Tina Dalianis

Human papillomavirus positive tonsil and tongue base cancer (HPV+TSCC/BOTSCC) is increasing epidemically and today constitutes 40% of all head and neck cancers. With combined chemoradiotherapy, approx. 80% of patients are cured, but in addition to serious side effects during the treatment, they also have persistent chronic side effects such as dry mouth, difficulty swallowing and speaking, which impairs quality of life and return to normal life and usual work. About 20% are not cured. Our previous studies have identified a series of prognostic markers in HPV+TSCC/BOTSCC that can now be tested as possible targets in targeted therapy and also for follow-up for earlier detection of recurrence. We want to study the markers we previously identified as possible targets for targeted therapy against HPV+ tonsil/tongue base cancer. We also want to evaluate how these together with quantification of HPV DNA in blood can be used to improve prognosis assessment at diagnosis and to detect and treat early recurrence during the follow-up. For the development of targeted therapies, cell cultures and in vivo models are used to identify the best combinations of these therapies depending on the tumor's specific molecular profile. For the in vivo tests, biopsy material from patient tumors is also used, with resp. molecular profiles such as the cell lines. Our goal is to increase survival and quality of life by improving diagnostics and follow-up with the prognostic markers we have found and also to be better prepared to treat successfully with targeted therapy in the event. relapse where today not all can be cured. Tumors' molecular profiles and response to therapy vary. Laboratory-wise, we therefore want to identify which combinations of new targeted therapies are best for each tumor cell line depending on its mutational profile and in in vivo models apply it to patient tumors with resp. mutation profiles. This will lead to more patients being cured and increase patient survival.

Human papillomavirus positive (HPV+) tonsil and base of tongue cancer (TSCC/BOTSCC) is increasing epidemically and with radiation therapy (RT) has a better prognosis than other head and neck cancers (HHC). HPV+TSCC/BOTSCC make up >35% of all HHC in Sweden. Schoolgirls are vaccinated against HPV, but the epidemic continues. Today, HHC is often treated with aggressive radiotherapy (RT) and chemotherapy (CT) and sometimes EGFR inhibitors, which cause severe side effects. Most HPV+ TSCC/BOTSCC patients should be able to receive milder therapy without affecting survival. Furthermore, the survival of poorer prognosis HPV+ TSCC/BOTSCC patients has not improved since treatment intensification, so new therapies are required. A) We want to improve prognostic assessment in HPV+ TSCC/BOTSCC to ease the therapy in case of good prognosis, and provide targeted therapy in case of worse prognosis. This is done i.a. by DNA sequencing of tumors in patients who have not relapsed and tumors and metastases in patients who have relapsed with the intention of finding markers that distinguish them

B) In the lab. tested TSCC/BOTSCC cell lines for new targeted therapies (where we have identified specific markers) individually and in combination and with chemotherapy to gain knowledge about which combinations are best for tumors with different profiles

C) We follow the TSCC/BOTSCC epidemic and the effects of the HPV vaccine in young people. A. A clinical goal is to identify more effective prognostic markers in TSCC/BOTSCC. The aim is to effectively predict the risk of relapse and better tailor treatment choices. Patients with a good prognosis can instead receive milder therapy with maintained safety. B. Through laboratory analyzes for tailored treatment selection, we investigate how tumors with different genetic profiles respond to different targeted therapies, alone or in combination with chemotherapy or radiation therapy. C. By following the ongoing HPV+TSCC/BOTSCC epidemic and effects of the HPV vaccine, we can follow if/when the epidemic will subside or if other HPV types will take over.

Human papillomavirus (HPV) positive tonsil and heavy bassic cancer has increased since the 1970s. Fortunately, more than 80% of patients are cured with radiation therapy only, but today, like many other head / neck cancer cases, many are treated with chemotherapy and EGFR inhibitors. This leads to side effects that prevent return to normal life and work. We believe it is very worrying to over-treat patients where this is not needed. The 20% of those who are not cured with radiation therapy also do not have a better survival rate for more intensive treatment. These patients therefore need alternative treatment methods to those used today. We want to be able to identify the patients who can receive mild treatment, and for those who do not respond to treatment, characterize the tumors to be able to provide more targeted therapy. With so-called NGS sequencing, protein profiling and immunohistochemistry, we have identified markers for both good and bad treatment responses where some have been validated while others need more research. We have also recently found markers that show poor treatment responses that are already used in other tumor types as targets for targeted therapy. We want to investigate whether the same type of targeted therapy has the effect even for tonsill / tongue bass cans that have corresponding markers. With the markers we have developed so far (eg CD8 + T cells, HPV16 E2, mRNA and others) and by identifying additional markers, we expect to be able to identify more than 70% of the patients with HPV positive cancer who can have mild treatment with primarily radiation therapy. For those who do not respond to today's treatment, we want to be able to offer alternative treatments that target specific proteins (ex. FGFR3, VEGF-A and others) based on protein and mutation analyzes of the individual tumors. Our research will lead to increased survival and better quality of life during and after treatment.

Human papillomavirus (HPV) positive tonsil and heavy bassic cancer has increased since the 1970s. Fortunately, more than 80% of patients are cured with radiation therapy only, but today, like many other head / neck cancer cases, many are treated with chemotherapy and EGFR inhibitors. This leads to side effects that prevent return to normal life and work. We believe it is very worrying to over-treat patients where this is not needed. The 20% of those who are not cured with radiation therapy also do not have a better survival rate for more intensive treatment. These patients therefore need alternative treatment methods to those used today. We want to be able to identify the patients who can receive mild treatment, and for those who do not respond to treatment, characterize the tumors to be able to provide more targeted therapy. With so-called NGS sequencing, protein profiling and immunohistochemistry, we have identified markers for both good and bad treatment responses where some have been validated while others need more research. We have also recently found markers that show poor treatment responses that are already used in other tumor types as targets for targeted therapy. We want to investigate whether the same type of targeted therapy has the effect even for tonsill / tongue bass cans that have corresponding markers. With the markers we have developed so far (eg CD8 + T cells, HPV16 E2, mRNA and others) and by identifying additional markers, we expect to be able to identify more than 70% of the patients with HPV positive cancer who can have mild treatment with primarily radiation therapy. For those who do not respond to today's treatment, we want to be able to offer alternative treatments that target specific proteins (ex. FGFR3, VEGF-A and others) based on protein and mutation analyzes of the individual tumors. Our research will lead to increased survival and better quality of life during and after treatment.

I) Human papillomavirus (HPV) is found in cervical cancer and in 70% of all tonsill and heavy-bark cancers following an epidemic increase detected by us.We have also shown that HPV positive (HPV +) tonsil and tongue-base cancers respond better to regular radiation therapy compared to the corresponding HPV negative cancer and other major neck cancer (HHC) (80% and 40% 5-year survival, respectively). Modern treatment of HHC consists of chemotherapy and aggressive radiation therapy with increased side effects, which 80% of patients with HPV + tonsill and tongue-base cancers are unlikely to need at all. II) Since 2007, 10 new human polyoma viruses have been discovered, one of which is in skin cancer. They may be found in other tumors. I) We want to identify all patients with HPV + tonsil and tongue-base cancer that respond well to regular radiation therapy by combining HPV + status with more prognostic markers. We have some promising markers that identify 20% of the patients, but more are needed to be able to offer patients with HPV + cancer with specific biomarkers for good prognosis, mild treatment with fewer side effects than today's intensive treatment. We also want to investigate the possibility of finding a screening test for prevention. II) We want to test for the 10 newly discovered HPyV in cancer in humans where one suspects correlation between cancer and infection. I) By combining previously identified markers with new markers and understanding their mechanisms, we hope to identify almost all patients HPV + tonsil and tongue bass with good prognosis. In clinical trials, these patients would be able to receive less tailor-made treatment where side effects such as difficulty in swallowing, speaking and breathing are reduced and patients to a greater extent return to normal social life and working life. This will also lead to savings for society that can benefit other patients. II) If new HPyVs are associated with cancer, one can potentially vaccinate risk groups with vaccines against these diseases.

I) Human papillomavirus (HPV) is found in cervical cancer and in 70% of all tonsill and heavy-bark cancers following an epidemic increase detected by us.We have also shown that HPV positive (HPV +) tonsil and tongue-base cancers respond better to regular radiation therapy compared to the corresponding HPV negative cancer and other major neck cancer (HHC) (80% and 40% 5-year survival, respectively). Modern treatment of HHC consists of chemotherapy and aggressive radiation therapy with increased side effects, which 80% of patients with HPV + tonsill and tongue-base cancers are unlikely to need at all. II) Since 2007, 10 new human polyoma viruses have been discovered, one of which is in skin cancer. They may be found in other tumors. I) We want to identify all patients with HPV + tonsil and tongue-base cancer that respond well to regular radiation therapy by combining HPV + status with more prognostic markers. We have some promising markers that identify 20% of the patients, but more are needed to be able to offer patients with HPV + cancer with specific biomarkers for good prognosis, mild treatment with fewer side effects than today's intensive treatment. We also want to investigate the possibility of finding a screening test for prevention. II) We want to test for the 10 newly discovered HPyV in cancer in humans where one suspects correlation between cancer and infection. I) By combining previously identified markers with new markers and understanding their mechanisms, we hope to identify almost all patients HPV + tonsil and tongue bass with good prognosis. In clinical trials, these patients would be able to receive less tailor-made treatment where side effects such as difficulty in swallowing, speaking and breathing are reduced and patients to a greater extent return to normal social life and working life. This will also lead to savings for society that can benefit other patients. II) If new HPyVs are associated with cancer, one can potentially vaccinate risk groups with vaccines against these diseases.

I) Human papillomavirus (HPV) is found in cervical cancer and in 70% of all tonsill and heavy-bark cancers following an epidemic increase detected by us.We have also shown that HPV positive (HPV +) tonsil and tongue-base cancers respond better to regular radiation therapy compared to the corresponding HPV negative cancer and other major neck cancer (HHC) (80% and 40% 5-year survival, respectively). Modern treatment of HHC consists of chemotherapy and aggressive radiation therapy with increased side effects, which 80% of patients with HPV + tonsill and tongue-base cancers are unlikely to need at all. II) Since 2007, 10 new human polyoma viruses have been discovered, one of which is in skin cancer. They may be found in other tumors. I) We want to identify all patients with HPV + tonsil and tongue-base cancer that respond well to regular radiation therapy by combining HPV + status with more prognostic markers. We have some promising markers that identify 20% of the patients, but more are needed to be able to offer patients with HPV + cancer with specific biomarkers for good prognosis, mild treatment with fewer side effects than today's intensive treatment. We also want to investigate the possibility of finding a screening test for prevention. II) We want to test for the 10 newly discovered HPyV in cancer in humans where one suspects correlation between cancer and infection. I) By combining previously identified markers with new markers and understanding their mechanisms, we hope to identify almost all patients HPV + tonsil and tongue bass with good prognosis. In clinical trials, these patients would be able to receive less tailor-made treatment where side effects such as difficulty in swallowing, speaking and breathing are reduced and patients to a greater extent return to normal social life and working life. This will also lead to savings for society that can benefit other patients. II) If new HPyVs are associated with cancer, one can potentially vaccinate risk groups with vaccines against these diseases.