Predictive Value of CD8 Expression and FoxP3 Methylation in Nasopharyngeal Carcinoma Patients Treated with Chemoradiotherapy in a Non-endemic Area.

Undifferentiated Nasopharyngeal Carcinoma (UNPC) is associated with Epstein-Barr Virus (EBV) and characterized by an abundant immune infiltrate potentially influencing the prognosis. Thus, we retrospectively assessed the significance of immunosuppression in the UNPC microenvironment as prognostic biomarker of treatment failure in a non-endemic area, and monitored the variation of systemic EBV-specific immunity before and after chemoradiotherapy (CRT). DNA and RNA were extracted from diagnostic biopsies obtained by tumor and adjacent mucosa from 63 consecutive EBV+ UNPC patients who underwent radical CRT. Among these patients 11 relapsed within 2 years. The expression of the EBV-derived UNPC-specific BARF1 gene and several immune-related genes was monitored through quantitative RT-PCR and methylation-specific PCR analyses. Peripheral T cell responses against EBV and BARF1 were measured in 14 patients (7 relapses) through IFN-γ ELISPOT assay. We found significantly higher expression levels of BARF1, CD8, IFN-γ, IDO, PD-L1, and PD-1 in UNPC samples compared to healthy tissues. CD8 expression was significantly reduced in both tumor and healthy tissues in UNPC patients who relapsed within two years. We observed a hypomethylated FOXP3 intron 1 exclusively in relapsed UNPC patients. Finally, we noticed a significant decrease in EBV- and BARF1-specific T-cells after CRT only in relapsing patients. Our data suggest that a high level of immunosuppression (low CD8, hypomethylated FoxP3) in UNPC microenvironment may predict treatment failure and may allow an early identification of patients who could benefit from the addition of immune modulating strategies to improve first line CRT.

Multidisciplinary treatment approach for primary thyroid spindle cell sarcoma: A case report.

A 25-year-old female with high-grade spindle cell sarcoma of the thyroid persistent after thyroidectomy performed at another hospital was referred to our institute. Chemotherapy followed by surgery with intraoperative radiotherapy and postoperative intensity-modulated radiotherapy were planned within the sarcoma board. Chemotherapy was discontinued after two cycles because of local disease progression and surgery with intraoperative radiotherapy, was anticipated. The treatment was completed with postoperative radiotherapy. After 36 months off-therapy, the patient was free of disease without significant late effects. Thyroid sarcomas are very rare and there is no consensus on their clinical management. Hence, case reports are useful to share treatment options. In this patient case, the histotype and the high-grade disease required a combined therapy program, managed in a multidisciplinary setting.

Long-term update of the 24954 EORTC phase III trial on larynx preservation.

The long-term results of the EORTC 24954 trial comparing sequential versus alternating chemotherapy and radiotherapy (RT) for patients with locally advanced laryngeal and hypopharyngeal cancer are reported. From 1996 to 2004, 450 patients were randomly assigned (1-1) to a sequential arm (SA = induction cisplatin-5fluorouracil followed by a 70Gy-RT for the responders or a total laryngectomy and post-operative RT for the non-responders) and an alternating arm (AA = cisplatin-5fluorouracil alternated with three 2-week courses of 20 Gy-RT for a total dose of 60 Gy). Median follow-up was 10.2 years. Ten-year survival with functional larynx (primary end-point) and overall survival were similar in both arms (18.7% and 33.6% in SA versus 18.3% and 31.6% in AA). Late toxicity was also similar; however, a trend for higher larynx preservation and better laryngeal function was observed in AA.

Head and neck cancer survivors patients and late effects related to oncologic treatment: update of literature.

Cancer survivorship represents a new challenge in the third Millennium. In Europe the number of cancer survivors was estimated to be 17,8 million in 2008 and this number is growing. Recent improvements in cancer survival are largely due to earlier diagnosis and advancements in treatment. Despite having favorable effects on cancer survival, radiation therapy, surgery treatment and combination chemotherapy regimens can also cause long-term organ damage and functional disabilities. In this paper we review the most important aspects of long-term toxicities in otolaryngology cancer survivors patients.

Dietary intakes of carotenoids and other nutrients in the risk of nasopharyngeal carcinoma: a case-control study in Italy.

BACKGROUND: Dietary habits have been related to the risk of nasopharyngeal carcinoma (NPC), but information on a wide range of macro- and micronutrients is still lacking, particularly for low-incidence countries. METHODS: We conducted a hospital-based case-control study in Italy on 198, histologically confirmed, NPC cases of Caucasian ethnicity of 18-76 years of age. Controls were 594 Caucasian cancer-free patients admitted to general hospitals for acute conditions. Nutrients intake was assessed through a validated food-frequency questionnaire. Adjusted odds ratios (ORs) and the corresponding confidence intervals (CIs) were estimated through logistic regression. RESULTS: Dietary intake of carotenoids were inversely related to NPC risk, notably carotene (OR for highest vs lowest quartile=0.46; 95% CI: 0.26-0.79), α-carotene (OR=0.57; 95% CI: 0.33-0.97), and ß-carotene (OR=0.42; 95% CI: 0.24-0.75). Increased NPC risk was observed for elevate cholesterol intake (OR=1.85; 95% CI: 1.12-3.05). CONCLUSION: Study findings suggest a protective effect of carotenoids against NPC in a low-risk population, adding further support to a possible beneficial role of a diet rich in fruits and vegetables in cancers of the head and neck.

Sentinel lymph node biopsy in squamous cell carcinoma of the head and neck: 10 years of experience.

Sentinel node (SN) biopsy of head and neck cancer is still considered investigational, and agreement on the width of the surgical sampling has not yet been reached. From May 1999 to Dec 2009, 209 consecutive patients entered a prospective study: 61.7% had primary tumour of the oral cavity and 23.9% of the oropharynx. SN was not found in 26 patients. Based on these data and definitive histopathological analysis, we proposed six hypothetic scenarios to understand the percentage of neck recurrences following different treatments Among patients with identified SN, 54 cases were pN+: 47 in SN and 7 in a different node. Considering the six hypothetic scenarios: "only SN removal", "SN level dissection", "neck dissection from the tumour site to SN level", "selective neck dissection of three levels (SND)", "dissection from level I to IV" and "comprehensive I-V dissection", neck recurrences could be expected in 6.5%, 3.8%, 2.18%, 2.73%, 1.09% and 1.09% of cases, respectively. SN biopsy can be considered a useful tool to personalize the surgical approach to a N0 carcinoma. The minimum treatment of the neck is probably dissection of the levels between the primary tumour and the level containing the SN(s). Outside the framework of a clinical study, the best treatment can still be considered SND.

Role of medical history and medication use in the aetiology of upper aerodigestive tract cancers in Europe: the ARCAGE study.

BACKGROUND: The study aimed to investigate the role of medical history (skin warts, Candida albicans, herpetic lesions, heartburn, regurgitation) and medication use (for heartburn; for regurgitation; aspirin) in the aetiology of upper aerodigestive tract (UADT) cancer. METHODS: A multicentre (10 European countries) case-control study [Alcohol-Related CAncers and GEnetic susceptibility (ARCAGE) project]. RESULTS: There were 1779 cases of UADT cancer and 1993 controls. History of warts or C. albicans infection was associated with a reduced risk [odds ratio (OR) 0.80, 95% confidence interval (CI) 0.68-0.94 and OR 0.73, 95% CI 0.60-0.89, respectively] but there was no association with herpetic lesions, heartburn, regurgitation or medication for related symptoms. Regurgitation was associated with an increased risk for cancer of the oesophagus (OR 1.47, 95% CI 0.98-2.21). Regular aspirin use was not associated with risk of UADT cancer overall but was associated with a reduced risk for cancer of oesophagus (OR 0.51, 95% CI 0.28-0.96), hypopharynx (OR 0.53, 95% CI 0.28-1.02) and larynx (OR 0.74, 95% CI 0.54-1.01). CONCLUSIONS: A history of some infections appears to be a marker for decreased risk of UADT cancer. The role of medical history and medication use varied by UADT subsites with aspirin use associated with a decreased risk of oesophageal cancer and suggestive of a decreased risk of hypopharyngeal and laryngeal cancers.

Submandibular approach and use of the harmonic instrument in lateral oral cavity and oropharyngeal oncologic surgery.

The approach to the surgical treatment of lateral oral cavity and oro-pharyngeal cancer has undergone many changes over the years, passing from a demolitive approach involving segmental resectioning of the mandible to a conservative approach with temporary mandibulotomy. The complications resulting from these two different approaches invited further review of the various indications related to them. The present report considers, through a retrospective analysis, whether the sub-mandibular approach, which envisages the use of the harmonic instrument, is an oncologically correct alternative and whether it actually reduces the number of early and late complications. From 2003 to 2009, 259 patients underwent surgery for lateral oral cavity and oro-pharyngeal cancer. A sub-mandibular approach was used in 163 patients, and a conservative trans-mandibular approach in 12. The results showed that the number of late complications and T recurrences was significantly lower in those patients in whom the sub-mandibular approach was carried out. There was no difference in the microscopic examination of the resection margins. The use of the harmonic instrument made it possible to perform "en bloc" (T+N) operations working in narrow spaces with less intra-operative bleeding, which contributed to adequate oncological radicality.

Socioeconomic factors associated with risk of upper aerodigestive tract cancer in Europe.

INTRODUCTION: In the European Union, there are 180,000 new cases of upper aerodigestive tract (UADT) cancer cases per year--more than half of whom will die of the disease. Socioeconomic inequalities in UADT cancer incidence are recognised across Europe. We aimed to assess the components of socioeconomic risk both independently and through their influence on the known behavioural risk factors of smoking, alcohol consumption and diet. PATIENTS AND METHODS: A multicentre case-control study with 2198 cases of UADT cancer and 2141 controls from hospital and population sources was undertaken involving 14 centres from 10 countries. Personal interviews collected information on demographics, lifetime occupation history, smoking, alcohol consumption and diet. Socioeconomic status was measured by education, occupational social class and unemployment. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed using unconditional logistic regression. RESULTS: When controlling for age, sex and centre significantly increased risks for UADT cancer were observed for those with low versus high educational attainment OR=1.98 (95% CI 1.67, 2.36). Similarly, for occupational socioeconomic indicators--comparing the lowest versus highest International Socio-Economic Index (ISEI) quartile for the longest occupation gave OR=1.60 (1.28, 2.00); and for unemployment OR=1.64 (1.24, 2.17). Statistical significance remained for low education when adjusting for smoking, alcohol and diet behaviours OR=1.29 (1.06, 1.57) in the multivariate analysis. Inequalities were observed only among men but not among women and were greater among those in the British Isles and Eastern European countries than in Southern and Central/Northern European countries. Associations were broadly consistent for subsite and source of controls (hospital and community). CONCLUSION: Socioeconomic inequalities for UADT cancers are only observed among men and are not totally explained by smoking, alcohol drinking and diet.

Phase 3 randomized trial on larynx preservation comparing sequential vs alternating chemotherapy and radiotherapy.

BACKGROUND: Both induction chemotherapy followed by irradiation and concurrent chemotherapy and radiotherapy have been reported as valuable alternatives to total laryngectomy in patients with advanced larynx or hypopharynx cancer. We report results of the randomized phase 3 trial 24954 from the European Organization for Research and Treatment of Cancer. METHODS: Patients with resectable advanced squamous cell carcinoma of the larynx (tumor stage T3-T4) or hypopharynx (T2-T4), with regional lymph nodes in the neck staged as N0-N2 and with no metastasis, were randomly assigned to treatment in the sequential (or control) or the alternating (or experimental) arm. In the sequential arm, patients with a 50% or more reduction in primary tumor size after two cycles of cisplatin and 5-fluorouracil received another two cycles, followed by radiotherapy (70 Gy total). In the alternating arm, a total of four cycles of cisplatin and 5-fluorouracil (in weeks 1, 4, 7, and 10) were alternated with radiotherapy with 20 Gy during the three 2-week intervals between chemotherapy cycles (60 Gy total). All nonresponders underwent salvage surgery and postoperative radiotherapy. The Kaplan-Meier method was used to obtain time-to-event data. RESULTS: The 450 patients were randomly assigned to treatment (224 to the sequential arm and 226 to the alternating arm). Median follow-up was 6.5 years. Survival with a functional larynx was similar in sequential and alternating arms (hazard ratio of death and/or event = 0.85, 95% confidence interval = 0.68 to 1.06), as were median overall survival (4.4 and 5.1 years, respectively) and median progression-free interval (3.0 and 3.1 years, respectively). Grade 3 or 4 mucositis occurred in 64 (32%) of the 200 patients in the sequential arm who received radiotherapy and in 47 (21%) of the 220 patients in the alternating arm. Late severe edema and/or fibrosis was observed in 32 (16%) patients in the sequential arm and in 25 (11%) in the alternating arm. CONCLUSIONS: Larynx preservation, progression-free interval, and overall survival were similar in both arms, as were acute and late toxic effects.

A prospective, randomized, double-blind comparison between parecoxib and ketorolac for early postoperative analgesia following nasal surgery.

BACKGROUND: The aim of this prospective, randomized, double-blind study was to compare the efficacy of parecoxibfor postoperative analgesia after endoscopic turbinate and sinus surgery, with the non-selective non-steroid anti-inflammatory drug (NSAID), ketorolac. METHODS: A total of 50 patients with an ASA physical status I-II, receiving functional endoscopic sinus surgery (FESS) and endoscopic turbinectomy after local infiltration with 1% mepivacaine, were randomly assigned to receive intravenous administration of either 40 mg parecoxib (N.=25) or 30 mg ketorolac (N.=25), 15 min before the discontinuation of anaesthesia and then every 8 h postoperatively. A blinded observer recorded the incidence and severity of pain upon admission to the postanesthesia care unit (PACU), as well as 10, 20, and 30 min after PACU admission. Thereafter, observations continued every 1 h for the first 6 h, and then 12 h and 24 h after surgery. RESULTS: The area under the curve of the visual analogue scale (AUCVAS) calculated during the study period was 635 (26-1 413) in the Parecoxib group and 669 (28-1 901) in the Ketorolac group (P=0.54). Rescue morphine analgesia was required by 12 patients (48%) in the Parecoxib group and 11 patients (44%) in the Ketorolac group (P<0.05); while mean morphine consumption was 5 +/- 2.5 mg and 5 +/- 2.0 mg in Ketorolac and Parecoxib groups, respectively (P<0.05). No differences in the incidence of side effects were recorded between the two groups. Patient satisfaction was similarly high in both groups, and all patients were discharged uneventfully 24 h after surgery. CONCLUSION: In patients undergoing endoscopic nasal surgery and local infiltration with 1% mepivacaine, parecoxib administered before discontinuing general anesthesia is as effective in treating early postoperative pain as ketorolac.

Body size and laryngeal cancer risk.

BACKGROUND: A few studies have analyzed the role of lifetime anthropometric measures on laryngeal cancer risk. PATIENT AND METHODS: This relation was investigated using a multicentre case-control study from Italy, conducted between 1992 and 2000, and including 460 incident, histologically confirmed laryngeal cancer cases, and 1088 controls admitted to the same network of hospitals as cases for acute, non neoplastic condition. Odds ratios (OR) and corresponding 95% confidence intervals (CI) were obtained from multiple logistic regression, including terms for major confounding factors, such as physical activity and energy intake. RESULTS: An inverse association with laryngeal cancer risk was found for body mass index (BMI) in both sexes (OR for the lowest compared to the highest quintile was 1.47, 95% CI 0.93-2.33 in men and 8.11, 95% CI 1.38-47.66 in women) and for BMI at age 50 years (OR=1.65, 95% CI 0.88-3.11) in men and 7.84, 95% CI 0.69-88.58 in women). An inverse association was also observed with waist-to-hip ratio (WHR) at diagnosis in men only (OR=4.56, 95% CI 2.62-7.95 for the lowest compared to the highest quintile). CONCLUSIONS: This study supports the existence of a relation between leanness and laryngeal cancer risk. In particular, men with less abdominal fat (characterized by a lower WHR) had an increased risk of laryngeal cancer.

An extended use of the sentinel node in head and neck squamous cell carcinoma: results of a prospective study of 100 patients.

Most studies concerning the use of the sentinel node technique in head and neck cancers have included clinically N0 patients with primary early stage tumours of the oral cavity or upper part of oropharynx; furthermore, node sampling has been performed during the same session, but separately from the tumour. The perspective of avoiding unnecessary neck dissection, without increasing the risk of delayed diagnosis of lymph node metastasis, is rewarding, not only for early stage tumours of the oral cavity but also for tumours in advanced stages and/or at different anatomic sites. In the attempt to establish the reliability of extended use of the sentinel node technique, 100 consecutive untreated patients (from 1999 to 2002) with tumours located in the oral cavity, oropharynx, hypopharynx and larynx, at any T stage, entered the study. N+ patients with paramedian tumours and contralateral clinically negative nodes were also enrolled. After injection of the 99mTc albumin microcolloid, pre- and intra-operative evaluations with a gamma-probe were done. N0 patients (59) were submitted to mono- or bilateral selective neck dissection; the N+ patients (41) received homolateral dissection of all levels and contralateral selective dissection. An en bloc resection of the tumour was performed both in N0 and N+ patients. In the N0 group, histological examination showed no evidence of metastases in "hot" nodes in 34 patients and also the remaining nodes were negative. Metastases were found in one or more of the gamma-probe positive nodes (14 cases), or in a closely located node at the same level (2 cases) or in a node close to a "hot" area of the submandibular salivary gland (1 case). In 8 patients, lymphoscintigraphy did not identify any sentinel node and histology of all lymph nodes was negative for metastases. In the N+ group, no metastases were found in the sentinel nodes of 21 patients and also the remaining nodes were negative; in 4 patients, metastases were found in sentinel nodes. In 16 patients, lymphoscintigraphy did not identify any sentinel node and histology of all lymph nodes was negative for metastases. In no patients were metastases found outside the level containing the lymph node identified as sentinel by the gamma-probe. In conclusion, the strategy of the sentinel node is reliable, but, to be confirmed as a standard approach, it requires trials with a larger number of patients. The technique requires a multidisciplinary and well "amalgamated" team. It may likely be used also in T3 and T4 oro-hypopharyngeal and laryngeal primary tumours and to determine surgical treatment of the contralateral neck in patients with N2a, N2b, N3 on T close to the midline.

Squamous cell carcinoma of the hypopharynx treated with surgery and radiotherapy.

A series of squamous cell carcinomas (SCC) of the hypopharynx treated with combined surgery and radiotherapy is presented to highlight the results of treatment at an early stage of disease. A retrospective mono-institutional analysis was performed on 153 previously untreated patients with SCC of the hypopharynx, seen between 1980 and 1995 at our institution. Univariate and multivariate analyses were performed using the Cox proportional hazard model. The overall five-year specific, and non-specific, disease survival rates were 68 per cent (95 per cent confidence interval, CI: 60-77) and 47 per cent (95 per cent CI: 39-56), respectively. Compared with other series, this study is characterized by treatment at an earlier stage, better prognosis, and a higher number of multiple malignancies. Twenty-two per cent of hypopharyngeal SCCs were diagnosed during the staging procedures for a different head and neck SCC and 14 per cent during the follow-up for a previous tumour. Multivariate survival analysis of clinical and pathological factors confirmed the clinical class of tumour (T) and node (N) and the nodal capsular rupture as prognosticators of disease.

Nasopharyngeal cancer WHO type II-III: monoinstitutional retrospective analysis with standard and accelerated hyperfractionated radiation therapy.

The aim of this study is to assess the impact of prognostic factors in patients with locoregionally advanced nasopharyngeal cancer (NPC), WHO type II-III, treated with two different radiation therapy (RT) schedules: standard radiation therapy (SRT), and accelerated hyperfractionated radiation therapy (HART), with or without sequential chemotherapy. Between January 1986 and December 1999, 78 consecutive NPC patients were treated either with SRT (until August 1993) or with HART (from September 1993). Of the 78 patients, 60 were males and 18 females, the median age was 56 years (range 14-83). Nine patients had a non-keratinizing carcinoma (WHO type II) and 69 an undifferentiated carcinoma (WHO type III). Five-year overall survival rate (OS) was 62%. Two months after RT, 73 patients were in complete remission. Disease-free survival (DFS) rates at 5 years were: 85% for the HART and 59% for the SRT group, respectively. A multivariate analysis, age (hazard ratio, HR=4.17 for > or = 60 vs. <50 years) and N-stage (HR=3.56 for N3a-N3b vs. N0-N1) were significant for survival, whereas N-stage (HR=8.23 for N3a-N3b vs. N0-N1) and RT schedule (HR=0.30 for HART vs. SRT) were significant for DFS. In our experience, HART achieved higher DFS rates than SRT; however, HART did not favourably affect OS. Toxicity was comparable in the two RT schedules.

Combined effect of tobacco and alcohol on laryngeal cancer risk: a case-control study.

OBJECTIVE: To provide information on the effects of alcohol and tobacco on laryngeal cancer and its subsites. METHODS: This was a case-control study conducted between 1992 and 2000 in northern Italy and Switzerland. A total of 527 cases of incident squamous-cell carcinoma of the larynx and 1297 hospital controls frequency-matched with cases on age, sex, and area of residence were included. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using multiple logistic regression. RESULTS: In comparison with never smokers, ORs were 19.8 for current smokers and 7.0 for ex-smokers. The risk increased in relation to the number of cigarettes (OR = 42.9 for > or = 25 cigarettes/day) and for duration of smoking (OR = 37.2 for > or = 40 years). For alcohol, the risk increased in relation to number of drinks (OR = 5.9 for > or = 56 drinks per week). Combined alcohol and tobacco consumption showed a multiplicative (OR = 177) rather than an additive risk. For current smokers and current drinkers the risk was higher for supraglottis (ORs 54.9 and 2.6, respectively) than for glottis (ORs 7.4 and 1.8) and others subsites (ORs 10.9 and 1.9). CONCLUSIONS: Our study shows that both cigarette smoking and alcohol drinking are independent risk factors for laryngeal cancer. Heavy consumption of alcohol and cigarettes determined a multiplicative risk increase, possibly suggesting biological synergy.

The EORTC quality of life questionnaire-head and neck 35 in Italian laryngectomized patients. European organization for research and treatment of cancer.

The aim of this study was to test the validity and reliability of the European organization for research and treatment of cancer (EORTC) quality of life questionnaire (QLQ)-head and neck (H&N) 35 in Italian laryngeal cancer patients. The original questionnaire was developed by the EORTC quality of life (QoL) study group and tested in H&N cancer patients from Norway, Sweden, and the Netherlands. The Italian translation of the questionnaire used in this study was made by a team of the CRO, National Cancer Institute, using a double-back translation method between independent translators. The translated EORTC QLQ-H&N35 was given to 99 patients with H&N cancer who had undergone total laryngectomy 1-26 years before and had been then treated with radiotherapy and, in some cases, chemotherapy. The questionnaire was re-administrated to 33 patients after 1 month to test its stability over time. It was structurally made up of seven scales (pain, swallowing, sense, speech, social eating, social contact, and sexuality) and 11 single items that considered the most important clinical aspects characterizing the QoL in H&N cancer patients. The statistical analysis of the indexes of validity and reliability confirmed the results obtained with other linguistic versions of the questionnaire. Our Italian version of the EORTC QLQ-H&N35 proved to be a statistically valid instrument to assess QoL in laryngectomized patients.

Comparison of the effect of smoking and alcohol drinking between oral and pharyngeal cancer.

To compare the separate and combined effects of alcohol drinking and smoking between the 2 sites, we evaluated 274 men with oral cancer, 364 with pharyngeal cancer and 1,254 controls, frequency-matched for age and area of residence, from Italy and Switzerland. Extremely elevated risk increases for oral cancer (odds ratio, OR = 228) and pharyngeal cancer (OR = 100) were found for the highest joint level of drinking (>/=77 drinks/week) and smoking (>/=25 cigarettes/day). Ratios of ORs between oral cancer and pharyngeal cancer vs. controls, obtained by polytomous logistic regression, suggested that the risk increase for oral cancer was about 2-fold greater than that for pharyngeal cancer at each combined level of smoking and drinking, except at low levels of drinking in smokers. A clear departure from risk difference additivity was present for both oral and pharyngeal cancer in individuals heavily exposed to both factors versus non-smoking abstainers/light drinkers. Our findings thus help explain observations from descriptive epidemiology that, if smoking level in a population does not change substantially, but alcohol consumption increases, increase in oral cancer would be greater than at any other site in the upper aero-digestive tract, including cancer of the pharynx.

Food groups, oils and butter, and cancer of the oral cavity and pharynx.

To elucidate the role of dietary habits, a study was carried out in 1992-1997 in the province of Pordenone in Northeastern Italy, and those of Rome and Latina in central Italy. Cases were 512 men and 86 women with cancer of the oral cavity and pharynx (lip, salivary glands and nasopharynx excluded) and controls were 1008 men and 483 women who had been admitted to local hospitals for a broad range of acute non-neoplastic conditions. The validated dietary section of the questionnaire included 78 foods or recipes and ten questions on fat intake patterns. After allowance for education, smoking, alcohol and total energy intake, significant trends of increasing risk with increasing intake emerged for soups, eggs, processed meats, cakes and desserts, and butter. Risk was approximately halved in the highest compared to the lowest intake quintile for coffee and tea, white bread, poultry, fish, raw and cooked vegetables, citrus fruit, and olive oil. The inverse association with oils, especially olive oil, was only slightly attenuated by allowance for vegetable intake. Thus, frequent consumption of vegetables, citrus fruit, fish and vegetable oils were the major features of a low-risk diet for cancer of the oral cavity and pharynx.