Days alive and out of hospital following primary surgery for oral cavity squamous cell carcinoma.

BACKGROUND: Days Alive and Out of Hospital (DAOH) is a recently introduced, readily obtainable postoperative outcome measure method that expresses procedure and disease-associated morbidity and mortality. In this study, we evaluated DAOH with 30- and 365-days follow-up periods after primary surgery (DAOH30 and DAOH365, respectively) for patients with oral cavity squamous cell carcinoma (OSCC). The aim of this study is to identify patient-, procedure- and disease-associated risk factors for patients treated with primary surgery for primary OSCC. MATERIAL AND METHODS: This retrospective cohort study from a prospective collected database represents patients from Eastern Denmark surgically treated for primary OSCC in the period 2000-2014. DAOH30 and DAOH365 were calculated and associations with patient characteristics including comorbidity, tumor characteristics, clinical outcomes such as length of stay, readmission, and mortality were evaluated. Tests for difference and significance between groups were assessed with Mann-Whitney U test and quantile linear regression. RESULTS: We included 867 patients (63% males, median age: 63 years (IQR 56-70 years)). Median DAOH30 and DAOH365 after OSCC surgery were 25 days (IQR 21-27 days) and 356 days (IQR 336-360 days), respectively. Alcohol consumption had a significant association with a lower DAOH365, p < 0.01, but not with DAOH30. Advanced T-stage, adjuvant radiotherapy (RT) and increased Charlson Comorbidity Index (CCI) score was significantly associated with a lower DAOH30 and DAOH365. CONCLUSION: In this population-based study in OSCC patients treated with primary surgery, we found that DAOH after 30 days was 25 days (83%), while DAOH after 365 days was 356 days (98%). Advanced T-stage acts as a predictor for significant DAOH30 and DAOH365 reduction while excessive alcohol consumption predicts a significant DAOH365 reduction. Readmission within 30 days following surgery was associated with further readmission within one year.

Expression patterns of uPAR, TF and EGFR and their potential as targets for molecular imaging in oropharyngeal squamous cell carcinoma.

The clinical introduction of molecular imaging for the management of oropharyngeal squamous cell carcinoma (OPSCC) relies on the identification of relevant cancer­specific biomarkers. The application of three membrane­bound receptors, namely urokinase­type plasminogen activator receptor (uPAR), tissue factor (TF) and EGFR have been previously explored for targeted imaging and therapeutic strategies in a broad range of solid cancers. The present study aimed to investigate the expression patterns of uPAR, EGFR and TF by immunohistochemistry (IHC) to evaluate their potential for targeted imaging and prognostic value in OPSCC. In a retrospective cohort of 93 patients with primary OPSCC, who were balanced into the 45 human papillomavirus (HPV)­positive and 48 HPV­negative groups, the IHC­determined expression profiles of uPAR, TF and EGFR in large biopsy or tumor resection specimens were analyzed. Using the follow­up data, overall survival (OS) and recurrence­free survival were measured. Specifically, associations between survival outcome, biomarker expression and clinicopathological factors were examined using Cox proportional hazards model and log­rank test following Kaplan­Meier statistics. After comparing the expression pattern of biomarkers within the tumor compartment with that in the adjacent normal tissues, uPAR and TF exhibited a highly tumor­specific expression pattern, whereas EGFR showed a homogeneous expression within the tumor compartment as well as a consistent expression in the normal mucosal epithelium and salivary gland tissues. The positive expression rate of uPAR, TF and EGFR in the tumors was 98.9, 76.3 and 98.9%, respectively. No statistically significant association between biomarker expression and survival outcome could be detected. Higher uPAR expression levels had a trend towards reduced OS according to results from univariate analysis (P=0.07; hazard ratio=2.01; 95% CI=0.92­4.37). Taken together, these results suggest that uPAR, TF and EGFR may be suitable targets for molecular imaging and therapy in OPSCC. In particular, uPAR may be an attractive target owing to their high positive expression rates in tumors and a highly tumor­specific expression pattern.

Second primary cancer following primary oral squamous cell carcinoma: a population-based, retrospective study.

BACKGROUND: Second primary cancer (SPC), defined as a metachronous solid cancer resulting from neither a recurrence of the primary cancer nor a metastasis, is a leading long-term cause of death for survivors of primary oral squamous cell carcinoma (OSCC). This study examined the risk of SPC following treatment of primary OSCC. MATERIALS AND METHODS: This semi-national, population-based, retrospective study included all patients with primary OSCC treated with curative intent in Eastern Denmark in 2000-2014. The presence of SPC was confirmed from medical records and the Danish Pathology Data Bank. The rate of SPC was compared to the occurrence of any cancer in the Eastern Danish population using data from the Danish Cancer Registry. RESULTS: A total of 936 patients with primary OSSC were enrolled. Of these, 219 patients (23%) were diagnosed with SPC during the follow-up (median 8.9 years, IQR: 5.4-12.6 years). The rate of SPC was four times higher than the occurrence of any cancer among the Eastern Danish population i.e., with a standardized incidence ratio (SIR) of 4.13 (95%CI: 3.55-4.80). SPCs were most frequently found in head and neck region (n = 97, SIR = 43.6), lower respiratory organs (n = 38, SIR = 5.6) and gastrointestinal organs (n = 33, SIR = 3.2) with increased SPC rates in all locations. Among patients who developed SPC within the study period the median time from OSCC to the first SPC was 4.4 years (IQR: 2.5-6.2). Significant associations were found between both smoking and excessive alcohol consumption after treatment of OSCC and the risk of SPC. CONCLUSIONS: A noteworthy increased rate of SPC following treatment of primary OSCC was found, especially in the head and neck region and in the lungs. Healthcare professionals should be aware of this increased risk.

The impact of tobacco smoking on survival of patients with oral squamous cell carcinoma: a population-based retrospective study.

BACKGROUND: This article aims to evaluate the impact of smoking status, accumulated tobacco exposure (ATE), and smoking cessation on overall- and disease-free survival (OS and DFS) of patients with oral squamous cell carcinoma (OSCC). MATERIAL AND METHODS: Patients with primary OSCC treated with curative intent between 2000 and 2019 in Copenhagen were included (n = 1808). Kaplan-Meier curves and multivariable Cox regression analyses were performed to compare the survival of patients with different smoking history. Interactions between ATE and (A) tumor subsite and (B) excessive alcohol consumption (EAC) on the survival were evaluated using multivariable Cox regression analyses with interaction terms. RESULTS: We included 1717 patients with known smoking status (62.8% males, median age: 64 years (IQR: 57-71 years)), who had a 5-year OS of 53.7% (95%CI: 49.8%-57.9%). Based on fully adjusted multivariable Cox regression analyses, significantly elevated hazard ratios (HRs) for OS and DFS were identified for current, but not former smokers, compared to never-smokers. An approximately linear relationship between continuous ATE and survival estimates was identified. ATE analyzed as a categorical variable showed significantly elevated HRs for OS of patients with all categories (060 PYs), however only for DFS of patients with >60 PYs, compared to 0 PYs. Furthermore, an unfavorable long-term prognosis was evident after >3.5 (OS) and >2.5 (DFS) years from diagnosis for patients who continued smoking compared to patients with smoking cessation at diagnosis. The survival estimates of patients with different tumor subsite and alcohol consumption differed with increasing ATE. CONCLUSION: Tobacco smoking (assessed as smoking status and ATE) was associated with inferior survival (OS and DFS) among patients with OSCC. Unfavorable long-term prognosis was significant for patients who continued smoking compared to patients with smoking cessation at diagnosis. The impact of ATE on survival of patients with OSCC may depend on the tumor subsite and/or alcohol consumption.

A Contemporary Systematic Review on Repartition of HPV-Positivity in Oropharyngeal Cancer Worldwide.

Significant variation in human papillomavirus (HPV) prevalence in oropharyngeal squamous cell carcinoma (OPSCC) across countries ranging from 11% in Brazil to 74% in New Zealand has been reported earlier. The aim of this study was to systematically review the most recently published studies on the occurrence of HPV in OPSCC globally. PubMed and Embase were systematically searched for articles assessing the occurrence of HPV+ OPSCC published between January 2016 and May 2021. Studies with a study period including 2015 and the following years were included. Both HPV DNA and/or p16 were accepted as indicators of HPV+ OPSCC. 31 studies were enrolled comprising 49,564 patients with OPSCC (range 12-42,024 patients per study) from 26 different countries covering all continents. The lowest occurrences of HPV+ OPSCC were observed in India (0%) and Spain (10%) and the highest occurrences were observed in Lebanon (85%) and Sweden (70%). We observed great variation in HPV prevalence in OPSCC worldwide varying from 0% to 85%. The highest occurrences of HPV+ OPSCC were found in general in Northern European countries, USA, Lebanon, China, and South Korea. We observed a trend of increase in HPV-positivity, indicating a mounting burden of HPV+ OPSCC.

The Effect of Prophylactic HPV Vaccines on Oral and Oropharyngeal HPV Infection-A Systematic Review.

Human papillomavirus (HPV) imposes an increased risk of developing cervical, anal and oropharyngeal cancer. In the Western world, HPV infection is currently the major cause of oropharyngeal cancer. The effectiveness of HPV vaccines for oral or oropharyngeal HPV infection is yet to be determined. This study conducted a systematic literature search in Pubmed and Embase. Studies investigating the impact of HPV vaccines on oral or oropharyngeal HPV infection were enrolled. This review reports the relative prevention percentage (RPP), including a risk of bias assessment as well as a quality assessment study. Nine studies were included (48,777 participants): five cross-sectional studies; one randomized community trial study (RCT); one longitudinal cohort study; and two case-control studies. A significant mean RPP of 83.9% (66.6-97.8%) was calculated from the cross-sectional studies, 82.4% in the included RCT and 83% in the longitudinal cohort study. Further, two case-control studies that measured antibody response in participants immunized with HPV vaccines were included. Respectively, 100% and 93.2% of participants developed HPV-16 Immunoglobulin G (IgG) antibodies in oral fluids post-vaccination. Analysis of the studies identified a significant decrease in vaccine-type oral or oropharyngeal HPV infections in study participants immunized with HPV vaccines across study designs and heterogenous populations. Further, a significant percentage of participants developed IgG antibodies in oral fluid post-vaccination.

Clinicopathologic characteristics of Burkitt lymphoma of the head and neck in a non-endemic region-a Danish nationwide study.

BACKGROUND: Burkitt lymphoma rarely presents in head and neck (H&N) in Western countries. AIMS/OBJECTIVES: We aimed to characterise clinicopathological features of H&N Burkitt lymphoma in Denmark representing a non-endemic region. MATERIAL AND METHODS: Clinical records were reviewed for a nationwide cohort of patients diagnosed with H&N Burkitt lymphoma in Denmark between 1980 and 2018. The diagnosis was histologically validated. RESULTS: Thirty-four patients with H&N Burkitt lymphoma (highest incidence in age group 0-9 years, male-to-female ratio 4.7:1) were included. Thirty-three lymphomas (97%) were extranodal. The tumour was visible at the clinical examination in 81% (n = 22) of the cases. The palatine tonsils were the most frequent location (n = 13, 38%) and 52% (n = 17) of the patients were diagnosed in advanced stage. Lymphoma was the tentative clinical diagnosis in 23% of the cases. The 5-year overall- and disease-specific survival was 78% and 81%, respectively. CONCLUSIONS: Due to the rarity of Burkitt lymphoma of the H&N, there is a high risk of clinical misdiagnosis. Our findings suggest which symptoms and clinical presentations to be aware of in the diagnostics work up that could lead to the diagnosis of Burkitt lymphoma.

The impact of HPV genotypes on survival in HPV-positive oropharyngeal squamous cell carcinomas: a systematic review.

BACKGROUND: Patients with HPV-positive (HPV+) oropharyngeal squamous cell carcinomas (OPSCCs) are known to have a better prognosis compared to patients with HPV-negative OPSCCs. AIMS/OBJECTIVES: To investigate the impact of specific HPV genotypes on survival in HPV + OPSCC. MATERIAL AND METHODS: A systematic search of PubMed and Embase for studies addressing the association between specific HPV genotypes and survival among patients with OPSCC was performed. RESULTS: Six studies (n = 1385 patients) published between 2013 and 2017 were included. Five studies (n = 1290 patients) found a better survival among HPV16 cases compared to other high-risk (HR) HPV genotypes (HPV 33, 18, 35, 31, 39, 52, 59, 45, 56, 67, 29, and 58), of which three studies (n = 933 patients) reached significant results. Two of these studies reported a five-year overall survival (OS) of 64.6% and 71.4% in HPV16 OPSCCs vs. 45.6% and 57.1% in HR non-HPV16 OPSCCs (p = .001 and p = .010, respectively), and the last study found a better OS among HPV16 cases with a hazard ratio (HR) of 0.35, 95%. CI [0.14;0.85], p = .02. CONCLUSIONS: Our findings indicate a favorable prognosis among patients with HPV16 OPSCC compared with HR non-HPV16 OPSCC. These results may be important when designing future trials and in the planning of follow-up regimes.

Risk Factors for Recurrence of Follicular Thyroid Cancer: A Systematic Review.

Background: In risk assessment of recurrence, papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC) are often grouped together as differentiated thyroid cancer (DTC). However, while risk factors affecting recurrence of PTC are well established, risk factors for recurrence of FTC are not. This systematic review examines risk factors for recurrence of FTC and evaluates their significance. Methods: A systematic search on PubMed and Embase was performed in September 2020, including studies evaluating risk factors for recurrence of FTC. A quality assessment of the enrolled studies was performed. Results: Nine studies (n = 1544 patients) from eight countries were included. The average recurrence rate was 13.6%, and distant metastasis (DM) constituted 64.8% of the recurrent cases. The risk factors examined were sex, age at diagnosis, primary tumor size, degree of invasiveness, focality, positive resection margin, lymph node (LN) metastasis, and DM at diagnosis. Risk factors correlated with recurrence of FTC were age older than 45 years, primary tumor size above 40 mm, widespread invasion, multifocality, positive resection margin, LN metastasis, and DM at diagnosis. Sex was not a statistically significant risk factor. Conclusions: We identified seven risk factors associated with recurrence of FTC. Age and multifocality were found to be of greater impact regarding recurrence risk of FTC compared with PTC. Future research needs to address the impact of different risk factors for recurrence of FTC particularly including age, primary tumor size, angioinvasion, and mutational status.

Impact of delay in diagnosis and treatment-initiation on disease stage and survival in oral cavity cancer: a systematic review.

AIM/OBJECTIVES: This study aimed to systematically review the literature on the impact of delay in diagnosis and treatment of oral cavity cancer. METHODS: PubMed and Embase were systematically searched for articles reporting impact of delay in diagnosis and treatment on cancer-stage and survival of oral cavity cancer. Studies comprising at least ten patients, and published since the year 2000, were included. RESULTS: Sixteen studies (n = 45,001, range: 62-18,677 per study, 83% men), from Australia, Asia, Europe, North America and South America, met the inclusion criteria. Eleven studies (n = 1,460) examined delay in diagnosis, while five studies (n = 43,541) reported delay in treatment. Eight of the eleven studies, examining delay in diagnosis (n = 1,220), analyzed the correlation between delay in diagnosis and tumor stage at diagnosis. Three studies found a significant correlation between patient delay and advanced stage at diagnosis (p < 0.05), whereas three other studies did not. The studies reporting a significant correlation were from Asian countries, whereas the three studies that did not find a correlation were from other continents. Studies reporting on professional delay and total diagnostic delay, generally, did not find a significant correlation with advanced cancer at diagnosis. Time to treatment (TTI), defined as time from diagnosis to treatment, was found significantly correlated with survival in three studies (p < 0.01, p < 0.001, p < 0.05), and nonsignificant in two studies. CONCLUSION: A significant correlation between patient delay and advanced stage cancer was reported in Asian studies only, while professional delay and total diagnostic delay were generally found to be non-correlated with advanced stage cancer at diagnosis. TTI was in some studies reported to be correlated with poorer outcome, while other studies did not report a correlation. One study presented that there was no clear advantage in overall survival (OS) for patients treated within 30 days, compared to patients treated between 30 and 44 days.

Incidence and survival of salivary gland cancer in children and young adults in Denmark: A nation-wide study for the period 1990-2015.

OBJECTIVES: The aim of this study was to evaluate incidence and survival of children and young adults with salivary gland cancer (SGC) in Denmark during the period 1990-2015. METHOD: We included all patients aged 0-24 years registered with primary SGC in the Danish Cancer Registry, the Danish Pathology Data Bank, or the DAHANCA database during 1990-2015. Patients were divided in two age-groups: children (0-17 years) and young adults (18-24 years). Incidence rates, overall survival (OS), and recurrence free survival (RFS) was evaluated in relation to age-group, sex, tumor location, tumor histology, and T-, N-, and M-classification. RESULTS: A total of 70 SGC patients between 0 and 24 years (67% female, n = 47) were included. Thirty-six were children at time of diagnosis, and 34 were young adults. The incidence was higher among young adults compared to children (0.29 vs. 0.11 per 100.000) and showed no significant change during the study period. There were no differences in the distribution of sex, tumor location, or tumor histology between children and young adults. The total 5 and 15-year survival rates were 97.1% and 91.7% for OS, and 97.1% and 83.1% for RFS. The survival rates showed no significant differences according to age-groups, sex, tumor location, or tumor histology. Patients diagnosed in stage T4 had significantly worse OS and RFS. CONCLUSION: The incidence of SGC among children and young adults in Denmark was low and stable in the period 1990-2015. The overall survival was very high, demonstrating the excellent prognosis for children and young adults with SGC.

The impact of comorbidities on survival in oral cancer patients: a population-based, case-control study.

BACKGROUND: Comorbidities have shown to highly influence the outcome and risk of death of head and neck cancer patients. The purpose of this study was to examine the comorbidities among oral cavity squamous cell carcinoma (OSCC) patients, and to investigate the impact of comorbidities on overall survival (OS) and recurrence free survival (RFS). METHODS: Patients diagnosed with OSCC in Eastern Denmark in the period 2000-2014 and treated with curative intend were included. Patients data were linked to the Danish National Patients Register to identify comorbidities based on the Charlson Comorbidity Index (CCI) at the time of diagnosis and five years after diagnosis. Each patient was age-and sex-matched in a 1:10 ratio with an age and sex matched reference group. RESULTS: A total of 1,183 patients and 11,830 controls were included. Overall this study found comorbidities to be more common among OSCC compared to the reference group both at the time of diagnosis and five years after. The 5-year OS among patients with a CCI score of zero, one, two, and three or above was 60%, 44%, 41%, and 40%, respectively. Similarly, the multivariate cox-regression analysis showed that patients with increasing CCI score also had an increasing risk of death compared to patients with no comorbidities. CONCLUSION: OSCC patients had significantly higher comorbidity burden at diagnosis and risk of developing additional comorbidities after diagnosis compared to the reference population. Survival outcomes decreased significantly with higher CCI.

Impact of time to treatment initiation for patients with oral cavity squamous cell carcinoma: a population-based, retrospective study.

BACKGROUND: The increasing incidence of oral cavity squamous cell carcinoma (OSCC) is challenging the capacity to treat patients efficiently. The aim of this study was to evaluate the impact of time to treatment initiation (TTI) on overall survival (OS) and recurrence free survival (RFS) for patients with primary OSCC. MATERIAL AND METHODS: All patients with primary OSCC treated with curative intent at Rigshospitalet in the period 2000-2014 with known date of diagnosis and treatment initiation were included. Correlation analyses between TTI and Charlson comorbidity index (CCI), UICC stage, and year of diagnosis were performed in addition to uni- and multivariate Cox proportional hazard regression analyses. Further, interaction analysis of TTI and UICC stage were conducted. RESULTS: Eight hundred and sixty-two patients (64% men) with a median age at diagnosis of 62 years (range: 28-95 years) were included. The median TTI was 31 days (range: 2-137 days). Correlation analyses showed correlations between TTI and CCI, TTI and UICC stage, and TTI and year of diagnosis (rho = -0.10, p-value = <.01; rho = 0.16, p-value = <.001; rho = -0.47 p-value = <.001). Univariate analyses showed a statistically significant increase in hazard ratio for both OS and RFS with a five-day increase in TTI (HR = 1.05, 95%CI: 1.02-1.07 and HR = 1.04, 95%CI: 1.02-1.07). However, when adjusting for age, sex, smoking, UICC stage, tumor sublocation, CCI, and year of diagnosis in a multivariate analysis, the increase in HR with TTI was not statistically significant. There was no statistically significant interaction between TTI and UICC stage. CONCLUSION: Survival of OSCC patients decreased with increasing TTI, yet not statistically significant in multivariate analysis. There was no difference in the effect of TTI between patients diagnosed in low or advanced stages.

Development of depression in patients with oral cavity cancer: a systematic review.

BACKGROUND: The incidence of oral cancer is approximately 300,000 patients annually. A cancer diagnosis and treatment affect both physical and mental issues. OBJECTIVES: The aim of this systematic review was to examine the development of depression in patients who have been treated for oral squamous cell carcinoma (OSCC). MATERIAL AND METHODS: PubMed and EMBASE were systematically searched for studies addressing depression among patients treated for OSCC and published within the past ten years. RESULTS: We identified three studies comprising 528 patients (range: 75-349), primarily men (66-83%), treated for OSCC from Europe and India. Tumour stage, treatment modality, and scales used to evaluate depressive symptoms varied in the studies. The European studies showed that 28% of the patients experienced depressive symptoms on the Hospital Anxiety and Depression Scale (HADS) and a mean of 8.0 on depression in the Brief Symptom Inventory (BSI). The Indian study showed a significant increase (p Value < .001) from moderate to severe depressive symptoms on the Depression, Anxiety, and Stress Scale-21 (DASS-21).Conclusion and Significance: This systematic review showed that OSCC patients are at risk of developing depressive symptoms after treatment, though severity of symptoms varied. This knowledge could preferably be implemented in future follow-up regimes.

Impact of surgical resection margins less than 5 mm in oral cavity squamous cell carcinoma: a systematic review.

Background: The width of the surgical resection margin impacts recurrence and survival in oral cavity squamous cell carcinoma (OSCC). The most commonly used definition of a clear margin is one larger than 5 mm, although due to anatomical restrictions to e.g. bone or vessels, this size is not always feasible. Margins less than 5 mm affect postsurgical strategies and prognoses, and further knowledge of margins smaller than 5 mm is needed.Aims/objectives: We aimed to systematically review the literature on the impact of surgical resection margins less than 5 mm addressing recurrence and survival in OSCC.Methods/materials: A systematic literature search was performed in the PubMed and EMBASE databases identifying studies regardless of publication date that examined margin less than 5 mm, with or without a comparison to size of 5 mm or greater, in patients with OSCC. We assessed the impact on recurrence and survival.Results: We identified six studies (n = 1514 patients); all studies, investigated recurrence, and three (n = 768 patients) evaluated survival. The studies had noteworthy variability in, e.g. follow-up times, anatomical sublocations, T- and N-stage classifications, and outcome measures. Five studies (n = 1387 patients) reported that margins smaller than 5 mm would be safe and would not affect survival or recurrence negatively compared to their own data on larger margins. One study reported that a clear resection margin greater than five mm was necessary to ensure optimal outcomes.Conclusion/significance: The literature showed significant bias and risk issues. In five of the included studies with 1387 patients, we found in selected cases, where margins larger than 5 mm are not possible, a tendency regarding resection margins less than 5 mm to be sufficient for the surgical treatment of patients with primary OSCC. However, the data is insufficient to enable altered recommendations of resection margins in patients with primary OSCC.

Rate of locoregional recurrence among patients with oropharyngeal squamous cell carcinoma with known HPV status: a systematic review.

Background: We aimed to review systematically the literature on locoregional recurrence rates in patients with HPV-positive and -negative oropharyngeal squamous cell carcinoma (OPSCC).Methods: PubMed and Embase databases were systematically searched using key words such as human papillomavirus, oropharyngeal squamous cell carcinoma with local, regional, and locoregional recurrence.Results: Nine studies (2974 patients with known HPV-status, 59% HPV-positive) were included. Among the HPV-positive and -negative patients, 69% and 58% had lymph node metastasis at diagnosis. At a median time to recurrence ranging from 8.4 to 13.2 months among the included studies, we found that a weighted average of 9% and 26% for HPV-positive and -negative patients experienced locoregional recurrence. Overall, the median follow-up time ranged from 21 to 83 months among the included studies.Conclusion: Recurrence rates for HPV-positive and -negative OPSCC patients were 9% and 26%, respectively, equating to an almost three times higher rate of locoregional recurrence among HPV-negative patients compared to HPV-positive patients.

The Impact of Comorbidity on Survival in Patients With Head and Neck Squamous Cell Carcinoma: A Nationwide Case-Control Study Spanning 35 Years.

BACKGROUND: Comorbidity is presumed to impact survival of head and neck squamous cell cancer (HNSCC) patients. However, the prevalence and prognostic impact of comorbidity in these patients is not yet well established. The aim of this study is to outline the comorbidity burden of HNSCC patients and investigate the relation to overall survival and cancer-specific mortality. METHODS: The comorbidity burden of patients registered with HNSCC in the Danish Cancer Registry between 1980 and 2014 was evaluated based on the Charlson Comorbidity Index (CCI). Patients' risks of comorbid conditions compared to age- and gender-matched controls were estimated by odds ratios (OR). The impact of comorbidity on overall survival and cancer-specific mortality was evaluated by Cox regression and Kaplan-Meier survival analysis. RESULTS: A total of 25,388 HNSCC patients were included (72.5% male; mean age 63.2 years at diagnosis; median follow-up 3.0 years). CCI at diagnosis was significantly higher in patients compared to controls (p < 0.001). The most common comorbid conditions among the patients were additional non-metastatic malignancy (10.9%) and cerebrovascular disease (7.7%). Compared to controls, patients had higher odds of metastatic malignancy (OR: 4.65; 95% CI: 4.21-5.15; p < 0.001), mild liver disease (OR: 6.95; 95% CI: 6.42-7.53; p < 0.001), and moderate-severe liver disease (OR: 7.28; 95% CI: 6.14-8.65; p < 0.001). The multivariate Cox analysis revealed increasing hazard ratios with increasing CCI and in coherence the Kaplan-Meier curves showed poorer overall survival and increased cancer-specific mortality in patients with higher CCI. CONCLUSION: HNSCC patients' comorbidity burden was significantly greater compared to the general population and increased comorbidity was correlated with increased cancer-related mortality.

High nodal FDG uptake increases risk of distant metastasis in patients with oropharyngeal squamous cell carcinoma.

BACKGROUND: The purpose of this study was to investigate if FDG uptake metrics in primary tumor and lymph node metastases in patients with oropharyngeal squamous cell carcinoma (OPSCC) has a prognostic value beyond UICC8 staging in a multiple endpoint model. METHODS: Patients with OPSCC treated with primary radiotherapy at Rigshospitalet in the period 2010-2017 were included. All patients had a pretreatment FDG PET/CT scan performed. Four cause-specific Cox regression models were built for the hazard ratios (HR) of recurrence in T-, N-, M-site, and death with no evidence of disease (NED), respectively. The following variables were included: T-, N-stage, p16 status, metabolic tumor volume, and FDG uptake in both primary tumor and lymph nodes. A competing risk analysis was performed and absolute risk estimates were estimated using the Aalen-Johansen method. RESULTS: Overall, 441 patients were included. Thirty-four patients had T-site recurrence, 31 N-site recurrence, 32 M-site recurrence, and 52 patients had death NED as event. Nodal FDG uptake had a significant impact on N- and M-site recurrence, with HRs of 2.13 (CI 1.20-3.77) and 2.18 (CI 1.16-4.10). The individual prognostication of absolute risk of the four events for any given patient can be assessed in the online tool (https://rasmussen.shinyapps.io/OPSCCmodelFDG_PET/). CONCLUSION: High nodal FDG uptake increases the risk of N- and M-site recurrence in patients with OPSCC in a competing risk scenario. The reported results are available in an easy applicable online tool and can help identify relevant candidates for future trials testing treatment approaches.

Current status of human papillomavirus positivity in oropharyngeal squamous cell carcinoma in Europe: a systematic review.

Background: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has been rising in the Western world in recent years. Human papillomavirus (HPV) infection is established as the main explanation.Aims/objectives: This study aims to review the most recently published studies on the repartition of HPV-positive OPSCC in Europe.Method and material: PubMed and Embase were systematically searched for articles addressing the distribution of HPV-positive and HPV-negative cases among OPSCC patients in Europe. Articles published in the period 2014-2018, with a study period including 2013 and the following years were included. The presence of HPV DNA and p16 overexpression, either solely or together, were accepted as indicators of HPV-positivity. Information on the anatomical sublocation of the tumour, definition of HPV-status, HPV type, HPV status, age, sex, TNM-stage, smoking habits and alcohol consumption were extracted.Results: Seven articles (n = 2075 patients, range: 22-926 patients per study) from seven European countries were included. The repartition of HPV-positivity ranged from 18% to 65%. The lowest occurrence of HPV-positivity was seen in Greece and the Netherlands, and the highest in Sweden and Denmark.Conclusion/significance: The highest share of HPV-positive patients with up to 65% was found in Nordic countries. The lowest share was found in Central and Southern European countries.