| 1. |
- Bersani, Cinzia, et al.
(författare)
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A model using concomitant markers for predicting outcome in human papillomavirus positive oropharyngeal cancer
- 2017
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Ingår i: Oral Oncology. - : Elsevier. - 1368-8375 .- 1879-0593. ; 68, s. 53-59
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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.
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| 2. |
- Bersani, Cinzia, et al.
(författare)
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MicroRNA-155,-185 and-193b as biomarkers in human papillomavirus positive and negative tonsillar and base of tongue squamous cell carcinoma
- 2018
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Ingår i: Oral Oncology. - : Elsevier. - 1368-8375 .- 1879-0593. ; 82, s. 8-16
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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.
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| 3. |
- Bersani, Cinzia, et al.
(författare)
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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
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Ingår i: Oncotarget. - : IMPACT JOURNALS LLC. - 1949-2553. ; 8:21, s. 35339-35350
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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.
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| 4. |
- Dahlgren, Liselotte, et al.
(författare)
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Differences in human papillomavirus type may influence clinical outcome in early stage cervical cancer.
- 2006
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 26:2A, s. 829-32
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The presence of human papillomavirus (HPV), the HPV type and viral load in early stage cervical carcinoma were investigated in order to elucidate whether any of these factors were important for clinical outcome. PATIENTS AND METHODS: Twelve patients who were disease-free 5 years after diagnosis were matched and compared with 12 patients who died within 2 years. The presence of HPV, HPV type and viral load in their tumours was examined by PCR. RESULTS: The distribution and load of HPV was similar in the 2 patient groups. HPV-16 was, however, significantly more common in tumours of the surviving patients than in those of patients who died (88.9% and 18.2%, respectively, p = 0.0152). CONCLUSION: HPV-16 was significantly more common in early stage carcinomas of patients surviving more than 5 years in comparison to early stage carcinomas of patients with a poor prognosis.
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| 5. |
- Dahlgren, Liselotte, et al.
(författare)
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Human papillomavirus is more common in base of tongue than in mobile tongue cancer and is a favorable prognostic factor in base of tongue cancer patients.
- 2004
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 112:6, s. 1015-9
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Tidskriftsartikel (refereegranskat)abstract
- The frequency of human papilloma virus (HPV) and its influence on clinical outcome was analyzed retrospectively in pre-treatment paraffin embedded biopsies from 110 patients with tongue cancer. The presence of HPV DNA was examined in 85 mobile tongue tumors and 25 base of tongue tumors by a polymerase chain reaction (PCR) with 2 general primer pairs, GP5+/6+ and CPI/IIG. When HPV-DNA was found, HPV-type specific primers and direct sequencing were used for HPV sub-type verification. Twelve of 110 (10.9%) samples were HPV-positive; 9 for HPV-16, 1 for HPV-33, 1 for HPV-35 and 1 could not be analyzed because of shortage of DNA. HPV was significantly more common in base of tongue tumors (10/25, 40.0%) compared to tumors of the mobile tongue (2/85, 2.3%). The influence of HPV on clinical outcome in mobile tongue cancer could not be studied, due to that HPV was present in too few cases. Of the 19 patients with base of tongue cancer that were included in the survival analysis, however, 7 patients with HPV-positive base of tongue cancer had a significantly favorable 5-year survival rate compared to the 12 HPV-negative patients. In conclusion, HPV is significantly more common in base of tongue cancer than in mobile tongue cancer, and has a positive impact on disease-specific survival in patients with base of tongue cancer.
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| 6. |
- Dahlstrand, Hanna, et al.
(författare)
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Human papillomavirus accounts both for increased incidence and better prognosis in tonsillar cancer.
- 2008
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 28:2B, s. 1133-8
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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.
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| 7. |
- Dahlstrand, Hanna, et al.
(författare)
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Presence of human papillomavirus in tonsillar cancer is a favourable prognostic factor for clinical outcome.
- 2004
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 24:3b, s. 1829-35
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this article is to review the current knowledge on the status and significance of human papillomavirus (HPV) in tonsillar cancer. Current data in scientific reports and data from the Karolinska Hospital and Karolinska Institute, Sweden, demonstrate that approximately half of all tonsillar cancer is HPV-positive. Moreover, patients with HPV-positive cancer have a lower risk of relapse and longer survival compared to patients with HPV-negative tonsillar cancer. The favourable outcome for patients harbouring HPV-positive tonsillar cancer cannot be attributed to increased radiosensitivity, since there is no significant difference in sensitivity to radiotherapy between HPV-positive and -negative tonsillar cancer. However, HPV-positive cancer exhibits less genetic instability i.e. shows a lower degree of aneuploidy and a tendency to have fewer chromosomal aberrations, when compared to HPV-negative tonsillar cancer.
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| 8. |
- Dalianis, Tina, et al.
(författare)
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Management of BK-virus infection - Swedish recommendations
- 2019
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Ingår i: Infectious Diseases. - : TAYLOR & FRANCIS LTD. - 2374-4235 .- 2374-4243. ; 51:7, s. 479-484
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Forskningsöversikt (refereegranskat)abstract
- BK-virus (BKV) associated nephropathy (BKVAN) and BKV associated haemorrhagic cystitis (HC) are complications of BKV infection/reactivation in renal and allogeneic haematopoietic stem cell transplantation (HSCT) patients, respectively. The task of how to manage these diseases was given to the chair by the Swedish Reference Group for Antiviral Therapy (RAV). After individual contributions by members of the working group, consensus discussions were held in a meeting on 23 January 2018 arranged by RAV. Thereafter, the recommendations were published in Swedish on November 2018. The current translation to English has been approved by all co-authors. High BKV serum levels suggest an increased risk for BKVAN and potential graft failure. For detection of BKVAN, careful monitoring of BKV DNA levels in serum or plasma is recommended the first year after renal transplantation and when increased creatinine serum levels of unknown cause are observed. Notably, a renal biopsy is mandatory for diagnosis. To reduce the risk for progression of BKVAN, there is no specific treatment, and tailored individual decrease of immunosuppression is recommended. For BKV-HC, BKV monitoring is not recommended, since BK-viruria frequently occurs in HSCT patients and the predictive value of BKV in plasma/serum has not been determined. However, the risk for BKV-HC is higher for patients undergoing myeloablative conditioning, having an unrelated, HLA-mismatched, or a cord blood donor, and awareness of the increased risk and early intervention may benefit the patients. Also for BKV-HC, no specific therapy is available. Symptomatic treatment, e.g. forced diuresis and analgesics could be of use.
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| 9. |
- de Flon, Caroline Haglund, et al.
(författare)
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High Levels of FGF11 Correlate with Poor Survival in Patients with Human Papillomavirus (HPV)-Positive Oropharyngeal Squamous Cell Carcinoma
- 2023
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Ingår i: Cancers. - : MDPI. - 2072-6694. ; 15:7
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Tidskriftsartikel (refereegranskat)abstract
- To better identify patients with human papillomavirus (HPV)-positive oropharyngeal cancer (OPSCC) and a poor prognosis after treatment, we compared the gene expression in tumours from patients with a poor or a favourable prognosis in a case-control setting. The results were thereafter validated in two separate cohorts on the RNA and protein levels. High RNA or protein expression of FGF11 was correlated with a poor patient survival in all three cohorts. Taken together, the data imply that FGF11 may play a major role in the prognosis of patients and that FGF11 could serve as a prognostic marker in HPV-positive oropharyngeal cancer.Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) is associated with a favourable prognosis. It has therefore been suggested that treatment should be individualized and separated by HPV status. However, additional prognostic markers are still needed before treatment can be individualized for this patient group. For this purpose, all patients diagnosed with HPV and p16-positive OPSCC in Stockholm 2000-2009, identified as having a partial/nonresponse to treatment and having viable tumour cells in their neck specimen with material available were categorized as cases. These were matched to controls (complete responders), and the differences in the gene expression were analysed. Two separate verification cohorts were identified including patients with HPV- and p16-positive OPSCC, and the data from the case-control study were verified by qPCR and immunohistochemistry (IHC) in the respective cohorts. A separation of gene expression in correlation with survival was observed in the case-control study, and FGF11 expression was identified as significantly differently expressed between the two groups. The prognostic role of FGF11 was validated in the two cohorts on the RNA and protein levels, respectively. Taken together, our findings suggest that FGF11 may indicate a poor prognosis in HPV-positive OPSCC and may serve as a prognostic biomarker.
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| 10. |
- Du, Juan, et al.
(författare)
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Prevalence of Oral Human Papillomavirus Infection among Youth, Sweden
- 2012
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Ingår i: Emerging Infectious Diseases. - : Centers for Disease Control and Prevention. - 1080-6040 .- 1080-6059. ; 18:9, s. 1468-1471
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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.
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| 11. |
- Eriksson, Mathilda, et al.
(författare)
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Utilization of a right-handed coiled-coil protein from archaebacterium Staphylothermus marinus as a carrier for cisplatin
- 2009
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 29:1, s. 11-18
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The nano-sized right-handed coiled-coil (RHCC) protein, originating from the archaebacterium Staphylothermus marinus, is stable at high salt concentrations, high temperatures, high pressures and extremes of pH. Its crystal structure reveals four hydrophobic cavities which can incorporate heavy metals. Nano-sized compounds have been used to carry cytotoxic drugs to tumours, avoiding delivery to healthy tissue, in part due to enhanced permeability in tumour blood vessels (enhanced permeability and retention effect). MATERIALS AND METHODS: The ability of RHCC to carry the platinum-containing chemotherapeutic drug cisplatin to cells, while retaining the cytotoxic potential was tested both in vitro and in vivo. RESULTS: RHCC was able to bind and enter cells in vitro and was not severely toxic or immunogenic in mice. Moreover, RHCC incorporated cisplatin, without inhibiting the cytotoxic potential of the drug against tumour cell lines in vitro or in vivo. CONCLUSION: RHCC can be used as a carrier of cisplatin without abrogating the effect of the drug.
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| 12. |
- Grandahl, Maria, et al.
(författare)
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A school-based educational intervention can increase adolescents’ knowledge and awareness about HPV
- 2016
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Konferensbidrag (refereegranskat)abstract
- Background / ObjectivesBackground: In Sweden HPV vaccination is offered to girls aged 10-12 years within the school-based vaccination program, while older girls (13-26 years) are offered the vaccine through the primary care. The vaccination rates are substantially lower (59%) among the catch-up group compared to the younger age group (82%). Adolescents have low awareness and knowledge about HPV, especially regarding cancer risks. The providers - school nurses - play a key role in providing such information. Upper secondary school students, aged 16 years, are by the school nurse offered a health interview, which includes a dialogue regarding their health, including sexual health. The health interview does however not include systematic information about HPV.Objectives: To improve adolescents’ knowledge and awareness about primary prevention of high risk HPV infection.MethodsMethods: A cluster-randomised controlled trial among upper secondary schools (n=18) was performed. Schools were first randomised to an intervention or control group, after which individual classes were randomised. In total, 832 students, boys and girls aged 16 years attending theoretical or vocational programs were invited to participate. In the end, 741 (89.1%) students completed the256study. The intervention was based on the Health Belief Model (HBM). School nurses delivered 30 minutes of face-to-face structured information about HPV, including cancer risks and HPV prevention (i.e. condom use and HPV vaccination) to the intervention group. Students in both groups completed questionnaires at baseline and at follow-up after three months. The control group received standard treatment, i.e. the regular health interview with the school nurse. Generalized estimating equation analyses were used for examining the results of the intervention.ResultsResults: The intervention had positive effects on the adolescents’ knowledge (p<0.001), with a 0.582 higher score for the intervention group compared to the control group. There were no differences in knowledge due to sex (p=0.093) or immigrant background (p=0.592). The intervention also increased awareness (p<0.001), with a 0.590 higher score for the intervention compared to the control. Again, there were no differences in awareness due to sex (p=0.183) or immigrant background (p=0.319).ConclusionConclusions: The school-based intervention delivered by school nurses, had favourable effects on knowledge and awareness about primary prevention of HPV among adolescents aged 16 years.
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| 13. |
- Grandahl, Maria, et al.
(författare)
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Catch-up HPV vaccination status of adolescents in relation to socioeconomic factors, individual beliefs and sexual behaviour
- 2017
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:11
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Tidskriftsartikel (refereegranskat)abstract
- In 2012, human papillomavirus (HPV) vaccination was introduced free of charge in the Swedish national school-based vaccination programme for 10-12-year-old girls, and as catch-up vaccination for young women. In Sweden, there is an ongoing discussion about including boys in the national vaccination programme. Few studies are undertaken about adolescents' knowledge, beliefs and HPV vaccination status in relation to socioeconomic status and sexual experience. Thus, the aim was to examine HPV catch-up vaccination status in adolescents in relation to 1) socioeconomic factors, 2) beliefs and knowledge about HPV prevention, and 3) sexual behaviour. The Health Belief Model was used as a theoretical framework. Upper secondary school students (n = 832) aged 16, randomly chosen from a larger sample, were invited to participate in conjunction with the general health interview with the school nurse. A total of 751/832 (90.3%), girls (n = 391, 52%) and boys (n = 360, 48%) completed the questionnaire. HPV vaccination was associated with ethnicity and the mothers' education level; i.e. girls with a non-European background and girls with a less educated mother were less likely to have received the vaccine (p<0.01 and p = 0.04 respectively). Vaccinated girls perceived HPV infection as more severe (p = 0.01), had more insight into women's susceptibility to the infection (p = 0.02), perceived more benefits of the vaccine as protection against cervical cancer (p<0.01) and had a higher intention to engage in HPV-preventive behaviour (p = 0.01). Furthermore, boys and girls were almost equally sexually experienced, although fewer girls had used condom during first intercourse with their latest partner (p = 0.03). Finally, HPV vaccinated girls were less likely to have unprotected sex (p<0.01). In summary, catch-up HPV vaccination among young girls was associated with a European background and high maternal education level, as well as more favourable beliefs towards HPV prevention and less sexual risk-taking. Further preventive measures should therefore be directed at the migrant population.
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| 14. |
- Grandahl, Maria, et al.
(författare)
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‘I also want to be vaccinated!’ – adolescent boys’ awareness and thoughts, perceived benefits, information sources, and intention to be vaccinated against Human papillomavirus (HPV)
- 2019
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Ingår i: Human Vaccines & Immunotherapeutics. - : Informa UK Limited. - 2164-5515 .- 2164-554X. ; 15:7-8, s. 1794-1802
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Tidskriftsartikel (refereegranskat)abstract
- This study investigates boys’ awareness and thoughts about human papillomavirus (HPV) and HPV vaccination, perceived benefits of vaccinating men, information sources and intention to be vaccinated against HPV. We used a qualitative approach and interviews were conducted with 31 upper secondary school male students. Two main themes 1) Promotion of equal health and 2) Increased knowledge facilitates the decision about HPV vaccination emerged from the analysis. The informants believed that it was important and fair to protect boys and girls equally against HPV. If HPV vaccination could prevent both girls and boys against an HPV-related disease, there was nothing to question or to discuss. It was not a matter of sex; it was a matter of equal rights. Moreover, an important reason for vaccinating boys was to prevent the transmission of the virus. However, the boys felt unsure and stated that they needed to know more. The school nurse and the school health were considered suitable both for distributing information and for providing the vaccinations.In conclusion, the participants were in favor of introducing HPV vaccination also for boys in the national vaccination program. Sex-neutral HPV vaccinations were viewed both as a way to stop the virus transmission and a means to promote equal health for the entire population.
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| 15. |
- Grandahl, Maria, et al.
(författare)
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School-based intervention for the prevention of HPV among adolescents : a randomised controlled study
- 2016
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Konferensbidrag (refereegranskat)abstract
- Background: Vaccination against human papillomavirus (HPV) is one important factor for preconception health and care. In Sweden a national vaccination programme for girls was implemented in 2012.Aim: To improve primary prevention of HPV infection by promoting vaccination and increased condom use among upper secondary school students at time for the general health interview with the school nurse.Methods: Randomised controlled trial among upper secondary schools (n=18). Participant schools were first randomised to the intervention or the control group, after which individual classes were randomised to be included or not. 832 students, both boys and girls aged 16 were invited to participate and in the end, 741 (89.1%) students completed the study. The intervention was based on the Health Belief Model (HBM). According to HBM a person’s health behaviour can be explained by individual beliefs regarding health actions. School nurses delivered 30 minute face-to-face structured information about HPV, including cancer risks and HPV prevention, i.e. condom use and HPV vaccination. Students in both groups completed questionnaires at baseline and after three months.Results: The intervention had positive effect on behaviour: girls in the intervention group chose to have themselves vaccinated to a significantly higher degree than the controls (p=0.02). There was also a significant effect on HBM total score (p=0.003), students in the intervention group had more favourable beliefs compared to the controls. The influence on the HBM parameters susceptibility and severity were also significant (p<0.001 for both variables). In addition, the intervention had significant effect on the intention to use condom (p=0.004).Conclusion: The school-based intervention increased HPV vaccination rates and had favourable effects on beliefs towards primary prevention of HPV in a diverse population of adolescents. These resultss provide the scientific support for the implication of nation-wide educational interventions with the potential to improve preconception health.
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| 16. |
- Grandahl, Maria, et al.
(författare)
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School-based intervention for the prevention of HPV among adolescents : a cluster randomised controlled study
- 2016
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To improve primary prevention of human papillomavirus (HPV) infection by promoting vaccination and increased condom use among upper secondary school students. Design: Cluster randomised controlled trial. Setting: 18 upper secondary schools in Sweden. Participants: Schools were first randomised to the intervention or the control group, after which individual classes were randomised so as to be included or not. Of the 832 students aged 16 years invited to participate during the regular individual health interview with the school nurse, 751 (90.2%) agreed to participate and 741 (89.1%) students completed the study. Interventions: The intervention was based on the Health Belief Model (HBM). According to HBM, a person's health behaviour can be explained by individual beliefs regarding health actions. School nurses delivered 30 min face-to-face structured information about HPV, including cancer risks and HPV prevention, by propagating condom use and HPV vaccination. Students in the intervention and the control groups completed questionnaires at baseline and after 3 months. Main outcome measures: Intention to use condom with a new partner and beliefs about primary prevention of HPV, and also specifically vaccination status and increased condom use. Results: All statistical analyses were performed at the individual level. The intervention had a significant effect on the intention to use condom (p=0.004). There was also a significant effect on HBM total score (p=0.003), with a 2.559 points higher score for the intervention group compared to the controls. The influence on the HBM parameters susceptibility and severity was also significant (p<0.001 for both variables). The intervention also influenced behaviour: girls in the intervention group chose to have themselves vaccinated to a significantly higher degree than the controls (p=0.02). No harms were reported. Conclusions: The school-based intervention had favourable effects on the beliefs about primary prevention of HPV, and increased the HPV vaccination rates in a diverse population of adolescents.
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| 17. |
- Green, Caroline, et al.
(författare)
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Combined treatment with radiotherapy, chemotherapy and avelumab results in regression of metastatic Merkel cell carcinoma and improvement of associated Lambert‑Eaton myasthenic syndrome : a case report
- 2022
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Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 24:5
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Tidskriftsartikel (refereegranskat)abstract
- Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroendocrine malignancy arising from mecha‑ noreceptors in the basal epidermis. Due to a pronounced risk of spread and a high propensity for recurrence after treatment, immediate treatment is of utmost importance. Lambert‑Eaton myasthenic syndrome (LEMS) is a paraneoplastic phenom‑ enon affecting the muscles with autoimmune pathophysiology, and >50% of known cases are associated with an underlying malignancy. In the present report, the case of a 67‑year‑old man presenting with progressive proximal muscle weakness, auto‑ nomic dysfunction and involuntary weight loss is described. Symptoms and detection of voltage‑gated calcium channel antibodies were consistent with LEMS. Distant metastases were found in the inguinal and iliac lymph nodes, and these were immunohistochemically confirmed to be of epithelial and neuroendocrine origin, consistent with MCC. Local radio‑ therapy and chemotherapy improved the symptoms; however, a change of treatment was required due to the side effects of the chemotherapy. Avelumab, an immune checkpoint inhibitor, was therefore introduced, and within a year the patient did not only experience tumor remission but also exhibited marked improvements in muscle strength and mobility. At present, 2 years later, the MCC is still in remission. To the best of our knowledge, the present report is the first to describe MCC with associated LEMS, which was successfully treated with avelumab after previous radiotherapy and chemotherapy, with both improved functional motor recovery and tumor reduc‑ tion. In conclusion, the present case report demonstrated that the present treatment strategy is a potential treatment option and could thus be considered in similar cases.
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| 18. |
- Grün, Nathalie, et al.
(författare)
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Human papillomavirus prevalence in mouthwashes of patients undergoing tonsillectomy shows dominance of HPV69, without the corresponding finding in the tonsils.
- 2017
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Ingår i: Infectious diseases (London, England). - : Informa UK Limited. - 2374-4243 .- 2374-4235. ; 49:8, s. 588-593
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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.
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| 19. |
- Gustafsson, Britt, et al.
(författare)
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KI, WU, and Merkel Cell Polyomavirus DNA was not Detected in Guthrie Cards of Children who Later Developed Acute Lymphoblastic Leukemia
- 2012
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Ingår i: Journal of pediatric hematology/oncology (Print). - 1077-4114 .- 1536-3678. ; 34:5, s. 364-367
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Tidskriftsartikel (refereegranskat)abstract
- Background: Neonatal dried blood spots (Guthrie cards) have been used to demonstrate a prenatal origin of clonal leukemia-specific genetic aberrations in several subgroups of childhood acute lymphoblastic leukemia (ALL). One hypothesis suggests that an infectious agent could initiate genetic transformation already in utero. In search for a possible viral agent, Guthrie cards were analyzed for the presence of 3 newly discovered polyomavirus Karolinska Institutet polymavirus (KIPyV), Washington University polyomavirus (WUPyV), and Merkel cell polyomavirus (MCPyV). Methods: Guthrie cards from 50 children who later developed ALL and 100 matched controls were collected and analyzed by standard or real-time polymerase chain reaction for the presence of the VP1 region of KIPyV, WUPyV, and MCPyV, and the LT region for MCPyV. Results and Conclusions: DNA from KIPyV, WUPyV, and MCPyV was not detected in neonatal blood samples from children with ALL or controls. Prenatal infections with these viruses are not likely to be etiological drivers for childhood leukemogenesis.
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| 20. |
- Hammarstedt, Lalle, et al.
(författare)
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The incidence of tonsillar cancer in Sweden is increasing.
- 2007
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Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; 127:9, s. 988-92
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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.
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| 21. |
- Jalouli, Jamshid, 1959-
(författare)
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Human Papilloma Virus, Epstein-Barr Virus, and Herpes Simplex Virus Type-1 in Oral Squamous Cell Carcinomas from Three Populations
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Most oral squamous cell carcinoma (OSCC) is believed to develop via a multistep process of cumulative gene damage in epithelial cells. Increasing incidence of OSCC and evidence that traditional risk factors may not be responsible directed us to investigate the prevalence of virus in pre- and malignant samples.The integration of the DNA from human papillomavirus (HPV), Epstein-Barr virus (EBV), and Herpes simplex (HSV) into the human genome is associated with the expression of oncogenes and the down-regulation of tumor-suppressor genes in OSCC carcinogenesis. This thesis compared samples from India and Sudan, two countries on two continents having a documented high incidence of oral cancer, with specimens from Sweden, with its known low incidence of oral cancer. Each region has, in addition to smoking, a unique non-smoked tobacco habits with documented carcinogenic effects. These countries also typify areas of low and high socioeconomic living conditions with their expected impact on disease development. The study populations were selected from tobacco users and nonusers with OSCC, oral sub-mucous fibrosis (India), oral lichen planus (Sweden), oral leukoplakia with and without dysplasia and snuff-induced lesions (Sweden and Sudan). An expedient method was developed for extracting DNA from old formalin-fixed and paraffin-embedded biopsies. The prevalence of HPV, EBV, and HSV was investigated using PCR/DNA sequencing and southern blot hybridization analysis. We found HPV and EBV to be most prevalent in samples of tissue characterized as normal, with decreasing prevalence in dysplastic and malignant lesions. This intriguing finding that prevalence decreases as neoplastic development proceeds warrants further investigation. Our data do not at first sight support the conclusion that viruses and tobacco use jointly interact with cell mechanisms in the development of oral cancer.
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| 22. |
- Kaliff, Malin, 1985-
(författare)
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Human papillomavirus and cellular biomarkers in cervical cancer
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cervical cancer (CC) is caused by a persistent infection of certain types of the human papillomavirus (HPV). Even though great progress has been made in strategies for prevention, and treatment of CC, there is still a need for improved methods in screening and management of women diagnosed with CC. The aim of this thesis was to gain further knowledge of CC by studying HPV-related or cellular biomarkers in precursors and established cancer.Mostly molecular methods were used for analysis of both tumour and screening samples. Among the studied biomarkers were HPV genotype, HPV multiplicity, viral load and methylation.Initially, HPV was detected in only 86% of the tumours; after careful reinvestigation of the negative samples, the final prevalence was 93%. The results show that analysis of long-term archived samples may require thorough and repeated analysis to obtain accurate results. In the HPV-positive tumour samples, 13% tested positive for multiple genotypes. This finding was associated with poor prognosis for the woman and could be a useful biomarker for prognostic assessment in CC. Viral load was analysed as a potential contributing factor for prognosis differences, however, no such association was detected.In the screening cohort, 40% of women with high-grade abnormalities were positive for HPV16 and 18, genotypes included in the vaccine used since 2012 in Sweden, while 88% were positive for the genotypes in the updated vaccine used since 2019. This indicates a large future reduction of high-grade abnormalities in the vaccinated cohorts, and baseline data like these are valuable for surveillance of genotype distribution in the coming decades. A methylation test targeting two human genes, proposed for use in screening, was tested on the screening samples. We detected no association between hypermethylation and HPV, but it was associated with increasing age, something that needs to be considered if using this method in screening.
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| 23. |
- Landin, David, et al.
(författare)
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Immune related proteins and tumor infiltratingCD8+ lymphocytes in hypopharyngeal cancer in relation to human papillomavirus (HPV) and clinical outcome
- 2020
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Ingår i: Head and Neck. - : John Wiley & Sons. - 1043-3074 .- 1097-0347. ; 42:11, s. 3206-3217
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hypopharyngeal cancer (HPSCC) shows a poor clinical outcome, while HPSCC, caused by human papillomavirus (HPV), presents a better outcome. Here, HPCC, immune proteins, and tumor infiltrating CD8+ lymphocytes (CD8+ TILs) were evaluated in relation to HPV and outcome.Methods: Fresh frozen tissue from four HPV-positive HPSCC, 39 HPV-negative HPSCC, and normal samples were analyzed for protein expression by the Proseek immuno-oncology immunoassay. CD8+ TIL numbers evaluated by immunohistochemistry on 144 formalin-fixed biopsies were analyzed in relation to clinical outcome.Results: Proteins differing between HPV-positive and negative HPSCC included CD8A, PD-L1, Fas ligand, and chemokines. High CD8+ TIL numbers were correlated to improve clinical outcome in HPV-negative HPSCC.Conclusions: High expression of immune proteins in HPV-positive HPSCC may explain the better clinical outcome. CD8+ TILs are of relevance for outcome of HPV-negative HPSCC, while tumors with high immune activity but poor patient survival suggest a role for immune therapy.
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| 24. |
- Landin, David, et al.
(författare)
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Post-Treatment Neck Dissection of Tonsillar and Base of Tongue Squamous Cell Carcinoma in the Era of PET-CT, HPV, and p16
- 2022
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Ingår i: Viruses. - : MDPI. - 1999-4915. ; 14:8
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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.
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| 25. |
- Lindquist, David, et al.
(författare)
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Human papillomavirus is a favourable prognostic factor in tonsillar cancer and its oncogenic role is supported by the expression of E6 and E7.
- 2007
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Ingår i: Molecular oncology. - : Wiley. - 1878-0261 .- 1574-7891. ; 1:3, s. 350-5
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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.
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| 26. |
- Lindquist, David, et al.
(författare)
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Intense CD44 expression is a negative prognostic factor in tonsillar and base of tongue cancer
- 2012
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Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 32:1, s. 153-161
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patients with tonsillar and base of tongue cancer, which are human papillomavirus (HPV) positive, have a better clinical outcome than those with HPV-negative tumors. The identification of additional predictive markers for response to therapy could still be of great use.MATERIALS AND METHODS: Tumor markers CD44, p16, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), E-cadherin, cyclooxygenase-2 (COX 2), Ki-67, and p27 were analyzed by immunochemistry, and HPV status was tested by polymerase chain reaction (PCR) in tumors from 73 patients and correlated to survival.RESULTS: High intensity CD44 staining (p=0.006) and high EGFR expression (p=0.026) were indicators of poor prognosis, while high p16 expression (p=0.021) and younger age (p=0.002) were positive prognostic markers for disease-specific survival. Furthermore, staining of CD44 (p=0.026) and age (p=0.002) were shown to be strong prognostic markers in multivariate analysis, which should be evaluated further for possible use in clinical practice.
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| 27. |
- Lindquist, David
(författare)
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Studies on the occurrence and effects of human papillomavirus in tumors of the head and neck
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The presence of human papillomavirus (HPV) in squamous cell carcinoma of the head and neck (HNSCC) was first reported in 1985. Since then, this association has been studied intensively and today there is substantial evidence for HPV as a causative agent and positive prognostic factor for clinical outcome in tonsillar cancer, but the association to other HNSCC is still unclear. The aim of this thesis was first to examine the presence of HPV in tongue cancer and to study its possible influence on disease outcome. Thereafter, the association between HPV and cdk inhibitor p16INK4a expression and a possible correlation to response to radiotherapy (RT) and survival was studied. A third aim of this thesis was to investigate if HPV is a potential risk factor for the increase in incidence of tonsillar cancer that has been observed in Sweden. Furthermore, presence of HPV, viral load and expression of the viral oncogenes E6 and E7 in tonsillar cancer was investigated and correlated to clinical outcome. In tongue cancer, HPV DNA detected by PCR was more commonly found in base of tongue cancer (40%) as compared to mobile tongue cancer (2.4%), and was a positive prognostic factor for survival in patients with base of tongue cancer. This finding indicates that HPV might not only be involved in tonsillar cancer, but also in base of tongue cancer, which has a similar histology and is also a part of oropharynx. In tonsillar cancer there was a strong correlation between a high expression of p16INK4a detected by immunohistochemistry (IHC) and presence of HPV detected by PCR. However, only high expression of p16INK4a, and not the presence of HPV, was shown to be a predictive factor for complete response to RT in tonsillar cancer. Nevertheless, both p16INK4a and HPV were positive predictive factors for clinical outcome. The incidence of tonsillar cancer and presence of HPV was studied in the Stockholm area during 1970-2002. HPV was detected by PCR in 49% of the patient samples and 87% of these were positive for HPV-16. The frequency of HPV positive tonsillar cancer increased 2.9-fold from 1970 to 2002 and during the same time period a parallel 2.8-fold increase in the incidence of tonsillar cancer was observed. These results strongly support HPV as a risk factor for the increase in incidence of tonsillar cancer. In the tonsillar cancer patients above, the finding of HPV as a positive prognostic factor in tonsillar cancer for clinical outcome was confirmed. In addition, HPV viral load and expression of the viral oncogenes E6 and E7 was analyzed with real time quantitative PCR and reverse transcriptase PCR in the HPV-16 positive tonsillar cancer samples. In most HPV-16 positive tumors, expression of E6 and E7 was ascertained. However, in contrast to earlier studies a high viral load was not correlated to survival. The findings of an increase in incidence of tonsillar cancer and a parallel increase in frequency of HPV positive tumors, a better disease specific survival, and the expression of viral oncogenes strongly support previous findings that HPV positive tonsillar cancer should be considered a different disease entity. If the now available prophylactic vaccines are included in the childhood vaccination program for girls, the possible effects on HPV positive tonsillar cancer should be discussed, since most patients with HPV positive tonsillar cancer are men.
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| 28. |
- Mehanna, Hisham, et al.
(författare)
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Prognostic implications of p16 and HPV discordance in oropharyngeal cancer (HNCIG-EPIC-OPC) : a multicentre, multinational, individual patient data analysis
- 2023
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Ingår i: The Lancet Oncology. - : Elsevier. - 1470-2045 .- 1474-5488. ; 24:3, s. 239-251
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Tidskriftsartikel (refereegranskat)abstract
- Background: p16(INK4a) (p16) immunohistochemistry is the most widely used biomarker assay for inferring HPV causation in oropharyngeal cancer in clinical and trial settings. However, discordance exists between p16 and HPV DNA or RNA status in some patients with oropharyngeal cancer. We aimed to clearly quantify the extent of discordance, and its prognostic implications.Methods: In this multicentre, multinational individual patient data analysis, we did a literature search in PubMed and Cochrane database for systematic reviews and original studies published in English between Jan 1, 1970, and Sept 30, 2022. We included retrospective series and prospective cohorts of consecutively recruited patients previously analysed in individual studies with minimum cohort size of 100 patients with primary squamous cell carcinoma of the oropharynx. Patient inclusion criteria were diagnosis with a primary squamous cell carcinoma of oropharyngeal cancer; data on p16 immunohistochemistry and on HPV testing; information on age, sex, tobacco, and alcohol use; staging by TNM 7th edition; information on treatments received; and data on clinical outcomes and follow-up (date of last follow-up if alive, date of recurrence or metastasis, and date and cause of death). There were no limits on age or performance status. The primary outcomes were the proportion of patients of the overall cohort who showed the different p16 and HPV result combinations, as well as 5-year overall survival and 5-year disease-free survival. Patients with recurrent or metastatic disease or who were treated palliatively were excluded from overall survival and disease-free survival analyses. Multivariable analysis models were used to calculate adjusted hazard ratios (aHR) for different p16 and HPV testing methods for overall survival, adjusted for prespecified confounding factors.Findings: Our search returned 13 eligible studies that provided individual data for 13 cohorts of patients with oropharyngeal cancer from the UK, Canada, Denmark, Sweden, France, Germany, the Netherlands, Switzerland, and Spain. 7895 patients with oropharyngeal cancer were assessed for eligibility. 241 were excluded before analysis, and 7654 were eligible for p16 and HPV analysis. 5714 (74middot7%) of 7654 patients were male and 1940 (25middot3%) were female. Ethnicity data were not reported. 3805 patients were p16-positive, 415 (10middot9%) of whom were HPV-negative. This proportion differed significantly by geographical region and was highest in the areas with lowest HPV-attributable fractions (r=-0middot744, p=0middot0035). The proportion of patients with p16+/HPV- oropharyngeal cancer was highest in subsites outside the tonsil and base of tongue (29middot7% vs 9middot0%, p<0middot0001). 5-year overall survival was 81middot1% (95% CI 79middot5-82middot7) for p16+/HPV+, 40middot4% (38middot6-42middot4) for p16-/HPV-, 53middot2% (46middot6-60middot8) for p16-/HPV+, and 54middot7% (49middot2-60middot9) for p16+/HPV-. 5-year disease-free survival was 84middot3% (95% CI 82middot9-85middot7) for p16+/HPV+, 60middot8% (58middot8-62middot9) for p16-/HPV-; 71middot1% (64middot7-78middot2) for p16-/HPV+, and 67middot9% (62middot5-73middot7) for p16+/HPV-. Results were similar across all European sub-regions, but there were insufficient numbers of discordant patients from North America to draw conclusions in this cohort.Interpretation: Patients with discordant oropharyngeal cancer (p16-/HPV+ or p16+/HPV-) had a significantly worse prognosis than patients with p16+/HPV+ oropharyngeal cancer, and a significantly better prognosis than patients with p16-/HPV- oropharyngeal cancer. Along with routine p16 immunohistochemistry, HPV testing should be mandated for clinical trials for all patients (or at least following a positive p16 test), and is recommended where HPV status might influence patient care, especially in areas with low HPV-attributable fractions.
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| 29. |
- Mellin Dahlstrand, Hanna, et al.
(författare)
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P16(INK4a) correlates to human papillomavirus presence, response to radiotherapy and clinical outcome in tonsillar carcinoma.
- 2005
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 25:6C, s. 4375-83
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Human papillomavirus (HPV) in tonsillar carcinoma is correlated with favourable clinical outcome. Here, p16(INK4A), in situ HPV DNA hybridisation (ISH) and HPVL1 capsid detection were evaluated in tonsillar carcinoma to predict the response to radiotherapy (RT) and prognosis. MATERIALS AND METHODS: Fifty-one pre-treatment paraffin-embedded tonsillar cancer biopsies were analysed. Immunohistochemistry (IHC) was used for p16(INK4A) and HPVL1 capsid analysis and PCR and ISH for HPV detection. RESULTS: High-risk HPV DNA was detected by PCR in 49% of the tumours. P16(INK4a) staining was correlated to HPV In the high-grade p16(INK4a) staining group, 94% had a complete RT response. High p16(INK4a) staining as well as the HPV PCR-positive cases had a favourable prognosis. HPV DNA ISH and L1 IHC could not predict RT response or clinical outcome. CONCLUSION: P16(INK4a) overexpression was correlated to HPV in tonsillar carcinoma and is useful for predicting RT response and prognosis in tonsillar carcinoma patients.
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| 30. |
- Mints, Michael, et al.
(författare)
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Tumour inflammation signature and expression of S100A12 and HLA class I improve survival in HPV-negative hypopharyngeal cancer
- 2021
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 11:1
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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.
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| 31. |
- Nordfors, Cecilia, et al.
(författare)
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Oral human papillomavirus prevalence in high school students of one municipality in Sweden
- 2013
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 45:11, s. 878-881
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Tidskriftsartikel (refereegranskat)abstract
- The rise in human papillomavirus (HPV) infection has been suggested to be responsible for the increased incidence of oropharyngeal cancer in the Western world. This has boosted interest in oral HPV prevalence and whether HPV vaccines can prevent oral HPV infection. In a previous study we showed oral HPV prevalenceto be almost 10% in youth aged 15-23 y attending a youth clinic in Stockholm, Sweden. However, this may not be a generalizable sample within the Swedish population. Therefore, mouthwashes were used to investigate oral HPV prevalence in 335 Swedish high school students aged 17-21 y (median age 18 y), from 1municipality with 140,000 inhabitants. The presence of HPV DNA in the oral samples, as examined by a Luminex-based assay, was significantly lower in this cohort, only 1.8% (3.1% in females and 0.6% in males), as compared to our previous study.
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| 32. |
- Näsman, Anders, et al.
(författare)
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Absent/weak CD44 intensity and positive human papillomavirus (HPV) status in oropharyngeal squamous cell carcinoma indicates a very high survival
- 2013
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Ingår i: Cancer Medicine. - : John Wiley & Sons. - 2045-7634. ; 2:4, s. 507-18
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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.
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| 33. |
- Näsman, Anders, et al.
(författare)
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Human Papillomavirus and Potentially Relevant Biomarkers in Tonsillar and Base of Tongue Squamous Cell Carcinoma
- 2017
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Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 37:10, s. 5319-5328
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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.
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| 34. |
- Näsman, Anders, et al.
(författare)
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Incidence of human papillomavirus (HPV) positive tonsillar carcinoma in Stockholm, Sweden : an epidemic of viral-induced carcinoma?
- 2009
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 125:2, s. 362-6
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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.
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| 35. |
- Priftakis, Peter, et al.
(författare)
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Human polyomavirus DNA is not detected in Guthrie cards (dried blood spots) from children who developed acute lymphoblastic leukemia
- 2003
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Ingår i: Medical and Pediatric Oncology. - : Wiley. - 0098-1532 .- 1096-911X. ; 40:4, s. 219-223
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Tidskriftsartikel (refereegranskat)abstract
- Background Epidemiological evidence has suggested that some childhood acute lymphoblastic leukemia (ALL) may be initiated in utero and may have an infectious etiology. The human polyomavirus JC virus (JCV) has been discussed as a candidate virus, but its presence has not been demonstrated in leukemia cells from children with ALL. The aim of this study was, therefore, to investigate if prenatal human polyomavirus infection could still indirectly be correlated to the development of childhood ALL. Procedure Fifty-four Guthrie cards (stored, dried blood spots filter papers, routinely collected from newborns for different screening analyses), collected at 3–5 days of age, from Swedish children who subsequently developed ALL, as well as from 37 healthy controls, were investigated by nested PCR for the presence of human polyomaviruses JCV and BK virus (BKV). Results JCV and BKV DNA were not detected in any of the Guthrie cards from ALL patients or from healthy controls, although all tested samples had amplifiable DNA as confirmed by an HLA DQ PCR. Conclusions JCV or BKV were not found in any of the dried blood spots of children who later developed ALL or in the healthy controls. These findings suggest that it is unlikely that childhood ALL is associated with an in utero infection with JCV or BKV, although it is not possible to exclude an association with an in utero infection that has become latent in the kidneys with very low levels of circulating virus at birth.
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| 36. |
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| 37. |
- Sivars, Lars, et al.
(författare)
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Human papillomavirus DNA detection in fine-needle aspirates as indicator of human papillomavirus-positive oropharyngeal squamous cell carcinoma : A prospective study
- 2017
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Ingår i: Head and Neck. - : Wiley. - 1043-3074 .- 1097-0347. ; 39:3, s. 419-426
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Tidskriftsartikel (refereegranskat)abstract
- Background. Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (SCC) has a better outcome than most head neck squamous cell carcinomas (HNSCCs) and an HPV-positive lymph node metastasis likely has an HPV-positive oropharyngeal SCC origin. Determining HPV-status in cervical lymph nodes by fine-needle aspiration cytology (FNAC) may be useful for diagnosis. Methods. FNACs from 66 patients with neck masses were prospectively examined for HPV DNA and HPV16 mRNA by a polymerase chain reaction (PCR)-based assay, and the data correlated to diagnosis and HPV-status obtained from histopathological specimens. Results. Aspirates from 17 of 66 patients, later diagnosed with HPV-positive oropharyngeal SCC, were HPV16 DNA-positive. HPV16 mRNA was detected in all cases with extractable RNA. All remaining FNACs, including 18 branchial cleft cysts, were HPV DNA-negative. HPV DNA status in the aspirates showed perfect concordance with corresponding biopsies. Conclusion. HPV16 DNA detection in fine-needle aspirations from neck masses is reliable and HPV16 DNA in a metastasis is a strong indicator of an HPV-positive oropharyngeal SCC.
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| 38. |
- Söderström, Karin, et al.
(författare)
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Regional recurrence of oropharyngeal cancer after definitive radiotherapy: a case control study.
- 2015
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Ingår i: Radiation Oncology. - : Springer Science and Business Media LLC. - 1748-717X. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Elective treatment of lymph nodes in oropharyngeal cancer (OPC) has impact on both regional recurrences (RR) and risk of late side effects. This study was performed to quantify the dose-dependent impact on RR and overall survival (OS) in a prospectively collected cohort of OPC from the ARTSCAN study with emphasis on elective treatment.
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| 39. |
- Zackrisson, Björn, et al.
(författare)
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Mature results from a Swedish comparison study of conventional versus accelerated radiotherapy in head and neck squamous cell carcinoma - The ARTSCAN trial
- 2015
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Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140 .- 1879-0887. ; 117:1, s. 99-105
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: This report contains the mature five-year data from the Swedish ARTSCAN trial including information on the influence of p16 positivity (p16+) for oropharyngeal cancers. Material and methods: Patients with previously untreated squamous cell carcinoma without distant metastases of the oral cavity, oropharynx, larynx (except T1-2, NO glottic cancers) and hypopharynx were included. Patients were randomised between accelerated fractionation (AF) (1.1 Gy + 2 Gy per day, 5 days/week for 4.5 weeks, total dose 68 Gy) and conventional fractionation (CF) (2 Gy per day, 5 days/week for 7 weeks, total dose 68 Gy). Human papillomavirus (HPV)-associated p16-expression was assessed retrospectively in tumour tissues from patients with oropharyngeal carcinoma. Results: There was no significant difference in loco-regional control (LRC) between AF and CF (log-rank test p = 0.75). LRC at 5 years was 65.5% for AF and 64.9% for CF. Overall survival (OS) was similar in both arms (p = 0.99). The estimated cancer specific survival (CSS) at 5 years was 62.2% (AF) and 63.3% (CF) (p = 0.99). 206 specimens were analysed for p16 with 153 specimens (74%) identified as p16+. P16 status did not discriminate for response to AF vs. CF with regard to LRC, OS or CSS. Patients with p16+ tumours had a statistically significant better overall prognosis compared with p16 tumours. Conclusion: This update confirms the results of the 2-year report. We failed to identify a positive effect resulting from AF with regards to LRC, OS and CSS. The addition of information on the HPV-associated p16 overexpression did not explain this lack of effect.
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| 40. |
- Zupancic, Mark, et al.
(författare)
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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
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Ingår i: Oral Oncology. - : Elsevier. - 1368-8375 .- 1879-0593. ; 151
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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.
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| 41. |
- Ährlund-Richter, Andreas, et al.
(författare)
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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
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Ingår i: Cancers. - : MDPI. - 2072-6694. ; 14:1
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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.
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