Second primary tumours in oropharyngeal squamous cell carcinoma

Improved diagnostic techniques and more effective treatment concepts have resulted in a growing number of patients with oropharyngeal cancer diagnosed with second primary tumours. In order to evaluate the relative number of patients with second primary tumours and to estimate the efficacy of diagnostic procedures, a retrospective evaluation of 981 patients with oropharyngeal cancer, who were treated during 20 years in one single medical centre, was performed. In total, 9.2% of the patients were affected by secondary cancer, 1.5% from tertiary cancer and 0.2% from quartary cancer. Of the multiple cancers, 27.8% occurred synchronously and 72.2% metachronously. If the index tumour was located at the oral floor or the pharynx, the risk of second primary tumours was enhanced; if the index tumour was located at the lips or the tongue, the risk was reduced. The 5-year survival of all examined patients was 34.1%; the survival of patients with multiple cancers was 62.3% at the diagnosis of the index tumour and dropped to 30.5% at the diagnosis of an additional malignancy. Of the second primary tumours, 23.2% were diagnosed by panendoscopy. We conclude that among patients with oropharyngeal cancer, the presence of second primary tumours always has to be considered and that panendoscopy is a valuable tool for their diagnosis.     

Metastatic tumours to the oral cavity: a survival study with a special focus on gingival metastases

Aims: To describe survival from oral metastases, particularly gingival metastases, and to identify clinical prognostic variables.
Materials and Methods: A series of 39 patients were studied, analysing age, gender, primary tumour site, oral metastases site and histological type.
Results: Mean age: 62.3±9.2 years, with similar prevalence by gender. The most frequent sites for primary tumours were the kidney (20.5%), lung (20.5%) and breast (20.5%). Gingival metastases represented 63.6% of all oral soft tissue metastases (7/11). The average time between primary tumour diagnosis and appearance of the gingival metastases was 9.7±13.4 months. The median survival time since gingival metastases appearance was 5.2 months [95% confidence interval (CI)=0–13.6]; no statistically significant difference with other oral locations was found by the Kaplan–Meier curves (log rank: 0.29; p >0.05). Oral metastases involving the gingiva were more frequently found in the maxilla (85.7% versus 14.3%), whereas intra-osseous metastatic tumours were more frequent in the mandible (77.8% versus 22.2%; p <0.05; odds ratio=21; 95% CI=2.0–210.1). None of the variables considered had a prognostic value as indicated by the Kaplan–Meier test.
Practical implications: The data in this paper show that 25% (and in other studies up to 37%) of oral metastases came from unknown primary tumours; thus a biopsy with histopathologic analysis is mandatory for every patient with a gingival mass.
Conclusions: This study reinforces the significance of gingival metastases as a poor prognosis indicator. Dental practitioners should suspect that gingival masses mimicking benign or inflammatory lesions may represent a sign of underlying malignant tumours.     

Second cancers following oral and pharyngeal cancer: Patients' characteristics and survival patterns

A survey was made of second primary cancers among patients who were enrolled in a large case-control investigation of oral and pharyngeal cancer, hereafter called oral cancer, during 1984–1985 in four areas of the United States. Among the original 1090 patients with oral cancer (nearly all squamous cell carcinomas), 107 developed a second cancer (one-half of them squamous cell) by the end of follow-up in June 1989 (average follow-up 2.6 years), with 69% occurring in the oral cavity, pharynx, oesophagus, larynx or lung. Rates of second tumours varied by age and socioeconomic status, but not sex or race, and were higher among those whose initial cancer was localised, even after adjusting for their longer survival. Long-term survival was lower among those with second cancers. Conditional on surviving for 2 years, the survival at 5 years was under 50% and nearly 70%, respectively, for those with versus those without a second cancer in the first 2 years. These findings confirm the exceptionally high rate of second cancers (especially of the aerodigestive tract) following oral cancer, describe the clinical and pathological features of patients with multiple cancers and indicate the importance of preventive measures.     

Electrochemotherapy in non-melanoma head and neck cancers: a retrospective analysis of the treated cases

Electrochemotherapy increases the permeability of tumours to drugs by electric voltages applied locally. Its value in tumours of the head and neck is unknown. We retrospectively reviewed a 2-centre database, and found 39 patients with squamous cell carcinoma (SCC) of the oral cavity or oropharynx (n=12) or non-melanoma skin tumours (n=27) who had been treated with bleomycin electrochemotherapy with needle electrodes. A further 3 patients were given cisplatin electrochemotherapy (n=2), or bleomycin electrochemotherapy by plate electrodes (n=1). Local toxicity was mild. The complete response rate was 38% and was associated with whether the tumour was primary or recurrent (p<0.001), its size (p=0.02), and the route by which the drug was given (p=0.02). We did not study enough patients with basal cell carcinomas to say whether the response was significantly better or not (p=0.07). Skin tumours and SCC of the oral cavity or oropharynx showed comparable complete responses (41% and 33%, p=0.73) and local control (1-year local progression-free survival, 51% compared with 59%, p=0.89), particularly if they were small (p=0.001), primary (p=0.002), chemonaive (p=0.03). Patients treated with cisplatin were unresponsive. Electrochemotherapy with bleomycin is an effective option for skin tumours of the head and neck and is a feasible alternative in highly selected (small, primary, and not previously treated by chemotherapy) SCC of the oral cavity and oropharynx.     

Microbiology of wound infection after oral cancer surgery

IntroductionThe aim of present study is to investigate the most common infection pathogen found in the postoperative wounds, following surgical treatment of oral and oropharyngeal cancer, in order to identify the most suitable antibiotic treatment.Patients and methodsWe analyzed patients with squamous cell cancer of oral and oropharyngeal region. In patients who developed postoperative wound infection, wound swabs were taken from three different sites: the cannula, wounds on the neck and wounds in the oral cavity.ResultsIn total 195 patients were included. The postoperative wound infection was detected in 115 patients (59%). In average, the swabs were taken 8 days after the surgery. The similar bacterial species from all three sites were detected in 24 patients (12,3%). In comparison, we found that there was statistically significant difference in the bacteria abundance from all three sites (p=0,031). There were significantly more bacteria in the wounds of the neck than cannula (p=0,007) and in the wounds in the oral cavity than cannula (p=0,002). No statistically significant difference between the wound on the neck and in the oral cavity was found. The most frequently isolated bacterial family was Enterobacteriaceae. Other more commonly isolated bacteria species were Staphylococcus spp. (G+), Pseudomonas aeruginosa (G-), Corynebacteruim spp. (G +) and Acinetobacter baumanii (G-).ConclusionBased on the most commonly isolated groups of pathogens we concluded that probably the best empiric antibiotic treatment of wound infections until antibiogram is completed might be achieved from the group of aminoglycosides or quinolones. Antibiotic therapy should be reviewed if necessary when antibiogram is completed.     

Experimental study of mineralization in mandibular bone distraction with irradiation during the consolidation phase

INTRODUCTION: This study aimed at assessing the effect of radiotherapy on regenerated bone mineralization and consolidation obtained by mandibular bone distraction. The planned application was a new immediate mandibular reconstruction technique in defects following surgery for oral cavity tumours requiring postoperative radiotherapy. MATERIAL AND METHODS: Ten sheep underwent bilateral mandibular bone distraction (control group). A second group of 6 sheep (study group) had bilateral mandibular bone distraction followed by irradiation on the 21st postoperative day. The animals were sacrificed on the 60th postoperative day. Radiographic and histomorphometric studies were performed. RESULTS: In the control group, 9 distraction sites out of 20 were consolidated. In the irradiated group, 9 out of 12 were consolidated. Histomorphometric analysis did not demonstrate any statistically significant difference between the osseous and cartilaginous samples, the trabecular thickness of the new bone, or the osteoid surface of basal bone in the control and test groups (p=0.126, 0.247, 0.792, 0.082). However, the osteoid surface of the regenerated bone in the test group was statistically smaller (p=0.017) than in the control group. CONCLUSION: In this experiment, radiotherapy did not hinder bone mineralization or consolidation following distraction of mandibular bone receiving irradiation on the 21st postoperative day. Bone distraction could be proposed for the repair of mandibular defects following surgery for oral tumours which require early postoperative radiotherapy.     

HPV and other risk factors of oral cavity/oropharyngeal cancer in the Czech Republic

OBJECTIVE: An association between high-risk human papillomavirus (HR HPV) infection and a risk of development of a subgroup of head and neck cancers has been proposed recently. The main risk factors of oral and oropharyngal cancer observed in our population are smoking and alcohol consumption. The incidence of oral/oropharyngeal tumours in the Czech Republic is relatively high and there are no data available about the prevalence of HPV DNA presence in these tumours. MATERIALS AND METHODS: Eighty patients with a primary oropharyngeal cancer were enrolled. The presence of HPV DNA has been evaluated by polymerase chain reaction in 68 cases from which the tumour tissue and demographical and clinical data were available. The typing of HPV was performed by nucleotide DNA sequencing. RESULTS: The HPV DNA was detected in 51.5% of samples tested. Among the HPV DNA positive tumours, 80% contained HPV16. In the analysed group there were 54 men and 14 women. The prevalence of HPV DNA was lower in oral (25%) than in oropharyngeal (57%) tumours, and higher in never smokers (100%) and never drinkers (68.8%). HPV DNA presence was not related to gender, age, number of lifetime sexual partners or practice of oral-genital sex, size of tumour or presence of regional metastases. CONCLUSIONS: The difference in the prevalence of HPV DNA positive tumours between cases of oral cavity and oropharyngeal carcinoma exposed and not exposed to tobacco or alcohol support the theory that HPV DNA positive tumours form an aetiologically distinct subgroup of head and neck tumours.     

Racial disparity in stage at diagnosis and survival among adults with oral cancer in the US

OBJECTIVES: To explore distribution of stage at diagnosis and relative survival rates among US adults with oral cavity cancer in relation to race, and over time. METHODS: We obtained 1973-2002 oral cancer incidence data from the Surveillance, Epidemiology, and End Results (SEER) Program, and computed proportions for each oral cavity site by stage at diagnosis, tumor size, and 5-year relative survival rates among Whites and Blacks. RESULTS: A total of 46 855 cases of oral cavity cancer were reported to the SEER registry among adults > or =20 years between 1973 and 2002. African-Americans had a significantly higher proportion of cancer, mainly in the tongue, that had spread to a regional node or to a distant site at diagnosis than Whites: 67% versus 49% of tongue cancers reported from 1973 to 1987 (P < 0.001), and 70% versus 53% of those reported from 1988 to 2002 (P < 0.001). They had a significantly higher proportion of tongue cancer that were >4 cm in diameter at time of diagnosis (59% versus 44%; P < 0.001), and black men in particular experienced lower 5-year relative survival rates than white men, in particular, for tongue cancer (25% versus 43% from 1973 to 1987, and 31% versus 53% from 1988 to 2002). CONCLUSION: There are significant racial disparities with respect to stage at diagnosis and survival among adults with oral cancer reported to the SEER registry from 1973 to 2002. One possible explanation for the lower survival among Blacks may be a difference in access to, and utilization of, healthcare services.     

Prognosis in mouth cancer: Tumour factors

524 patients with histologically proven squamous cell carcinoma of the oral cavity who were previously untreated are studied for prognostic factors. There were various associations between T stage and site; T₂ being more common in buccal cancer, T₁ in tongue cancer, T₄ in floor of mouth tumours and T₂ in the roof of the mouth. Floor of mouth cancer tended to be more frequently associated with positive cervical lymph nodes than were other sites (45%). Well-differentiated tumours tended not to be associated with nodal disease (66%). Small tumours tended not to be associated with nodal metastases whereas large ones were. Univariate analysis of observed survival showed that well differentiated tumours had a slightly better survival than poorly-differentiated tumours (a difference of 8%). Survival fell with increasing T stage and with increasing pT stage. Positive resection margins and advanced pT stage in particular had a dismal prognosis. Survival also fell with increasing N stage and with increasing pathological N stage and extranodal rupture adversely affected prognosis. When the data were analysed by Cox's multivariate regression only two factors were found to be significant. These were T stage and N stage. Both were highly significant predictors of survival; survival falling with increasing stage.     

Performance and survival outcomes of defect-driven versus specimen-driven method of frozen section intraoperative margin assessment in oral cancers

Margin status is one of the most important prognostic factors in oral cancers. Intraoperative frozen section (FS) can be performed to ensure a margin-negative resection, however the method of FS assessment is debatable. The aim of this study was to compare the defect-driven (DDA) versus specimen-driven (SDA) approach for intraoperative assessment of tumour margins in oral cancer resections and their impact on loco-regional recurrence and survival. The primary study endpoint was margin status determined from the final histopathological examination report. Secondary endpoints were disease recurrence and survival. This retrospective cohort study compared the two methods of FS in terms of their performance and survival outcomes. All oral squamous cell carcinoma patients who underwent surgery as the primary treatment from January 2018 to February 2019 were included. The involved margin rate was slightly lower with SDA than DDA (7.5% vs 11.8%), however the difference was not statistically significant. The recurrence rate was higher with DDA (19/51, 37.2%) than SDA (14/53, 26.4%), although this was not statistically significant. Local recurrence-free survival (DDA 62% vs SDA 75%; P = 0.653) and overall survival (DDA 76% vs SDA 78%; P = 0.300) at 18 months of follow-up were comparable. There was no significant difference in sensitivity or specificity of intraoperative FS for margin assessment between SDA and DDA. The type of intraoperative FS technique used did not affect loco-regional recurrence or overall survival.     

Angiogenic factors in squamous cell carcinoma of the oral cavity: do they have prognostic relevance?

INTRODUCTION: Angiogenesis is a cascade-like mechanism which is essential for tumour growth and metastasis. Therefore the existence of angiogenic molecules and the density of activated endothelial cells in individual tumours is of major interest. MATERIAL/PATIENTS: In order to evaluate the prognostic significance of these molecules, the distribution pattern was studied of vascular endothelial growth factor (VEGF) and activated endothelial cells in tumours and normal, healthy oral mucosal specimens from 51 consecutive patients with primary oral squamous cell carcinoma. STUDY DESIGN: Frozen sections (vascular endothelial growth factor) and paraffin-embedded sections (endoglin, CD105) were investigated quantitatively by immunohistochemistry. The Pearson correlation, the non-parametric Mann-Whitney test, the non-parametric Wilcoxon rank sum test with multiple comparisons and the non-parametric Kruskal-Wallis test with multiple comparisons were used for statistical analyses. RESULTS: Endoglin expression in tumour tissue was significantly higher than in normal healthy mucosa (P<0.001). T1 tumours showed a significantly lower staining for endoglin compared with T2, T3 and T4 tumours but there was no increase with each T stage. No statistical correlation was found between VEGF expression and endoglin staining. CONCLUSIONS: Even though there is controversy about the prognostic relevance of VEGF, our results suggest that the factor is not suitable to decide prognosis in oral cancer. Endoglin may have a significant role in the development of squamous cell carcinoma of the oral cavity and might be relatively more specific than commonly used endothelial markers.     

Association of preoperative low skeletal muscle mass with postoperative complications after selective neck dissection

Skeletal muscle mass (SMM) is an emerging predictive and prognostic factor in head and neck cancer patients. The aim of this study was to investigate the predictive value of low SMM for postoperative complications in clinically T1–2 oral cavity cancer patients undergoing selective neck dissection. A retrospective study in clinically T1–2 oral cavity cancer patients who underwent selective neck dissection between 2011 and 2017 was performed. The predictive value of low SMM for the occurrence of postoperative complications and prolonged hospital stay was evaluated. SMM was measured using pre-treatment imaging (computed tomography or magnetic resonance imaging) at the level of the third cervical vertebra (C3). In total, 53 patients were included, of whom 42 (79.2%) had low SMM. Patients with low SMM were not significantly more likely to experience postoperative complications (odds ratio 1.28, P = 0.73) when compared to patients without low SMM. No statistically significant difference in mean duration of hospital stay was seen between these patient groups. In conclusion, low SMM was found not to predict postoperative complications in T1–2 oral cavity cancer patients who underwent neck dissection.     

The role of yearly chest radiography in the early detection of lung cancer following oral cancer

In a study of 213 patients with oral cancer, we investigated the incidence and prognosis of lung malignancies in patients offered a yearly chest radiography in the follow-up. Three conclusions can be drawn. (1) Metastatic or primary lung cancer was diagnosed in 22 (10.3%) patients. The 2-year actuarial incidence rate of lung cancer following cancer of the oral cavity is 13%. No new lung cancers were detected after 2 years follow-up. This suggests that after this period, yearly chest radiography may be superfluous for the early detection of lung cancer. (2) The survival rate of patients with a lung malignancy following cancer of the oral cavity is poor (1-year = 25%). The survival rate of patients detected by the yearly chest radiography without symptoms is higher than for patients detected after symptoms (p = 0.006). It is not clear to what extent this different survival rate is biased by lead-time and selection of patients with a favourable prognosis. A randomized study would be required to assess whether patients with oral cancer do benefit from the yearly chest radiography compared with no regular chest radiography. (3) Of 22 patients with lung cancer, 13 (59%) were detected by chest radiography without symptoms. In the first year following oral cancer, 11 patients were diagnosed with lung cancer. Only 4 of these 11 patients (36%) were detected by chest radiography in an asymptomatic stage. The detection of patients with lung cancer in an asymptomatic stage may be increased by more frequent chest radiography examinations in the 1st year following oral cancer.     

Multiple primary tumours following head and neck cancer in southern England during 1961–98

BACKGROUND: Successful initial treatment of oral and oro-phayngeal cancer has led to the emergence of second primary tumours (SPTs). Population data are meagre. METHODS: Occurrence of multiple primary cancers following a malignancy in a head and neck site was computed using data from a population-based cancer registry covering a population of 14 million. RESULTS: Among 59,958 subjects reported to the registry, 5.5% males and 3.6% females developed a second primary cancer. At the sites studied, a total of 2771 second primary cancers were found, compared with an expected number of 2341. The standardised incidence ratio (SIR) for contracting a new primary cancer was 1.14 (95% CI=1.09-1.19) for men and 1.34 (95% CI=1.24-1.44) for women. There was a significantly increased risk for a second cancer in most of the upper aerodigestive tract sites that are generally regarded as tobacco associated, with an SIR for subsequent oral cancer of 5.56 in men and 15.31 in women. Subjects first detected with a pharyngeal cancer experienced the highest SIR for a subsequent tumour. Excluding tobacco-associated sites, the risk of a subsequent cancer was not significantly raised in either sex (SIR 0.87 (95% CI 0.81-0.93) for men; SIR 0.99 (95% CI 0.90-1.09) for women). CONCLUSIONS: The relative risk for multiple primary cancer was higher in younger subjects, those detected with a head and neck cancer during the 1990s as compared with earlier decades of the study, and among patients who received radiotherapy for their first tumour. By 20 years from the time of the first head and neck cancer, we estimate that approximately 30% of male patients and 20% of female patients will have developed an SPT.     

Prediction of occult cervical lymph node metastasis in patients with stage I -II squamous cell carcinoma of the oral cavity

The presence of lymph node metastasis is the most important prognostic factor in oral cancer. The purpose of this study was to find useful markers for predicting occult cervical lymph node metastasis in patients with stage I or II squamous cell carcinoma of the oral cavity. We investigated 6 clinicopathologic factors and 2 genetic markers to predict late or occult cervical metastasis in 33 patients with stage I and II oral squamous cell carcinoma who underwent partial glossectomy through the mouth without elective neck dissection. In this study, we performed fluorescence in situ hybridization (FISH) with specimens obtained by fine-needle aspiration biopsies (FNA biopsies) of primary oral cancer material, to investigate numerical aberration of the gene. Late cervical lymph node metastasis occurred in 16 of the 33 patients (48.5%) during follow-up after treatment of the primary tumor. Factors significantly associated with the development of cervical metastasis were the mode of invasion (p = 0.009), cyclin D1 (p = 0.003) and EGFR numerical aberration (p = 0.024). The rate of disease-free survival from metastatic disease was significantly lower in patients with mode of invasion 4 C-4 D than in those with 1-3, and was significantly lower in patients with cyclin D 1 or EGFR gene numerical aberrations than in those without such aberrations (log rank test, p = 0.0064, p = 0.0016 or p = 0.0150). Our results indicate that patients with stage I - II squamous cell carcinoma of the oral cavity with the mode of invasion 4 C or 4 D, cyclin D 1 and EGFR gene numerical aberration should be considered a high-risk group for late cervical lymph node metastasis.     

Is dental care utilization associated with oral cavity cancer in a large sample of community‐based United States residents?

Abstract – Objectives: Cancer of the oral cavity and pharynx remains one of the 10 leading causes of cancer deaths in US. Besides smoking and alcohol consumption, there are no well‐established risk factors. While poor dental care had been implicated, it is unknown if lack of dental care, implying poor dental hygiene predisposes to oral cavity cancer. This study aimed to assess the relationship between dental care utilization during the past 12 months and the prevalence of oral cavity cancer. Methods: A cross‐sectional design of the National Health Interview Survey of Adult, noninstitutionalized US residents (n = 30 475) was used to assess the association between dental care utilization and self‐reported diagnosis of oral cavity cancer. Chi‐square statistic was used to examine the crude association between the explanatory variable, dental care utilization and other covariates, while unconditional logistic regression was used to assess the relationship between oral cavity cancer and dental care utilization. Results: There were statistically significant differences between those who utilized dental care during the past 12 months and those who did not with respect to education, income, age, marital status, and gender (P < 0.05), but not health insurance coverage (P = 0.53). In addition, those who utilized dental care relative to those who did not were 65% less likely to present with oral cavity cancer, prevalence odds ratio (POR), 0.35, 95% confidence interval (CI), 0.12–0.98. Further, higher income, advanced age, people of African heritage, and unmarried status were statistically significantly associated with oral cavity cancer (P < 0.05), but health insurance coverage, alcohol use, and smoking were not, P > 0.05. After simultaneously controlling for the relevant covariates, the association between dental care and oral cavity cancer did persist but imprecise. Thus, when compared with those who did not use dental care, those who did were 62% less likely to be diagnosed with oral cavity cancer, adjusted POR, 0.38, 95% CI, and 0.13–1.10. Conclusions: Among US adults residing in community settings, use of dental care during the past 12 months was marginally statistically significantly associated with oral cavity cancer, but clinically relevant in assessing oral cavity cancer prevalence in this sample. However, because of the nature of our data, which restricts temporal sequence, a large sample prospective study that may identify modifiable factors associated with oral cavity cancer development, namely poor dental care is needed.     

Elective management of the neck in oral cavity squamous carcinoma: current concepts supported by prospective studies

The incidence of occult cervical metastasis in oral cavity cancer, even in early stages, is significant, necessitating elective treatment of the neck in a majority of cases. There is no method of imaging or other examination that will detect microscopic foci of metastatic disease in cervical lymph nodes. Immunohistochemical and molecular analysis of neck specimens reveals the incidence of occult metastases to be higher than revealed by light microscopy with ordinary hematoxylin and eosin staining. The neck may be treated electively by surgery or irradiation. Surgery has the advantage of permitting pathological staging of the neck, avoiding unnecessary radiation treatment and indicating cases where adjuvant therapy should be employed. As oral cavity cancer rarely metastasizes to level V, a radical or modified radical neck dissection of all five node levels is not necessary. Selective dissection of levels I–III (“supraomohyoid neck dissection”) is the usual procedure of choice for elective dissection of the neck. Most of the relatively small number of isolated metastasis to level IV are from primary tumours of the tongue, which are known to produce “skip” metastases. Thus an “extended supraomohyoid neck dissection” of levels I–IV is recommended by some authors for elective treatment of the neck in tongue cancer. A number of recent prospective multi-institutional studies have demonstrated that sublevel IIB is rarely involved with isolated metastasis from oral cavity primary tumours, except from some tongue cancers. Thus it is justifiable to omit dissection of sublevel IIB in elective treatment of most cases of oral cavity cancer. Bilateral neck dissection should be performed in elective treatment of tumours involving midline structures, and in patients with ipsilateral neck metastasis.     

Prevention of oral cancer

Etiology control is the most important primary prevention of oral cancer. The use of tobacco and alcohol increases the risk of a squamous cell carcinoma of the oral mucosa. The dentist can play an important role in the secondary prevention or screening for premalignant lesions, asymptomatic malignancies and second primary tumours of the oral cavity. Because of their age, edentulous patients run a high risk of oral cancer. Therefore, a regular oral check-up of these patients should be recommended.     

Second primary tumours after a squamous cell carcinoma of the oral cavity or oropharynx using the cumulative incidence method

The aim of this study was to define the incidence of second primary tumours (SPTs) after treatment of a first primary oral or oropharyngeal squamous cell carcinoma (SCC) and to define patient groups with an increased or decreased risk of developing SPT with adjustment for competing risks. Cancer registry data from 917 consecutive patients with primary oral or oropharyngeal SCC were reviewed. Outcomes considered were the incidence and location of the SPT. Cumulative incidence was assessed instead of cumulative risks for SPTs. 149 patients (16%) developed a metachronous SPT (median follow-up time 2.6 years). The 5-year and 10-year cumulative incidence was 13% (S.E. 1.2) and 21% (S.E. 1.7), respectively. Most SPT developed in the upper aerodigestive tract (n = 65) and lungs (n = 35). No statistically significant risk factors were identified when considering patient and index tumour characteristics. The advantage of this study was the large and homogeneous patient population and the correction for competing risks, resulting in a lower but more accurate estimation of the incidence of SPTs. Despite this lower, but still continuous risk, regular follow-up for over 10 years is indicated for all patients treated for cancer of the oral cavity and oropharynx.     

Expression of p53 protein correlates with decreased survival in patients with areca quid chewing and smoking-associated oral squamous cell carcinomas in Taiwan

Expression of p53 protein was examined in oral squamous cell carcinoma (SCC) from patients who were areca quid (AQ) chewers and/or tobacco smokers, using anti-p53 antibodies with an immunoperoxidase technique. Positive p53 stain was observed in 47 of 81 (58%) cases of oral SCC. p53 overexpression was found to higher in patients without AQ chewing and smoking habits than in patients with these two habits (80% vs 52%, P=0.076). No significant correlation was found between p53 expression and the patients' age, sex, cancer location, clinical staging, primary tumor TNM status, or histological differentiation of SCC. The Kaplan-Meier analysis showed that the prognosis for patients with p53-negative tumors was significantly better than that for patients with p53-positive tumors (P<0.05). A significant correlation was also observed between positive lymph node status and poor prognosis (P<0.05). These results suggest that p53 may serve as an adjuvant marker of poor survival in patients with oral SCCs in Taiwan.