| 1. |
- Hammarstedt, Lilian, et al.
(författare)
-
Human papillomavirus as a risk factor for the increase in incidence of tonsillar cancer
- 2006
-
Ingår i: Int J Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 119:11, s. 2620-3
-
Tidskriftsartikel (refereegranskat)abstract
- Smoking and alcohol are well-known etiological factors in tonsillar cancer. However, as in cervical cancer, human papillomavirus (HPV) is currently found in a sizable proportion of tonsillar cancer. Recent reports from the U.S. and Finland show an increase in the incidence of tonsillar cancer, without a parallel rise in smoking and alcohol consumption. This study investigates whether the incidence of tonsillar cancer has also changed in Sweden and whether a possible explanation of the increase is a higher proportion of HPV-positive tonsillar cancer. The incidence of tonsillar cancer between 1970 and 2002 in the Stockholm area was obtained from the Swedish Cancer Registry. In parallel, 203 pretreatment paraffin-embedded tonsillar cancer biopsies taken during 1970-2002 from patients in the Stockholm area were tested for presence of HPV DNA by PCR. The incidence of tonsillar cancer increased 2.8-fold (2.6 in men and 3.5 in women) from 1970 to 2002. During the same period, a significant increase in the proportion of HPV-positive tonsillar cancer cases was observed, as it increased 2.9-fold (p < 0.001). The distribution of HPV-positive cases was 7/30 (23.3%) in the 1970s, 12/42 (29%) in the 1980s, 48/84 (57%) in the 1990s and 32/47 (68%) during 2000-2002. We have demonstrated a highly significant and parallel increase both in the incidence of tonsillar cancer and the proportion of HPV-positive tumors. Hence, HPV may play an important role for the increased incidence of tonsillar cancer. This should definitely influence future preventive strategies as well as treatment for this type of cancer.
|
|
| 2. |
- Hammarstedt, Lalle, et al.
(författare)
-
The incidence of tonsillar cancer in Sweden is increasing.
- 2007
-
Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; 127:9, s. 988-92
-
Tidskriftsartikel (refereegranskat)abstract
- CONCLUSIONS: The incidence of tonsillar cancer in Sweden is increasing, particularly among men. Risk factors other than smoking may have contributed to the observed secular trend in men. In women, however, smoking can be a part of the explanation. Further studies to look at changes in other environmental factors, such as human papilloma virus (HPV) infection, are clearly warranted. OBJECTIVES: Head and neck cancer is related to smoking habits and smoking has decreased substantially during the last 30 years in Sweden. However, there is suspicion that the incidence of tonsillar cancer has increased in the last 30 years as it has in the USA and Finland, in spite of reduced prevalence of known risk factors. The time trends of oral and oropharygeal cancer have been studied in Sweden, but not tonsillar cancer specifically. SUBJECTS AND METHODS: We used the Swedish Cancer Registry to assess the secular trend of incidence of tonsillar cancer in Sweden since 1960. For comparison we investigated the incidence of other oral cancers and lung cancer, which are also smoking-related. The prevalence of smoking was investigated for reference. Age-standardized incidence rates were calculated and linear regression was used to evaluate secular trends. RESULTS: The incidence of tonsillar cancer increased by 2.6% per year in men and 1.1% in women. No similar increase was seen in the other oral cancers. For lung cancer there was a decrease in the incidence in men, but in women the incidence is still increasing.
|
|
| 3. |
|
|
| 4. |
- Astradsson, Thorsteinn
(författare)
-
Systemic inflammation and prognostic markers in patients with head and neck cancer
- 2024
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Patients with head and neck cancer (HNC) often present with weight loss and malnutrition caused by systemic inflammation and dysphagia. This thesis explores the effects of systemic and local inflammation in the context of head and neck cancer treatment. The main aim of Paper I was to investigate whether trismus after radiotherapy affects the 5-year overall survival rate in a cohort of 244 patients with HNC. The maximum interincisal opening (MIO) of the patients was measured before treatment, 2, 6, and 12 months after the termination of radiotherapy, and trismus was defined as MIO ≤ 35 mm. All patients received instructions on jaw-opening exercises. The highest prevalence of trismus at 12 months was seen in patients with oral cancer (44%) and oropharyngeal cancer (37%) and it can be concluded that these patients should primarily be offered jaw-opening exercises. Patients with trismus at 12 months after termination of treatment had a tendency towards a worse overall 5-year survival rate than patients without trismus (p=0.64).Paper II explored the expression levels of cytokines and growth factors in serum before and up to one year after treatment. The cohort consisted of 30 patients with HNC and blood was drawn on four occasions and analyzed for 10 cytokines and 4 growth factors. Patients who received chemoradiotherapy had higher expression levels of IL-1β, IL-6, and IL-10 than other treatment groups at 7 weeks after the start of treatment. Patients with recurrence within 12 months after termination of treatment had higher expression levels of IL-1β, IL-6, IL-8, and IL-10 than the remaining patients at 7 weeks.In Paper III the expression levels of 83 immuno-oncologically significant proteins were determined at the same four time points as in Paper II in a cohort of 180 patients with HNC using a proteomics technique. Fifteen proteins had either decreased or increased expression levels at 7 weeks compared to pre-treatment expression levels. Treatment with radiotherapy with concomitant cisplatin was shown to be connected to significantly decreased expression of 13 proteins at 7 weeks after the start of treatment compared to radiotherapy which demonstrates an immunomodulatory effect of cisplatin also apparent in Paper II.The aim of Paper IV was to investigate how pre-treatment body mass index and fat free mass index correlate with early death in a cohort of 404 patients with head and neck squamous cell carcinoma (HNSCC). Body mass composition was measured at diagnosis using bioelectrical impedance analysis. Patients who died within 6 months of the start of treatment had significantly lower FFMI at diagnosis compared with patients who survived beyond 6 months (17.6 kg/m2 and 19.5 kg/m2, respectively, p=0.035). It can be recommended that assessment of fat free mass index should be included in the management of patients with HNSCC prior to treatment.
|
|
| 5. |
- Gebre-Medhin, Maria, et al.
(författare)
-
ARTSCAN III : A randomized phase III study comparing chemoradiotherapy with cisplatin versus cetuximab in patients with locoregionally advanced head and neck squamous cell cancer
- 2021
-
Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 39:1, s. 38-47
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE We performed an open-label randomized controlled phase III study comparing treatment outcome and toxicity between radiotherapy (RT) with concomitant cisplatin versus concomitant cetuximab in patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC; stage III-IV according to the Union for International Cancer Control TNM classification, 7th edition). MATERIALS AND METHODS Eligible patients were randomly assigned 1:1 to receive either intravenous cetuximab 400 mg/m2 1 week before start of RT followed by 250 mg/m2/wk, or weekly intravenous cisplatin 40 mg/m2, during RT. RT was conventionally fractionated. Patients with T3-T4 tumors underwent a second random assignment 1:1 between standard RT dose 68.0 Gy to the primary tumor or dose escalation to 73.1 Gy. Primary end point was overall survival (OS) evaluated using adjusted Cox regression analysis. Secondary end points were locoregional control, local control with dose-escalated RT, pattern of failure, and adverse effects. RESULTS Study inclusion was prematurely closed after an unplanned interim analysis when 298 patients had been randomly assigned. At 3 years, OS was 88% (95% CI, 83% to 94%) and 78% (95% CI, 71% to 85%) in the cisplatin and cetuximab groups, respectively (adjusted hazard ratio, 1.63; 95% CI, 0.93 to 2.86; P 5 .086). The cumulative incidence of locoregional failures at 3 years was 23% (95% CI, 16% to 31%) compared with 9% (95% CI, 4% to 14%) in the cetuximab versus the cisplatin group (Gray’s test P 5 .0036). The cumulative incidence of distant failures did not differ between the treatment groups. Dose escalation in T3-T4 tumors did not increase local control. CONCLUSION Cetuximab is inferior to cisplatin regarding locoregional control for concomitant treatment with RT in patients with locoregionally advanced HNSCC. Additional studies are needed to identify possible subgroups that still may benefit from concomitant cetuximab treatment.
|
|
| 6. |
- Grün, Nathalie, et al.
(författare)
-
Human papillomavirus prevalence in mouthwashes of patients undergoing tonsillectomy shows dominance of HPV69, without the corresponding finding in the tonsils.
- 2017
-
Ingår i: Infectious diseases (London, England). - : Informa UK Limited. - 2374-4243 .- 2374-4235. ; 49:8, s. 588-593
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 7. |
- Hammarstedt, Lalle
(författare)
-
Tonsillar cancer : incidence, prevalence of HPV and survival
- 2008
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Since human papilloma virus (HPV) in the mid 1980ies was first observed in squamous cell carcinoma of the head and neck, its role and impact, especially on oral and oropharyngeal cancer, have attracted extensive interest. The aim of this thesis was to investigate if the clinical impression of increased incidence of tonsillar cancer was true, and if HPV could be linked to this increase. Molecular evidence that HPV could exert its transforming capacity in tonsillar cancer was searched for as well as if the presence of HPV had prognostic value. The Swedish Cancer Register was used to assess the incidence rates of tonsillar cancer over time. There was a significant increase since the register started, especially pronounced the last 15 years and in men. Paraffin embedded diagnostic biopsies were analysed to estimate the prevalence of HPV in tonsillar cancer in Stockholm between 1970-2002. Two hundred and three cases could be examined and the HPV prevalence was found to have increased from 23 % in the 70ies to 68 % in 2000-2002. HPV was found to be a strong favorable prognostic factor and patients harbouring HPV positive tumors fared better. In addition, HPV viral load and expression of the viral oncogenes E6 and E7 were analyzed and in most HPV-16 positive tumors, expression of E6 and E7 was ascertained. Survival for patients with tonsillar cancer was assessed in a nationwide setting to see if the increased prevalence of HPV had any impact. The Swedish Cancer Register was used to evaluate the relative survival in tonsillar cancer since 1960 and the Stockholm cohort was studied thoroughly to determine if the improved survival was due to diagnostic or therapeutic improvements. The relative survival has increased, both in men and women, and when analysing the Stockholm cohort this could not be explained by improved treatment or earlier diagnosis. It is feasable that the increased survival of tonsillar cancer the last decades is caused by and closely related to the increase in HPV related tonsillar cancer. This thesis report a parallel and substantial increase in the incidence of tonsillar cancer and the prevalence of HPV in tonsillar cancer in Sweden. HPV positive cases express their oncogenes and patients with HPV positive tumors have a significantly better disease specific survival. Finally, survival in tonsillar cancer improved in all over Sweden the last 40 years. This should pave way for future trials when planning treatment and also be addressed when discussing vaccination.
|
|
| 8. |
- Hammarstedt-Nordenvall, Lalle, et al.
(författare)
-
Distribution of sentinel nodes from parotid tumors - A feasibility study
- 2023
-
Ingår i: Cancer Medicine. - : John Wiley & Sons. - 2045-7634. ; 12:9, s. 19667-19672
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Optimum management of the N0 neck is unresolved in parotid salivary gland cancer. Sentinel node biopsy (SNB) can reliably detect microscopic lymph node metastasis and its ' clinical use is increasing for head and neck tumors. The object of this study was to establish whether the technique is applicable to detect distribution of sentinel nodes for parotid tumors.Materials and Methods: Prosepective observational study in 30 patients with benign or low-grade T1-T2N0 malignant tumors in the parotid gland planned for surgical treatment. Distribution of SN was detected with a preoperative ultrasound-guided peritumoral injection with a technetium-99 (Tc-99 m) laballed tracer followed by a SPECT-CT and intraoperative measurement in the neck and parotidal tissue. In patients with cytologically suspected malignant tumor or highly unclerar cytology, SNB was also performed.Results: Sentinel nodes (SNs) were detected in 26/30 cases. Out of these, 7 presented with only one SN, whereas multiple sentinel nodes where detected in 19 cases. No SNs were found in neck level 1. SN was detected in level 5 independent of tumor location within the parotid gland. An intraparotidal distribution of SNs was more frequent in larger tumors.Conclusions: The use of SN-technique in the planning of surgical treatment of parotid tumors seems feasible. It may be of clinical value for patients with parotid cancer to enable a more accurate staging and to detect occult metastasis in the SNs within the parotid as well as in the neck, enabaling the possibility to surgically remove all positive SNs at primary surgery and with reduced surgical morbidity.
|
|
| 9. |
- Högmo, Anders, et al.
(författare)
-
Base of tongue squamous cell carcinomas, outcome depending on treatment strategy and p16 status. A population-based study from the Swedish Head and Neck Cancer Register
- 2022
-
Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 61:4, s. 433-440
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The base of tongue squamous cell carcinoma (BOTSCC) is mainly an HPV-related tumor. Radiotherapy (EBRT) ± concomitant chemotherapy (CT) is the backbone of the curatively intended treatment, with brachytherapy (BT) boost as an option. With four different treatment strategies in Sweden, a retrospective study based on the population-based Swedish Head and Neck Cancer Register (SweHNCR) was initiated.Material and methods: Data on tumors, treatment and outcomes in patients with BOTSCC treated between 2008 and 2014 were validated through medical records and updated as needed. Data on p16 status were updated or completed with immunohistochemical analysis of archived tumor material. Tumors were reclassified according to the UICC 8th edition.Results: Treatment was EBRT, EBRT + CT, EBRT + BT or EBRT + CT + BT in 151, 145, 82 and 167 patients respectively (n = 545). A p16 analysis was available in 414 cases; 338 were p16+ and 76 p16−. 5-year overall survival (OS) was 68% (95% CI: 64–72%), with76% and 37% for p16+ patients and p16− patients, respectively. An increase in OS was found with the addition of CT to EBRT for patients with p16+ tumors, stages II–III, but for patients with tumor stage I, p16+ (UICC 8) none of the treatment strategies was superior to EBRT alone.Conclusion: In the present retrospective population-based study of BOTSCC brachytherapy was found to be of no beneficial value in curatively intended treatment. An increase in survival was found for EBRT + CT compared to EBRT alone in patients with advanced cases, stages II and III (UICC 8), but none of the regimes was significantly superior to EBRT as a single treatment modality for stage I (UICC 8), provided there was p16 positivity in the tumor. In the small group of patients with p16− tumors, a poorer prognosis was found, but the small sample size did not allow any comparisons between different treatment strategies.
|
|
| 10. |
- Landin, David, et al.
(författare)
-
Post-Treatment Neck Dissection of Tonsillar and Base of Tongue Squamous Cell Carcinoma in the Era of PET-CT, HPV, and p16
- 2022
-
Ingår i: Viruses. - : MDPI. - 1999-4915. ; 14:8
-
Tidskriftsartikel (refereegranskat)abstract
- Human-papillomavirus (HPV)-positive tonsillar and base of tongue carcinomas (TSCC/BOTSCC) are rising in incidence and treatments with radiotherapy, chemoradiotherapy (RT/CRT), and neck dissections (NDs) have several side effects. Therefore, an improved selection of patients needing salvage NDs would be beneficial. We examined the prevalence and localisations of viable tumour cells in neck lymph nodes in patients post-RT/CRT, identified by fluorodeoxyglucose positron-emission tomography with computer-tomography (FDG PET-CT), with a focus on HPV-associated tumours. Patients with 217 TSCC/BOTSCC with tumours assessed for HPV-DNA and p16(INK4a) undergoing FDG PET-CT 12 weeks after treatment and/or an ND were included. The FDG PET-CT data were compared with the findings in the pathology report after the ND. In total, 36/217 (17%) patients were selected for an ND due to positive findings in post-treatment FDG PET-CT. Of these, 35/36 were HPV-associated, 10/36 (28%) had viable tumour cells in the pathology reports of the neck specimen, and 8/10 (80%) were consistent with the FDG PET-CT findings, while 2/36 (5%) were missed by FDG PET-CT. We conclude that FDG PET-CT 12 weeks after RT/CRT is useful, but not completely reliable for finding all the metastases of HPV-associated TSCC/BOTSCC. Nonetheless, our data indicate that an ND could be more selectively guided by FDG PET-CT.
|
|
