Lalle Hammarstedt-Nordenvall

Incidence of human papillomavirus positive tonsillar and base of tongue carcinoma: A stabilisation of an epidemic of viral induced carcinoma?

AIM To investigate whether the rise during the past decades in the incidence of tonsillar and base of tongue squamous cell carcinoma (TSCC and BOTSCC) and the proportion of human papillomavirus (HPV) positive cancer has continued in Stockholm. PATIENTS AND METHODS Pre-treatment biopsies (n=252) available from 280 patients diagnosed with TSCC and BOTSCC during 2008-2012 in the County of Stockholm were tested for HPV DNA by a multiplex bead-based assay. Incidence records were acquired from the Swedish Cancer Registry. The data obtained were evaluated together with previous figures from 1970 to 2007. RESULTS HPV DNA was present in 186/252 (74%) of TSCC and BOTSCC biopsies obtained during 2008-2012 in Stockholm. In this region the age-standardised incidence, including the prevalence of HPV-positive and HPV-negative TSCC stabilised 2007-2012 compared to 2000-2006, while for BOTSCC throughout 1998-2012 the same parameters increased moderately (p<0.05, for all). In parallel, from 2000 to 2006 through 2007-2012 in Sweden, the age-standardised incidence of both TSCC and BOTSCC continued to rise (p=0.012 and p=0.001 respectively). CONCLUSION During 2000-2012 the age-standardised incidence and the proportion of HPV-positive TSCC have stabilised at a high level, while the proportion of HPV-negative cancer has remained at a low level in Stockholm, whereas for BOTSCC all parameters are increasing moderately. In contrast, in Sweden the incidence of both TSCC and BOTSCC is still increasing. We hypothesise that the HPV epidemic could be stabilising, first for TSCC, but so far not for BOTSCC, in e.g. some urban areas, while previous trends for both tumours persist at other geographic locations.

HLA Class I and II Expression in Oropharyngeal Squamous Cell Carcinoma in Relation to Tumor HPV Status and Clinical Outcome

HPV-DNA positive (HPVDNA+) oropharyngeal squamous cell carcinoma (OSCC) has better clinical outcome than HPV-DNA negative (HPVDNA-) OSCC. Current treatment may be unnecessarily extensive for most HPV+ OSCC, but before de-escalation, additional markers are needed together with HPV status to better predict treatment response. Here the influence of HLA class I/HLA class II expression was explored. Pre-treatment biopsies, from 439/484 OSCC patients diagnosed 2000-2009 and treated curatively, were analyzed for HLA I and II expression, p16INK4a and HPV DNA. Absent/weak as compared to high HLA class I intensity correlated to a very favorable disease-free survival (DFS), disease-specific survival (DSS) and overall survival (OS) in HPVDNA+ OSCC, both in univariate and multivariate analysis, while HLA class II had no impact. Notably, HPVDNA+ OSCC with absent/weak HLA class I responded equally well when treated with induction-chemo-radiotherapy (CRT) or radiotherapy (RT) alone. In patients with HPVDNA- OSCC, high HLA class I/class II expression correlated in general to a better clinical outcome. p16INK4a overexpression correlated to a better clinical outcome in HPVDNA+ OSCC. Absence of HLA class I intensity in HPVDNA+ OSCC suggests a very high survival independent of treatment and could possibly be used clinically to select patients for randomized trials de-escalating therapy.

The human carotid body releases acetylcholine, ATP and cytokines during hypoxia

What is the central question of this study? Data on human carotid body (CB) function are limited. The aim of this study was therefore to investigate whether the human CB releases acetylcholine, ATP or cytokines during hypoxia. What is the main finding and its importance? Using human CBs, we demonstrate hypoxia‐induced acetylcholine and ATP release, suggesting that these neurotransmitters, as in several experimental animal models, play a role in hypoxic signalling also in the human carotid body. Moreover, the human CB releases cytokines upon hypoxia and expresses cytokine receptors as well as hypoxia‐inducible factor proteins HIF‐1α and HIF‐2α in glomus cells, indicating their role in immune signalling and oxygen sensing, respectively, in accordance with previous animal data.

Validation of a Swedish version of the Facial Disability Index (FDI) and the Facial Clinimetric Evaluation (FaCE) scale.

Abstract Conclusion: Swedish versions of the Facial Disability Index (FDI) and Facial Clinimetric Evaluation (FaCE) scale are psychometrically valid. Both questionnaires can be used for clinical studies on peripheral facial palsy patients, and provide important information on quality of life. Objectives: To translate and validate Swedish versions of the FDI and FaCE scale in patients with peripheral facial palsy. Methods: Translation of the original questionnaires followed international guidelines. Internal consistency and test–retest stability were assessed in adult patients with stable peripheral facial palsy. Facial function was examined with the Sunnybrook and House-Brackmann scales. Subjects answered the questionnaires twice with a 2-week interval. Validity was assessed by comparing FDI and FaCE scale scores to SF-36 and Sunnybrook/House-Brackmann scores. Results: Ninety-three patients were included, 53% women and 47% men, mean age 56.9 years and mean duration of palsy 51.9 months. The questionnaires showed good/excellent psychometric properties with Cronbachs α scores between 0.76 and 0.92. In the test–retest analysis, intra-class correlation coefficients were very good for both questionnaires with scores of 0.83–0.97. Both questionnaires showed good sensitivity to discriminate between patients with varying degrees of facial dysfunction. Moderate to strong correlation was found between the social domains in the questionnaires when compared with the equivalent domains in SF-36.

A model for predicting clinical outcome in patients with human papillomavirus-positive tonsillar and base of tongue cancer.

AIM To combine clinical and molecular markers into an algorithm for predicting outcome for individual patients with human papillomavirus (HPV) DNA/p16(INK4a) positive tonsillar and base of tongue squamous cell carcinoma (TSCC and BOTSCC). BACKGROUND Head-neck cancer treatment has become more intensified, comprising not only surgery and radiotherapy, but also induction/concomitant chemotherapy and targeted therapy. With less treatment, 3-year disease free survival (DFS) is 80% for HPV-positive TSCC and BOTSCC. An 85-100% 3-year DFS is observed for HPV(+) TSCC and BOTSCC with absence of HLA class I, or CD44 expression, or high CD8(+) tumour-infiltrating lymphocyte (TIL) counts suggesting that therapy could be tapered for many if patients could be identified individually. PATIENTS AND METHODS Patients treated curatively, with HPV DNA/p16(INK4a) positive tumours examined for HLA class I and II, CD44 and CD8(+)TILs, were included. An L1-regularised logistic regression was used to evaluate the effect of the biomarker data, age, stage, diagnosis, smoking and treatment on 3-year risk of death or relapse on a training cohort of 197 patients diagnosed 2000-2007 and validated on a cohort of 118 patients diagnosed 2008-2011. RESULTS The variables finally included in the model were HLA class I, CD8(+) TILs, age, stage and diagnosis (TSCC or BOTSCC). The model showed acceptable discrimination and calibration. The discriminative ability of the model did not diminish after validation (AUC=0.77). CONCLUSION To our knowledge, this is the first model to utilise information from several markers to predict an individual probability of clinical outcome for patients with HPV DNA/p16(INK4a) positive tumours.

Cancer of the gingiva

Cancer of the gingiva is a rare disease in the Western World. It most commonly affects elderly population. Because of its rarity, the reporting on the disease is sparse and often grouped with other subsites of oral cancer, which makes conclusions difficult to interpret. The aim of this paper is to review the literature on gingival cancer as a specific subsite of oral cancer and report on published prognostic factors as well as treatment of local and regional disease. We also present differences between gingival cancer subgroups, mandibular and maxillary gingival cancer. In addition, both surgical and oncological treatments are reviewed. It seems that surgery is the preferred initial treatment approach for the majority of patients with gingival cancer, although adjuvant radiation, with or without chemotherapy, is commonly recommended to increase locoregional control.

Sinonasal malignancies in Sweden 1960-2010; a nationwide study of the Swedish population.

INTRODUCTION Sinonasal malignancies (SNM) are rare and the prognosis is generally poor. Recently, a change in incidence for SNM has been reported. In this study, we investigated population-based trends for SNM in Sweden. METHODS We identified 3,221 patients from the Swedish National Cancer Registry diagnosed with primary malignancies arising from the nasal cavity, paranasal sinuses, or both, during the period 1960 through 2010. Incidence, gender and age, anatomical sites and relative survival were investigated. RESULTS The incidence for SNM decreased except for sinonasal malignant melanoma (SNMM) and adenoid cystic cancer (even though a very small group) during the study period. More than 50 % of the malignancies involved the nasal cavity. The five-year relative survival was highest for adenoid cystic cancer followed by adenocarcinoma. SNMM and undifferentiated carcinoma had the poorest prognosis. CONCLUSION We found that the incidence for SNM has decreased during the study period 1960 through 2010, except for SNMM that has increased.

Management of the neck in node-positive tonsillar cancer

Abstract Conclusion: Neck dissection (ND) may not be warranted for those patients with complete response in the neck. Human papillomavirus (HPV)-positive or -negative tumour does not affect this recommendation. Objectives: Treatment of tonsillar cancer varies considerably worldwide, although non-surgical treatment, e.g. radiotherapy (RT), possibly combined with chemotherapy (CRT), is gradually coming to be regarded as the first line of therapy. However, the optimal treatment of nodal disease remains controversial, and the fundamental question is if and when to perform ND. Methods: We performed a retrospective analysis of all patients with tonsillar cancer treated in the Stockholm area between 2000 and 2006. An analysis of node-positive tumours was done and the neck specimen was investigated for the presence of viable tumour cells after RT. A sub-analysis of HPV status was also carried out. Results: Following complete response after RT, 2% of patients showed viable cells in the neck specimen, compared with 60% in patients who did not show complete response. HPV-positive tumours had the same proportion of viable tumour cells in the neck specimen as HPV-negative tumours.

Human papillomavirus and survival of patients per histological subsite of tonsillar squamous cell carcinoma

Current data advocate that oropharyngeal squamous cell carcinoma (OPSCC) should be divided into subsites when evaluating the presence of human papillomavirus (HPV) and prognosis. More specifically, tonsillar squamous cell carcinoma (TSCC) and base of tongue squamous cell carcinoma (BOTSCC) have much higher HPV prevalence compared to other OPSCC. Moreover, patients with HPV positive (HPV+) TSCC and BOTSCC have a better prognosis as compared to patients with HPV negative (HPV−) corresponding tumors, while the prognostic role of HPV in other OPSCC is unclear. Furthermore, in a recent report from Denmark, TSCC was further subclassified into specified TSCC (STSCC) and nonspecified TSCC (NSTSCC), with HPV significantly more prevalent in STSCC. In this study, the histopathological influence of HPV prevalence and survival in TSCC was analyzed in a TSCC cohort with known HPV status, of patients diagnosed 1970–2002 in Stockholm. In total, 139 TSCC biopsies with both tumor and adjacent normal tissue were separated into STSCC and NSTSCC. HPV was significantly more commonly found in STSCC than in NSTSCC. Patients with HPV+ STSCC had a better disease‐specific and overall survival as compared to patients with HPV+ NSTSCC, but no survival differences were observed in patients with HPV− STSCC and NSTCC. These findings confirm previous reports and suggest that TSCC subsite may also be of relevance for clinical outcome and should be further followed up in future studies.

Human papillomavirus prevalence in mouthwashes of patients undergoing tonsillectomy shows dominance of HPV69, without the corresponding finding in the tonsils

Abstract Background: The role of human papillomavirus (HPV) in tonsillar squamous cell carcinomas (TSCC) is of interest, since a considerable proportion of TSCC in Sweden and other Western countries is HPV positive. Nevertheless, the natural history of HPV in normal tonsils, and the progression from localized infection to pre-malignant lesion to cancer are poorly understood. The aim of this study was to investigate whether HPV types found in mouthwash samples correlated to those in tonsillar tissue from the same individuals undergoing tonsillectomy. Methods: Mouthwash samples from 232 patients, aged 3–56 years, undergoing tonsillectomy, the majority with chronic tonsillitis, were collected at the time of surgery and analysed for the presence of 27 HPV types by a bead based multiplex assay. Results: An HPV prevalence of 10.3% (24/232) was observed in mouthwash samples, with HPV 69 being the dominant type (10/24). Ten patients were positive for high risk HPV (HPV 16, 33, 35, 45, 56, 59). None of the tonsils resected from patients with HPV-positive mouthwash samples were positive for HPV. Conclusions: Despite an oral HPV prevalence of 10.3% in mouthwash samples from tonsillectomized patients, with dominance of HPV 69, none of the corresponding tonsillar samples exhibited the presence of HPV.