Tina Dalianis - Academia.edu (original) (raw)

Papers by Tina Dalianis

Anticancer Research/Anticancer research, Mar 27, 2024

Adenoid cystic carcinoma (AdCC) is a rare cancer originating from secretory glands with unknown a... more Adenoid cystic carcinoma (AdCC) is a rare cancer originating from secretory glands with unknown aetiology. It is one of the most dominant malignant salivary tumours (MST). However, it can arise in other areas of the head and neck region and in secretory glands outside this area. It occurs at all ages, but is more frequent between 50-70 years of age and more common in females than in males. The symptoms of AdCC are generally unspecific and the clinical diagnosis of AdCC maybe challenging, partially due to its heterogenous histopathology and indolent growth. Moreover, there is a lack of good prognostic markers, and due to its rarity, it is difficult to predict which therapeutic methods are the most optimal for each patient, especially since very late recurrences occur. This review presents some major characteristics of AdCC and some current treatments for this disease. Adenoid cystic carcinoma (AdCC) is a rare type of malignancy with a yet unknown aetiology originating from secretory glands (1-4). Notably, it is one of the most common malignant salivary tumours (MST) accounting for approximately 10% of all tumours in the major salivary glands and 30% of all tumours in the minor salivary glands (2). The presence of AdCC is however not limited to the salivary glands. It can arise in other locations within the head and neck region as well as in secretory glands outside the head neck region such as, for example, in the oesophagus, the breast, the lung and the vulva (2). It can occur at all ages, but it is predominant in the middle ages and is more common in females than in males (3). AdCC presents with unspecific symptoms, and its clinical diagnosis is challenging, especially due to its indolent growth and lack of reliable specific diagnostic markers. The initial treatment is surgery, frequently followed by adjuvant radiotherapy, but in spite an aggressive treatment regimen late relapses are common (3). Evidently, and also due to its rare occurrence, AdCC presents both a diagnostic and clinical challenge. In this review, we therefore describe some aspects with regard to the diagnosis of AdCC as well as its treatment in parallel with some data on its anatomical and molecular complexity. In addition, we present current treatment options and some of the benefits of combining various therapies and possible aspects of future therapies. Adenoid Cystic Carcinoma in the Context of Head and Neck Cancer-Epidemiology and Risk Factors Head and neck cancer (HNC) is the 6 th most common cancer worldwide with around 900,000 new cases and >400,000 deaths yearly (5, 6). Important risk factors for HNC are smoking, alcohol, opium, betel quid chewing, oral infections, radiation exposure, personal history of HNC and more recently even viral infections, e.g., human papillomavirus (HPV) and Epstein-Barr Virus (EBV). However, for some HNC e.g., malignant salivary gland tumours (MST), including adenoid cystic carcinoma (AdCC), risk factors are still mainly unknown (1-5, 7). Recently, in many Western countries, due to a decrease in smoking, the spectra of various HNCs have changed. We are seeing a steady decrease in smoking related HNC but instead a parallel rise in HPV associated head and neck cancer has been disclosed (8-10).

PubMed, Apr 1, 1996

In BMT patients, shedding of BK virus (BKV) in the urine has been strongly but not absolutely cor... more In BMT patients, shedding of BK virus (BKV) in the urine has been strongly but not absolutely correlated to hemorrhagic cystitis (HC). The possible presence of human polyomaviruses in peripheral blood leukocytes (PBLs), plasma, serum and urine in BMT patients and an association with HC was investigated by a nested PCR assay. Samples from allogeneic BMT patients with and without HC as well as from autologous BMT patients were analyzed. Human polyomaviruses were detected in urine and blood samples of both allogeneic and autologous BMT patients with and without HC. An association between the presence of a specific human polyomavirus in blood and HC was thus not observed.

Human Vaccines & Immunotherapeutics, Dec 20, 2018

This study investigates boys' awareness and thoughts about human papillomavirus (HPV) and HPV vac... more 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.

Oral Oncology, Jul 1, 2018

Three-year disease-free survival (DFS) is 80% for human papillomavirus (HPV) positive tonsillar a... more 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.

British Journal of Cancer, May 24, 2018

BACKGROUND: The proxy marker for human papillomavirus (HPV), p16, is included in the new AJCC 8th... more BACKGROUND: The proxy marker for human papillomavirus (HPV), p16, is included in the new AJCC 8th/UICC 8th staging system, but due to incongruence between p16 status and HPV infection, single biomarker evaluation could lead to misallocation of patients. We established nomograms for overall survival (OS) and progression-free survival (PFS) in patients with oropharyngeal squamous cell carcinoma (OPSCC) and known HPV-DNA and p16 status, and validated the models in cohorts from high-and low-prevalent HPV countries. METHODS: Consecutive OPSCC patients treated in Denmark, 2000-2014 formed the development cohort. The validation cohorts were from Sweden, Germany, and the United Kingdom. We developed nomograms by applying a backward-selection procedure for selection of variables, and assessed model performance. RESULTS: In the development cohort, 1313 patients, and in the validation cohorts, 344 German, 503 Swedish and 463 British patients were included. For the OS nomogram, age, gender, combined HPV-DNA and p16 status, smoking, T-, N-, and M-status and UICC-8 staging were selected, and for the PFS nomogram the same variables except UICC-8 staging. The nomograms performed well in discrimination and calibration. CONCLUSIONS: Our nomograms are reliable prognostic methods in patients with OPSCC. Combining HPV DNA and p16 is essential for correct prognostication. The nomograms are available at www.orograms.org.

PubMed, Dec 13, 2005

Background: Human papillomavirus (HPV) in tonsillar carcinoma is correlated with favourable clini... more 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.

Oral Oncology, Sep 1, 2015

Objectives: Hypopharyngeal cancer is a subset of head neck squamous cell carcinoma (HNSCC) with p... more Objectives: Hypopharyngeal cancer is a subset of head neck squamous cell carcinoma (HNSCC) with particularly poor prognosis. Human papillomavirus (HPV) is a risk factor for some HNSCC, and its presence is of prognostic value for certain subsites. However, its influence on survival in hypopharyngeal cancer has not been thoroughly investigated. Here we examine HPV DNA and p16 INK4a (p16) overexpression in relation to clinical outcome. Materials and Methods: Hypopharyngeal tumour biopsies from 82 patients diagnosed 2008-2013 were examined for presence of HPV DNA by a bead-based multiplex assay and for p16 expression by immunohistochemistry, and the obtained data compared to that acquired previously from 109 patients diagnosed 2000-2007 at the same clinic. A survival analysis was then performed on 142 patients (from both studies) treated with curative intent and a 3-year follow-up time. Results: Of the tumour biopsies 3/82 (3.7%) were HPV16 DNA and p16 positive, while 12/82 (14.6%) were p16 positive, equivalent to that in the previous study. Overall 3-year survival was significantly more favourable for patients with HPV16 DNA and p16 positive tumours as compared to survival of the other patients (86% vs. 31%, p = 0.0185). A similar but not statistically significant trend was found for disease specific survival. Conclusion: HPV DNA and p16 positive hypopharyngeal cancer was rare and had not increased, but had a better clinical outcome as compared to other HPV-unrelated hypopharyngeal cancer. In addition, p16 overexpression was not a suitable surrogate marker for presence of HPV or for prediction of survival in this type of cancer.

Papillomavirus Research, Dec 1, 2017

Objectives: Human papillomavirus (HPV) as a risk factor in oropharyngeal squamous cell carcinoma ... more Objectives: Human papillomavirus (HPV) as a risk factor in oropharyngeal squamous cell carcinoma (OPSCC) is well established. However, accumulating data imply that the OPSCC concept is too unspecific with regard to HPV prevalence and clinical importance. To further study the role of HPV in OPSCC by sub-site, a systematic review and meta-analysis was performed. Material and method: PubMed was searched and all studies reporting HPV data (p16/HPV DNA/RNA) in both "lymphoepithelial associated" (i.e. tonsillar and base of tongue cancer; TSCC and BOTSCC respectively) and "non-lymphoepithelial" ("other" OPSCC) OPSCC were included. Pooled odds ratios by HPV detection method were analysed using a random effects model. Results: In total, 58 unique patient cohorts were identified. Total HPV prevalence in TSCC/BOTSCC was 56%, 95%CI: 55-57% (59%, 95%CI: 58-60% for TSCC only) as compared to 19%, 95%CI: 17-20%, in "other" OPSCC. Significant association of HPV to TSCC/BOTSCC vs. "other" OPSCC was observed no matter HPV detection method used, but statistical homogeneity was only observed when studies using algorithm based HPV detection were pooled. Conclusion: HPV prevalence differs markedly between OPSCC sub-sites and while the role of HPV in TSCC/ BOTSCC is strong, the role in "other" OPSCC is more uncertain and needs further evaluation.

Wiley Encyclopedia of Molecular Medicine, Jan 15, 2002

Journal of Cytology and Histology, 2014

Aim: To test for human papillomavirus (HPV) DNA in material obtained from p16INK4a (p16) immunohi... more Aim: To test for human papillomavirus (HPV) DNA in material obtained from p16INK4a (p16) immunohistochemistry (IHC) stained slides of formalin-fixed paraffin-embedded (FFPE) tumor biopsies. Background: HPV is a favorable prognostic factor in oropharyngeal squamous cell carcinoma (OSCC), where tonsillar and base of tongue squamous cell carcinoma (TSCC and BOTSCC) dominate. Hence. HPV DNA testing as a predictive marker is desirable even when FFPE material is unavailable. Glass slides with p16 staining, often used as a surrogate marker for HPV, are however generally available. Furthermore, the combination of HPV DNA and p16 positivity is established as being better than testing for HPV DNA, or p16 alone, and almost equivalent as testing for E6 and E7 mRNA for determining HPV driven OSCC. Presence of HPV DNA was therefore examined in cells from glass slides previously stained for p16. Materials and methods: DNA extracted from cells scraped off glass slides from 23 TSCC; 24 BOTSCC and 50 cancers of unknown primary (CUP) of the head and neck, with known HPV DNA and p16 status was tested for presence of HPV by a bead-based multiplex assay. Results: DNA was obtained from 95.9% of the TSCC/BOTSCC/CUP slides and exhibited 93.5% (87/93) concordance with the HPV DNA status of the original FFPEs, with 38/42 (90.5%) of the originally HPV DNA positive/p16 positive remaining HPV DNA positive and all HPV DNA negative samples staying negative. Conclusion: A 93.5% concordance was obtained between the HPV DNA status of the original FFPEs and DNA obtained from p16 stained glass slides. Of the HPV DNA positive IHC samples 38/38 100% were derived from HPV DNA positive/p16 positive FFPE biopsies, while all HPV DNA negative samples stayed HPV-negative. This approach allows for safer identification of HPV-positive tumors, and useful for following patients with HPV-positive tumors in retrospective studies and for future decision-making.

Journal of Virology, Dec 1, 1983

Antibodies were raised against the sequence Glu-Glu-Glu-Glu-Tyr-Met-Pro-Met-Glu, which represents... more Antibodies were raised against the sequence Glu-Glu-Glu-Glu-Tyr-Met-Pro-Met-Glu, which represents a part of the middle T antigen of polyomavirus that is considered to be important in inducing the phenotype of transformed cells. The antibodies reacted with native as well as denatured middle T antigens. In addition, the antibodies immunoprecipitated a cellular protein with an apparent molecular weight of 130,000 (130K) from mouse and rat cells. In some cases, a 33K protein was also immunoprecipitated. Immunoprecipitation of middle T antigen as well as 130K and 33K proteins was blocked by the peptide. The antibodies labeled microfilaments of untransformed mouse, rat, human, and chicken cells by immunofluorescence. This labeling was also blocked by the peptide. The labeling pattern and distribution under a variety of conditions were indistinguishable from those of anti-actin antibodies, although no evidence has been obtained to indicate that the anti-peptide antibodies react with actin. The 130K protein migrated in sodium dodecyl sulfate-polyacrylamide gel electrophoresis slightly slower than chicken gizzard vinculin (130K) and slightly faster than myosin light-chain kinase of chicken smooth muscle (130K). Neither of these proteins absorbed the antipeptide antibodies. The 33K protein does not seem to be tropomyosin (32K to 40K). The early region of polyomavirus encodes three proteins in an overlapping manner. They are commonly called large, middle, and small T antigens (12, 16, 22, 55). Middle T antigen is a main inducer of the phenotype of transformed cells (24), and without it transformation does not occur. Middle T antigen alone can transform established lines of cells (54), although large and possibly small T antigens may also be required for the full expression of the phenotype of transformation in low amounts of mitogenic growth factors in culture medium (40). Large or small T antigens alone cannot transform cells (5, 26, 40, 45). Middle T antigen has a molecular weight of 49,000 (49K) and migrates in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) as a 55K to 60K protein (20, 23, 44). The amino-terminal half of middle T antigen is almost completely homologous to small T antigen. The carboxyl-terminal half of middle T antigen is the unique region, a large part of which is encoded in a region of the viral genome

Oncology Reports, May 5, 2023

Medulloblastoma (MB), grouped as either WNT-activated, Sonic hedgehog (SHH)-activated, or non-WNT... more Medulloblastoma (MB), grouped as either WNT-activated, Sonic hedgehog (SHH)-activated, or non-WNT/non-SHH group 3, accounts for almost 20% of all childhood brain cancers. In spite of current intensive treatments, not all patients are cured and survivors suffer from severe side-effects. The present study therefore examined the effects of the poly-ADP-ribose polymerase (PARP) and WEE1-like protein kinase (WEE1) inhibitors, BMN673 and MK-1775, respectively, alone or in combination on four MB cell lines. More specifically, the MB cell lines, DAOY, UW228-3, MED8A and D425, were tested for their sensitivity to BMN673 and MK-1775 alone or in combination, using cell viability, cell confluency and cytotoxicity assays. The effects on the cell cycle phases were also examined using FACS analysis. Monotherapy with BMN673 and MK-1775 exerted dose-dependent inhibitory effects on the viability of almost all MB cell lines. Notably, when BMN673 and MK-1775 were used in combination, synergistic effects were noted in the SHH group cell lines (DAOY and UW228-3), but not in the already WEE1-sensitive group 3 (MED8A and D425) lines. Moreover, the combination treatment decreased the percentage of cells in the G1 phase and induced the novel distribution of both DAOY and UW228-3 cells in the S and G2/M phases, with the UW228-3 cells exhibiting a greater delay. To conclude, MK-1775 was efficient in all and BMN673 in most cell lines, and their combined use exerted synergistic effects on the SHH, but not the group 3 cell lines. These data suggest that MK-1775 alone may be of interest for all MB cell lines, and that the combination of PARP/WEE1 inhibitors may provide possible therapeutic opportunities for the therapy of SHH MBs. Their use warrants further investigations in the future.

Frontiers in Oncology, Sep 24, 2021

Objectives: Medulloblastoma (MB) is treated with surgery and chemotherapy, with or without irradi... more Objectives: Medulloblastoma (MB) is treated with surgery and chemotherapy, with or without irradiation, but unfortunately >20% of the patients are not cured, and treatment comes with serious long-term side effects, so novel treatments are urgently needed. Phosphoinositide 3-kinases (PI3K), fibroblast growth factor receptors (FGFR), and cyclin-D kinases (CDK) play critical roles in cancer, and especially PI3K is crucial in MB, so here targeted therapies against them were explored. Methods: MB cell lines DAOY and UW228-3 were exposed to PI3K (BYL719), FGFR (JNJ-42756493), and CDK4/6 (PD-0332991) inhibitors, as single or combined treatments, and their viability, cell confluence, apoptosis, and cytotoxicity were examined. Moreover, the inhibitors were combined with cisplatin, vincristine, or irradiation. Results: Single treatments with FGFR, PI3K, or CDK4/6 inhibitors decreased viability and proliferation slightly; however, when combining two inhibitors, or the inhibitors with irradiation, sensitivity was enhanced and lower doses could be used. A more complex pattern was obtained when combining the inhibitors with cisplatin and vincristine. Conclusions: The data suggest that combination treatments with PI3K, FGFR, and CDK4/6 inhibitors for MB could be beneficial and their use should be pursued further. Likewise, their combination with irradiation gave positive effects, while the addition of cisplatin and vincristine resulted in more complex patterns, which need to be investigated further.

Molecular and Clinical Oncology, Oct 13, 2016

Human papillomavirus (HPV), in addition to smoking and alcohol, is a cause of oropharyngeal squam... more Human papillomavirus (HPV), in addition to smoking and alcohol, is a cause of oropharyngeal squamous cell carcinoma (OPSCC), particularly of the tonsils and base of the tongue (TSCC and BOTSCC, respectively). Moreover, HPV-positive TSCC and BOTSCC are associated with a better outcome compared with their HPV-negative counterparts (80 vs. 40% 3-year disease-free survival rate, respectively) and their incidence has increased in several countries. Recently, accumulating evidence of HPV in a considerable proportion of cancers of unknown primary (CUP) in the head and neck region and in a small proportion of hypopharyngeal SCCs has been reported. Furthermore, HPV-positive tumours, particularly cases with HPV DNA positivity in combination with overexpression of p16, also tend to have a better clinical outcome compared with that of the corresponding HPV-negative tumours. This finding is particularly prominent in HPV-positive CUPs of the head and neck region, where the primary tumour likely originates from the oropharynx. Thus, the determination of HPV status and p16 expression may be of value for the diagnosis and treatment of CUP of the head and neck region and may also be of value for hypopharyngeal cancers in the future. However, for hypopharyngeal cancer as well as other non-OPSCCs, additional studies per subsite on the effect of HPV status on survival are required. Contents 1. Introduction 2. CUP of the head and neck region 3. HPV in hypopharyngeal cancer 4. HPV in non-OPSCC sites other than CUP and hypopharyngeal cancer 5. Conclusions

Journal of Internal Medicine, Dec 9, 2019

N€ asman A, Du J, Dalianis T (Karolinska Institutet, Stockholm, Sweden). A global epidemic increa... more N€ asman A, Du J, Dalianis T (Karolinska Institutet, Stockholm, Sweden). A global epidemic increase of an HPV-induced tonsil and tongue base cancerpotential benefit from a pan-gender use of HPV vaccine (Review).

Supplemental Figure 2 legend: Shown are age-specific cumulative incidences of tonsillectomies dur... more Supplemental Figure 2 legend: Shown are age-specific cumulative incidences of tonsillectomies during 1970-2009 in Sweden across the year of birth (i.e. birth cohort).

Supplemental Figure 1: Description of tonsillectomy cohort for the Swedish nation-wide study (197... more Supplemental Figure 1: Description of tonsillectomy cohort for the Swedish nation-wide study (1970-2009.)Supplemental Table 1: Clinical indications for tonsillectomy, stratified by calendar period and age at tonsillectomy. Supplemental Table 2: Clinical indications for tonsillectomies conducted as in-patient versus out-patient procedures (2006-2009.) Supplemental Table 3: Association of tonsillectomy with risk of head and neck cancers, stratified by age at tonsillectomy, gender, and calendar era of tonsillectomy.Supplemental Table 4: Sensitivity analyses of the association of tonsillectomy with risk of head and neck cancers.

PLOS ONE, Nov 3, 2017

In 2012, human papillomavirus (HPV) vaccination was introduced free of charge in the Swedish nati... more 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 HPVpreventive 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.

Background: Rising incidence of oropharyngeal cancers in numerous countries since the 1970s has b... more Background: Rising incidence of oropharyngeal cancers in numerous countries since the 1970s has been attributed to increased oral human papillomavirus (HPV) exposure. However, the contribution of coincidental declines in the surgical removal of the tonsils (tonsillectomy) is unknown. We quantified the association of tonsillectomy with risk of tonsillar, other oropharyngeal, and other head and neck cancers and the contribution of declines in tonsillectomies to cancer incidence trends.Methods: We conducted a nation-wide cohort study in Sweden (1970–2009). Tonsillectomies (N = 225,718) were identified through national patient registers, which were linked with the cancer register. Cancer incidence in the tonsillectomy cohort was compared with Sweden's general population through standardized incidence ratios (SIR).Results: Tonsillectomies were associated with reduced risk of tonsil cancers [SIRs 1+ years post-tonsillectomy = 0.31; 95% confidence interval (CI), 0.08–0.79 and 5+ years post-tonsillectomy = 0.17; 95% CI, 0.02–0.62], but unrelated to other oropharyngeal or other head and neck cancers (SIRs 1+ years post-tonsillectomy = 1.61; 95% CI, 0.77–2.95 and 0.92; 95% CI, 0.64–1.27, respectively). The cumulative incidence of tonsillectomy declined significantly (40%–50%) during 1970–2009. However, tonsil cancer incidence significantly increased during 1970–2009 both without and with corrections for declines in tonsillectomies (relative risks per 5-year periods = 1.23, P < 0.001 and 1.20, P < 0.001, respectively).Conclusions: The reduced tonsil cancer risk with tonsillectomy reflects the removal of most of the relevant tissue. The absence of associations with other head and neck cancers indicates that tonsillectomy may not impact carcinogenesis at other sites.Impact: The significant increases in oropharyngeal cancer incidence since the 1970s in Sweden appear independent of declines in tonsillectomies, reinforcing increased oral HPV exposure as the likely cause. Cancer Epidemiol Biomarkers Prev; 25(6); 944–50. ©2016 AACR.

Journal of Clinical Oncology, May 20, 2009

6030 Background: Numerous studies has shown an increase of the incidence of tonsillar squamous ce... more 6030 Background: Numerous studies has shown an increase of the incidence of tonsillar squamous cell carcinoma (SCC) both in the USA and in Sweden. This increase in incidence is despite a decreasing prevalence in smoking, a well-known risk factor for developing tonsillar cancer. The proportion of human papillomavirus (HPV) positive tonsillar SCC has also been shown to increase. This study aims to examine the incidence of tonsillar SCC and the proportion of HPV positive tonsillar SCC between 2003–2007 in the County of Stockholm, Sweden in correlation to data from 1970–2002. Methods: All patients (n = 120) diagnosed with tonsillar SCC during 2003–2007 in the County of Stockholm were included in this study. Ninety-eight pre-treatment biopsies were available and presence of HPV DNA and HPV-16 E6 and E7 mRNA were tested by PCR and RT-PCR. Incidence data between 2003–2007 for Sweden and in the County of Stockholm was obtained from the Swedish Cancer Registry. Data reported from 1970 to 2002 was also obtained for comparison. Results: HPV DNA was present in 83/98 (85%) of the tonsillar SCC biopsies from 2003–2007. Of the 77 HPV-16 positive tumors, HPV-16 E6 and E7 mRNA were found in 98% of the analyzed cases. The proportion of HPV-positive cancers had significantly increased both from 1970 to 2007 (p &amp;amp;lt; 0.0001) as well from 2000 to 2007 (p &amp;amp;lt; 0.01), with 68% (95% 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 1970–2007, in parallel with a decline of HPV-negative tumors. Conclusions: Today, almost all tonsillar SCC in the County of Stockholm is HPV positive, and the incidence of HPV-positive cancers is still increasing. The data suggest that we are dealing with an epidemic of a virus-induced carcinoma, and that soon practically all tonsillar SCC will be HPV positive; a similar situation observed in cervical cancer. No significant financial relationships to disclose.