| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Bark, Rusana, et al.
(författare)
-
Sentinel node-assisted neck dissection in advanced oral squamous cell carcinoma - A new protocol for staging and treatment
- 2023
-
Ingår i: Cancer Medicine. - : Wiley-Blackwell. - 2045-7634. ; 12:11, s. 12524-12534
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Sentinel lymph node biopsy (SLNB) is used to improve the staging of and guide treatment in patients with early-stage T1-T2 N0 oral squamous cell carcinoma (OSCC). The role of sentinel nodes (SNs) and the use of SN-technique in advanced OSCC (T3-T4 and/or N+) remain to be evaluated. This study investigates the nodal drainage and the rate of positive SNs (SNs+) in all stages of OSCC.Materials and Methods: In total, 85 patients with T1-T4 OSCC diagnosed 2019-2021 were included. We used a prolonged interval between peritumoral injection of radionuclide and SPECT-CT to include all SNs.Results: Patients with advanced OSCC presented a higher proportion of contralateral lymphatic drainage and a higher rate of SN+ compared to patients with early-stage disease. T3-T4 and N+ tumors presented a tendency for a higher rate of contralateral lymphatic drainage compared to T1-T2 and N0 tumors (p = 0.1). The prevalence of positive nodes (SNs+) was higher among patients with advanced disease, T3-T4 versus T1-T2 (p = 0.0398).Conclusion: SN-assisted ND enables identification and removal of all SNs + and has the potential for more accurate staging and could possibly give prognostic advantages regarding regional recurrence for all OSCC patients, especially among those with advanced disease. The precise localization of the SNs + also suggests that a more individualized ND approach might be possible in the future even for patients with advanced OSCC.
|
|
| 6. |
- Bersani, Cinzia, et al.
(författare)
-
A model using concomitant markers for predicting outcome in human papillomavirus positive oropharyngeal cancer
- 2017
-
Ingår i: Oral Oncology. - : Elsevier. - 1368-8375 .- 1879-0593. ; 68, s. 53-59
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Head-neck cancer therapy has become intensified. With radiotherapy alone, 3-year disease-free survival (DFS) is 80% for HPV-positive TSCC/BOTSCC and better for patients with favorable characteristics, suggesting therapy could be tapered for some, decreasing side-effects. Therefore, we built a model to predict progression-free survival for patients with HPV-positive TSCC and BOTSCC. Material and methods: TSCC/BOTSCC patients treated curatively between 2000 and 2011, with HPV16 DNA/E7 mRNA positive tumors examined for CD8(+) TILs, HPV16 mRNA and HLA class I expression were included. Patients were split randomly 65/35 into training and validation sets, and LASSO regression was used to select a model in the training set, the performance of which was evaluated in the validation set. Results: 258 patients with HPV DNA/E7 mRNA positive tumors could be included, 168 and 90 patients in the respective sets. No treatment improved prognosis compared to radiotherapy alone. CD8(+) TIL counts and young age were the strongest predictors of survival, followed by T-stage <3 and presence of HPV16 E2 mRNA. The model had an area under curve (AUC) of 76%. A model where the presence of three of four of these markers defined good prognosis captured 56% of non-relapsing patients with a positive predictive value of 98% in the validation set. Furthermore, the model identified 35% of our cohort that was over-treated and could safely have received de-escalated therapy. Conclusion: CD8(+) TIL counts, age, T-stage and E2 expression could predict progression-free survival, identifying patients eligible for randomized trials with milder treatment, potentially reducing side effects without worsening prognosis.
|
|
| 7. |
- Bersani, Cinzia, et al.
(författare)
-
MicroRNA-155,-185 and-193b as biomarkers in human papillomavirus positive and negative tonsillar and base of tongue squamous cell carcinoma
- 2018
-
Ingår i: Oral Oncology. - : Elsevier. - 1368-8375 .- 1879-0593. ; 82, s. 8-16
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Three-year disease-free survival (DFS) is 80% for human papillomavirus (HPV) positive tonsillar and base of tongue cancer (TSCC/BOTSCC) treated with radiotherapy alone, and today's intensified therapy does not improve prognosis. More markers are therefore needed to more accurately identify patients with good prognosis or in need of alternative therapy. Here, microRNAs (miRs) 155, 185 and 193b were examined as potential prognostic markers in TSCC/BOTSCC.Material and methods: 168 TSCC/BOTSCC patients diagnosed 2000-2013, with known data on HPV-status, CD8(+) tumour infiltrating lymphocytes, tumour staging and survival were examined for expression of miR-155, -185 and -193b using Real-Time PCR. Associations between miR expression and patient and tumour characteristics were analysed using univariate testing and multivariate regression.Results: Tumours compared to normal tonsils showed decreased miR-155 and increased miR-193b expression. miR-155 expression was associated with HPV-positivity, low T-stage, high CD8(+) TIL counts and improved survival. miR-185 expression was associated with HPV-negativity and a tendency towards decreased survival, while miR-193b expression was associated with higher T-stage, male gender and lower CD8(+) TIL counts, but not with outcome. Upon Cox regression, miR-185 was the only miR significantly associated with survival. Combining miR-155 and miR-185 to predict outcome in HPV+ patients yielded an area under curve (AUC) of 71%.Conclusion: Increased miR-155 expression was found as a positive predictor of survival, with the effect mainly due to its association with high CD8(+) TIL numbers, while miR-185 independently associated with decreased survival. Addition of these miRs to previously validated prognostic biomarkers could improve patient stratification accuracy.
|
|
| 8. |
- Bersani, Cinzia, et al.
(författare)
-
Targeted sequencing of tonsillar and base of tongue cancer and human papillomavirus positive unknown primary of the head and neck reveals prognostic effects of mutated FGFR3
- 2017
-
Ingår i: Oncotarget. - : IMPACT JOURNALS LLC. - 1949-2553. ; 8:21, s. 35339-35350
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Human papillomavirus positive (HPV+) tonsillar cancer (TSCC), base of tongue cancer (BOTSCC) and unknown primary cancer of the head and neck (HNCUP) have better outcome than corresponding HPV- cancers. To find predictive markers for response to treatment, and correlations and differences in mutated oncogenes and suppressor genes between HPV+ TSCC/BOTSSCC and HPV+ HNCUP and HPV- TSCC/BOTSCC targeted next-generation sequencing was performed of frequently mutated regions in 50 cancer related genes.PATIENTS AND METHODS: DNA from 348 TSCC/BOTSCC and 20 HNCUP from patients diagnosed 2000-2011, was sequenced by the Ion Proton sequencing platform using the Ion AmpliSeq Cancer Hotspot Panel v2 to identify frequently mutated regions in 50 cancer related genes. Ion Torrent Variant Caller software was used to call variants.RESULTS: 279 HPV+ TSCC/BOTSCC, 46 HPV- TSCC/BOTSCC and 19 HPV+ HNCUP samples qualified for further analysis. Mutations/tumor were fewer in HPV+ TSCC/BOTSCC and HNCUP, compared to HPV- tumors (0.92 vs. 1.32 vs. 1.68). Differences in mutation frequency of TP53 and PIK3CA were found between HPV+ TSCC/BOTSCC and HNCUP and HPV- TSCC/BOTSCC. In HPV+ TSCC/BOTSCC presence of FGFR3 mutations correlated to worse prognosis. Other correlations to survival within the groups were not disclosed.CONCLUSIONS: In HPV+ TSCC/BOTSCC mutation of PIK3CA was most frequently observed, while TP53 mutations dominated in HPV- TSCC/BOTSCC. In HPV+ TSCC/ BOTSCC and HNCUP, mutations/tumor were similar in frequency and fewer compared to that in HPV- TSCC/BOTSCC. Notably, FGFR3 mutations in HPV+ TSCC/BOTSCC indicated worse prognosis.
|
|
| 9. |
- Bjørndal, Lars, et al.
(författare)
-
Randomised clinical trial on deep caries excavation 3-5 yr follow-up
- 2012
-
Ingår i: Journal of dental research. - : Sage Publications. ; 91:Spec Iss b
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Objectives: Long term follow-up data based on randomised clinical trials are needed in relation to deep caries treatment. The aim of the present trial is to investigate the beneficial and harmful long term effects of stepwise excavation during two visits versus one completed excavation of deep caries in permanent teeth in adults. Methods: Consecutive patients contacting clinical units in Sweden and Denmark were included. The trial is a centrally randomised patient- and observer-blinded multicenter trial, with two parallel intervention groups. A sample size calculation showed that 134 patients were needed in each group. Taking dropouts into account, a total of 314 patients fulfilled well-defined inclusion and exclusion criteria and were centrally block-randomised stratified by age and pain. Inclusion criteria: (i) Person ≥ 18 yrs having deep caries with or without pain (ii) x-ray showing primary caries into the inner 1/4 of the dentin, with the presence of a radiopaque zone at the pulpal wall. Success was defined as unexposed pulp with sustained pulp vitality without apical radiolucency after follow-up. Blinded evaluation of 1½ follow-up has previously been carried out in 106 patients (stepwise excavation group) and 93 patients (direct complete excavation) (Bjørndal et al. 2010, EJOS). Results: At 3-5 yr follow up there was a statistically significantly higher success with stepwise excavation [difference: 11.5%, 95% confidence interval (0.5; 22.2)] versus a direct complete excavation procedure, being similarly with the short term follow-up data. 53.3% (n = 102) of the material has been controlled and no significant differences were noted between the two intervention groups in terms of patients not yet controlled, lost patients and failures (Table). Conclusion: A stepwise excavation procedure still seems preferable after a long term follow up and presumably related to the reduced risk of exposing the inflamed pulp associated with deep caries.
|
|
| 10. |
- Bjørndal, Lars, et al.
(författare)
-
Randomized Clinical Trials on Deep Carious Lesions : 5-Year Follow-up
- 2017
-
Ingår i: Journal of Dental Research. - : Sage Publications. - 0022-0345 .- 1544-0591. ; 96:7, s. 747-753
-
Tidskriftsartikel (refereegranskat)abstract
- Deep caries presents a dilemma in terms of which treatment that will render an optimal prognosis by maintaining pulp vitality with absence of apical pathology. Previously, 2 randomized clinical trials were performed testing the short-term effects of stepwise carious tissue removal versus nonselective carious removal to hard dentin with or without pulp exposure. The aim of this article was to report the 5-y outcome on these previously treated patients having radiographically well-defined carious lesions extending into the pulpal quarter of the dentin but with a well-defined radiodense zone between the carious lesion and the pulp. In this long-term study, 239 of 314 (76.2%) patients were analyzed. The stepwise removal group had a significantly higher proportion of success (60.2%) at 5-y follow-up compared with the nonselective carious removal to hard dentin group (46.3%) ( P = 0.031) when pulp exposures per se were included as failures. Pulp exposure rate was significantly lower in the stepwise carious removal group (21.2% vs. 35.5%; P = 0.014). Irrespective of pulp exposure status, the difference (13.3%) was still significant when sustained pulp vitality without apical radiolucency and unbearable pain was considered (95% confidence interval, 3.1-26.3, P = 0.045). After pulp exposure, only 9% ( n = 4) of the analyzed patients were assessed as successful, indicating that the prognosis is highly dubious following conventional pulp-capping procedures (direct pulp capping or partial pulpotomy) in deep carious lesions in adults. In conclusion, the stepwise carious removal group had a significantly higher proportion of pulps with sustained vitality without apical radiolucency versus nonselective carious removal of deep carious lesions in adult teeth at 5-y follow-up (ClinicalTrials.gov NCT00187837 and NCT00187850).
|
|
| 11. |
- Dahlstrand, Hanna, et al.
(författare)
-
Human papillomavirus accounts both for increased incidence and better prognosis in tonsillar cancer.
- 2008
-
Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 28:2B, s. 1133-8
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this review is to present the current knowledge on the status and significance of human papillomavirus (HPV) in tonsillar cancer. An increase in the incidence of tonsillar cancer has been reported and recent data suggest that this increase is due to an increased proportion of HPV in these tumours. Furthermore, patients with HPV positive cancer have been shown to have a lower risk of relapse and longer survival compared to patients with HPV-negative tonsillar cancer. Tailoring individual treatment in tonsillar cancer may be of importance in order to reduce patient suffering as well as to increase patient survival. Finally, the fact that the presence of HPV-type 16 E6 and E7 mRNA has been ascertained in tonsillar cancer suggests that HPV-16 indeed is an aetiological factor associated with the disease and that preventive vaccination for this patient group should be discussed.
|
|
| 12. |
- Du, Juan, et al.
(författare)
-
Prevalence of Oral Human Papillomavirus Infection among Youth, Sweden
- 2012
-
Ingår i: Emerging Infectious Diseases. - : Centers for Disease Control and Prevention. - 1080-6040 .- 1080-6059. ; 18:9, s. 1468-1471
-
Tidskriftsartikel (refereegranskat)abstract
- Human papillomavirus (HPV) causes cervical, head, and neck cancers. We studied 483 patients at a youth clinic in Stockholm, Sweden, and found oral HPV prevalence was 9.3% and significantly higher for female youth with than without cervical HPV infection (p = 0.043). Most oral HPV types matched the co-occurring cervical types.
|
|
| 13. |
- 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.
|
|
| 14. |
- Lindquist, David, et al.
(författare)
-
Human papillomavirus is a favourable prognostic factor in tonsillar cancer and its oncogenic role is supported by the expression of E6 and E7.
- 2007
-
Ingår i: Molecular oncology. - : Wiley. - 1878-0261 .- 1574-7891. ; 1:3, s. 350-5
-
Tidskriftsartikel (refereegranskat)abstract
- From 1970 to 2002 in the Stockholm area, we revealed a parallel three-fold increase in the incidence of tonsillar cancer and the proportion of human papillomavirus (HPV) positive tonsillar cancer cases, indicating a possible role of HPV infection in this disease. We have now examined whether HPV and viral load in pre-treatment tonsillar cancer biopsies correlates to disease prognosis, and whether the presence of HPV-16 E6 and E7 mRNA could be ascertained. The presence of HPV-16, but not viral load, in tonsillar cancer was shown to be a favourable prognostic factor for clinical outcome. Moreover, E6 and/or E7 were expressed in almost all assessable HPV-16 positive cases, supporting an oncogenic role of HPV-16 in tonsillar cancer.
|
|
| 15. |
- Liwing, Johan, et al.
(författare)
-
Improved survival in myeloma patients : starting to close in on the gap between elderly patients and a matched normal population
- 2014
-
Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 164:5, s. 684-693
-
Tidskriftsartikel (refereegranskat)abstract
- The outcome for multiple myeloma patients has improved since the introduction of bortezomib, thalidomide and lenalidomide. However, studies comparing new and conventional treatment include selected patient groups. We investigated consecutive patients (n = 1638) diagnosed in a defined period and compared survival with a gender- and age-matched cohort Swedish population (n = 9 340 682). Median overall survival for non-high-dose treated patients was 2.8 years. The use of bortezomib, thalidomide or lenalidomide in first line therapy predicted a significantly longer overall survival (median 4.9 years) compared to conventional treatment (2.3 years). Among non-high-dose treated patients receiving at least 2 lines with bortezomib, thalidomide or lenalidomide, 69% and 63% have survived at 3 and 5 years as compared to 48% and 22% with conventional drugs and 88% and 79% in the matched cohort populations, respectively. The median overall survival in high-dose treated patients was 6.9 years. Of these patients, 84% survived at 3 years and 70% at 5 years as compared to 98% and 95% in the matched cohort population. Overall survival in the best non-high-dose treated outcome group is closing the gap with the matched cohort. Upfront use of new drugs is clearly better than waiting until later lines of treatment.
|
|
| 16. |
- Mints, Michael, et al.
(författare)
-
Tumour inflammation signature and expression of S100A12 and HLA class I improve survival in HPV-negative hypopharyngeal cancer
- 2021
-
Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- Hypopharyngeal squamous cell carcinoma (HPSCC) has a very poor prognosis. Local surgery may increase survival, but is often avoided due to significant post-op co-morbidities. Since prognostic markers are lacking, the aim was to find predictive biomarkers that identify patients whose response to oncological treatment is poor and who may benefit from primary surgery to increase survival. Pretreatment biopsies from 23 HPSCC patients, 3 human papillomavirus (HPV) positive and 20 HPV-negative, were analyzed for expression of 750 mRNAs using the Nanostring nCounter IO360 panel in relation to 3-year survival. Validation was performed through immunohistochemistry (IHC) for HLA class I and S100A12 in 74 HPV-negative HPSCC samples. Clustering identified a subset of HPV-negative HPSCC with favorable prognosis and a gene expression signature overexpressing calgranulins and immune genes, distinct from that of HPV-positive HPSCC. Enrichment analysis showed immune signaling, including the tumor inflammation signature, to be enriched in surviving patients. IHC validation confirmed high S100A12 and HLA class I expression to correlate with survival in HPV-negative HPSCC. This shows that immune activity is strongly related to survival in HPV-negative HPSCC. Enrichment of the tumor inflammation signature indicates a potential benefit of immunotherapy. Low expression of both HLA class I and S100A12 could be used to select patients for local surgery.
|
|
| 17. |
- Moberg, B., et al.
(författare)
-
Operational noise optimization of aircraft approaches
- 2021
-
Ingår i: Proceedings of INTER-NOISE 2021 - 2021 International Congress and Exposition of Noise Control Engineering. - : Institute of Noise Control Engineering (INCE). ; , s. 499-507
-
Konferensbidrag (refereegranskat)abstract
- The characteristics of an aircraft as a noise source changes as the pilots slow the aircraft down and extend flaps and landing gear in preparation for landing. In the OPNOP project, the possibility to use this variation in noise generation to minimize noise at a specified location is examined. Such analysis requires an increased understanding about aircraft noise generation as the aircraft changes configuration and speed during the approach, where theoretical models available can be overly simplistic and of little use for this purpose. Using flight data from 113 Airbus A321 flights, and corresponding noise measurements on the ground, this study reports on the findings forming the foundation on which further analysis will be conducted. Findings relate to: a comparison between models and actual measurements, the distance variability to the runway for various flap selections and extension of the landing gear as well as a comparison between flight data and on-ground noise measurements. Captured data suggest that it should be possible to use speed and configuration recommendations to reduce noise over selected approach areas. Future research will include scenario generation and incorporate flight data from an earlier study to increase validity.
|
|
| 18. |
|
|
| 19. |
- Naimi-Akbar, Aron, et al.
(författare)
-
Mortality among sons of female dental personnel : a national cohort study
- 2014
-
Ingår i: Journal of Perinatal Medicine. - : Walter de Gruyter. - 0300-5577 .- 1619-3997. ; 42:5, s. 655-661
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: Dental personnel are exposed to mercury when using dental amalgam. This exposure constitutes a potential hazard to offspring of women working in dentistry. The present study examined increased mortality risk in offspring of mothers working in dentistry.Methods: Mortality was compared between sons of dental personnel and sons of nondental health-care personnel. Hazard ratios were calculated for three decades (1960s-1980s), when the magnitude of mercury exposure in dentistry was likely to have varied.Results: During the 1960s, there was a statistically significant increase in the risk of neonatal mortality for sons of dental nurses when compared with sons of assistant nurses: hazard ratio (HR) 1.82 (95% confidence interval, CI: 1.04-3.22). There was no increased risk in the subsequent decades, but a trend test demonstrated a consistent decrease in the risk over the three decades: HR for trend 0.63 (95% CI: 0.44-0.90). The raised mortality risk was limited to neonatal mortality. The comparison between dentists and physicians had insufficient statistical power.Conclusions: There is no increased mortality risk among sons of female dentists after the 1960s. Although the results should be interpreted with caution, they suggest a modestly raised risk of neonatal mortality, during the 1960s, when exposure to mercury was thought to be highest.
|
|
| 20. |
|
|
| 21. |
- Norhammar, Anna, et al.
(författare)
-
Undetected Dysglycemia Is an Important Risk Factor for Two Common Diseases, Myocardial Infarction and Periodontitis : A Report From the PAROKRANK Study
- 2019
-
Ingår i: Diabetes Care. - : NLM (Medline). - 0149-5992 .- 1935-5548. ; 42:8, s. 1504-1511
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Information on the relationship among dysglycemia (prediabetes or diabetes), myocardial infarction (MI), and periodontitis (PD) is limited. This study tests the hypothesis that undetected dysglycemia is associated with both conditions. RESEARCH DESIGN AND METHODS: The PAROKRANK (Periodontitis and Its Relation to Coronary Artery Disease) study included 805 patients with a first MI and 805 matched control subjects. All participants without diabetes (91%) were examined with an oral glucose tolerance test. Abnormal glucose tolerance (AGT) (impaired glucose tolerance or diabetes) was categorized according to the World Health Organization. Periodontal status was categorized from dental X-rays as healthy (≥80% remaining alveolar bone height), moderate (79-66%), or severe (<66%) PD. Odds ratios (ORs) and 95% CIs were calculated by logistic regression and were adjusted for age, sex, smoking, education, marital status, and explored associated risks of dysglycemia to PD and MI, respectively. RESULTS: AGT was more common in patients than in control subjects (32% vs. 19%; P < 0.001) and was associated with MI (OR 2.03; 95% CI 1.58-2.60). Undetected diabetes was associated with severe PD (2.50; 1.36-4.63) and more strongly in patients (2.35; 1.15-4.80) than in control subjects (1.80; 0.48-6.78), but not when categorized as AGT (total cohort: 1.07; 0.67-1.72). Severe PD was most frequent in subjects with undetected diabetes, and reversely undetected diabetes was most frequent in patients with severe PD. CONCLUSIONS: In this large case-control study previously undetected dysglycemia was independently associated to both MI and severe PD. In principal, it doubled the risk of a first MI and of severe PD. This supports the hypothesis that dysglycemia drives two common diseases, MI and PD.
|
|
| 22. |
- Näsman, Anders, et al.
(författare)
-
Absent/weak CD44 intensity and positive human papillomavirus (HPV) status in oropharyngeal squamous cell carcinoma indicates a very high survival
- 2013
-
Ingår i: Cancer Medicine. - : John Wiley & Sons. - 2045-7634. ; 2:4, s. 507-18
-
Tidskriftsartikel (refereegranskat)abstract
- Patients with human papillomavirus DNA positive (HPVDNA+) oropharyngeal squamous cell carcinoma (OSCC) have better clinical outcome than those with HPV DNA negative (HPVDNA-) OSCC upon intensive oncological treatment. All HPVDNA+ OSCC patients may not require intensive treatment, however, but before potentially deintensifying treatment, additional predictive markers are needed. Here, we examined HPV, p16(INK4a), and CD44 in OSCC in correlation to clinical outcome. Pretreatment tumors from 290 OSCC patients, the majority not receiving chemotherapy, were analyzed for HPV DNA by Luminex and for p16(INK4a) and CD44 by immunohistochemistry. 225/290 (78%) tumors were HPVDNA+ and 211/290 (73%) overexpressed p16(INK4a), which correlated to presence of HPV (P < 0.0001). Presence of HPV DNA, absent/weak CD44 intensity staining correlated to favorable 3-year disease-free survival (DFS) and overall survival (OS) by univariate and multivariate analysis, and likewise for p16(INK4a) by univariate analysis. Upon stratification for HPV, HPVDNA+ OSCC with absent/weak CD44 intensity presented the significantly best 3-year DFS and OS, with >95% 3-year DFS and OS. Furthermore, in HPVDNA+ OSCC, p16(INK4a)+ overexpression correlated to a favorable 3-year OS. In conclusion, patients with HPVDNA+ and absent/weak CD44 intensity OSCC presented the best survival and this marker combination could possibly be used for selecting patients for tailored deintensified treatment in prospective clinical trials. Absence of/weak CD44 or presence of human papillomavirus (HPV) DNA was shown as a favorable prognostic factors in tonsillar and tongue base cancer. Moreover, patients with the combination of absence of/weak CD44 and presence of HPV DNA presented a very favorable outcome. Therefore, we suggest that this marker combination could potentially be used to single out patients with a high survival that could benefit from a de-escalated oncological treatment.
|
|
| 23. |
- Näsman, Anders, et al.
(författare)
-
Human Papillomavirus and Potentially Relevant Biomarkers in Tonsillar and Base of Tongue Squamous Cell Carcinoma
- 2017
-
Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 37:10, s. 5319-5328
-
Forskningsöversikt (refereegranskat)abstract
- Human papillomavirus (HPV)-positive tonsillar- and base of tongue cancer is increasing epidemically and has much better outcome than corresponding HPV-negative cancer and most other head and neck cancers with around 80% 3-year disease free survival with conventional radiotherapy and surgery. Consequently, most HPV-positive cancer patients may not require the intensified chemoradiotherapy given to many head and neck cancer patients and would, with tapered treatment, avoid several severe side-effects. Moreover, intensified therapy has not improved survival and treatment alternatives are needed. To identify patients eligible for tapered or targeted therapy, additional biomarkers are required. Several studies have, therefore, focused on finding predictive markers, some of which are also potentially targetable. To conclude, better-tailored therapy, either as tapered or targeted, is important for increasing numbers of patients with HPV-positive tonsillar- and base of tongue cancer. This review deals with some of these issues and presents some promising markers.
|
|
| 24. |
- Näsman, Anders, et al.
(författare)
-
Incidence of human papillomavirus (HPV) positive tonsillar carcinoma in Stockholm, Sweden : an epidemic of viral-induced carcinoma?
- 2009
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 125:2, s. 362-6
-
Tidskriftsartikel (refereegranskat)abstract
- In the county of Stockholm, between 1970 and 2002, we have previously reported a 3-fold parallel increase in the incidence of tonsillar squamous cell carcinoma (SCC) and the proportion of human papillomavirus (HPV) positive tonsillar SCC. Here, we have followed the above parameters in all patients (n = 120) diagnosed with tonsillar SCC during 2003-2007 in the same area, and also in correlation to our previous data. Ninety-eight pretreatment biopsies were available and presence of HPV DNA and HPV-16 E6 and E7 RNA were tested by polymerase chain reaction (PCR) and RT-PCR. Incidence data were obtained from the Swedish Cancer Registry. Data reported from 1970 to 2002 were also obtained for comparison. HPV DNA was present in 83 of 98 (85%) of the tonsillar SCC biopsies from 2003 to 2007 and 77 of these were HPV-16 positive. HPV-16 E6 and E7 RNA were found in 98% of 52 analyzed HPV-16 positive cases. The proportion of HPV-positive cancers had significantly increased both from 1970 to 2007 (p < 0.0001) as well from 2000 to 2007 (p < 0.01), with 68% (95% confidence interval (CI), 53-81) 2000-2002; 77% (95% CI, 63-87) 2003-2005; and 93% (95% CI, 82-99) 2006-2007. The incidence rate of HPV-positive tumors almost doubled each decade between 1970 and 2007, in parallel with a decline of HPV-negative tumors. In conclusion, the incidence of HPV-positive cancers is still increasing in the County of Stockholm, suggesting an epidemic of a virus-induced carcinoma, with soon practically all tonsillar SCC being HPV positive, as in cervical cancer.
|
|
| 25. |
- Näsman, Anders
(författare)
-
Studies on the influence of human papillomaviruses (HPV) and other biomarkers on the prevalence of oropharyngeal cancer and clinical outcome
- 2013
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Oropharyngeal squamous cell carcinoma (OSCC), where tonsillar (TSCC) and base of tongue squamous cell carcinoma (BOTSCC) dominate, is increasing and is now the most common head and neck squamous cell carcinoma (HNSCC) in Sweden. Smoking and alcohol are risk factors for HNSCC, but in 2007, human papillomavirus (HPV) infection was also recognized as a risk factor for OSCC. Notably, HPV positive OSCC has a much better clinical outcome than and HPV negative OSCC. The last decade treatment of HNSCC, including OSCC, has been intensified with chemoradiotherapy, due to the generally poor prognosis of HNSCC. Such treatment, with more side effects, is likely needless for most HPV positive OSCC, but since around 20% of the patients do not do well, additional markers are needed to single out patients with an expected favourable outcome before possible de-escalation of treatment. Aims: To follow incidence and HPV prevalence in OSCC over time in order to understand why OSCC has increased. To search for additional predictive biomarkers in HPV positive OSCC, to more safely de-escalate treatment. Results: In papers I-II we showed that the prevalence of HPV in TSCC had increased significantly in Stockholm from 23% (1970-1979); to 28% 1980-1989; to 57% 1990-1999; to 79% 2000-2007. Notably, also during the 2000s there was a significant increase in HPV prevalence, from 68% 2000-2002; to 77% 2003-2005; up to 93% 2006-2007. Likewise, HPV prevalence also increased in BOTSCC, from 58% 1998-2001 to 84% 2006-2007. The increase in HPV prevalence was paralleled by an increase in incidence of TSCC and BOTSCC, and when estimating the HPV incidence in TSCC, the incidence had increased 7-fold from 1970 to 2006. In paper III we found that HPV positive TSCC had significantly more CD8+ and Foxp3+ tumour infiltrating lymphocytes (TILs), and that a high CD8+TIL count was correlated with a favourable clinical outcome in both HPV positive and negative TSCC. In addition, a high CD8+ count and a high CD8+/Foxp3+ ratio were significantly correlated with a favourable 3-year disease-free survival in HPV positive and negative TSCC respectively. In papers IV-V, we show that absence of “classical” HLA class I intensity staining was correlated with a favourable disease-free survival, disease-specific survival, overall survival and progression-free survival in patients with HPV positive OSCC, and to a worse clinical outcome in patients with HPV negative OSCC. Moreover in paper V, patients with HPV positive OSCC with absence of /or weak “classical” HLA class I intensity staining presented a very high survival that was independent of treatment regime. HLA-E, -G was also analysed in TSCC, but without any outcome correlation. In addition, HLA class II expression was analysed and found to be more common in HPV positive than HPV negative OSCC, but correlated to better clinical outcome only in the latter group. Conclusion: A parallel increase in incidence as well as HPV prevalence in TSCC and BOTSCC was demonstrated suggesting HPV infection being responsible for the epidemic increase in OSCC. Finally, HPV positive TSCC or OSCC with high CD8+ TIL counts or with absent/weak HLA class I intensity staining presented a very good clinical outcome, suggesting that these markers could potentially be used to select patients for prospective randomised trials de-escalating oncological treatment.
|
|
| 26. |
- Palma, Marzia, et al.
(författare)
-
T Cells In Chronic Lymphocytic Leukemia Display Dysregulated Expression Of Immune Checkpoints And Activation Markers
- 2017
-
Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 102:3, s. 562-572
-
Tidskriftsartikel (refereegranskat)abstract
- Chronic lymphocytic leukemia is characterized by impaired immune functions largely due to profound T-cell defects. T-cell functions also depend on co-signaling receptors, inhibitory or stimulatory, known as immune checkpoints, including cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed death-1 (PD-1). Here we analyzed the T-cell phenotype focusing on immune checkpoints and activation markers in chronic lymphocytic leukemia patients (n=80) with different clinical characteristics and compared them to healthy controls. In general, patients had higher absolute numbers of CD3+ cells and the CD8+ subset was particularly expanded in previously treated patients. Progressive patients had higher numbers of CD4+ and CD8+ cells expressing PD-1 compared to healthy controls, which was more pronounced in previously treated patients (P=0.0003 and P=0.001, respectively). A significant increase in antigen-experienced T cells was observed in patients within both the CD4+ and CD8+ subsets, with a significantly higher PD-1 expression. Higher numbers of CD4+ and CD8+ cells with intracellular CTLA-4 were observed in patients, as well as high numbers of proliferating (Ki67+) and activated (CD69+) CD4+ and CD8+ cells, more pronounced in patients with active disease. The numbers of Th1, Th2, Th17 and regulatory T cells were substantially increased in patients compared to controls (P<0.05), albeit decreasing to low levels in pre-treated patients. In conclusion, chronic lymphocytic leukemia T cells display increased expression of immune checkpoints, abnormal subset distribution, and a higher proportion of proliferating cells compared to healthy T cells. Disease activity and previous treatment shape the T-cell profile of chronic lymphocytic leukemia patients in different ways.
|
|
| 27. |
- Rudberg, Ann-Sofie, et al.
(författare)
-
Long-term health-related quality of life, survival and costs by different levels of functional outcome six months after stroke
- 2018
-
Ingår i: European Stroke Journal. - : SAGE PUBLICATIONS LTD. - 2396-9873 .- 2396-9881. ; 3:2, s. 157-164
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Information about the impact of functional outcome after stroke is currently missing on health-related quality of life, survival and costs. This information would be valuable for health economic evaluations and for allocation of resources in stroke health care. Patients and methods: Data on 297 Swedish patients included in the Third International Stroke Trial were analysed including functional outcome at six months (measured by Oxford Handicap Scale), health-related quality of life up to 18 months (EQ-5D-3L) and survival up to 36 months. We used record linkage to collect data on costs up to 36 months, using national patient registers. Results: Patients with a better functional outcome level at six months had a significantly better health-related quality of life at 18 months (p<0.05), better long-term survival (p<0.05) and lower costs (p<0.001), for all time points up to 36 months. The difference in costs was mainly due to differences in days spent in hospital (p<0.005). Discussion: This study showed an association between functional outcome at six months and health-related quality of life up to 18 months, and costs up to 36 months. Conclusion: Functional outcome six months after stroke is an important determinant of health-related quality of life, survival and costs over 36 months. Effective interventions aimed at reducing short-term disability levels are therefore also expected to reduce the overall burden of stroke.
|
|
| 28. |
- Ryden, Lars, et al.
(författare)
-
Periodontitis Increases the Risk of a First Myocardial Infarction A Report From the PAROKRANK Study
- 2016
-
Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 133:6, s. 576-583
-
Tidskriftsartikel (refereegranskat)abstract
- Background The relationship between periodontitis (PD) and cardiovascular disease is debated. PD is common in patients with cardiovascular disease. It has been postulated that PD could be causally related to the risk for cardiovascular disease, a hypothesis tested in the Periodontitis and Its Relation to Coronary Artery Disease (PAROKRANK) study. Methods and Results Eight hundred five patients (<75 years of age) with a first myocardial infarction (MI) and 805 age- (mean 628), sex- (male 81%), and area-matched controls without MI underwent standardized dental examination including panoramic x-ray. The periodontal status was defined as healthy (80% remaining bone) or as mild-moderate (from 79% to 66%) or severe PD (<66%). Great efforts were made to collect information on possibly related confounders (approximate to 100 variables). Statistical comparisons included the Student pairwise t test and the McNemar test in 2x2 contingency tables. Contingency tables exceeding 2x2 with ranked alternatives were tested by Wilcoxon signed rank test. Odds ratios (95% confidence intervals) were calculated by conditional logistic regression. PD was more common (43%) in patients than in controls (33%; P<0.001). There was an increased risk for MI among those with PD (odds ratio, 1.49; 95% confidence interval, 1.21-1.83), which remained significant (odds ratio, 1.28; 95% confidence interval, 1.03-1.60) after adjusting for variables that differed between patients and controls (smoking habits, diabetes mellitus, years of education, and marital status). Conclusions In this large case-control study of PD, verified by radiographic bone loss and with a careful consideration of potential confounders, the risk of a first MI was significantly increased in patients with PD even after adjustment for confounding factors. These findings strengthen the possibility of an independent relationship between PD and MI.
|
|
| 29. |
- Vähäsarja, Niko, et al.
(författare)
-
Neurological disease or intellectual disability among sons of female Swedish dental personnel
- 2016
-
Ingår i: Journal of Perinatal Medicine. - Berlin, Germany : Walter de Gruyter. - 0300-5577 .- 1619-3997. ; 44:4, s. 453-460
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Prenatal exposure to elemental mercury may be a potential hazard for the offspring of female dental personnel working with dental amalgam. The aim of this study was to investigate whether potential in utero exposure to mercury might have affected the development of nervous system of the sons of Swedish female dental personnel leading to an increased risk of neurological disease or intellectual disability.Material and methods: We used national Swedish registers to investigate risks for diseases potentially related to adverse effects on neurodevelopment. Sons of female dentists (n=1690) and dental nurses (n=10,420) were compared with cohorts consisting of sons of other female healthcare personnel. Due to changes in mercury exposure in dentistry during the study period, analyses were stratified by decade of birth. Hazard ratios (HRs) were calculated using Cox proportional hazard models.Results: We found no elevated risk for neurological disease, epilepsy or intellectual disability among the sons of dental personnel during any of the decades studied. HRs for neurological disease among the dental nurse cohort were even below 1.00 during the 1970s and 1980s. A low number of events resulted in uncertainty regarding results in the dentist cohort.Conclusions: We did not find any support for the hypothesis that mercury exposure in Swedish dentistry during the 1960s, 1970s or 1980s had any effect on the incidence of neurological disease or intellectual disability among the sons of female dental personnel. Our results imply that current use of dental amalgam should not represent an elevated risk for neurological disease or intellectual disability among the offspring of dental personnel.
|
|
| 30. |
- Yektaei-Karin, Elham, et al.
(författare)
-
Modulation of leukotriene signaling inhibiting cell growth in chronic myeloid leukemia
- 2017
-
Ingår i: Leukemia and Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 58:8, s. 1903-1913
-
Tidskriftsartikel (refereegranskat)abstract
- Although tyrosine kinase inhibitors (TKIs) have dramatically improved clinical outcome in chronic myeloid leukemia (CML), cure rarely occurs. This may be due to BCR-ABL-independent, aberrant signaling pathways, one of which leads to leukotriene (LT) formation. Well-recognized as inflammatory mediators, LT can also affect oncogenic mechanisms of several tumors. We have previously discovered elevated LT-synthesis and up-regulated cysteinyl-LT-inducing enzyme in CML. Here we report on dose-dependent inhibition of CML cell growth exerted by specific blockers of LT-signaling. Thus, the cysteinyl-LT1-receptor-antagonist montelukast significantly reduced the growth of K562, KCL22, and KU812 cells, as well as primary CD34(+) blood cells from two CML patients. Adding montelukast to the TKI imatinib caused combined inhibition. No effect was seen on normal bone marrow cells. Similarly, growth inhibition was also observed with the 5-lipoxygenase (LO)-inhibitor BWA4C, the 5-LO-activating-protein-(FLAP)-inhibitor licofelone and the LTB4(BLT1)-receptor-antagonist LY293111. Thus, blocking of aberrant LT-signaling may provide an additional, novel therapeutic possibility in CML.
|
|
| 31. |
- Zupancic, Mark, et al.
(författare)
-
Human papillomavirus (HPV) load is higher in HPVDNA/p16 positive than in HPVDNA positive/p16 negative oropharyngeal squamous cell carcinoma but does not differ significantly between various subsites or correlate to survival
- 2024
-
Ingår i: Oral Oncology. - : Elsevier. - 1368-8375 .- 1879-0593. ; 151
-
Tidskriftsartikel (refereegranskat)abstract
- ObjectivePatients with human papillomavirus DNA positive (HPVDNA+) and p16ink4a overexpressing (p16+) oropharyngeal squamous cell carcinoma (OPSCC), especially those with cancer in the tonsillar and base of tongue subsites as compared to other OPSCC subsites have a better outcome than those with only HPVDNA+ or only p16+ cancer. Likewise having a high viral load has been suggested to be a positive prognostic factor. We therefore hypothesized, that HPV viral load could vary depending on OPSCC subsite, as well as with regard to whether the cancer was HPVDNA+ and p16+, or only HPVDNA+, or only p16+ and that this affected outcome.Material and methodsTo address these issues HPV viral load was determined by HPV digital droplet (dd) PCR in tumor biopsies with previously known HPVDNA/p16 status from 270 OPSCC patients diagnosed 2000–2016 in Stockholm, Sweden. More specifically, of these patients 235 had HPVDNA+/p16+, 10 had HPVDNA+/p16-, 13 had HPVDNA-/p16+ and 12 had HPVDNA-/p16- cancer.ResultsWe found that HPVDNA+/p16+ OPSCC had a significantly higher viral load than HPVDNA+/p16- OPSCC. Moreover, there was a tendency for a higher viral load in the tonsillar and base of tongue OPSCC subsites compared to the other subsites and for a low viral load to correlate to a better clinical outcome but none of these tendencies reached statistical significance.ConclusionTo conclude, the mean viral load in HPVDNA+/p16+ OPSCC was higher than in HPVDNA+/p16- OPSCC, but there was no statistically significant difference in viral load depending on OPSCC subsite or on clinical outcome.
|
|
| 32. |
- Ährlund-Richter, Andreas, et al.
(författare)
-
Whole-exome sequencing of HPV positive tonsillar and base of tongue squamous cell carcinomas reveals a global mutational pattern along with relapse-specific somatic variants
- 2022
-
Ingår i: Cancers. - : MDPI. - 2072-6694. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- To identify predictive/targetable markers in human papillomavirus positive (HPV+) ton-sillar and base of tongue cancer (TSCC/BOTSCC), whole-exome sequencing (WES) of tumours of patients with/without recurrence was performed. Forty primary tumours and adjacent normal tissue were separated by micro-dissection from formalin-fixed paraffin-embedded tissue from patients treated with curative intent 2000–2014 at Karolinska University Hospital. Successful sequencing was obtained in primary tumours of 18 patients without and primaries of 17 with local or distant recurrence, as well as in 10 corresponding recurrences (i.e., five local relapses and five distant metas-tases) from these 17 patients. One variant—a high-impact deletion in the CDC27 gene—was observed only in primaries of 5/17 patients that had a recurrence after full treatment but in none of those without recurrence. In addition, 3 variants and 26 mutated genes, including CDC27, BCLAF1 and AQP7, were present in at least 30% of all primary tumours independent of prognosis. To conclude, a CDC27 deletion was specific and found in ~30% of samples from patients with a local relapse/distant metastasis and could, therefore, potentially be a prospective marker to predict prognosis. Commonly mutated genes, such as BCLAF1, should be further studied in the context of targeted therapy.
|
|
