Squamous cell carcinomas of the head and neck in Fanconi anemia: risk, prevention, therapy, and the need for guidelines.

Fanconi anemia (FA) is a rare recessive DNA repair disorder that is clinically characterized by congenital malformations, progressive bone marrow failure, and increased incidence of malignancies, especially acute myeloid leukemia and squamous cell carcinomas of the head and neck (HNSCCs) and the anogenital regions. On a cellular level, typical features of the disorder are a high degree of genomic instability and an increased sensitivity to bi-functionally alkylating agents. So far, germ-line defects in 15 different FA genes have been identified. Some of these FA genes are also established as tumor susceptibility genes for familiar cancers.In recent years, the prevention and therapy of HNSCCs in FA patients has become more important as the percentage of patients surviving into adulthood is rising. HNSCCs appear in very young FA patients without common risk factors. Since cisplatin-based chemotherapy in combination with radiotherapy, essential parts of the standard treatment approach for sporadic HNSCCs, cannot be used in FA patients due to therapy-associated toxicities and mortalities even with reduced dosing, surgery is the most important treatment option for HNSCCs, in FA patients and requires an early and efficient detection of malignant lesions. So far, no uniform treatment protocol for the management of HNSCCs in FA patients exists. Therefore, we propose that the information on affected FA patients should be collected worldwide, practical therapeutic guidelines developed and national treatment centers established.

Estimating the prevalence of and treatment patterns for juvenile onset recurrent respiratory papillomatosis in Australia pre-vaccination: a pilot study.

BACKGROUND: Recurrent respiratory papillomatosis (RRP) causes serious morbidity. RRP in Australia may be eliminated in the near future following the implementation of a national vaccination program using a human papillomavirus (HPV) vaccine that protects against infection with HPV types 6 and 11, those responsible for RRP. Baseline data on RRP prevalence and disease burden in Australia are lacking. METHODS: Three study methods were used to estimate the burden of juvenile onset RRP in Australia. We conducted a retrospective chart review of RRP cases treated at The Children's Hospital at Westmead over 10 years, examined the coding of these cases, and then calculated and applied the positive predictive value of the codes to national data to estimate the prevalence of RRP in Australia. We also conducted an online survey of otolaryngologists in Australia who manage RRP. RESULTS: Nineteen patients were treated at the hospital over 10 years, involving 359 admissions. We estimate that between 33 and 56 RRP cases aged <20 are being treated nationally per year (0.6-1.1 per 100 000 persons), with children 5-9 years having a higher estimated rate of 1.2-1.8 per 100 000. Among 39 otolaryngologists treating juvenile onset RRP, the majority (73%) treated RRP in a paediatric tertiary hospital, and used the microdebrider for ablation of lesions. CONCLUSIONS: Our estimates of RRP disease burden agree with international estimates. As a small number of clinicians treat RRP nationally, we believe that establishment of a national RRP register is both feasible and necessary to monitor the impact of vaccination.

[Prophylactic and therapeutic vaccines against human papilloma virus]. / Prophylaktische und therapeutische Vakzinen gegen humane Papillomviren.

Infection with human papilloma virus (HPV) has been identified as the cause of recurrent papillomatosis and of a subgroup of squamous cell carcinomas of the head and neck. A change in prevalence of these lesions, especially for oropharyngeal carcinoma, can be expected as a consequence of the introduction of prophylactic HPV vaccines for young women, targeting the most frequent high- and low-risk HPV subtypes. Vaccination for the major low-risk HPV types has proven to be highly effective against genital warts and activity against papillomatosis can be expected. The possibilities of prophylactic HPV vaccination as well as new developments and the rationale for therapeutic vaccines are discussed on the basis of the current literature.

Reduced risk of head and neck second primary tumors after radiotherapy.

BACKGROUND AND PURPOSE: With radiotherapy of primary tumors of the head and neck, a significant dose reaches the surrounding mucosa. The field cancerization and second field tumor theories state that premalignant lesions are present in the mucosa even at the time of primary tumor treatment. We tested the hypothesis that exposure to irradiation stabilizes subclinical premalignant lesions. This would reduce the rate of second primary tumors in the upper aerodigestive tract (UADT). MATERIALS AND METHODS: The cohort consisted of 346 patients treated for small localized squamous cell carcinoma of the oral cavity (T1-2, N0, and M0). The rate of UADT second primary tumors was compared between 247 patients exposed to radiation (case subjects) and 99 patients unexposed to radiation (control subjects). RESULTS: Median time to UADT second primary tumor was 8.6 years for irradiated patients and 3.9 years for controls (p=0.007). Through the first 5 years after the treatment of the primary tumor, the relative risk of developing a new UADT tumor for irradiated patients compared to controls was 0.12 (p<0.001). After 5 years the risk increased for irradiated cases. A corresponding change in risk was not found for controls. CONCLUSIONS: A slower rate of second primary tumors was seen within UADT mucosa exposed to irradiation. This could suggest a preventive effect by radiation on malignant transformation of subclinical premalignant foci.

Secular trend in U.S. black-white disparities in selected alcohol-related cancer incidence rates.

AIMS: To examine secular trends in incidence rates for the cancer types most strongly associated with alcohol in African Americans (blacks) and whites. METHODS: Average annual age-standardized incidence rates (ASIRs) for years of diagnosis 1973-1975 through 2000-2002 were analysed for squamous cell carcinomas of the oral cavity pharynx, oesophagus and larynx in U.S. blacks and whites by sex, using data from a group of high-quality population-based cancer registries. Also examined were National Health Interview Survey (NHIS) results on prevalence of current drinking and cigarette smoking among the U.S. population, and U.S. age-standardized mortality rates for alcoholic liver disease-damage from 1979 to 2003. RESULTS: In 1973-1975, ASIRs were greater in blacks than whites for cancers of the oesophagus and larynx but not oral cavity pharynx, and peaks in the disparity reached in the 1980's were followed by declines except for laryngeal cancer (the cancer most strongly associated with tobacco). By 2000-2002, black-white disparities in ASIRs were highest for oesophagus (black/white ratio 4.3 for males and 2.9 for females) but lower for laryngeal cancer and small or non-existent for oral cavity pharynx. NHIS data showed that by the 1970s the U.S. black/white ratios of prevalence were slightly > 1.0 for current smoking but 0.9 (and 0.7 by 1997 and 2003) for current drinking. Disparities in alcoholic liver disease had disappeared by 2003. CONCLUSIONS: Further declines in black-white disparities in cancer rates may occur (allowing for lag times), but the larger disparities for oesophageal cancer support the need to explore etiologic factors interacting with alcohol that continue to differ in prevalence between blacks and whites.

Dietary antioxidant intake in patients at risk for second primary cancer.

OBJECTIVES: To analyze dietary antioxidant intake for head and neck cancer patients at risk for development of second primary cancers. STUDY DESIGN: Prospective observational study. METHODS: Twenty-four patients underwent three random, unscheduled, 24-hour dietary recalls over a 15-day period within 6 to 60 months after successful treatment for stage I or II oral cavity squamous cell carcinoma. RESULTS: The study sample had a lower mean daily dietary intake of fruits and vegetables and antioxidant nutrients, including vitamins A, C, E, and total carotenes than age- and sex-matched historic control subjects (all P <.05 except vitamin A). A positive linear correlation was noted between daily servings of F&V and dietary intake of vitamins A, C, E, and total carotenoids (all P <.05 except vitamin A). Compared to current recommendations, the study sample had lower mean daily dietary intake of vitamins A, C, and E (P =.81,.06, and <.01) and servings of fruits and vegetables (P <.01). When vitamin supplements were included in the analysis, mean daily intake exceeded recommended dietary allowance (RDA) for vitamins A, C, and E (all P <.05). CONCLUSION: This study suggests that patients treated for early-stage oral cavity carcinoma, at risk for second primary cancers, have a statistically significant deficiency in dietary (food) sources of antioxidant nutrients when compared with both historic control subjects and current recommendations. Vitamin supplementation significantly exceeded current RDAs. Because increased fruit and vegetable intake, but not vitamin supplementation exceeding RDA, is associated with reduced cancer risk, physicians may consider recommending at least five daily servings of fruits and vegetables as an alternative to vitamin supplementation.

Chemoprevention of aerodigestive tract cancers.

Epithelial cancers are a major worldwide health problem. Since the mid-1970s, advances in multidisciplinary cancer therapeutics have only slightly improved the mortality rate from epithelial malignancies. Chemoprevention is the use of specific natural or synthetic chemical agents to reverse, suppress, or prevent progression to invasive cancer. Chemopreventive medicine is based on translating basic biologic research into clinical chemical interventions, thus attempting to impede carcinogenesis. Its principles build on the concepts of field cancerization (diffuse epithelial injury that results from carcinogen exposure) and multistep carcinogenesis (a stepwise accumulation of cellular and genetic alterations that progress to cancer). Chemoprevention targets the carcinogenic process at earlier and potentially more reversible stages, focusing on the inhibition of one or many steps in the progression towards cancer. Strategies of chemoprevention include primary prevention in groups at high risk, reversal of premalignant lesions, and prevention of second primary tumors.

[In vitro determination of the cytotoxic activity of saliva samples of smokers]. / In-vitro-Bestimmung zytotoxischer Aktivität in Speichelproben von Rauchern.

BACKGROUND: The question arised whether saliva can be included in populations monitoring of high risk groups for the development of head and neck squamous cell carcinomas. Cytotoxic mechanisms strongly influence the carcinogenesis of squamous cell carcinomas. PATIENTS AND METHODS: Saliva specimen of 131 abusing and non-abusing probands were tested on their biological (cytotoxic) effects to draw conclusions on the individual cancer risk. To determine the cytotoxic activity of saliva, we used the "plating efficiency index" of lungfibroblasts of the chinese hamster. RESULTS: We found significantly increased cytotoxic effects in the saliva of smoking probands (p < 0.002). Regularly combined smoking and drinking of alcohol led to a highly significant increased risk of cytotoxic saliva in the tested persons (odds ratio: 17.4; p < 0.005). CONCLUSIONS: Including patients with head and neck squamous cell carcinomas, ongoing studies must prove the practical relevance of this biomarker for estimating the relative cancer risk in the upper aerodigestive tract.

[Biomarkers of carcinogenesis of the upper and lower airway epithelium and the role of chemoprevention]. / Biomarqueurs de carcinogenèse des voies aériennes et place de la chimioprévention.

Lung as well as head and neck cancer represent an important public health problem worldwide, with lung cancer being the leading cause of cancer death in western countries. Although early stage disease is often curable with surgery or radiotherapy, the majority of patients present with advanced disease in which despite advances in combined modality therapy the outcomes have not dramatically improved. Furthermore, patients cured of their initial early stage lung or head and neck carcinoma are at high risk for development of second primary tumors, which pose the main threat to their survival. An alternative approach in reducing the incidence and thus mortality of these cancers is chemoprevention, the use of agents to reverse, halt or delay carcinogenesis. The carcinogenesis process in lung and head and neck cancer results from a dysregulation of cellular proliferation, differentiation and cell death resulting from field-wide exposure of the upper and lower airway track to tobacco smoking. This review article presents main data regarding the actual understanding of lung and head and neck carcinogenesis, as well as results of major chemoprevention trials in this field.

Costs of posttreatment surveillance for patients with upper aerodigestive tract cancer.

OBJECTIVES: To determine the range of recommended follow-up strategies for patients with upper aerodigestive tract cancer treated with curative intent and to estimate the cost of follow-up. DESIGN: Economic analyses of the costs associated with 31 follow-up strategies (12 generic and 19 site specific) identified from a MEDLINE search of the literature for 1978 to 1997 and a search of major textbooks. Generic strategies are not specific for site or histology and are exclusive of strategies designed for the rare patient, ie, patients who would not be considered average in terms of clinical characteristics. Charge data obtained from the Part B Medicare Annual Data File and the Hospital Outpatient Bill File were used as a proxy for cost. SETTING: Ambulatory care. MAIN OUTCOME MEASURES: Nationwide Medicare-allowed charges and an actual-charge proxy for 5 years of surveillance after treatment for upper aerodigestive tract cancer. RESULTS: Medicare-allowed charges for 5-year follow-up ranged from a low of $739 to a high of $14,079 for the generic and site-specific strategies combined and from $739 to $4646 for the 12 generic strategies alone. When Medicare-allowed charges were converted to a proxy for actual charges using a conversion ratio of 1.62, the range was $1198 to $22,807 for all strategies combined (a 19-fold difference in charges) and $1198 to $7597 for the generic strategies alone (a 5-fold difference in charges). CONCLUSIONS: Charges vary extensively across surveillance strategies, particularly if site-specific strategies are considered, although the potential benefit of more intensive, higher-cost strategies on survival or quality of life has yet to be demonstrated.

[Is endoscopy of the respiratory-digestive tract under general anesthesia useful in the screening for cancer of the superior respiratory-digestive tract synchronous with lung cancer?]. / L'endoscopie des voies aéro-digestives sous anesthésie générale est-elle utile au dépistage des cancers des voies aéro-digestives supérieures synchrones des cancers bronchiques?

The frequency of lung cancers associated with synchronous head and neck malignancies can be evaluated between 1.5 to 2%. The purpose of our work was to determine if complete endoscopic head and neck examination performed under general anesthesia was superior than clinical head and neck examination for the diagnosis of these synchronous additional tumors. From july 1991 to august 1992, we realised a prospective study on 58 consecutive patients suffering from pulmonary removable lung cancers. All the patients had a clinical head and neck examination during the preoperative period. Immediately before thoracotomy a complete endoscopy of head and neck aerian and digestive tract was performed. During this last examination 18 new macroscopical lesions were discovered in 13 patients: benign lesions (n = 17), oral cavity and laryngeal dysplasia (n = 1). The one gingivolingual sulcus carcinoma, already discovered by the clinical examination, was confirmed. This study suggests that complete head and neck endoscopy is not superior than clinical examination for the diagnosis of synchronous malignancies before lung cancers removal.

[Smoking and infections, tumors of the ENT area]. / Rauchen und Infektionen, Geschwülste im HNO-Gebiet.

Smoking disturbs health and causes inflammations und tumors in the upper respiratory tract. Passive smoking is also dangerous, especially for children of smoking parents. Health is incompatible with smoking.

[Prospects and indications for the prevention of respiratory tract tumors]. / Prospettive ed indicazioni per la prevenzione.

Respiratory cancers are suitable targets for primary prevention, since their causes are largely known and can be eliminated. Reasonable short-term objectives include the reduction of tobacco use (and alcohol abuse), the control of exposure to carcinogens in the workplace, as well as the reduction of air pollution in the general environment. The International Agency for Research on Cancer has estimated that in countries like Italy the elimination of cigarette smoking could reduce larynx cancer by 85% (if accompanied by a decrease in alcohol consumption), and lung cancer by 80% in males and 60% in females. An almost complete elimination of exposure to carcinogens in the workplace could potentially reduce lung cancer by 10%, whereas eliminating exposure to asbestos could certainly reduce pleural cancer by more than 50%. The proportion of lung cancer attributable to pollution in the general environment is unclear. Preventive measures require legislative support. Since October 1991, stores throughout Italy, in compliance with a new law, started carrying the first cigarette packages that included warnings against the hazards of smoking. Not since Law 584 of 1975, which forbids smoking in public places, has such an important legislative measure been passed. As a consequence of Law 584, smoking in many public places (e.g. movie theaters and, more recently, domestic flights) is today unthinkable, and these restrictions have been widely integrated into the Italian way of life. In developed countries, there is no doubt that the reduction of cancer due to the elimination of tobacco would be greater than that due to eliminating exposure to risk factors in the workplace.(ABSTRACT TRUNCATED AT 250 WORDS)

Multiple cancers of the upper aero-digestive tract: the challenge of risk factor identification.

Carcinomas of the upper aero-digestive tract (UADT) are among the most common neoplasms, particularly in developing countries. The generally poor prognosis for UADT cancer patients is further complicated by the occurrence during follow-up of additional cancers of the same or related sites. Proper quantification of the incidence of these second cancers and characterization of their risk factors have been plagued with methodological difficulties. The effects of tobacco and alcohol consumption vary with anatomic site, which requires that matching or adjustment by site be performed in any comparisons between single primary and multiple primary patients. Clinical variables, such as disease extension, treatment and survival, also influence risk of second malignancies. However, these parameters are also strongly interrelated, which makes it difficult to characterize their individual associations with risk or to control for their confounding effects when examining other variables. These shortcomings should be taken into consideration in the design of studies searching for genetic and other inter-individual variations in susceptibility to multiple UADT malignancies.

[General aspects of secondary prevention and possible interventions applicable to squamous carcinoma of the upper respiratory-digestive tract]. / Aspetti generali di prevenzione secondaria e possibili interventi applicativi sul carcinoma squamoso delle vie aero-digestive superiori.

The authors report some aspects of secondary prevention, including screening programs. General standards for screening programs are first analyzed; standards including a) definition of the problem and its social importance; b) tumor natural history; c) diagnostic test characteristics; d) therapeutic possibilities; e) evaluation of results. The problem of selective screenings are then discussed as they attempt to reduce costs and maximize benefits.