Prevalence and prognosis of synchronous distant metastatic tonsil squamous cell carcinomas.

BACKGROUND: To analyze the prevalence proportions and prognostic factors of synchronous distant metastases in patients with tonsil squamous cell carcinomas (TSCC). METHODS: TSCC patients were extracted from the Surveillance, Epidemiology and End Results (SEER) database between 2010 and 2014. We examined the association between clinical manifestations and distant metastases using Chi-squared tests. Predictors of 5-year survival were assessed using univariate and multivariate analyses. RESULTS: A total of 6193 patients were analyzed and lung was the most common site of distant metastases. Poorly/undifferentiated differentiation was found to be significantly correlated with lung metastasis (p=0.033) and liver and bone metastases were associated with African American (p=0.000 and p=0.000, respectively). A higher T classification was associated with higher prevalence of lung, liver, bone and brain metastasis (p=0.000, p=0.000, p=0.000 and p=0.007, respectively). The same results were found in N classification in lung, liver, and bone metastasis (p=0.000, p=0.000, and p=0.000, respectively). Worse prognosis was associated with older age, Blacks, lower grade, higher T and N classification, no surgery therapy and more metastatic sites. CONCLUSION: Lung was the most frequent lesion of synchronous distant metastases and liver and bone metastases were associated with African American. Higher T and N classification were independent prognostic parameters for higher prevalence of lung, bone, liver and brain metastasis. Worse prognosis was associated with older age, African Americans, lower grade, higher T and N classification, no surgery therapy and more metastatic sites.

[Clinicopathologic characteristics and prognositic indicators of tonsillar mantle cell lymphoma].

Objective: To investigate clinicopathological features and prognosis of tonsillar mantle cell lymphoma(TMCL). Methods: Clinical data of 25 patients with TMCL at Beijing Friendship Hospital, Capital Medical University from 2002 to 2016 were included. All the cases were reviewed microscopically. Various immunohistochemical stains were performed using the MaxVision two-step method. IgH/CCND1 gene fusion was detected by fluorescent in situ hybridization(FISH). Additionally, randomly selected 40 cases of non-tonsil MCL of the same period were compared. Results: Among all mantle cell lymphomas (MCL), TMCL accounted for 5.6%(25/449). The median age of the patients was 60 years(range: 44-82 years) with a M∶F ratio of 5.3 to 1.0. The main symptoms were sore throat and foreign body sensation and patients usually presented with enlargement or mass of tonsil. At the early stage of the disease, 18 cases(72.0%) were clinically misdiagnosed as tonsillitis. Lymph node involvement was present in 76.0%(19/25) of the patients. There were 4 cases(16.0%)with current splenic involvement, 11 cases(44.0%) with pharyngeal focal recidivism, and 3 cases(12.0%) with involvement of other non-lymphoid organs. Morphologically, tonsillar architectures were effaced at various degrees. Eighteen MCL cases showed classical type and 7 cases were blastoid variant. All tumors were positive for CD20 and cyclin D1. 92.0%(23/25) tumors showed weakly positive or positive expression for CD5. FISH test that IgH/CCND1 gene fusion was positive in two CD5 negative classical cases. 18 patients(72.0%) had a median follow-up time of 26 months(range: 6-81 months). The difference of survival rate between stage Ⅰ-Ⅱ and stage Ⅲ-Ⅳ patients was not statistically significant(P>0.05). Compared with NTMCL, TMCL was found to have higher proportion of stage Ⅰ-Ⅱ disease (χ(2)=12.789, P<0.01), lower the proportion of non-lymphatic organ involvement (χ(2)=8.125, P<0.01), and better prognosis (χ(2)=4.351, P=0.037). Conclusion: The incidence of TMCL is low and prone to be misdiagnosed as tonsillitis. Patients with TMCL are more likely at stage Ⅰ-Ⅱ at presentation and the prognosis is better than that of NTMCL.

Double positivity for HPV DNA/p16 in tonsillar and base of tongue cancer improves prognostication: Insights from a large population-based study.

The aim was to explore the overall survival (OS) for palatine tonsillar squamous cell carcinoma (TSCC), subdivided, according to certainty of tonsillar tumour origin, into specified tonsillar squamous cell carcinomas (STSCCs) and nonspecified tonsillar squamous cell carcinomas (NSTSCCs), and base of tongue squamous cell carcinoma (BSCC) when stratifying for HPV DNA status, p16 expression and combined HPV/p16 status. We included all patients (n = 797) diagnosed with TSCCs and BSCCs in Eastern Denmark as registered in the Danish Head and Neck Cancer Group (DAHANCA) database and the Danish Pathology Databank, 2000-2010. Patients were treated according to national guidelines (radiotherapy +/- concomitant cisplatin). All specimens were analysed using HPV DNA PCR and p16 immunohistochemistry. Clinical information was retrieved from the DAHANCA database and the Danish National Patient Registry. Information on vital status was obtained from the Danish Civil Registration System. We observed improved OS for HPV+/p16+ BSCCs compared to HPV-/p16- (hazard ratio for death [HR], 0.15; 95% CI, 0.09-0.24). Among STSCCs, HPV+/p16+ showed the lowest HR (0.19, 95% CI, 0.13-0.29); whereas, HPV-/p16+ showed an intermediate HR (0.39; 95% CI, 0.22-0.70). For NSTSCCs, HPV+/p16+ and HPV-/p16+ showed similar OS (HRs, 0.39; 95% CI, 0.26-0.59; and 0.48; 95% CI, 0.24-0.95, respectively). Combined HPV+/p16+ was a significantly better prognostic marker in BSCCs and STSCCs than HPV DNA and p16, alone (all p-values < 0.05). Whereas, combined testing in NSTSCC was not better than p16 (p = 0.53), alone. In conclusion, double positivity for HPV/p16 in conjunction with the certainty of tumour site improved prognosis.

Radiotherapy alone or combined with chemotherapy as definitive treatment for squamous cell carcinoma of the tonsil.

This study is aimed at updating our institution's experience with definitive radiotherapy (RT) for squamous cell carcinoma of the tonsil. We reviewed 531 patients treated between 1983 and 2012 with definitive RT for squamous cell carcinoma of the tonsil. Of these, 179 patients were treated with either induction (n = 19) or concomitant (n = 160) chemotherapy. Planned neck dissection was performed on 217 patients: unilaterally in 199 and bilaterally in 18 patients. Median follow-up was 5.2 years for all patients (range 0.1-31.6 years) and 8.2 years for living patients (range 1.9-31.6 years). The 5-year local control rates by T stage were as follows: T1, 94 %; T2, 87 %; T3 79 %; T4, 70 %; and overall, 83 %. Multivariate analysis revealed that local control was significantly influenced by T stage and neck dissection. The 5-year cause-specific survival rates by overall stage were as follows: I, 94 %; II, 88 %; III, 87 %; IVA, 75 %; IVB, 52 %; and overall, 78 %. Multivariate analysis revealed that cause-specific survival was significantly influenced by T stage, N stage, overall stage, fractionation, neck dissection, sex, and ethnicity. Of 77 patients treated with ipsilateral fields only, contralateral neck failure occurred in 1 %. The rate of severe complications was 12 %. Definitive RT for patients with tonsillar squamous cell carcinoma provides control rates equivalent to other modalities with a comparatively low incidence of late complications. Patients with anterior tonsillar pillar or tonsillar fossa primaries that are well lateralized with no base of tongue or soft palate extension may be treated with ipsilateral fields.

Ipsilateral radiotherapy for squamous cell carcinoma of the tonsil.

The purpose of this study is to update our institution's experience with ipsilateral radiation therapy (RT) for squamous cell carcinoma of the tonsillar area. Outcome study of 76 patients treated between 1984 and 2012 with ipsilateral RT for squamous cell carcinoma of the tonsil. Patients had either cT1 (n = 41, 54 %) or cT2 (n = 35, 46 %) primaries and cN0 (n = 27, 36 %), cN1 (n = 15, 20 %), cN2a (n = 8, 11 %), or cN2b (n = 26, 34 %) nodal disease. Of these, 32 (42 %) patients underwent a planned neck dissection and 21 (28 %) patients received concomitant chemotherapy. Median follow-up for all patients was 7.1 years (range 0.1-27.2) and 7.8 years (range 2.1-27.2 years) for living patients. The 2- and 5-year control and survival rates were as follows: local control, 98.6 and 96.9 %; local-regional control 95.8 and 92.6 %; cause-specific survival 95.9 and 93.1 %; and overall survival, 92.1 and 83.8 %. One patient failed in the contralateral, non-radiated neck 3 years after primary treatment. Univariate analysis revealed that overall survival was significantly influenced by whether the patient had a primary tumor in the anterior tonsillar pillar versus the tonsillar fossa with the latter performing better. The incidence of severe late complications was 16 %. Ipsilateral RT for patients with squamous cell carcinoma of the anterior tonsillar pillar or tonsillar fossa with no base of tongue or soft palate extension is an efficacious treatment that provides excellent control rates with a relatively low incidence of late complications.

Analysis of Charges Associated with Definitive Nonsurgical Therapy for Early-Stage Lateralized Tonsil Cancer.

OBJECTIVE: The cost of treatment as it affects comparative effectiveness is becoming increasingly more important. Because cost data are not readily available, we evaluated the charges associated with definitive nonsurgical therapy for early-stage lateralized tonsil cancers. METHODS: Patients treated with unilateral radiation therapy (RT) for T1 or T2 tonsil cancer between 1995 and 2007 were retrospectively reviewed. Total and radiation-specific charges, from 3 months before to 4 months after radiation, were adjusted for inflation. All facets of treatment were evaluated for significant associations with total billing. RESULTS: Eighty-four patients were identified. Three-year overall survival, disease-specific survival, and recurrence-free survival were 97 % [95 % confidence interval (CI) 0.88-0.99], 98 % (95 % CI 0.89-1), and 96 % (95 % CI 0.88-0.99), respectively. The median for radiation-specific charges was $60,412 (range $16,811-$84,792). The median for total charges associated with treatment was $109,917 (range $36,680-$231,895). Total billing for treatment was significantly associated with the year of diagnosis (p = 0.008), intensity-modulated radiation therapy versus wedge pair RT (p = 0.005), preradiation direct laryngoscopy (p < 0.0001), chemotherapy (p < 0.0001), gastrostomy tube placement (p = 0.004), and postradiation neck dissection (p = 0.005). CONCLUSIONS: Although cost data for treatment are not readily available, historically, the recovery rate is approximately 30 %. The charges associated with definitive nonsurgical therapy for early-stage lateralized tonsil cancer have a wide range likely due to treatment-related procedures, the use of chemotherapy, and evolving RT technologies. These benchmark data are important given renewed interested in primary surgery for tonsil cancer. Cost of care, disease control, and functional outcomes will be critical for comparisons of effectiveness when selecting treatment modalities.

Human papillomavirus-related cell cycle markers can predict survival outcomes following a transoral lateral oropharyngectomy for tonsillar squamous cell carcinoma.

OBJECTIVES: To identify the prognostic implications of human papillomavirus (HPV)-related cell cycle marker profiles in patients who have received a transoral lateral oropharyngectomy (TLO) as a primary treatment for tonsillar squamous cell carcinoma (TSCC). PATIENTS AND METHODS: Immunohistochemical profiles of HPV-related cell cycle markers, including p16, pRb, cyclin D1, p53, and the HPV DNA status of 42 consecutive TSCC patients who underwent TLO-based treatments were analyzed. The prognostic value of each marker was evaluated. RESULTS: Univariate analysis indicated that high p16, low pRb, and low p53 expression levels are significantly associated with a good disease-free and overall survival outcome. Clinicopathological parameters and the HPV DNA status did not show prognostic significance. When adjusted for age, overall stage and treatment strategy, a high p16 and low pRb level remained an effective prognostic marker for good survival outcomes. A high p16/low pRb combination showed superior survival prediction ability over high p16 or low pRb alone. CONCLUSION: HPV-related cell cycle markers may also be good indicators for predicting survival after TLO for TSCC. The de-escalation TLO surgery approach would be more effective if performed under the stringent guidance of these markers.

Prognostic significance of syndecan-1 expression in squamous cell carcinoma of the tonsil.

BACKGROUND: Syndecan-1 (SDC1) is reported to modulate several key processes of tumorigenesis and to show variable expression in many cancers. The cause of these variations in expression is not known to date. In this study, we compared SDC1 status with clinicopathologic parameters to evaluate the prognostic implications of SDC1 status on squamous cell carcinoma (SCC) of the tonsil. METHODS: In 56 cases of tonsillar SCC, we screened SDC1 expression using immunohistochemistry and analyzed the relationships between SDC1 expression and clinicopathological parameters. To identify the cause of the changes in SDC1 expression seen in tumors, we measured the gene dosage of SDC1 in tumor cells using fluorescent in situ hybridization. RESULTS: SDC1 expression was found in cancer cells in 36 cases (64.3 %) of tonsillar SCC. It was associated with lymph node metastasis (p = 0.010) and a positive surgical resection margin (p = 0.014). On the other hand, it was not significantly correlated with sex, age, smoking status, degree of differentiation, T stage, or distant metastasis. We could not find any copy-number variation of SDC1 in the cases showing increased SDC1 immunopositivity. In addition, strong SDC1 expression in the tumor cells predicted a shorter overall survival (p = 0.020, log-rank). CONCLUSIONS: We showed that SDC1 expression is associated with N stage and the status of resection margin involvement in SCC of the tonsil. With respect to survival, there were unfavorable outcomes in cases with SDC1 positivity. More studies are needed to better understand the role of SDC1 in the progression and invasiveness of tonsillar SCC.

Reduced impact of nodal metastases as a prognostic factor for tonsil cancer in the HPV era.

Metastatic lymph nodes (LN) are an adverse prognostic factor in head and neck squamous cell carcinoma (SCC). In this study, we tested the hypothesis that nodal metastases have reduced impact on survival in tonsil cancer in the HPV-predominant era. Incidence and mortality data of tonsil and oral cavity SCC between 1988 and 2007 were obtained from the SEER database. Based on published literature, we considered cases of tonsil cancer from 1988 to 1997 as the pre-HPV cohort (N = 752), and 1998-2007 as the HPV-predominant cohort (N = 2,755). Comparing the two cohorts, Kaplan-Meier 5-year overall survival (OS) for tonsil SCC improved from 54.0 to 74.3 % (p < 0.0001), and cancer-specific survival (CSS) improved from 66.0 to 82.9 % (p < 0.0001). Stratifying by LN involvement showed improved OS in the HPV-predominant cohort with one (63.6 vs. 79.7 %, p < 0.0001), two to three (54.2 vs. 75.9 %, p < 0.0001), four to eight (40.3 vs. 68.9 %, p < 0.0001), and greater than eight positive nodes (25.5 vs. 41.9 %, p < 0.0001). While metastatic LNs still negatively affect prognosis, their impact on OPC survival has diminished in the HPV-predominant era. This finding provides a rationale for additional studies of the prognostic significance of LN metastases in OPC cohorts of defined HPV status, and supports the concept that HPV-related OPC is a disease distinct from "classical" OPC, with unique prognostic features.

Human papillomavirus, smoking status and outcomes in tonsillar squamous cell carcinoma.

It is now clear that the two separate entitles of tonsillar cancer, HPV induced and non-HPV induced (smoking induced), have significantly different presenting stage and outcomes. A significant proportion of patients with human papillomavirus positive tonsillar cancer have had exposure to smoking. We examined the combined effect of human papillomavirus and smoking on the outcomes and determined whether smoking can modify the beneficial effect of human papillomavirus. A total of 403 patients from nine centers were followed up for recurrence or death for a median of 38 months. Determinants of the rate of loco-regional recurrence, death from tonsillar cancer and overall survival were modeled using Cox regression. Smoking status was a significant predictor of overall survival (p = 0.04). There were nonstatistically significant trends favoring never smokers for loco-regional recurrence and disease specific survival. In addition, there was no statistically significant interactions between smoking and human papillomavirus (p-values for the interaction were 0.26 for loco-regional recurrence, 0.97 for disease specific survival and 0.73 for overall survival). The effect of smoking on loco-regional recurrence and disease specific survival outcomes was not statistically significant, nor was there significant evidence that the effect of smoking status on these outcomes was modified by HPV status. Irrespective of HPV status, however, smokers did have poorer overall survival than never-smokers, presumably due to effects of smoking that are unrelated to the primary cancer.

Carcinoma of the pharynx and tonsils in an occupational cohort of asphalt workers.

BACKGROUND: We investigated a possible association between pharyngeal/tonsillar carcinoma and mixed carcinogen exposures in an asphalt roll company in Italy that used asbestos until 1979, when a new factory was built using a different production process. METHODS: We evaluated all workers involved in the entire production history of the company, divided into two subcohorts based on exposure status (workers in the original factory, 1964-1979, and those who worked only in the new factory, 1980-1997). We ascertained the vital status of the study population in February 2001. RESULTS: Among the subset of workers in the earlier subcohort, there were five deaths from pharyngeal/tonsillar carcinoma for a standardized mortality ratio of 21 (95% confidence interval = 8.8-51). No cases were recorded among workers hired after 1979. CONCLUSION: The increased standardized mortality ratio for this relatively rare cancer among workers exposed before 1979 may have been due to carcinogenic exposures at the plant.

Survival in patients with human papillomavirus positive tonsillar cancer in relation to treatment.

The incidence of tonsillar cancer and the proportion of human papillomavirus (HPV) positive tonsillar cancer cases have increased in the last decades. In parallel, treatment for tonsillar cancer has been intensified e.g., by accelerated radiotherapy, and chemotherapy, resulting in more side effects. Patients with HPV-positive tonsillar cancer have better prognosis than those with HPV-negative tumors, and the former group could hypothetically benefit from reduced, less-toxic treatment without compromising survival. Here, we therefore evaluated possible differences in overall and disease-specific survival after different oncological treatments in 153 patients with HPV DNA- and P16-positive tonsillar cancer who were diagnosed and treated with intent to cure between 2000 and 2007, in Stockholm, Sweden. Of these patients, 86 were treated with conventional radiotherapy, 40 were treated with accelerated radiotherapy and 27 were treated with chemoradiotherapy. There were no significant differences in overall or disease-free survival between the groups. However, there was a trend, implying a beneficial effect of the intensified treatment, with chemoradiotherapy being better than radiotherapy despite that more patients had stage IV disease in the former group; and accelerated radiotherapy being better than conventional radiotherapy. This needs to be followed further in larger more homogenous groups of patients. In conclusion, patients with HPV-positive tonsillar cancer treated with conventional- or accelerated radiotherapy or chemoradiotherapy disclosed similar survival rates. The trend for better survival and less metastasis after intensified treatment underlines the need for large prospective studies comparing less intense to more intense treatment (chemoradiotherapy).

Improved survival among patients with base of tongue and tonsil cancer in the United States.

OBJECTIVE: To examine if survival has changed over the last 20 years in patients with base of tongue and tonsil cancers in the United States. METHODS: Using SEER data, we employed Kaplan-Meier method to draw survival curves and calculate survival rates, and estimated adjusted hazard ratios (HR). RESULTS: From the 1980s to the 2000s, the 5-year overall survival rates statistically significantly improved by 100% from 25 to 51% among patients with one primary base of tongue cancer and 28-60% among those with one primary tonsil cancer (p values for trend <0.001). In addition, the 5-year cancer-specific survival improved by 222.4 and 276%, respectively, among two types of patients. Survival improvement was more pronounced among male patients than among female patients regardless of young or old age, while the improvement was generally consistent among patients with different tumor stages and treatment methods. In contrast, however, those patients with subsequent multiple cancers showed no improvement in overall survival over time. CONCLUSIONS: The survival of patients with base of tongue and tonsil cancer has significantly improved over the last decades in the United States. Whether the improvement is associated with HPV infection, screening, or early detection is worthy to study in future.

Gender and ethnic disparities in incidence and survival of squamous cell carcinoma of the oral tongue, base of tongue, and tonsils: a surveillance, epidemiology and end results program-based analysis.

BACKGROUND: Squamous cell carcinomas (SCC) of the oral tongue (OT) and of the base of the tongue and tonsils (BTT) differ with respect to etiology, treatment and prognosis. Human papillomavirus has been linked to the increased incidence of BTT, yet, the trends in incidence of BTT and OT tumors among gender and ethnic origin groups have not been well examined. We sought to examine the trend in gender-, ethnic origin- and age-specific incidence of these tumors over time. METHODS: Data were obtained from the Surveillance, Epidemiology and End Results Program of the US National Cancer Institute. We examined temporal trends in sex- and ethnic origin-specific incidence of SCC by calculating the annual percent changes followed by joinpoint analyses evaluating changes in trend. RESULTS: While BTT increased in age-adjusted rates among white males with a more pronounced increase observed in the mid-1990s, white females experienced a significant increase in incidence of OT tumors. Patients with advanced OT carcinoma had a significantly lower survival compared to those with advanced BTT disease; however, patients with early-stage OT tumors had a better survival compared to patients with BTT. CONCLUSIONS: While the increase in incidence of BTT tumors in white men is likely human papillomavirus driven, more studies are needed to elucidate the increasing incidence of OT tumors in white women. The differences in outcomes across ethnic origin groups are also described and discussed.

Relationships between metastasis-associated protein (MTA) 1 and lymphatic metastasis in tonsil cancer.

We evaluated immunohistochemically the expression profiles of metastasis-associated protein (MTA) 1 and their associations with lymph node metastasis in tonsil cancer. Immunohistochemical analysis of 43 tonsillar neoplasm tissues was performed using antibodies raised to MTA1. Depth of tumor invasion, lymph node metastasis, and clinical outcomes were assessed. Clinical N0 patients were divided into two groups: N0a, negative for MTA1; N0b, positive for MTA1. Occult node metastasis was reevaluated according to the revised clinical N staging system taking account of MTA1 expression. The expression rate of MTA1 was 41.9%. There was a significant correlation between the expression of MTA1 and lymph node metastasis (P = 0.034*). MTA1 had a sensitivity of 53.3% and a specificity of 84.6% for identification of cervical metastases. When cN0b patients were considered to be N+, the recalculated rate of occult metastasis fell from 50% to 7.6% (the false-positive rate remained unchanged). MTA1 was found to be a useful molecular marker to predict lymphatic metastasis in tonsil cancer.

Treatment of Early Stage Tonsil Cancer in the Age of Human Papillomavirus-Associated Malignancies.

OBJECTIVE: To investigate the patterns of care and outcomes of treatment of early stage tonsil cancers, controlling for human papillomavirus (HPV) status. STUDY DESIGN: Historical cohort study. SETTING: National Cancer Database (NCDB). METHODS: Review of the NCDB between 2010 and 2017 for all T1-2N0M0 tonsillar squamous cell carcinoma (SCC). Demographics, clinical characteristics, HPV status, treatment regimens, and survival were analyzed. RESULTS: A total of 4720 patients were identified with early stage SCC of the tonsil. Most were tested for HPV (2759 [58.5%]). Among tested patients, 1758 (63.7%) were positive for HPV and 1001 (36.3%) were negative for HPV. HPV-positive patients had higher 3-year survival compared to HPV-negative patients (93.2% vs 77.8%, P < .001). Among HPV-positive patients, there was no significant difference in survival between treatment cohorts. However, in the HPV-negative cohort, 3-year survival was higher in both bimodality surgical-based settings (tonsillectomy + neck dissection + radiotherapy, 86.0% vs chemoradiotherapy, 69.6%, P = .01) and for all surgical-based treatments when compared to nonsurgical management (84.6% vs 69.3%, P < .001). This difference was maintained in multivariable regression controlling for age, sex, comorbidities, clinical T stage, and treatments. In a subpopulation of HPV-negative patients propensity score matched by all factors significant in multivariable analysis, 3-year survival remained higher in the surgically treated group compared to the nonsurgically treated cohort (84.9% vs 67.1%, P < .001). CONCLUSIONS: Surgical- or radiation-based treatment resulted in similar survival in early stage HPV-positive tonsil cancer. Surgical-based treatments were associated with longer survival in HPV-negative cancers. These findings should be further investigated in a randomized prospective trial.

Role of radiation therapy in primary tonsil large B cell lymphoma: a SEER-based analysis.

BACKGROUD: Primary tonsil diffuse large B cell lymphoma (PT-DLBCL) is an uncommon disease entity. The role of radiation therapy (RT) in PT-DLBCL is debatable in both the pre- and post- rituximab era. The purpose of this study was to evaluate the treatment outcome and establish a prognostic model in PT-DLBCL based on the Surveillance, Epidemiology, and End Results (SEER) database. MATERIALS AND METHODS: Data of 1214 PT-DLBCL patients diagnosed between 1975 and 2016 were extracted from SEER 18. The effect of RT was assessed for the entire cohort and subgroups by stages using univariate, multivariate Cox regression analyses and propensity score matching (PSM). RESULTS: The entire cohort included 1043 patients with early-stage (ES) PT-DLBCL and 171 patients with advanced-stage (AS) disease. A decreasing trend of RT utilization in the ES cohort after 2002 was observed. 47.4% of patients in ES received RT, whereas 25.1% in AS underwent RT. RT significantly improved overall survival in both univariate (P < 0.001) and multivariate (P = 0.002) analyses. PSM analysis further validated the survival advantage of RT (P = 0.002). A nomogram was established to predict the potential survival benefit. Subgroup analysis revealed RT was significantly associated with overall survival in ES patients of PT-DLBCL (P = 0.001) and in the rituximab era (P = 0.001) but not in those with AS disease (P = 0.241). CONCLUSIONS: This population-based study encloses the largest sample of PT-DLBCL to date and demonstrates a favorable survival role of RT in early stages rather than advanced stages. The established nomogram helps to identify high risk patients to improve prognosis.

T but not N stage predicts survival for patients with tonsillar carcinoma treated with external radiotherapy and brachytherapy.

BACKGROUND: Our aim was to determine the efficacy of a therapeutic schedule including external radiation and brachytherapy in a consecutive and retrospective series of tonsillar carcinoma patients. PATIENTS AND METHODS: Ninety-six patients with tonsillar carcinoma were treated between 1988 and 2000 and were followed up for at least for three years. All patients were treated with accelerated hyperfractionated external radiotherapy, 68 patients had additional brachytherapy and 69 patients with advanced stages also received chemotherapy. There was no planned surgery even though 73% had N+ disease. Eleven patients with persistent neck nodes underwent ultimate salvage surgery. RESULTS: The overall three-year survival (OS) was 70%. OS for the T stage was T1 90%, T2 89%, T3 54% and T4 60%. The corresponding numbers for the N stage were N0 61.5%, N1 73%, N2 78% and N3 66%. Accordingly OS was influenced by the T stage (p>0.001) rather than by N stage. Only four patients with salvage surgery had viable tumour cells in the specimen, their survival was not inferior. DISCUSSION: The primary tumour stage is an essential determinant for survival in patients with irradiated tonsillar carcinoma. Neck dissection should be confined only as a salvage procedure.

[Human papilloma virus in head and neck cancer]. / Humane Papillomaviren bei Kopf-Hals-Karzinomen.

Human papilloma viruses (HPV) may cause head and neck squamous cell carcinomas. HPV associated carcinomas mostly occur in the oropharynx and particularly in the palatine tonsil and base of tongue. Carcinomas at other sites are infrequently caused by HPV. The viral proteins E6 and E7 are crucial for malignant transformation. They functionally interfere with cellular proteins maintaining genomic integrity such as p53 and cell cycle control such as retinoblastoma protein. However, unlike carcinogens such as tobacco smoke, the virus does not disrupt the coding genes. Reliable HPV detection methods in histological specimens include in situ hybridisation of high risk DNA and immunohistochemical detection of p16. HPV positivity does not proof a causal relation between HPV and tumour. High risk HPV are also detectable in 10-20% of normal mucosal specimens. Irrespective of the various modalities available for treatment, HPV associated head and neck cancers have a better prognosis than their carcinogen caused counterparts. HPV positivity does not object to surgical treatment.

Prognostic impact of resection margin involvement in surgically managed HPV-positive tonsil cancer.

OBJECTIVES: To find out the role of resection margin involvement in surgically managed HPV-positive tonsil cancer. MATERIALS AND METHODS: The study included 94 subjects with HPV-positive tonsil cancer undergoing surgical treatment. We evaluated the relationships between the resection margin status, clinicopathological factors, and oncological outcome. RESULTS: The rate of resection margin involvement was 22.3% (21/94) after ablative surgery. Margin involvement, lymphatic invasion, and extracapsular spread were associated with the 5-year disease-free survival (DFS) and disease-specific survival (DSS) rate in univariate analysis. Multivariate Cox regression analysis confirmed a significant association between the margin involvement and 5-year DFS rate (HR = 4.602; 95% CI = 1.202-17.620; p = 0.026) and 5-year DSS rate (HR = 12.826; 95% CI = 1.399-117.593; p = 0.024). The incidence of resection margin involvement was significantly higher in patients with larger tumors (35.19 ± 15.07 mm vs. 25.53 ± 10.32 mm, p = 0.011) and more invasive tumors (17.84 ± 7.90 mm vs. 13.46 ± 6.88 mm, p = 0.037). The cutoff value of tumor size and depth of invasion for resection margin involvement was 29.5 mm (74% sensitivity and 63% specificity) and 14.5 mm (74% sensitivity and 61% specificity), respectively. CONCLUSION: Resection margin involvement was significantly correlated with tumor size and the depth of invasion in HPV-positive tonsil cancer. Furthermore, resection margin involvement was associated with adverse outcomes.