A B S T R A C T PurposeHuman papillomavirus type 16 (HPV16) infection is causing an increasing number of oropharyngeal cancers in the United States and Europe. The aim of our study was to investigate whether HPV antibodies are associated with head and neck cancer risk when measured in prediagnostic sera. MethodsWe identified 638 participants with incident head and neck cancers (patients; 180 oral cancers, 135 oropharynx cancers, and 247 hypopharynx/larynx cancers) and 300 patients with esophageal cancers as well as 1,599 comparable controls from within the European Prospective Investigation Into Cancer and Nutrition cohort. Prediagnostic plasma samples from patients (collected, on average, 6 years before diagnosis) and control participants were analyzed for antibodies against multiple proteins of HPV16 as well as HPV6, HPV11, HPV18, HPV31, HPV33, HPV45, and HPV52. Odds ratios (ORs) of cancer and 95% CIs were calculated, adjusting for potential confounders. All-cause mortality was evaluated among patients using Cox proportional hazards regression. Results HPV16E6 seropositivity was present in prediagnostic samples for 34.8% of patients with oropharyngeal cancer and 0.6% of controls (OR, 274; 95% CI, 110 to 681) but was not associated with other cancer sites. The increased risk of oropharyngeal cancer among HPV16 E6 seropositive participants was independent of time between blood collection and diagnosis and was observed more than 10 years before diagnosis. The all-cause mortality ratio among patients with oropharyngeal cancer was 0.30 (95% CI, 0.13 to 0.67), for patients who were HPV16 E6 seropositive compared with seronegative. ConclusionHPV16 E6 seropositivity was present more than 10 years before diagnosis of oropharyngeal cancers. J Clin Oncol 31:2708-2715. © 2013 by American Society of Clinical Oncology INTRODUCTIONHuman papillomavirus type 16 (HPV16) is recognized as a cause of virtually all cervical cancers and of a substantial proportion of other anogenital cancers and oropharyngeal cancers. 1 The association between HPV16 and cancers of the oral cavity and larynx is less clear but, if associated, the attributable proportion is small. 1 HPV16 has been associated with a rapid increase in the incidence of oropharynx cancer in some parts of the world, notably in the United States, Sweden, and Australia, where it is now responsible for more than 50% of cases.2-4 If current trends continue, the annual number of oropharyngeal cancers in the United States may soon surpass the number of cervical cancers. 2The only evidence for the temporal relationship between HPV exposure and development of head and neck cancers (HNC) comes from a study within the Nordic serum banks linked to tumor registries: a significant 14-fold increased risk for cancer of the oropharynx was reported for seropositivity to the L1 capsid protein of HPV16.5 Antibodies against HPV L1 represent cumulative past HPV infection from multiple possible anatomic sites (ie, genital, anal, or oral), are common in controls, and © 2013 by American Society o...

All members of the multiprofessional team need to be aware of the struggles with food and eating experienced by patients with head and neck cancer during the convalescent period. It is therefore important that the follow-up focuses on all aspects of food, eating and meals as a part of a holistic approach.

BACKGROUNDIt is well recognized that many patients with head and neck carcinoma have problems with food intake and malnutrition. The objective of the current study was to determine the clinical pattern of patients with nonneoplastic stricture of the upper esophagus after radiotherapy for head and neck carcinoma.METHODSA retrospective chart study of 22 patients with stricture of the proximal esophagus diagnosed between 1993 and 1999 at Karolinska Hospital was performed. The dose volume histograms of the first 2 cm and 5 cm, respectively, of the proximal esophagus were calculated.RESULTSFive of the patients (23%) had total obliteration. The first 2 cm of the esophagus received at least 60 grays (Gy) in > 80% of the volume. Radiation injury was not reported to occur at doses < 60 Gy. There was a correlation found between dysphagia during radiotherapy and the development of proximal esophageal stricture. Stricture was diagnosed 1–60 months (median, 6 months) after radiotherapy. In 18 patients, the stricture was treated with single or repeated endoscopic dilation. These treatments allowed a nearly normal diet in 78% of the patients.CONCLUSIONSStricture of the upper esophagus is one deglutition disorder that is reported to occur after radiotherapy for head and neck carcinoma. In the current study, the authors emphasize the importance of knowing the tolerance of the normal esophagus to irradiation as well as early diagnosis of stricture of the proximal esophagus because this condition may lead to physical and emotional distress. Cancer 2003;97:1693–700. © 2003 American Cancer Society.DOI 10.1002/cncr.11236

Trismus, a well-known sequelae after treatment of head and neck cancer, decreases a patient's oral function and quality of life. The main objectives of this study were to: 1) investigate the long-term prevalence of radiation-induced trismus in patients treated for head and neck cancer according to two different fractionation schedules; and 2) model a dose-response relationship for trismus. Material and methods. Patients were recruited from the Swedish ARTSCAN trial, a prospective randomised multicentre study comparing conventional and accelerated fractionation. A total of 124 patients agreed to a clinical ENT examination 21-127 months (median 66 months) after beginning radiation therapy. Trismus-related scores were assessed using the EORTC H&N35 Quality of Life questionnaire. The TheraBite ® range of motion scale was used to measure maximal interincisal distance. The dose-response relationship for structures important for mastication and the temporomandibular joints was investigated by normal tissue complication probability modelling. results. No significant differences in patient-reported trismus or maximal interincisal distance were found between the two trial arms. Patient-reported moderate to high scores regarding trismus increased from 3% at the start of radiation therapy to 25% at the long-term follow-up. Maximal interincisal distance correlated significantly with patient-reported scores of trismus. The best dose-response fit to the endpoint data was found for the dose to the ipsilateral masseter. conclusions. Trismus is a persistent complication after radiotherapy with 3D-conformal radiation therapy. We found no difference between the severity and prevalence of trismus between conventional and accelerated fractionation, but a significant correlation between the absorbed dose to the mastication structures and opening of the mouth. Further prospective studies may determine whether a reduced dose to structures important for mastication using intensitymodulated radiation therapy will reduce problems with trismus.

BackgroundCisplatin is a cornerstone anticancer drug with pronounced ototoxicity, whereas oxaliplatin, a platinum derivative with a different clinical profile, is rarely ototoxic. This difference has not been explained.MethodsIn HCT116 cells, cisplatin (20 μM)-induced apoptosis was reduced by a calcium chelator from 9.9-fold induction (95% confidence interval [CI] = 8.1- to 11.7-fold), to 3.1-fold induction (95% CI = 2.0- to 4.2-fold) and by superoxide scavenging from 9.3-fold (95% CI = 8.8- to 9.8-fold), to 5.1-fold (95% CI = 4.4- to 5.8-fold). A guinea pig model (n = 23) was used to examine pharmacokinetics. Drug concentrations were determined by liquid chromatography with post-column derivatization. The total platinum concentration in cochlear tissue was determined by inductively coupled plasma mass spectrometry. Drug pharmacokinetics was assessed by determining the area under the concentration–time curve (AUC). Statistical tests were two-sided.ResultsIn HCT116 cells, cisplatin (20 μM)-induced apoptosis was reduced by a calcium chelator from 9.9-fold induction (95% confidence interval [CI] = 8.1- to 11.7-fold to 3.1-fold induction) (95% CI = 2.0- to 4.2-fold) and by superoxide scavenging (from 9.3-fold, 95% CI = 8.8- to 9.8-fold, to 5.1-fold, 95% CI = 4.4- to 5.8-fold). Oxaliplatin (20 μM)-induced apoptosis was unaffected by calcium chelation (from 7.1- to 6.2-fold induction) and by superoxide scavenging (from 5.9- to 5.6-fold induction). In guinea pig cochlea, total platinum concentration (0.12 vs 0.63 μg/kg, respectively, P = .008) and perilymphatic drug concentrations (238 vs 515 μM × minute, respectively, P < .001) were lower after intravenous oxaliplatin treatment (16.6 mg/kg) than after equimolar cisplatin treatment (12.5 mg/kg). However, after a non-ototoxic cisplatin dose (5 mg/kg) or the same oxaliplatin dose (16.6 mg/kg), the AUC for perilymphatic concentrations was similar, indicating that the two drugs have different cochlear pharmacokinetics.ConclusionCisplatin- but not oxaliplatin-induced apoptosis involved superoxide-related pathways. Lower cochlear uptake of oxaliplatin than cisplatin appears to be a major explanation for its lower ototoxicity.

PurposeThis retrospective single-institution cohort study aims to evaluate if therapeutic approach, tumour site, tumour stage, BMI, gender, age and civil status predict body weight loss and to establish the association between weight loss on postoperative infections and mortality.MethodsConsecutive patients with head and neck cancer were seen for nutritional control at a nurse-led outpatient clinic and followed-up for 2 years after radiotherapy. Demographic, disease-specific and nutrition data were collected from case records. The primary outcome measure was maximum body weight loss during the whole study period.ResultsThe nadir of body weight loss was observed 6 months after radiotherapy. In total, 92 patients of 157 (59%) with no evidence of residual tumour after treatment received enteral nutrition. The mean maximum weight loss for patients receiving enteral nutrition and per oral feeding was 13% and 6%, respectively (p < 0.001). Using multivariate analysis, tumour stage (p < 0.001) was the only independent factor of maximum weight loss. Weight loss was not significantly related to risk for postoperative infection.ConclusionsWeight loss is frequently noted among head and neck cancer patients during and after treatment. Weight loss was not found to be associated with postoperative infections and mortality. Nutritional surveillance is important in all patients, but special attention should be given to those on enteral nutrition and those with more advanced disease.

Background Weight loss is common among patients with squamous cell carcinoma of the head and neck (SCCHN) and is mainly due to tumor and treatment related factors. The aim of the present study was to evaluate weight loss in patients with SCCHN undergoing two different radiotherapy (RT) schedules.Material and methodsNutritional data were analyzed from the ARTSCAN study, a controlled randomized prospective Swedish multicenter study conducted with the aim of comparing conventional fractionation (2.0 Gy per day, total 68 Gy during 7 weeks) and accelerated fractionation (1.1 + 2.0 Gy per day, total 68 Gy during 4.5 weeks). Seven hundred and fifty patients were randomized and 712 patients were followed from the start of RT in the present nutritional study.ResultsThe patients had a weight loss of 11.3% (± 8.6%) during the acute phase (start of RT up to five months after the termination of RT). No difference in weight loss was seen between the two RT fractionation schedules (p = 0.839). Three factors were significantly predictive for weight loss during the acute phase, i.e. tumor site, overweight/obesity or lack of tube feeding at the start of RT. Moreover, the nadir point of weight loss occurred at five months after the termination of RT.ConclusionThe results of the present study showed no difference in weight loss between the two RT fractionation schedules and also highlight that weight loss in SCCHN is a multifactorial problem. Moreover, the nadir of weight loss occurred at five months after the termination of treatment which calls for more intense nutritional interventions during the period after treatment.

Smoking was consistently associated with increase in oropharyngeal cancer risk in models stratified by HPV16 seropositivity. In addition, we report that the prevalence of oropharyngeal cancer increases with smoking for both HPV16-positive and HPV16-negative persons. The impact of smoking on HPV16-positive oropharyngeal cancer highlights the continued need for smoking cessation programmes for primary prevention of head and neck cancer.