPV tumor infection status. Ninety-six OPSCC patients were treated from 1992 to 1999 compared with 136 patients from 2000 to 2008. The 5-year disease-specific survival (DDS) and overall survival (OS) were recorded, while the health-related quality of life (HRQoL) scores were obtained from some of the cured patients. Thirty-eight (40 %) in the first period and 86 OPSCCs (63 %) in the second period were hr-HPV+. In the first period, 16 versus 62 patients in the last period were treated by neck dissection, primary tumor surgery, and RT. DSS among all the hr-HPV-negative patients in the first period was 51 versus 55 % in the second period, and the corresponding OS was 33 versus 31 %, respectively. The DSS among all the hr-HPV+ patients was 78 % in the first period versus 77 % in the second period, while the OS was 71 versus 69 %, respectively. The HRQoL scores among successfully treated patients were worse following surgery, plus RT than RT only. The hr-HPV-adjusted 5-year survival in OPSCC patients was similar between the two time periods. A decreased HRQoL was associated with surgical therapy, which indicates that hr-HPV+ OPSCC patients may be treated by primary RT followed by major surgery only if RT treatment fails.

Brown E, Owen R, Harden F, et al.
Head and neck adaptive radiotherapy: Predicting the time to replan.
Asia Pac J Clin Oncol. 2016; 12(4):460-467 [PubMed] Related Publications
AIM: Head and neck (H&N) cancer patients can undergo anatomical change throughout radiotherapy treatment. Adaptive radiotherapy (ART) is effective in addressing the impact of this change on the planned dose distribution. The aim of this study was to identify pretreatment factors that influence the need for and timing of replanning for patients receiving chemoradiotherapy for node-positive nasopharyngeal (NPC) and oropharyngeal carcinoma (OPC).
METHODS: Of 110 patients enrolled in a prospective H&N ART study, 21 (19%) underwent a second planning scan (re-CT) and were included in this review. Univariate and multivariate analysis was used to compare those patients who were replanned with those that were not. Factors influencing the timing of replanning were assessed including patient and tumor characteristics and structure volume details.
RESULTS: Of the five replanned patients, three were diagnosed with NPC (P = 0.06) and had significantly larger initial nodal volumes (median volume 140.3 cc vs. 39.1 cc, P = 0.019). Overall the median time of re-CT was significantly different between replanned and non-replanned patients, with replanned patients having an earlier re-CT: median fraction 18 versus fraction 23 (P = 0.01). Specifically, NPC patients who were replanned had a re-CT performed earlier than OPC patients (median fraction 11 vs. 20).
CONCLUSION: For H&N patients with large nodes receiving definitive chemoradiotherapy, replanning may be considered at the commencement of week 3 for NPC patients and in week 4 of treatment for OPC patients. This information may facilitate a forward planning approach to H&N ART that enables allocation of departmental resources prior to treatment commencement.

Nguyen NP, Nguyen LM, Thomas S, et al.
Oral sex and oropharyngeal cancer: The role of the primary care physicians.
Medicine (Baltimore). 2016; 95(28):e4228 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: We aimed to study the prevalence of oral sex and its possible association with human papillomavirus (HPV) 16 infection in the development of oropharyngeal cancer in the US population for possible prevention.
METHODS: We conduct a systemic review on the prevalence of oral sex among Americans among different age groups, the prevalence of HPV 16 infection reported in oropharyngeal cancer, and correlation between oral sex and oropharyngeal cancer.
RESULTS: Oral sex is prevalent among adolescents and sexually active adults. Sixty percent of oropharyngeal cancer reported in the United States is associated with HPV 16 infections. Individuals who practiced oral sex with multiple partners are at risk for developing oropharyngeal cancer and need to be informed about practicing safe sex or getting vaccination.
CONCLUSION: Family physicians will play a key role in prevention and educating the public about the risk of oral sex.

Zumsteg ZS, Cook-Wiens G, Yoshida E, et al.
Incidence of Oropharyngeal Cancer Among Elderly Patients in the United States.
JAMA Oncol. 2016; 2(12):1617-1623 [PubMed] Related Publications
Importance: An escalating incidence of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) has been reported predominantly among middle-aged adults. However, HPV infection is believed to occur many years before cancer develops, and tissue studies suggest that HPV DNA is found in the majority of OPSCC diagnosed in patients 65 years or older.
Objective: To update the trends in OPSCC incidence using US cancer registry data, with an emphasis on age-specific trends.
Design, Setting, and Participants: Data from the Surveillance, Epidemiology, and End Results (SEER) database (2000-2012) were queried to compare changes in incidence and survival trends in OPSCC with selected tobacco-related cancers (larynx, oral cavity, hypopharynx, lung) and an HPV-related cancer (anus). A total of 40 264 patients who received a diagnosis of OPSCC from 2000 to 2012 were included. Elderly patients were defined as those 65 years or older.
Main Outcomes and Measures: The annual percentage change in OPSCC incidence from 2000 to 2012, stratified according to age group.
Results: Among the 40 264 patients who received a diagnosis of OPSCC from 2000 to 2012, 13 313 (33.1%) were aged 65 years or older and 80.3% were male. Significant increases in the age-adjusted incidence of OPSCC were observed during the study period for both younger adults aged 45 to 64 years (annual percentage change [APC], 2.31; 95% CI, 1.76-2.86; P < .001) and patients 65 years or older (APC, 2.92; 95% CI, 2.32-3.51; P < .001). These changes were driven predominantly by base-of-tongue and tonsil cancers in men. Concomitantly, the incidence of tobacco-associated head and neck cancers decreased for elderly patients (larynx: APC, -1.54; 95% CI, -2.00 to -1.08; P < .001; oral cavity: APC, -1.23; 95% CI, -1.84 to -0.62; P = .001; hypopharynx: APC, -2.44; 95% CI, -3.01 to -1.86; P < .001), whereas the incidence of anal cancer significantly increased (APC, 4.42; 95% CI, 3.28 to 5.57; P < .001). Furthermore, improved overall and cause-specific survival over time were observed for both younger and elderly patients with OPSCC. Nevertheless, absolute cause-specific survival remained worse for elderly patients (3-year CSS, 60.8%; 95% CI, 59.6%-61.9%) in comparison with those aged 45 to 64 years (75.7%; 95% CI, 75.1%-76.4%; P < .001).
Conclusions and Relevance: The incidence of OPSCC is increasing among elderly patients in the United States, likely driven by HPV-associated cancers. Given the unique challenges related to treating elderly patients with OPSCC, their limited enrollment in clinical trials, and the aging US population, clinical studies investigating improved therapeutic strategies for elderly patients with HPV-positive OPSCC should be performed.

Cracchiolo JR, Roman BR, Kutler DI, et al.
Adoption of transoral robotic surgery compared with other surgical modalities for treatment of oropharyngeal squamous cell carcinoma.
J Surg Oncol. 2016; 114(4):405-11 [PubMed] Free Access to Full Article Related Publications
BACKGROUND AND OBJECTIVES: Transoral robotic surgery (TORS) has increased for treatment of oropharyngeal squamous cell carcinoma (OPSCC). To define the adoption of TORS, we analyzed patterns of surgical treatment for OPSCC in the US.
METHODS: Cases of T1-T3 OPSCC treated with surgery between 2010 and 2013 from the National Cancer Database were queried.
RESULTS: Of 3,071 patients who underwent primary surgical management for T1-T3 OPSCC, 846 (28%) underwent TORS. On multivariable analysis, low tumor stage (T2 vs. T1: OR 0.75, CI 0.37-0.51, P < 0.0001; T3 vs. T1: O.R. 0.33, CI 0.28-0.38, P < 0.0001), treatment at an academic cancer center (O.R. 2.23, C.I. 1.29-3.88, P = 0.004) and treatment at a high volume hospital (34-155 cases vs. 1-4 cases: O.R. 9.07, C.I. 3.19-25.79, P < 0.0001) were associated with increased TORS approach. Significant geographic variation was observed, with high adoption in the Middle Atlantic. Positive margin rates were lower when TORS was performed at a high volume versus low volume hospital (8.2% vs. 16.7% respectively, P = 0.001).
CONCLUSIONS: Tumor and non-tumor factors are associated with TORS adoption. This analysis suggests uneven diffusion of this technology in the treatment of OPSCC. J. Surg. Oncol. 2016;114:405-411. © 2016 Wiley Periodicals, Inc.

Okami K
Clinical features and treatment strategy for HPV-related oropharyngeal cancer.
Int J Clin Oncol. 2016; 21(5):827-835 [PubMed] Related Publications
Among head and neck squamous cell carcinoma (HNSCC), the incidence of oropharyngeal SCC (OPSCC) is increasing in contrast to carcinoma with origin in other subsites. Human papillomavirus (HPV) is now recognized as a significant risk factor of the carcinogenesis of OPSCC. The HPV-related OPSCC patients tend to be relatively young, less exposed to tobacco and alcohol, and have a relatively high socioeconomic status and education level, which is distinct from HPV-unrelated classical OPSCC. The neck metastases tend to be aggressive and cystic. The better response to treatment resulting in improved prognosis of HPV-related OPSCC led to reconsidering the clinical staging and treatment approaches. Clinical trials of treatment deintensification to reduce the acute and late toxicity without compromising efficacy have been conducted. This review of HPV-related OPSCC focuses on current and generally accepted facts regarding the biology, epidemiology, and therapeutic strategy of this new disease entity.

Costa EF, Santos ES, Liutti VT, et al.
Association between polymorphisms in genes related to DNA base-excision repair with risk and prognosis of oropharyngeal squamous cell carcinoma.
J Cancer Res Clin Oncol. 2016; 142(9):1917-26 [PubMed] Related Publications
PURPOSE: We examined the influence of OGG1 c.977C>G (rs1052133), APEX1 c.444T>G (rs1130409), XRCC1 c.-77T>C (rs3213245), c.580C>T (rs1799782), c.839G>A (rs25489) and c.1196G>A (rs25487) single-nucleotide polymorphisms (SNPs), involved in base-excision repair (BER) pathway, on oropharyngeal squamous cell carcinoma (OPSCC) risk and prognosis.
METHODS: Aiming to identify the genotypes, DNA from 200 consecutive OPSCC patients and 200 controls was analyzed by PCR-RFLP. The prognostic impact of genotypes of SNPs on progression-free survival (PFS) and overall survival of OPSCC patients was examined using the Kaplan-Meier estimates and Cox regression analyses.
RESULTS: XRCC1 c.580CT or TT genotypes (19.5 vs. 11.0 %, P = 0.04) and XRCC1 TTGG haplotype from c.-77T>C, c.580C>T, c.839G>A and c.1196G>A SNPs (17.5 vs. 10.0 %, P = 0.04) were more common in patients with OPSCC than in controls. Carriers of combined genotypes of c.580C>T and TTGG haplotype of XRCC1 gene were under 3.35- and 3.22-fold increased risk of OPSCC than others. For survival analysis, we selected only patients with tumor at stage IV. The median follow-up time was 24.5 months. At 24 months of follow-up, PFS was shorter in patients with OGG1 c.977CC genotype when compared with others genotypes (35.5 vs. 52.1 %, log-rank test, P = 0.03). After multivariate Cox analysis, patients with OGG1 c.977CC genotype had more chance to present tumor progression when compared with others (HR 1.68, P = 0.02).
CONCLUSIONS: Our data present, for the first time, evidence that inherited OGG1 c.977C>G; XRCC1 c.-77T>C, c.580C>T, c.839G>A and c.1196G>A abnormalities of DNA BER pathway are important determinants of OPSCC and predictors of patient outcomes.

Franzese C, Fogliata A, Franceschini D, et al.
Treatment: Outcome and Toxicity of Volumetric Modulated Arc Therapy in Oropharyngeal Carcinoma.
Anticancer Res. 2016; 36(7):3451-7 [PubMed] Related Publications
BACKGROUND/AIM: Radiotherapy is a common approach for treating squamous cell carcinoma (SCC) of the oropharynx. We aimed to analyze toxicity and outcome of patients affected by oropharyngeal SCC treated with volumetric modulated arc therapy (VMAT).
PATIENTS AND METHODS: Fifty-four patients presenting advanced orophayngeal carcinoma who were treated with radical radiotherapy were analyzed. All patients were treated with VMAT-RapidArc, with simultaneous integrated boost in 33 fractions for a dose of 69.96 Gy to the high-risk, and of 54.45 Gy to the low-risk volume.
RESULTS: Median follow-up was 23 months. In eight cases, locoregional relapse was observed (median time to relapse=10.7 months). Four among eight local recurrences appeared in the high-dose target volume. The 1- and 2-year actuarial disease-free survival rates were 88% and 80%, respectively. The 1- and 2-year actuarial overall survival rates were 94% and 87%, respectively.
CONCLUSION: VMAT for oropharyngeal SCC treatment is effective and safe, with interesting rates of control of disease and survival.

Morand GB, Madana J, Da Silva SD, et al.
Survival and quality of life in oropharyngeal cancer patients treated with primary chemoradiation after salivary gland transfer.
J Laryngol Otol. 2016; 130(8):755-62 [PubMed] Related Publications
OBJECTIVES: Salivary gland transfer surgery can reduce xerostomia in oropharyngeal squamous cell carcinoma patients undergoing primary chemoradiation. A potential drawback of salivary gland transfer is the treatment delay associated with the surgery, and its complications. This study aimed to determine whether the treatment delay affects patient survival and to evaluate patient quality of life after salivary gland transfer.
METHODS: A retrospective analysis of 138 patients (salivary gland transfer group, n = 58; non-salivary gland transfer group, n = 80) was performed. Patient survival was compared between these groups using multivariate analysis. Salivary gland transfer patients were further evaluated for surgical complications and for quality of life using the head and neck module of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire.
RESULTS: Salivary gland transfer and non-salivary gland transfer patients had comparable baseline clinical characteristics. Salivary gland transfer patients experienced a median treatment delay of 16.5 days before chemoradiation (p = 0.035). Multivariate analysis showed that this did not, however, correspond to a survival disadvantage (p = 0.24 and p = 0.97 for disease-free and disease-specific survival, respectively). A very low complication rate was reported for the salivary gland transfer group (1.7 per cent). Questionnaire scores for the item 'xerostomia' were very low in salivary gland transfer patients.
CONCLUSION: The treatment delay associated with salivary gland transfer surgery does not negatively affect patient survival. Oropharyngeal squamous cell patients have an excellent quality of life after salivary gland transfer.

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