Oropharyngeal Cancer
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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

Information Patients and the Public (8 links)


Information for Health Professionals / Researchers (4 links)

Latest Research Publications

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

Maiti PK, Ray A, Mitra TN, et al.
The effect of honey on mucositis induced by chemoradiation in head and neck cancer.
J Indian Med Assoc. 2012; 110(7):453-6 [PubMed]
The aim of this study was to evaluate the effect of pure natural honey on radiation-induced mucositis. Fifty-five patients diagnosed with head and neck cancer requiring radiation to the oropharyngeal mucosal area were divided into two groups (study arm-28 and control arm-27) to receive either chemoradiation or chemoradiation plus topical application of honey. Patients were treated using a telecobalt machine at 2 Gy per day, five times a week up to a total dose of 66 Gy. in the study arm, patients were advised to take 20 ml of honey 15 minutes before, 15 minutes after and similar amount at bed time. Patients were evaluated every week for the development of radiation mucositis using the WHO grading system. There was significant reduction in the symptomatic grades 3 and 4 mucositis in honey-treated patients compared to controls ie, 18% versus 41% for grade 3 and 4% versus 22% for grade 4 mucositis. Seventy-one per cent of patients treated with topical honey showed no change or a positive gain in body weight. In the control group also 22% had no weight loss, though none showed weight gain. Furthermore, it didn't affect blood sugar level when initial fasting blood sugar level was < 150 mg%. Honey is a cheap, simple, easily available and effective agent in reducing radiation-induced mucositis. Within the limits of this study the results showed the application of natural honey is effective in managing radiation induced mucositis, which warrants further multicentric randomised trials to validate the findings.


Park G, Lee SW, Kim SY, et al.
Can concurrent chemoradiotherapy replace surgery and postoperative radiation for locally advanced stage III/IV tonsillar squamous cell carcinoma?
Anticancer Res. 2013; 33(3):1237-43 [PubMed]
AIM: To compare surgery and postoperative radiotherapy (PORT) with the non-surgical combination of chemotherapy and radiation therapy (CCRT) for locally advanced squamous cell carcinoma (SCC) of the tonsil by measuring treatment outcomes and treatment-related complications.
PATIENTS AND METHODS: The records of 114 patients with non-metastatic stage III/IV tonsillar SCC treated between July, 1998 and December, 2010 were reviewed retrospectively. Among the 114 patients, 65 received PORT and 49 received CCRT. In the PORT group, treatment included wide surgical resection of the tumor with neck dissection and administration of PORT to the primary tumor bed with a median dose of 60 Gy. In the CCRT group, a median dose of 70 Gy was delivered to the gross tumor, and 46 patients received concurrent chemotherapy with i.v. cisplatin. The median follow-up time was 58 months in the PORT group and 44 months in the CCRT group.
RESULTS: There was no significant difference between PORT and CCRT in terms of 5-year locoregional recurrence-free survival (88.4% vs. 91.4%, p=0.68), distant metastasis-free survival (88.9% vs. 92.3%, p=0.60), disease-free survival (79.5% vs. 84.2%, p=0.63) or overall survival (78.9% vs. 88.9%, p=0.45). More CCRT patients than PORT patients experienced grade 3 (or higher) hematological toxicities and grade 2 pharyngitis during treatment. Chronic toxicity, manifested as swallowing difficulty, dry mouth and trismus, was similar between the two treatment groups.
CONCLUSION: CCRT provides similar levels of local and distant control in patients with locally advanced tonsillar SCC as PORT, yet fails to show any superiority in preserving functions such as swallowing, saliva production, and mastication.


Mizumoto M, Hashii H, Senarita M, et al.
Proton beam therapy for malignancy in Bloom syndrome.
Strahlenther Onkol. 2013; 189(4):335-8 [PubMed]
BACKGROUND AND PURPOSE: Bloom syndrome is a DNA repair disorder that is hypersensitive to radiotherapy. We describe the first case in which proton beam therapy (PBT) was used in a patient with Bloom syndrome to treat oropharyngeal cancer.
PATIENTS AND METHODS: The patient was a 32-year-old woman with Bloom syndrome who was diagnosed with oropharyngeal cancer staged as T2N2bM0 poorly differentiated squamous cell carcinoma. The primary tumor was located on the right tongue base and extended to the right lateral pharyngeal wall. Several right upper region lymph nodes were positive for metastases.
RESULTS: We selected PBT in anticipation of dose reduction to normal tissue. The clinical target volume was defined as the area of the primary tumor and lymph node metastases plus an 8-mm margin. After treatment with 36 GyE (Gray equivalent) in 20 fractions (4-5 fractions per week), dietary intake was decreased by mucositis and intravenous hyperalimentation was started. Termination of treatment for 2.5 weeks was required to relieve mucositis. Administration of 59.4 GyE in 33 fractions markedly reduced the size of the primary tumor, but also caused moderate mucositis that required termination of PBT. One month later, lung metastases and breast cancer developed and the patient died 9 months after PBT. At this time the reduction in size of the primary tumor was maintained without severe late toxicity.
CONCLUSION: We obtained almost complete response for a radiosensitive patient with a deficiency of DNA repair, indicating the excellent dose concentration of proton beam therapy.


Al-Mamgani A, van Rooij P, Verduijn GM, et al.
The impact of treatment modality and radiation technique on outcomes and toxicity of patients with locally advanced oropharyngeal cancer.
Laryngoscope. 2013; 123(2):386-93 [PubMed]
OBJECTIVES/HYPOTHESIS: To investigate the impact of treatment modality and radiation technique on oncologic outcomes and toxicity of patients with locally advanced oropharyngeal cancer (OPC).
STUDY DESIGN: Retrospective analysis of outcomes and toxicity.
METHODS: Between 2000 and 2011, 204 consecutive patients with locally advanced OPC were treated with definitive (chemo)radiotherapy using 3-dimensional conformal (3DCRT) or intensity-modulated radiotherapy (IMRT). Endpoints were local control (LC), regional control (RC), disease-free survival (DFS), cause-specific survival (CSS), and overall survival (OS), and toxicity.
RESULTS: After a median follow-up of 44 months (range 4-134), the 5-year Kaplan-Meier estimates of LC, RC, DFS, CSS, and OS were 78%, 92%, 60%, 64%, and 48%, respectively. Grade 3 mucositis and dysphagia (feeding-tube dependency) were reported in 75% and 65%, respectively. The overall incidence of grade ≥ 2 and grade 3 late toxicities were 44% and 16%, respectively. Dysphagia and xerostomia were the most frequently reported late toxicity. Chemotherapy was significantly predictive for improved outcomes and increased toxicity. IMRT was significantly correlated with reduced toxicity.
CONCLUSIONS: Compared to radiation alone, chemoradiotherapy significantly improved oncologic outcomes, but with significantly increased toxicity. Compared to 3DCRT, the introduction of IMRT resulted in a significant reduction of acute and late toxicity with slightly better, or at least comparable, outcomes. Despite the improvements achieved by the implementation of chemo-IMRT, different new strategies to further improve outcome and reduce toxicity need to be thoroughly investigated in prospective, preferably, randomized trials.


O'Sullivan B, Huang SH, Siu LL, et al.
Deintensification candidate subgroups in human papillomavirus-related oropharyngeal cancer according to minimal risk of distant metastasis.
J Clin Oncol. 2013; 31(5):543-50 [PubMed]
PURPOSE: To define human papillomavirus (HPV) -positive oropharyngeal cancers (OPC) suitable for treatment deintensification according to low risk of distant metastasis (DM).
PATIENTS AND METHODS: OPC treated with radiotherapy (RT) or chemoradiotherapy (CRT) from 2001 to 2009 were included. Outcomes were compared for HPV-positive versus HPV-negative patients. Univariate and multivariate analyses identified outcome predictors. Recursive partitioning analysis (RPA) stratified the DM risk.
RESULTS: HPV status was ascertained in 505 (56%) of 899 consecutive OPCs. Median follow-up was 3.9 years. HPV-positive patients (n = 382), compared with HPV-negative patients (n = 123), had higher local (94% v 80%, respectively, at 3 years; P < .01) and regional control (95% v 82%, respectively; P < .01) but similar distant control (DC; 90% v 86%, respectively; P = .53). Multivariate analysis identified that HPV negativity (hazard ratio [HR], 2.9; 95% CI, 2.0 to 5.0), N2b-N3 (HR, 2.9; 95% CI, 1.8 to 4.9), T4 (HR, 1.8; 95% CI, 1.2 to 2.9), and RT alone (HR, 1.8; 95% CI, 1.1 to 2.5) predicted a lower recurrence-free survival (RFS; all P < .01). Smoking pack-years > 10 reduced overall survival (HR, 1.72; 95% CI, 1.1 to 2.7; P = .03) but did not impact RFS (HR, 1.1; 95% CI, 0.7 to 1.9; P = .65). RPA segregated HPV-positive patients into low (T1-3N0-2c; DC, 93%) and high DM risk (N3 or T4; DC, 76%) groups and HPV-negative patients into different low (T1-2N0-2c; DC, 93%) and high DM risk (T3-4N3; DC, 72%) groups. The DC rates for HPV-positive, low-risk N0-2a or less than 10 pack-year N2b patients were similar for RT alone and CRT, but the rate was lower in the N2c subset managed by RT alone (73% v 92% for CRT; P = .02).
CONCLUSION: HPV-positive T1-3N0-2c patients have a low DM risk, but N2c patients from this group have a reduced DC when treated with RT alone and seem less suited for deintensification strategies that omit chemotherapy.


Perisanidis C, Mittlböck M, Dettke M, et al.
Identifying risk factors for allogenic blood transfusion in oral and oropharyngeal cancer surgery with free flap reconstruction.
J Oral Maxillofac Surg. 2013; 71(4):798-804 [PubMed]
PURPOSE: Several observational studies in head and neck cancer have reported that allogenic blood transfusion is associated with increased postoperative complications, increased risk of tumor recurrence, and worse prognosis. The aim of this study was to identify preoperative and intraoperative factors predicting blood transfusion in patients undergoing surgery for oral and oropharyngeal cancer.
PATIENTS AND METHODS: We conducted a retrospective cohort study of patients undergoing tumor resection and free flap reconstruction for locally advanced oral and oropharyngeal squamous cell carcinoma between 2000 and 2008. The primary outcome variable was perioperative exposure to allogenic blood transfusion. Univariate and multivariate logistic regression models were used to determine predictors of blood transfusion.
RESULTS: A cohort of 142 participants was found eligible. In a multivariate model, Charlson score ≥ 1 (OR, 5.2; 95% CI, 1.4 to 19.3; P = .01), preoperative hemoglobin levels ≤ 12 g/dl (OR, 4.4; 95% CI, 1.2 to 16.2; P = .03), bone resection (OR, 5.1; 95% CI, 1.5 to 17.8; P = .01), and osseous free tissue transfer (OR, 8.8; 95% CI, 1.0 to 74.8; P = .046) were independently associated with an increased risk of blood transfusion.
CONCLUSION: Our study identified patient- and surgery-related factors predicting a higher risk of exposure to allogenic blood transfusion. This readily available preoperative information could be used to better stratify patients according to their transfusion risk and may thereby guide blood conservation strategies in high-risk patients.


More YI, Tsue TT, Girod DA, et al.
Functional swallowing outcomes following transoral robotic surgery vs primary chemoradiotherapy in patients with advanced-stage oropharynx and supraglottis cancers.
JAMA Otolaryngol Head Neck Surg. 2013; 139(1):43-8 [PubMed]
OBJECTIVES: To evaluate functional swallowing outcomes in patients undergoing transoral robotic surgery vs primary chemoradiotherapy for the management of advanced-stage oropharynx and supraglottis cancers.
DESIGN: Prospective nonrandomized clinical trial.
SETTING: Academic research.
PATIENTS: We studied 40 patients with stage III or stage IVA oropharynx and supraglottis squamous cell carcinoma. Group 1 comprised 20 patients who received transoral robotic surgery with adjuvant therapy, while group 2 comprised 20 patients whose disease was managed by primary chemoradiotherapy.
MAIN OUTCOME MEASURES: Patients completed the M. D. Anderson Dysphagia Inventory (MDADI) before treatment and then at follow-up visits at 3, 6, and 12 months. The MDADI scores were analyzed and compared.
RESULTS: The median follow-up period for both groups was 14 months (range, 12-16 months). When comparing the median MDADI scores between group 1 and group 2, we found no statistically significant differences before treatment or at the 3-month follow-up visit. However, this difference was significant at the posttreatment visits at 6 months (P = .004) and 12 months (P = .006), where group 1 had better swallowing MDADI scores. We also found significant differences in swallowing MDADI scores between the groups at the 6-month posttreatment visit for patients with T1, T2, and T3 disease and at the 12-month follow-up visit for patients with T2 and T3 disease, where group 1 had significantly better MDADI scores. Comparing tumor subsites, group 1 fared significantly better at the follow-up visits at 6 months (P = .02) and 12 months (P = .04) for patients with primary tumor at the tonsil. Compared with group 2, group 1 patients having base of tongue cancers exhibited significantly better swallowing MDADI scores at the 6-month follow-up visit (P = .02), and group 1 patients having lateral oropharynx disease had significantly better swallowing MDADI scores at the 12-month follow-up visit (P = .04).
CONCLUSION: Advanced-stage oropharynx and supraglottis cancers managed by transoral robotic surgery with adjuvant therapy resulted in significantly better swallowing MDADI outcomes at the follow-up visits at 6 and 12 months compared with tumors treated by primary chemoradiotherapy.


Santeufemia DA, Tumolo S, De Paoli A, et al.
Chemo/tomotherapy stereotactic body radiation therapy (chemo/SBRT) for the salvage treatment of esophageal carcinoma following trimodality therapy: a case report.
Tumori. 2012 Sep-Oct; 98(5):143e-145e [PubMed]
BACKGROUND: Esophageal cancer (EC) patients presenting a local recurrence following trimodality therapy (chemoradiaton and surgery) have limited palliative treatment options when the three major modalities of therapy have been exhausted. In addition, some patients experience a local recurrence or develop a metachronous cancer in a previously irradiated site, without evidence of systemic disease. For these patients there is a potential for cure, although the risk of further distant recurrences remains high.
CASE REPORT: We report of a successful concomitant chemo/SBRT treatment in a case of locally advanced metachronous squamous cervical EC, which was diagnosed in a patient previously treated with trimodality therapy for a squamous tonsillar carcinoma.
RESULT: Chemo/SBRT seems to be a reasonable salvage option for patients without distant metastases who have exhausted standard therapies.
CONCLUSIONS: Our experience also suggests that a concomitant chemo/SBRT treatment appears to be either feasible or effective and chemo/SBRT can be considered also in selected patients affected by EC with squamous histology and with neoplastic infiltration of the trachea.


Giraldi G, De Luca d'Alessandro E
The HPV infection in males: an update.
Ann Ig. 2012 Nov-Dec; 24(6):497-506 [PubMed]
The role of Human papillomavirus (HPV) in malignant and non-malignant genital diseases in females is well known and the corresponding epidemiological burden has been widely described, in males instead, less is known about the role of the virus in anal, penile and head and neck cancer, and the burden of malignant and non-malignant HPV-related diseases. There are many types of HPV that can infect the epithelium: some types can cause genital warts (low risk genotype), other types (high risk genotypes) can cause cancers of the penis, anus or oropharynx. Relative to females, males tend to be less knowledgeable about the infection: some may view its consequences as less likely and severe for themselves than for females, and thus could perceive vaccination as unnecessary. Including boys in the vaccination program generally exceeded conventional thresholds of good value for money, even under favorable conditions of vaccine protection and health benefits; however, uncertainty still exists in many areas that can either strengthen or attenuate the findings achieved.


Shinozaki T, Hayashi R, Ebihara M, et al.
Mucosal defect repair with a polyglycolic acid sheet.
Jpn J Clin Oncol. 2013; 43(1):33-6 [PubMed]
OBJECTIVE: Early-stage oral or oropharyngeal carcinomas are often treated with surgical resection. Resulting wounds that are too large for primary closure can be covered with skin grafts or patches made from various biomaterials. Recently, polyglycolic acid sheets have been used for this purpose.
METHODS: We treated six patients with large wounds resulting from the resection of oral or oropharyngeal squamous cell carcinoma by grafting polyglycolic acid sheet patches. All patients were initially treated at the National Cancer Center East Hospital from March 2010 through July 2012. After mucosal resection, the wounds were covered with polyglycolic acid sheet patches attached with fibrin glue. Oral intake was started 4 days after surgery.
RESULTS: Mucosal resection was the initial treatment in seven patients (five with oral squamous cell carcinoma and two with oropharyngeal squamous cell carcinoma). The polyglycolic acid sheet patches became detached in two patients (on the day of surgery and on postoperative day 6), who then required large doses of analgesics. A patient who underwent tooth extraction also required large doses of analgesics. The other four patients required only small doses of analgesics. One patient had bleeding at the surgical site. No adverse effects were caused by the polyglycolic acid sheet patch or by fibrin glue.
CONCLUSIONS: Our study has shown that grafting of a polyglycolic acid sheet patch is effective and provides good pain control for patients with large, open wounds after mucosal resection of oral or oropharyngeal squamous cell carcinoma. We plan to evaluate tissue contraction and oral intake after polyglycolic acid patch grafting.


Grimes R, Garcia-Buitrago MT, Jorda M, et al.
p16INKa immunocytochemistry in fine-needle aspiration cytology smears of metastatic head and neck squamous cell carcinoma.
Acta Cytol. 2013; 57(1):33-7 [PubMed]
OBJECTIVES: Patients with head and neck squamous cell carcinoma (HNSCC) may initially present with neck metastases diagnosed by fine-needle aspiration (FNA). In these patients, it is critical to locate the primary site so that targeted therapy can be administered. Nearly a quarter of HNSCC are associated with human papillomavirus (HPV) infection. The great majority of HPV-related primaries originate in the oropharynx. p16INKa (p16) functions as a surrogate marker of HPV infection. We sought to determine if expression of p16 by immunocytochemistry (ICC) in neck metastases could assist in localizing the primary site to the oropharynx.
STUDY DESIGN: Diagnostic FNA cytology smears of neck metastases from 90 patients with biopsy-proven primary HNSCC were reviewed. Papanicolaou-stained slides were directly subjected to ICC, using p16 antibody.
RESULTS: Twenty-seven (30%) tumors expressed p16 by ICC; 74% of these p16-positive tumors were metastases from oropharynx. There was a significantly higher proportion of p16 expression in patients with primary oropharyngeal carcinoma (47%) versus those whose primary tumor was non-oropharyngeal (15%; p = 0.0013).
CONCLUSIONS: p16 expression in FNA cytology smears of metastatic HNSCC is a useful indicator of oropharyngeal origin and can be used to help localize the primary site in cases where this is not clinically evident.


Guan X, Sturgis EM, Song X, et al.
Pre-microRNA variants predict HPV16-positive tumors and survival in patients with squamous cell carcinoma of the oropharynx.
Cancer Lett. 2013; 330(2):233-40 [PubMed] Article available free on PMC after 28/04/2014
To identify non-tumor biomarkers for prediction of tumor HPV status and prognosis of patients with squamous cell carcinoma of the oropharynx (SCCOP), we evaluated the association of single nucleotide polymorphisms (SNPs) in pre-miRNAs with HPV16 status and survival for SCCOP patients. We analyzed HPV16 status in tumor specimens and genotyped four SNPs in pre-miRNAs (hsa-mir-146a rs2910164 G>C, hsa-mir-149 rs2292832 G>T, hsa-mir-196a2 rs11614913 C>T, and hsa-mir-499 rs3746444 A>G) in 309 SCCOP patients. Unconditional logistic regression models were used for calculation of odds ratio (OR) and 95% confidence intervals (CIs), and Kaplan-Meier analysis and Cox proportional hazards regression were used to evaluate associations. We found that statistically significant associations with HPV16-positive SCCOP and survival were found for hsa-mir-146a rs2910164 and hsa-mir-196a2 rs11614913, while such similar associations were not observed for hsa-mir-149 rs2292832 and hsa-mir499 rs3746444. Compared with those with corresponding hsa-mir-146a CG/CC and has-mir-196a2 CC genotypes, the hsa-mir-146a GG and hsa-mir-196a2 CT/TT wild-type genotypes were significantly associated with HPV16-positive tumor status (adjusted OR, 2.4; 95% CI, 1.4-4.1 and adjusted OR, 2.1, 95% CI, 1.2-3.6), respectively. Patients having hsa-mir-146a rs2910164 GG and hsa-mir196a2 rs11614913 CT/TT genotypes had significantly better overall, disease-specific, and disease-free survival compared with those having the corresponding CG/CC and CC genotypes, respectively. Furthermore, these genotypes were significantly associated with reduced risk of overall death, death owing to disease, and recurrence after adjustment for important prognostic confounders including HPV status, smoking, and stage. Our findings indicate pre-miRNA polymorphisms may predict tumor HPV16-positive SCCOP cases and may be prognostic biomarkers for SCCOP.


Corey A
Pitfalls in the staging of cancer of the oropharyngeal squamous cell carcinoma.
Neuroimaging Clin N Am. 2013; 23(1):47-66 [PubMed]
The face of oropharyngeal squamous cell carcinoma (OPSCC) is changing. It has a dichotomous nature, with 1 subset of the disease associated with tobacco and alcohol use and the other having proven association with human papilloma virus infection. Imaging plays an important role in the staging and surveillance of OPSCC, and a detailed knowledge of the anatomy and pitfalls is critical. This article will review the detailed anatomy of the oropharynx and epidemiology of OPSS, along with its staging, patterns of spread, and treatment.


Northridge ME, Manji N, Piamonte RT, et al.
HPV, oropharyngeal cancer, and the role of the dentist: a professional ethical approach.
J Health Care Poor Underserved. 2012; 23(4 Suppl):47-57 [PubMed]
Human papillomavirus (HPV) is an emerging risk factor for oropharyngeal cancer, especially among younger patients, and must be thoughtfully addressed by the dental community. The professional ethical decision-making model first advanced by Ozar and Sokol for use by dentists at chairside (define the dilemma, assess the facts, identify and rank the alternatives, and choose a course of action) was modified to delineate clearly inputs, considerations, and feedback loops based on what is professionally and ethically at stake in advising patients. As the link between HPV and oropharyngeal cancer is established through scientific studies, the role of the dentist in primary and secondary prevention will be crucial. In the absence of definitive evidence, the professional ethical decision-making framework presented here allows dentists to systematically work through available alternatives. Ultimately, the role of the dentist is to use discretion in choosing a professional and ethical course of action for each patient.


Broglie MA, Soltermann A, Haile SR, et al.
Quality of life of oropharyngeal cancer patients with respect to treatment strategy and p16-positivity.
Laryngoscope. 2013; 123(1):164-70 [PubMed]
OBJECTIVES/HYPOTHESIS: To assess the quality of life in long-term survivors with oropharyngeal cancer (OPSCC), compare the results with our historic cohort in relation to the radiation technique, and explore the influence of treatment strategy and p16 expression on quality of life (QoL).
STUDY DESIGN: Retrospective chart analysis and patient response to EORTC QLQ-C30 and EORTC QLQ-H&N35 survey questionnaires.
METHODS: 98/120 (82%) survivors treated by primary intensity modulated chemoradiation (n = 55), or surgery with (n = 30) or without (n = 13) adjuvant radiotherapy (RT), completed and returned the questionnaires.
RESULTS: Surgically treated patients complained about significantly less troubles with dry mouth and teeth compared to the nonsurgically treated group. Comparing patients treated with surgery alone and those receiving any kind of RT (primary or adjuvant) the latter group complained about significantly more problems. Patients with p16-positive tumors demonstrated significantly higher tumor stages, but significantly better scores in physical and role functions.
CONCLUSIONS: Early disease can be treated with high long-term QoL by surgery alone. Primary surgery with postoperative RT in selected patients with limited primary tumors and advanced neck disease renders excellent QoL. Our results suggest that IMRT is superior to former radiation techniques with regard to QoL, and should be considered as standard of care in patients undergoing RT for OPSCC. Patients with p16 positive tumors appear to show not only a better outcome but also report on a better QoL.


Al-Saleh MA, Armijo-Olivo S, Thie N, et al.
Morphologic and functional changes in the temporomandibular joint and stomatognathic system after transmandibular surgery in oral and oropharyngeal cancers: systematic review.
J Otolaryngol Head Neck Surg. 2012; 41(5):345-60 [PubMed]
BACKGROUND: Interruption of mandibular continuity in transmandibular (mandibulotomy and mandibulectomy) surgery for tumour resection in the oral cavity and oropharynx may alter oral and temporomandibular joint (TMJ) morphology and function.
OBJECTIVE: To critically analyze available evidence regarding the effects of transmandibular surgeries on morphologic and functional changes in the TMJ and stomatognathic system.
DATA SOURCES: Electronic search of Medline, Embase, Evidence-Based Medicine Reviews, Ovid HealthStar, and Scopus and hand searches.
INCLUSION CRITERIA: Any article investigating the TMJ morphologic changes and/or functional outcomes following transmandibular surgeries. RESULTS AND SYNTHESIS METHODS: Two hundred seventy-one articles were obtained through the electronic database scan and six articles via a hand search. Twelve full articles were initially selected as potentially meeting the eligibility for this review; however, only five articles finally fulfilled the study inclusion criteria and were analyzed for their methodology. All articles used clinical records and/or patient reports to evaluate TMJ pain, motion, dental occlusion, mouth opening, and deflection during opening as outcome measures. In only four articles was a clinical examination conducted after surgery, with associated patients' interviews and reports. The quality of all included articles was considered poor with a high risk of bias according to the Research Triangle Institute item bank quality of assessment.
CONCLUSION: Based on the limited available evidence for this systematic review and a high risk of bias of the analyzed articles, no firm conclusions can be established regarding the effects of transmandibular surgery on morphologic and functional changes in the TMJ and stomatognathic system.


Disini L, Connor S
Improved edge delineation using a low-flow and delayed-phase contrast-enhanced protocol for computed tomography imaging of oral cavity and oropharyngeal malignancies.
Clin Radiol. 2013; 68(2):167-72 [PubMed]
AIM: To determine whether contrast-enhanced computed tomography (CT) performed with a high flow rate and short delay protocol or a lower flow rate and longer delay protocol resulted in better enhancement of the oral cavity and oropharyngeal tumour and tumour edge delineation.
MATERIALS AND METHODS: Patients with squamous cell carcinomas of the upper aerodigestive tract (UAT) who underwent contrast-enhanced CT using 100 ml contrast material with 300 mg iodine/ml were selected for this comparison study. The protocols studied used a high flow rate and short scan delay (2 ml/s and 50 s) and a lower flow rate and longer delay (1 ml/s and 100 s). Contrast enhancement by radiodensity in Hounsfield units of the tumour site, poorest and clearest tumour boundaries and contralateral lateral pterygoid muscle were measured using a region of interest tool. A t-test statistical analysis was used to compare both protocols.
RESULTS: The lower flow and longer delay protocol maximized contrast differences at both the poorest and clearest definition boundaries of the tumour (p ≤ 0.01 and p ≤ 0.05, respectively) and the pterygoid muscle (p ≤ 0.01). There was no significant difference in contrast enhancement within the central homogeneous tumour site.
CONCLUSION: A lower flow and longer delay protocol (1 ml/s and 100 s) provided better enhancement of the delineation of the tumour edge and surrounding musculature than a high flow rate and short delay protocol (2 ml/s and 50 s). Both protocols achieved similar central tumour enhancement.


Poovaneswaran S, Paleri V, Charlton F, et al.
Cutaneous metastases from head and neck squamous cell carcinoma.
Med J Malaysia. 2012; 67(4):430-2 [PubMed]
The presence of cutaneous metastases in squamous cell carcinomas of the head and neck (SCCHN) is rare and associated with a dismal prognosis. It is vital to distinguish these lesions from direct invasion of the skin by SCCHN or primary cutaneous malignancies as the prognosis is vastly different and so is the management. In this case report, we present four cases of cutaneous metastases and also briefly review the literature pertaining to this phenomenon.


Nyflot MJ, Harari PM, Yip S, et al.
Correlation of PET images of metabolism, proliferation and hypoxia to characterize tumor phenotype in patients with cancer of the oropharynx.
Radiother Oncol. 2012; 105(1):36-40 [PubMed] Article available free on PMC after 13/10/2013
UNLABELLED: Spatial organization of tumor phenotype is of great interest to radiotherapy target definition and outcome prediction. We characterized tumor phenotype in patients with cancers of the oropharynx through voxel-based correlation of PET images of metabolism, proliferation, and hypoxia.
METHODS: Patients with oropharyngeal cancer received (18)F-fluorodeoxyglucose (FDG) PET/CT, (18)F-fluorothymidine (FLT) PET/CT, and (61)Cu-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM) PET/CT. Images were co-registered and standardized uptake values (SUV) were calculated for all modalities. Voxel-based correlation was evaluated with Pearson's correlation coefficient in tumor regions. Additionally, sensitivity studies were performed to quantify the effects of image segmentation, registration, noise, and segmentation on R.
RESULTS: On average, FDG PET and FLT PET images were most highly correlated (R(FDG:FLT) = 0.76, range 0.53-0.85), while Cu-ATSM PET showed greater heterogeneity in correlation to other tracers (R(FDG:Cu-ATSM) = 0.64, range 0.51-0.79; R(FLT:Cu-ATSM) = 0.61, range 0.21-0.80). Of the tested parameters, correlation was most sensitive to image registration. Misregistration of one voxel lead to ΔR(FDG) = 0.25, ΔR(FLT) = 0.39, and ΔR(Cu-ATSM) = 0.27. Image noise and reconstruction also had quantitative effects on correlation. No significant quantitative differences were found between GTV, expanded GTV, or CTV regions.
CONCLUSIONS: Voxel-based correlation represents a first step into understanding spatial organization of tumor phenotype. These results have implications for radiotherapy target definition and provide a framework to test outcome prediction based on pretherapy distribution of phenotype.


Del Mistro A, Baboci L, Frayle-Salamanca H, et al.
Oral human papillomavirus and human herpesvirus-8 infections among human immunodeficiency virus type 1-infected men and women in Italy.
Sex Transm Dis. 2012; 39(11):894-8 [PubMed]
BACKGROUND: Oral human papillomavirus (HPV) and human herpesvirus-8 (HHV8) infections are sexually transmitted and respectively associated with the development of oropharyngeal carcinoma and Kaposi sarcoma. The aim of the study was to evaluate HPV prevalence and its possible correlation with HHV8 oral shedding, in relation to sex, human immunodeficiency virus (HIV) behavioral risk factor, and immune function.
METHODS: The study population comprised 100 HIV-infected individuals divided into 3 groups: (1) 38 men who have sex with men (MSM), (2) 24 heterosexual men, and (3) 38 women. DNA was obtained from cells of unstimulated whole saliva. Human papillomavirus sequences were searched for by polymerase chain reaction (PCR) with MY09/MY11 primers or by nested PCR with GP5+/GP6+ primers as the second step. Typing was accomplished by restriction fragment length polymorphism analysis or by direct sequencing or by reverse line blot. Human herpesvirus-8 sequences were detected and quantified by nested PCR and real-time PCR, respectively.
RESULTS: Oral HPV infection was present in 37 (prevalence, 37%) of 100 (13 with high-risk and 24 with low-risk types) patients; the most frequent types were HPV16, HPV6, HPV10, HPV61, HPV66, and HPV83. Human herpesvirus-8 DNA was detected in 46 (46%) of 100 subjects. Both infections had the highest prevalence among MSM and the lowest among women; women had a lower prevalence of high-risk HPV types than did both male groups (P = 0.05). An inverse correlation was observed with concomitant oral HHV8 infection (P = 0.007).
CONCLUSIONS: High prevalence of oral HPV and HHV8 infections was observed; MSM had the highest figures, despite better control of HIV infection.


Edelstein ZR, Schwartz SM, Hawes S, et al.
Rates and determinants of oral human papillomavirus infection in young men.
Sex Transm Dis. 2012; 39(11):860-7 [PubMed]
BACKGROUND: Little is known about the rates and determinants of oral human papillomavirus (HPV) infection, an infection that is etiologically linked with oropharyngeal cancers.
METHODS: A cohort of male university students (18-24 years) was examined every 4 months (212 men, 704 visits). Oral specimens were collected via gargle/rinse and swabbing of the oropharynx. Genotyping for HPV-16 and 36 other α-genus types was performed by polymerase chain reaction-based assay. Data on potential determinants were gathered via clinical examination, in-person questionnaire, and biweekly online diary. Hazards ratios (HR) were used to measure associations with incident infection.
RESULTS: Prevalence of oral HPV infection at enrollment was 7.5%, and 12-month cumulative incidence was 12.3% (95% confidence interval [CI], 7.0, 21.3). Prevalence of oral HPV-16 was 2.8% and 12-month cumulative incidence was 0.8% (95% CI, 0.1%-5.7%). None of the incident oral HPV infections and 28.6% of the prevalent oral HPV infections were detected more than once. In a multivariate model, incident oral HPV infection was associated with recent frequency of performing oral sex (≥1 per week: HR, 3.7; 95% CI, 1.4-9.8), recent anal sex with men (HR, 42.9; 95% CI, 8.8-205.5), current infection with the same HPV type in the genitals (HR, 6.2; 95% CI, 2.4-16.4), and hyponychium (HR, 11.8, 95% CI, 4.1-34.2).
CONCLUSIONS: Although nearly 20% of sexually active male university students had evidence of oral HPV infection within 12 months, most infections were transient. Human papillomavirus type 16 was not common. Sexual contact and autoinoculation appeared to play independent roles in the transmission of α-genus HPV to the oral cavity of young men.


Park S, Ko YH
A unique case of blastoid variant of mantle cell lymphoma with an aberrant CD5-/CD10+/Bcl-6+/CD56+ immunophenotype: a case report.
Tumori. 2012 Jul-Aug; 98(4):e111-4 [PubMed]
The neural adhesion molecule CD56 is normally expressed on natural killer cells and subsets of T cells and is commonly found in hematolymphoid neoplasms. Expression of CD56 is very rare in B-cell lymphoma and most reported CD56-positive cases were diffuse large B-cell lymphomas. Cases of CD56-positive mantle cell lymphoma (MCL) have not previously been described in the literature. We present a case of CD56-positive MCL. To the best of our knowledge, this is the first case report of MCL expressing CD56.


Hunter KU, Schipper M, Feng FY, et al.
Toxicities affecting quality of life after chemo-IMRT of oropharyngeal cancer: prospective study of patient-reported, observer-rated, and objective outcomes.
Int J Radiat Oncol Biol Phys. 2013; 85(4):935-40 [PubMed] Article available free on PMC after 15/03/2014
PURPOSE: To test the hypothesis that intensity modulated radiation therapy (IMRT) aiming to spare the salivary glands and swallowing structures would reduce or eliminate the effects of xerostomia and dysphagia on quality of life (QOL).
METHODS AND MATERIALS: In this prospective, longitudinal study, 72 patients with stage III-IV oropharyngeal cancer were treated uniformly with definitive chemo-IMRT sparing the salivary glands and swallowing structures. Overall QOL was assessed by summary scores of the Head Neck QOL (HNQOL) and University of Washington QOL (UWQOL) questionnaires, as well as the HNQOL "Overall Bother" question. Quality of life, observer-rated toxicities (Common Toxicity Criteria Adverse Effects scale, version 2), and objective evaluations (videofluoroscopy assessing dysphagia and saliva flow rates assessing xerostomia) were recorded from before therapy through 2 years after therapy. Correlations between toxicities/objective evaluations and overall QOL were assessed using longitudinal repeated measures of analysis and Pearson correlations.
RESULTS: All observer-rated toxicities and QOL scores worsened 1-3 months after therapy and improved through 12 months, with minor further improvements through 24 months. At 12 months, dysphagia grades 0-1, 2, and 3, were observed in 95%, 4%, and 1% of patients, respectively. Using all posttherapy observations, observer-rated dysphagia was highly correlated with all overall QOL measures (P<.0001), whereas xerostomia and mucosal and voice toxicities were significantly correlated with some, but not all, overall QOL measures, with lower correlation coefficients than dysphagia. Late overall QOL (≥6 or ≥12 months after therapy) was primarily associated with observer-rated dysphagia, and to a lesser extent with xerostomia. Videofluoroscopy scores, but not salivary flows, were significantly correlated with some of the overall QOL measures.
CONCLUSION: After chemo-IMRT, although late dysphagia was on average mild, it was still the major correlate of QOL. Further efforts to reduce swallowing dysfunction are likely to yield additional gains in QOL.


Zappacosta R, Rosini S, Aiello FB, et al.
Solitary plasmacytoma of the tonsillar site associated with actinomyces infection: the possible role of IL-6.
J Biol Regul Homeost Agents. 2012 Jul-Sep; 26(3):571-5 [PubMed]
ExtraMedullary Plasmacytoma (EMP) is a rare plasma cell tumor. It can occur in the upper aerodigestive tract and presents as a large nodule causing local compressive symptoms. A 79-year old woman presented to Otorhinolaryngology Department with progressive hearing loss and no other symptoms. Following PET/TC examination due to the suspicion of a lymphoproliferative disease, the patient underwent tonsillectomy and the diagnosis of solitary EMP was formulated. In addition to that, the histological examination of the tonsillar tissue revealed large colonies of filamentous bacteria, showing abundant sulphur granules and Splendore-Hoeppli phenomenon; these evidences indicating the presence of a chronic Actinomyces infection. Immunohistochemical analysis demonstrated a marked IL-6 immunoreactivity of the neoplastic plasma cells. Interestingly, a marked IL-6 immunoreactivity was also found in the tissue surrounding the Actinomyces colonies. In the present study we report for the first time a solitary EMP associated with Actinomycosis. It is tempting to speculate that the unsuspected and untreated Actinomyces infection, through chronic IL-6 production, could contribute to the neoplastic transformation of plasma cells.


Lohavanichbutr P, Houck J, Doody DR, et al.
Gene expression in uninvolved oral mucosa of OSCC patients facilitates identification of markers predictive of OSCC outcomes.
PLoS One. 2012; 7(9):e46575 [PubMed] Article available free on PMC after 15/03/2014
Oral and oropharyngeal squamous cell carcinomas (OSCC) are among the most common cancers worldwide, with approximately 60% 5-yr survival rate. To identify potential markers for disease progression, we used Affymetrix U133 plus 2.0 arrays to examine the gene expression profiles of 167 primary tumor samples from OSCC patients, 58 uninvolved oral mucosae from OSCC patients and 45 normal oral mucosae from patients without oral cancer, all enrolled at one of the three University of Washington-affiliated medical centers between 2003 to 2008. We found 2,596 probe sets differentially expressed between 167 tumor samples and 45 normal samples. Among 2,596 probe sets, 71 were significantly and consistently up- or down-regulated in the comparison between normal samples and uninvolved oral samples and between uninvolved oral samples and tumor samples. Cox regression analyses showed that 20 of the 71 probe sets were significantly associated with progression-free survival. The risk score for each patient was calculated from coefficients of a Cox model incorporating these 20 probe sets. The hazard ratio (HR) associated with each unit change in the risk score adjusting for age, gender, tumor stage, and high-risk HPV status was 2.7 (95% CI: 2.0-3.8, p = 8.8E-10). The risk scores in an independent dataset of 74 OSCC patients from the MD Anderson Cancer Center was also significantly associated with progression-free survival independent of age, gender, and tumor stage (HR 1.6, 95% CI: 1.1-2.2, p = 0.008). Gene Set Enrichment Analysis showed that the most prominent biological pathway represented by the 71 probe sets was the Integrin cell surface interactions pathway. In conclusion, we identified 71 probe sets in which dysregulation occurred in both uninvolved oral mucosal and cancer samples. Dysregulation of 20 of the 71 probe sets was associated with progression-free survival and was validated in an independent dataset.


Melvin TA, Eliades SJ, Ha PK, et al.
Neck dissection through a facelift incision.
Laryngoscope. 2012; 122(12):2700-6 [PubMed]
OBJECTIVES/HYPOTHESIS: To determine the feasibility and safety of neck dissection through a facelift incision.
STUDY DESIGN: Prospective case series.
METHODS: Cadavers and live subjects underwent neck dissection using a facelift incision with and without endoscopic assistance. In the live facelift neck dissection (FLND), the preoperative surgical indications, staging, adjuvant therapy, intraoperative technical procedure, pathology reports on lymph nodes, and short-term outcomes were reviewed.
RESULTS: FLND was successfully performed in four cadavers and four live subjects, including selective (less than five neck levels removed) and comprehensive (levels I-V removed) neck dissections. All levels were accessible through this approach, with additional retraction required for levels I and IV. Endoscopic assistance was required in one neck dissection for adequate visualization. Short-term complications and number of excised lymph nodes were comparable to those from traditional neck dissection approaches.
CONCLUSIONS: Open neck dissection through a facelift incision is feasible and offers an alternate approach to traditional incisions. This can be performed without requiring robotic assistance and with endoscopic assistance only in certain cases. Endoscopic assistance can offer enhanced visualization of the surgical field and complement open direct approaches in neck dissection. Although FLND offers improved cosmetic outcomes when compared to those of traditional neck incisions, further study is required to determine its efficacy and indications.


Chen AM, Li J, Beckett LA, et al.
Differential response rates to irradiation among patients with human papillomavirus positive and negative oropharyngeal cancer.
Laryngoscope. 2013; 123(1):152-7 [PubMed]
OBJECTIVES/HYPOTHESIS: To evaluate the responsiveness of human papillomavirus (HPV) -positive and HPV-negative oropharyngeal cancer to intensity-modulated radiotherapy (IMRT), using axial imaging obtained daily during the course of image-guided radiotherapy (IGRT).
STUDY DESIGN: Observational cohort study with matched-pair analysis of patients irradiated for HPV-positive and HPV-negative oropharygeal cancer.
METHODS AND MATERIALS: Ten patients treated by IMRT to 70 Gy for locally advanced, HPV-positive squamous cell carcinoma of the oropharynx were matched to one HPV-negative control subject by age, gender, performance status, T-category, tumor location, and the use of concurrent chemotherapy. The gross tumor volume (GTV) was delineated on daily IGRT scans obtained via kilovoltage cone-beam computed tomography (CBCT). Mathematical modeling using fitted mixed-effects repeated measure analysis was performed to quantitatively and descriptively assess the trajectory of tumor regression.
RESULTS: Patients with HPV-positive tumors experienced a more rapid rate of tumor regression between day 1 of IMRT and the beginning of week 2 (-33% Δ GTV) compared to their counterparts with HPV-negative tumors (-10% Δ GTV), which was statistically significant (p<0.001). During this initial period, the average absolute change in GTV was -22.9 cc/week for HPV-positive tumors and -5.9 cc/week for HPV-negative tumors (p<0.001). After week 2 of IMRT, the rates of GTV regression were comparable between the two groups.
CONCLUSIONS: HPV-positive oropharyngeal cancers exhibited an enhanced response to radiation, characterized by a dramatically more rapid initial regression than those with HPV-negative tumors. Implications for treatment de-intensification in the context of future clinical trials and the possible mechanisms underlying this increased radiosensitivity will be discussed.


Brana I, Siu LL
Locally advanced head and neck squamous cell cancer: treatment choice based on risk factors and optimizing drug prescription.
Ann Oncol. 2012; 23 Suppl 10:x178-85 [PubMed]
Despite the policy changes to decrease tobacco consumption and therapeutic advances in this disease, squamous cell carcinomas arising from the head and neck (HNSCC) continue to represent a common neoplasm and a leading cause of cancer-related mortality in Europe and worldwide. although different approaches have been evaluated, no treatment has currently been shown to be superior to cisplatin (Platinol, Corden Pharma) based chemoradiation in locally advanced HNSCC. Based on retrospective subgroup analyses from multiple large clinical trials, human papillomavirus (HPV) status has been shown to be a validated prognostic factor in oropharyngeal tumors. Patients with HPV-related tumors, especially those who are non-smokers, have generally excellent outcome as their tumors are highly sensitive to both chemotherapy and radiation, whereas those with tobacco-related and HPV-negative tumors, who continue to represent substantial number of cases in Europe, have worse prognosis with tumors that are more resistant to treatment. The goal of treatment de-intensification in patients with favorable risk is to avoid long-term and late toxicity, but this must be achieved without compromise of treatment efficacy. For those with risk factors that portend a worse prognosis, the question remains whether addition to or modification of conventional treatment regimens would improve upon therapeutic index. Innovative clinical trial designs specifically tailored to these risk groups are urgently needed.


Holzinger D, Schmitt M, Dyckhoff G, et al.
Viral RNA patterns and high viral load reliably define oropharynx carcinomas with active HPV16 involvement.
Cancer Res. 2012; 72(19):4993-5003 [PubMed]
Oropharyngeal squamous cell carcinomas (OPSCC) that are associated with human papilloma virus (HPV) infection carry a more favorable prognosis than those that are HPV-negative. However, it remains unclear which biomarker(s) can reliably determine which OPSCC specimens are truly driven by HPV infection. In this study, we analyzed 199 fresh-frozen OPSCC specimens for HPV DNA, viral load, RNA expression patterns typical for cervical carcinomas (CxCaRNA(+)), and the HPV-targeted tumor suppressor protein p16(INK4a) as markers for HPV infection. In this set of specimens, there was a 49% prevalence of DNA for the cancer-associated HPV type 16 (HPV(+)). However, there was only a 16% prevalence of high viral load and only a 20% prevalence of CxCaRNA(+), a marker of HPV16 carcinogenic activity. Among the CxCaRNA(+) tumors, 78% of the specimens exhibited overexpression of p16(INK4a), which also occurred in 14% of the HPV-negative tumors. Using a multivariate survival analysis with HPV negativity as the reference group, CxCaRNA(+) as a single marker conferred the lowest risk of death [HR = 0.28, 95% confidence interval (CI), 0.13-0.61] from oropharyngeal cancer, closely followed by high viral load (HR = 0.32, 95% CI, 0.14-0.73). In contrast, a weaker inverse association was found for OPSCC that were HPV(+) and p16(INK4a) high (HR = 0.55, 95% CI, 0.29-1.08). In summary, our findings argued that viral load or RNA pattern analysis is better suited than p16(INK4a) expression to identify HPV16-driven tumors in OPSCC patient populations.


Amin N, Reddy K, Westerly D, et al.
Sparing the larynx and esophageal inlet expedites feeding tube removal in patients with stage III-IV oropharyngeal squamous cell carcinoma treated with intensity-modulated radiotherapy.
Laryngoscope. 2012; 122(12):2736-42 [PubMed]
OBJECTIVES/HYPOTHESIS: To evaluate the effect of larynx and esophageal inlet sparing on dysphagia recovery after intensity-modulated radiotherapy (IMRT) for stage III-IV oropharyngeal squamous cell carcinoma.
STUDY DESIGN: Retrospective study.
METHODS: Of 88 patients treated with IMRT, 38 were planned with a larynx + esophageal inlet mean dose <50 Gy constraint, 27 with a larynx alone mean dose constraint of <50 Gy, and 23 without a larynx/esophagus constraint. All had a percutaneous endoscopic gastrostomy (PEG) tube placed before IMRT, which was removed when the patient could swallow and maintain weight. All IMRT plans were retrieved, and the larynx; esophageal inlet; and superior, middle, and inferior constrictors were contoured. Dosimetric data were correlated with PEG tube dependence duration.
RESULTS: The PEG tube was removed within 3, 6, 9, and 12 months after IMRT in 24%, 61%, 71%, and 83% of patients, respectively. Median times to PEG tube removal were 3.7 and 8.6 months (P = .0029) in patients planned with or without a larynx/larynx + esophageal inlet dose constraint. A mean dose to the larynx + esophageal inlet of ≤60 Gy reduced the median PEG tube duration from 10.8 to 6.1 months (P = .02), compared to >60 Gy. Mean pharyngeal constrictor doses in patients receiving a mean dose to the larynx + esophageal inlet of ≤50 Gy versus >50 Gy were: 60 Gy and 69 Gy, 55 Gy and 67 Gy, and 47 Gy and 57 Gy, for the superior, middle, and inferior constrictors, respectively (P < .0001).
CONCLUSIONS: A dose constraint on the larynx and esophageal inlet during IMRT planning reduces dose to pharyngeal constrictors and expedites PEG tube removal.


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