Genome-wide association meta-analysis identifies 48 risk variants and highlights the role of the stria vascularis in hearing loss.

Hearing loss is one of the top contributors to years lived with disability and is a risk factor for dementia. Molecular evidence on the cellular origins of hearing loss in humans is growing. Here, we performed a genome-wide association meta-analysis of clinically diagnosed and self-reported hearing impairment on 723,266 individuals and identified 48 significant loci, 10 of which are novel. A large proportion of associations comprised missense variants, half of which lie within known familial hearing loss loci. We used single-cell RNA-sequencing data from mouse cochlea and brain and mapped common-variant genomic results to spindle, root, and basal cells from the stria vascularis, a structure in the cochlea necessary for normal hearing. Our findings indicate the importance of the stria vascularis in the mechanism of hearing impairment, providing future paths for developing targets for therapeutic intervention in hearing loss.

SARS-CoV-2 requires acidic pH to infect cells.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cell entry starts with membrane attachment and ends with spike (S) protein-catalyzed membrane fusion depending on two cleavage steps, namely, one usually by furin in producing cells and the second by TMPRSS2 on target cells. Endosomal cathepsins can carry out both. Using real-time three-dimensional single-virion tracking, we show that fusion and genome penetration require virion exposure to an acidic milieu of pH 6.2 to 6.8, even when furin and TMPRSS2 cleavages have occurred. We detect the sequential steps of S1-fragment dissociation, fusion, and content release from the cell surface in TMPRRS2-overexpressing cells only when exposed to acidic pH. We define a key role of an acidic environment for successful infection, found in endosomal compartments and at the surface of TMPRSS2-expressing cells in the acidic milieu of the nasal cavity.

Initial surgical management of sporadic medullary thyroid cancer: Guidelines based optimal care - A systematic review.

INTRODUCTION: Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor from parafollicular cells that produce calcitonin (Ct). Despite several existing guidelines for the surgical management of sporadic MTC (sMTC), optimal initial surgical management of the thyroid, the central and the lateral neck remains a matter of debate. METHODS: A systematic review in PubMed and Scopus for current guidelines addressing the surgical management of sMTC and its referenced citations was conducted as per the PRISMA guidelines. RESULTS: Two-hundred and one articles were identified, of which 7 met the inclusion criteria. Overall, guidelines vary significantly in their recommendations for the surgical management of sMTC. Only one guideline recommended partial thyroidectomy for limited disease, but the possibility to avoid completion thyroidectomy in selected cases is acknowledged in 42% (3/7) of the remaining guidelines. The majority of guidelines (71.4%; 5/7) recommended prophylactic central neck dissection (CND) for all patients while the remaining two guidelines recommended CND based on Ct level and tumor size. The role of prophylactic lateral neck dissection based on preoperative Ct levels was recommended by 42% (3/7) of guidelines. Overall, these guidelines are based on low-quality evidence, mostly single-center retrospective series, some of which are over 20 years old. CONCLUSION: Current surgical management guidelines of sMTC should be revised, and ought to be based on updated data challenging current recommendations, which are based on historic, low-quality evidence. Partial thyroidectomy may become a viable option for small, limited tumors. Prospective, multi-center studies may be useful to conclude whether prophylactic ND is necessary in all sMTC patients.

Psychosocial factors and patient and healthcare delays in large (class T3-T4) oral, oropharyngeal, and laryngeal carcinomas.

BACKGROUND: Psychosocial factors and socioeconomic status have been associated with incidence, survival, and quality of life among patients with head and neck cancer. We investigated the association between different psychosocial factors, socioeconomic status, and patient delays in T3-T4 oral, oropharyngeal, and laryngeal cancer. PATIENTS AND METHODS: We conducted a nationwide prospective questionnaire-based study (n = 203) over a 3-year period. RESULTS: We found no association between psychosocial factors (depression, social isolation, loneliness, and cynical hostility) and patient delay. Depression was three times more common among head and neck cancer patients compared with the general Finnish population. Head and neck cancer patients had lower educational levels and employment status, and were more often current smokers and heavy drinkers. CONCLUSIONS: Although we found no association between patient delay and psychosocial factors, patients diagnosed with a large head and neck cancer appeared to have a lower socioeconomic status and higher risk for developing depression, which should be considered in clinical practice.

The prognostic role of single cell invasion and nuclear diameter in early oral tongue squamous cell carcinoma.

BACKGROUND: The clinical significance of single cell invasion and large nuclear diameter is not well documented in early-stage oral tongue squamous cell carcinoma (OTSCC). METHODS: We used hematoxylin and eosin-stained sections to evaluate the presence of single cell invasion and large nuclei in a multicenter cohort of 311 cases treated for early-stage OTSCC. RESULTS: Single cell invasion was associated in multivariable analysis with poor disease-specific survival (DSS) with a hazard ratio (HR) of 2.089 (95% CI 1.224-3.566, P = 0.007), as well as with disease-free survival (DFS) with a HR of 1.666 (95% CI 1.080-2.571, P = 0.021). Furthermore, large nuclei were associated with worse DSS (HR 2.070, 95% CI 1.216-3.523, P = 0.007) and with DFS in multivariable analysis (HR 1.645, 95% CI 1.067-2.538, P = 0.024). CONCLUSION: Single cell invasion and large nuclei can be utilized for classifying early OTSCC into risk groups.

Endoscopic management of sinonasal tumours in the Nordic university hospitals: a survey.

PURPOSE: The Nordic countries (27 M) all have comparable, publicly funded healthcare systems, and the management of sinonasal tumours is centralised to the 21 university hospitals. We sought to assess and compare the treatment practice of sinonasal tumours across the Nordic countries. METHODS: A web-based questionnaire was sent to all university hospital departments of otorhinolaryngology-head and neck surgery in the Nordic countries. RESULTS: Answers were obtained from all 21 Nordic university hospitals. The endoscopic approach was widely utilised by all, with most (62%) centres reporting 3-4 surgeons performing endoscopic sinonasal tumour surgery. Finland reported the lowest rates of centralisation among university hospitals despite having the highest number of 0.1-1 M catchment population hospitals. Most centres (88%) opted for the endoscopic approach in a patient case warranting medial maxillectomy. In a case of a Kadish C esthesioneuroblastoma, most (52%) of the centres preferred an endoscopic approach. Most centres (62%) reported favouring the endoscopic approach in a case describing a juvenile angiofibroma. Regarding a case describing a sinonasal undifferentiated carcinoma, consensus was tied (38% vs. 38%) between endoscopic resection followed by postoperative (chemo)radiotherapy (RT/CRT) and induction chemotherapy followed by RT/CRT or surgery followed by RT/CRT. CONCLUSION: Endoscopic approach was widely utilised in the Nordic countries. The case-based replies showed differences in treatment practice, both internationally and nationally. The rate of centralisation among university hospitals remains relatively low, despite the rarity of these tumours.

Enhanced recovery after surgery (ERAS) protocol improves patient outcomes in free flap surgery for head and neck cancer.

BACKGROUND: In recent years, enhanced recovery after surgery (ERAS) guidelines have been developed to optimize pre-, intra-, and postoperative care of surgical oncology patients. The aim of this study was to compare management outcome of patients undergoing head and neck cancer (HNC) surgery with free flap reconstruction at our institution before and after the implementation of the ERAS guidelines. METHODS: This retrospective study comprised 283 patients undergoing HNC surgery with free flap reconstruction between 2013 and 2020. Patients operated before and after the implementation of the ERAS protocol in October 2017 formed the pre-ERAS group (n = 169), and ERAS group (n = 114), respectively. RESULTS: In the pre-ERAS group the mean length of stay (LOS) and intensive care unit length of the stay (ICU-LOS) were 20 days (range 7-79) and 6 days (range 1-32), and in the ERAS group 13 days (range 3-70) and 5 days (range 1-24), respectively. Both LOS (p < 0.001) and ICU-LOS (p = 0.042) were significantly reduced in the ERAS group compared to the pre-ERAS group. There were significantly fewer medical complications in the ERAS group (p < 0.003). No difference was found between the study groups in the surgical complication rate or in the 30-day or 6-month mortality rate after surgery. CONCLUSIONS: We found reduced LOS, ICU-LOS, and medical complication rate, but no effect on the surgical complication rate after implementation of the ERAS guidelines, which supports their use in major HNC surgery.

Occupational variation in incidence of oropharyngeal cancer in the Nordic countries.

PURPOSE: Evaluate the occupational variation in incidence of oropharyngeal cancer (OPC). METHODS: We calculated standardized incidence ratios (SIRs) of OPC in occupational categories in the Nordic countries relative to the entire national populations. The data covered 6155 OPC cases. RESULTS: Among men high risk of OPC was observed, among else, in waiters (SIR 6.28, 95% CI 4.68-8.26), beverage workers (SIR 3.00, 95% CI 1.72-4.88), and artistic workers (SIR 2.97, 95% CI 2.31-3.76). Among women high risk of OPC was observed in waiters (SIR 2.02, 95% CI 1.41-2.81) and packers (SIR 1.73, 95% CI 1.07-2.64). The lowest SIRs were observed in female gardeners (SIR 0.27, 95% CI 0.12-0.51) and male farmers (SIR 0.30, 95% CI 0.25-0.35). CONCLUSION: The 20-fold variation in incidence of OPC between occupations needs further investigation in studies with detailed information on occupational and non-occupational risk factors.

Presence of herpesviruses, parvoviruses, and polyomaviruses in sinonasal lymphoma.

PURPOSE: Sinonasal lymphoma (SL) is a rare lymphatic neoplasm of the nasal cavities, paranasal sinuses and nasopharynx. Whereas some risk factors for SL subtypes have been identified, their aetiology is unknown. Along with other predisposing factors, the viral association of lymphomas, such as Epstein-Barr virus (EBV) and Burkitt and Hodgkin lymphomas, is well-established. Modern molecular biology techniques have enabled the discovery of novel human viruses, exemplified by the protoparvovirus cutavirus (CuV), associated with cutaneous T-cell lymphoma. These findings, and the anatomical location of the sinonasal tract with its rich microbiome and infectious agents, justify in-depth studies among SL. METHODS: We analysed the presence of 20 viruses of Orthoherpesviridae, Parvoviridae, and Polyomaviridae by qPCR in 24 SL tumours. We performed RNAscope in situ hybridisation (RISH) to localize the viruses. Parvovirus-specific IgG was analysed by enzyme immunoassay and targeted next-generation sequencing (NGS) was applied to detect CuV in plasma. RESULTS: We detected viral DNA in 15/24 (63%) tumours; nine of EBV, six of human herpesvirus (HHV) -7, four each of HHV-6B and parvovirus B19, two of cytomegalovirus, and one each of CuV and Merkel-cell polyomavirus. We found tumours with up to four viruses per tumour, and localized CuV and EBV DNAs by RISH. Two of the ten plasma samples exhibited CuV IgG, and one plasma sample demonstrated CuV viremia by NGS. CONCLUSION: Viruses were frequent findings in SL. The EBV detection rate was high in diffuse large B-cell lymphoma, and co-detections with other viruses were prevalent.

Integration of 3D-printed middle ear models and middle ear prostheses in otosurgical training.

BACKGROUND: In otosurgical training, cadaveric temporal bones are primarily used to provide a realistic tactile experience. However, using cadaveric temporal bones is challenging due to their limited availability, high cost, and potential for infection. Utilizing current three-dimensional (3D) technologies could overcome the limitations associated with cadaveric bones. This study focused on how a 3D-printed middle ear model can be used in otosurgical training. METHODS: A cadaveric temporal bone was imaged using microcomputed tomography (micro-CT) to generate a 3D model of the middle ear. The final model was printed from transparent photopolymers using a laser-based 3D printer (vat photopolymerization), yielding a 3D-printed phantom of the external ear canal and middle ear. The feasibility of this phantom for otosurgical training was evaluated through an ossiculoplasty simulation involving ten otosurgeons and ten otolaryngology-head and neck surgery (ORL-HNS) residents. The participants were tasked with drilling, scooping, and placing a 3D-printed partial ossicular replacement prosthesis (PORP). Following the simulation, a questionnaire was used to collect the participants' opinions and feedback. RESULTS: A transparent photopolymer was deemed suitable for both the middle ear phantom and PORP. The printing procedure was precise, and the anatomical landmarks were recognizable. Based on the evaluations, the phantom had realistic maneuverability, although the haptic feedback during drilling and scooping received some criticism from ORL-HNS residents. Both otosurgeons and ORL-HNS residents were optimistic about the application of these 3D-printed models as training tools. CONCLUSIONS: The 3D-printed middle ear phantom and PORP used in this study can be used for low-threshold training in the future. The integration of 3D-printed models in conventional otosurgical training holds significant promise.

Occupation and tongue cancer in Nordic countries.

PURPOSE: Almost 200,000 tongue cancers were diagnosed worldwide in 2020. The aim of this study was to describe occupational risk variation in this malignancy. METHODS: The data are based on the Nordic Occupational Cancer (NOCCA) study containing 14.9 million people from the Nordic countries with 9020 tongue cancers diagnosed during 1961-2005. The standardized incidence ratio (SIR) of tongue cancer in each occupational category was calculated using national incidence rates as the reference. RESULTS: Among men, the incidence was statistically significantly elevated in waiters (SIR 4.36, 95% confidence interval (CI) 3.13--5.92), beverage workers (SIR 3.42, 95% CI 2.02-5.40), cooks and stewards (SIR 2.55, 95% CI 1.82-3.48), seamen (SIR 1.66, 95% CI 1.36-2.00), journalists (SIR 1.85, 95% CI 1.18-2.75), artistic workers (SIR 2.05, 95% CI 1.54-2.66), hairdressers (SIR 2.17, 95% CI 1.39-3.22), and economically inactive persons (SIR 1.57, 95% CI 1.42-1.73). Among women, the SIR was statistically significantly elevated only in waitresses (SIR 1.39, 95% CI 1.05-1.81). Statistically significant SIRs ≤ 0.63 were observed in male farmers, gardeners, forestry workers and teachers, and in female launderers. CONCLUSIONS: These findings may be related to consumption of alcohol and tobacco, but the effect of carcinogenic exposure from work cannot be excluded.

Herpesviruses, polyomaviruses, parvoviruses, papillomaviruses, and anelloviruses in vestibular schwannoma.

Etiology of vestibular schwannoma (VS) is unknown. Viruses can infect and reside in neural tissues for decades, and new viruses with unknown tumorigenic potential have been discovered. The presence of herpesvirus, polyomavirus, parvovirus, and anellovirus DNA was analyzed by quantitative PCR in 46 formalin-fixed paraffin-embedded VS samples. Five samples were analyzed by targeted next-generation sequencing. Viral DNA was detected altogether in 24/46 (52%) tumor samples, mostly representing anelloviruses (46%). Our findings show frequent persistence of anelloviruses, considered normal virome, in VS. None of the other viruses showed an extensive presence, thereby suggesting insignificant role in VS.

Significant risk of second primary cancer among laryngeal squamous cell carcinoma patients even after 20 years.

BACKGROUND: Evidence on the risk of second primary cancer (SPC) following primary laryngeal squamous cell carcinoma (LSCC) is limited, especially in Europe. METHODS: Patients diagnosed with primary LSCC from 1953-2018 were retrieved from the Finnish Cancer Registry. A total of 6241 LSCC patients were identified adding to 49,393 person-years (PY) of follow-up until the end of 2019. Only one patient emigrated and was lost to follow-up. Both standardized incidence ratios (SIR) and excess absolute risk (EAR) per 1000 person-years at risk (PYR) of second primary cancer (SPC) were calculated relative to the general population. Only non-laryngeal SPCs diagnosed six months after diagnosis of primary LSCC were included. RESULTS: A SPC was diagnosed in 1244 LSCC patients (20% of all LSCC patients) over the 65-year period, predominantly in men (92%, n = 1170). Out of all SPCs, 34% were diagnosed within 0.5 to 5 years and 66% after 5 years from primary LSCC. Among male patients, the overall SIR for SPC at any location was 1.61 (95% CI: 1.52-1.71), corresponding to 9.49 excess SPCs per 1000 PYR (95% CI: 8.19-11). The corresponding SIR for women was 1.47 (95% CI: 1.15-1.84), yielding 4.82 excess SPCs per 1000 PYR (95% CI: 2.36-9.84). The risk remained significant even after 20 years of follow-up (SIR for all 1.73, 95% CI: 1.49-2.01 and EAR 16.8 per 1000 PY, 11.88-23.75). The risk for SPC was also significantly elevated in all age groups, except <40. The highest SIRs were for SPCs arising in the mouth/pharynx (SIR for all 3.08, 95% CI: 2.36-3.95 and EAR 0.80 per 1000 PY, 0.55-1.15) and lungs (3.02, 2.75-3.30 and 5.90 per 1000, 5.13-6.78). CONCLUSION: Patients with LSCC as primary cancer have a 60% excess risk for an SPC, especially for tobacco-associated cancers, remaining significantly elevated even decades after treatment.

Although prior research on the risk of second primary cancer (SPC) among laryngeal squamous cell carcinoma (LSCC) patients has been conducted in other regions, the European perspective remains notably underrepresented. Moreover, studies on the subject focusing especially on LSCC are, even globally, only a few. The present study, with over 6000 LSCC patients followed-up over six decades, consists of the largest reported cohort of LSCC patients in Europe, and with the longest follow-up. Patients with LSCC as a primary cancer have a 60% excess risk for an SPC, which remains significantly elevated even 20 years after the diagnosis of the first primary cancer, especially for those with a tobacco/alcohol-related cancer. Healthcare professionals should be aware of the SPC risk among LSCC survivors who should be counseled about this phenomenon.

Incidence of head and neck cancer among first-generation immigrants and their children in Finland.

INTRODUCTION: Limited data exist regarding head and neck cancer (HNC) burden among immigrants who may have distinct characteristics, and hence different incidence rates from the general population. Variations in behavioral habits, cultural lifestyle, or diet may cause variations across different subgroups. METHODS: The whole immigrant population of Finnish residents born abroad, and their children were retrieved for the years 1970-2017. First-generation immigrants are defined as individuals born abroad, excluding their children (even if born abroad). The study comprised 0.5 million first-generation immigrants and 0.3 million children, contributing to 6 million and 5 million person-years of follow-up, respectively. Standardized incidence ratios (SIR) and excess absolute risk (EAR) per 100,000 person-years at risk were calculated to quantify the risk of HNC among immigrants relative to the general Finnish population. RESULTS: The overall risk of any HNC was not increased among first-generation male immigrants (SIR 1.00, 95% CI: 0.88-1.15), but significantly elevated for cancer of the pharynx (SIR 1.56, 95% CI: 1.22-1.95), and larynx (SIR 1.38, 95% CI: 1.02-1.83) and decreased for lip (SIR 0.38, 95% CI: 0.20-0.67). The increased risk of pharyngeal cancer was highest among male immigrants from Asia Pacific (SIR 4.21, 95% CI: 2.02-7.75). First-generation immigrant women had a significantly reduced risk of any HNC (SIR 0.45, 95% CI: 0.37-0.55), which remained even after stratification by site. We observed no increased risk of any HNC among the children of first-generation immigrants. CONCLUSION: Healthcare professionals need to recognize the groups at higher HNC risk. Efforts to address the main etiological risk factors, such as smoking, are needed among the selected immigrant populations, that haven't yet reached similar decreasing trends, as in for example smoking, as the main population.NOVELTY AND IMPACTCurrently, globally, over 280 million people live outside their country of birth. Limited data exist regarding head and neck cancer (HNC) burden among immigrants who may have distinct characteristics and hence different incidence rates from the general population. Immigrant studies can provide novel data by shedding light on risk alterations and the pace of acculturation of different populations.

Cancer incidence among visual artists: 45 years of follow-up in four Nordic countries.

INTRODUCTION: Professional visual artists constitute a heterogeneous vocational group, including, but not limited to painters, photographers, textile artists, and sculptors who may face exposure to workplace hazardous substances and lifestyle factors that may contribute to the development of selected cancers. The objective of this registry-based cohort study was to assess the cancer incidence among Nordic visual artists. MATERIALS AND METHODS: This study is based on data from the Nordic Occupational Cancer (NOCCA) project that combines census data of 15 million people from all Nordic countries and cancer registries from 1961 to 2005. For the present study we selected a cohort of visual artists from Finland, Iceland, Norway, and Sweden. Standardized incidence ratio (SIR) analyses were conducted with the cancer incidence rates for the entire national study populations used as reference rates. RESULTS: In male visual artists, there were statistically significant excesses in cancers of the tongue (SIR 2.91, 95% confidence interval 1.74-4.55), oral cavity (2.09, 1.26-3.27), pharynx (2.18, 1.45--3.15), testis (1.91, 1.11-3.05), renal pelvis (2.48, 1.42-4.03) and bladder (1.33, 1.14-1.55). The risk was significantly decreased for cancers of the lip (0.45, 0.18-0.93) and stomach (0.65, 0.50-0.84). In female visual artists, the only significantly increased risk was observed for breast cancer (1.29, 1.13-1.48) and the only significantly decreased risk for stomach cancer (0.43, 0.17-0.88). The incidence of lung cancer was close to the population average in both sexes. CONCLUSIONS: The non-elevated incidence of lung cancer suggests a similar prevalence of smoking between visual artists and the general population, while the elevated risk of cancers of mouth and pharynx among male visual artists is suggestive of more widespread alcohol drinking. The excess risk of urogenital cancers might be associated with exposure to solvents.

The exposure of visual artists to carcinogens remains unstudied and equivocal. The current study suggests that visual artists carry an overall cancer risk that is slightly above the risk among the general population of the four Nordic countries. We observed in men over two-fold excess risks of cancers of the tongue, oral cavity, pharynx, and renal pelvis, and also a significant risk of testis and bladder cancers.

Occupational variation in the incidence of lip cancer in the Nordic countries.

INTRODUCTION: While certain occupations, such as agriculture and fishery, have been associated with an increased risk of lip cancer, the occupational risk profile of lip cancer and its change over time remain poorly known. This study aims to evaluate the incidence of lip cancer across different occupations in the Nordic countries. METHODS: The Nordic Occupational Cancer Study (NOCCA) covers 14.9 million people and includes 45 years of cancer incidence data, from 1961 to 2005, linked to occupational categories for all the five Nordic populations. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were used to quantify the risk of lip cancer across occupational categories relative to the entire national populations. RESULTS: There were a total of 14,477 male and 3008 female lip cancer patients identified during follow up. The highest SIRs were observed among male fishermen (SIR 2.26, 95% CI: 2.04-2.50), gardeners (SIR 1.60, 95% CI: 1.48-1.72), and farmers (SIR 1.60, 95% CI: 1.55-1.66). A significantly reduced risk of lip cancer (SIR < 0.50) was observed among male physicians, teachers, religious workers, artistic workers, journalists, administrators, printers, waiters, and hairdressers. Among women, no occupations were associated with an increased risk of lip cancer. CONCLUSIONS: The incidence of lip cancer varies widely between outdoor and indoor occupations. Occupations involving outdoor activity and exposure to sunlight show the most elevated SIRs.

Certain outdoor occupations, such as agriculture and fishery, have been associated with an increased risk of lip cancer. However, the occupational risk profile of lip cancer and its change over time remain poorly known. This study highlights the excess risk of lip cancer among men with outdoor occupations and further corroborates previous studies. Efforts to counsel outdoor workers on the risk and prevention of lip cancer are needed to reduce the societal burden of the disease.

Current management of xerostomia in head and neck cancer patients.

Radiotherapy (RT) continues to play a key role in the management of head and neck cancer (HNC). Xerostomia remains a principal detriment to the quality of life (QoL) for 80 % of surviving patients receiving head and neck radiation. Radiation-induced injury to the salivary glands is dose-dependent, and thus efforts have been focused on decreasing radiation to the salivary glands. Decreased saliva production reduces both short-term and long-term quality of life in head and neck survivors by impacting on taste and contributing to dysphagia. Several radioprotective agents to the salivary gland have been investigated. Although not widely practiced, surgical transfer of the submandibular gland prior to RT is the mainstay of surgical options in preventing xerostomia. This review focuses on the strategies to improve xerostomia following radiation therapy in head and neck cancers.

Costs of oropharyngeal squamous cell cancer treatment in Finland.

BACKGROUND: Oropharyngeal squamous cell carcinoma (OPSCC) can be treated with definitive (chemo)radiotherapy ((C)RT) or primary surgical treatment (PST) with or without postoperative oncologic treatment. The prognosis of OPSCC does not essentially depend on the treatment modality, which allows to consider secondary decision-making aspects such as treatment costs when recommending an individual treatment modality. We attempted to analyze the costs associated with definitive (C)RT and PST in the treatment of OPSCC in Finland. MATERIALS AND METHODS: We included 73 patients diagnosed with OPSCC at the Helsinki University Hospital (HUS) (Helsinki, Finland) in 2019 and 2020. Treatment costs were defined as the costs incurred in the specialized medical care during the first 12 months after the diagnosis was established. RESULTS: Definitive RT and definitive CRT were on a 1-year horizon associated with median costs of approximately 10 700€ and 13 300€, respectively; while, the median costs of PST equaled about 40 600€. The costs of definitive (C)RT mostly consisted of the costs of (chemo)radiotherapy sessions; while, the operating room costs and the costs of intensive care and stay on a ward drove the costs of PST. CONCLUSIONS: PST is associated with 2-3 times higher median costs than definitive (C)RT in Finland. The finding differs from the results previously reported in North America, which is related, e.g., to differences in the treatment practices as well as in the regulation of the health care systems.

The risk of second primary cancer after nasopharyngeal cancer: a systematic review.

PURPOSE: Second primary cancers (SPCs) after nasopharyngeal cancer (NPC) are rare, but have an impact on the follow-up of this patient population. The aim of this study is to systematically review the literature to determine the prevalence and most typical sites of SPCs after NPC. METHODS: We searched the databases of PubMed, Web of Science, and Scopus for articles on SPCs after NPC. The Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines were followed. RESULTS: This review includes data on 89 168 patients with NPC from 21 articles. The mean occurrence for SPCs was 6.6% and varied from 4.9% in endemic areas to 8.7% in non-endemic areas. The most frequent locations of SPCs were oral cavity, pharynx, nose and paranasal sinuses, esophagus and lung. CONCLUSION: There is an increased risk for a SPC after NPC management, especially in non-endemic areas. However, their mean rate is lower than after other head and neck carcinomas.

Hypopharyngeal carcinoma in Finland from 2005 to 2014: outcome remains poor after major changes in treatment.

PURPOSE: Hypopharyngeal carcinoma (HPC) is typically diagnosed at late stages, the patients tend to have serious co-morbidities, distant relapses are frequent, and the related mortality remains high. The treatment paradigm of HPC has remarkably changed from primary surgical approach toward definitive, platinum-based concomitant chemoradiotherapy (CRT). Our aim was to analyze the HPC treatment approaches and outcome in a nationwide series and to make a comparison with a previously published corresponding nationwide patient cohort from the period 1990-1999. METHODS: We retrospectively reviewed all patients diagnosed with HPC at the five university hospitals in Finland between 2005 and 2014. RESULTS: The cohort comprised 231 patients. Treatment with curative intent was offered for 175 (76%) patients and consisted of definitive radiotherapy (RT) or CRT in 156 (89%) patients, while 20 (11%) patients had primary surgery with or without adjuvant RT or CRT. The 5-year estimates for overall survival (OS) and disease specific survival (DSS) for the whole study group were 22.7% and 36.5%, respectively. For patients treated with curative intent, the 5-year estimates for OS and DSS were 29.4% and 44.3%, respectively. CONCLUSIONS: The treatment approach of HPC in Finland has changed thoroughly, as in the 1990s, 63% of HPC patients with curative treatment intent underwent primary surgery with or without RT, while in the current study, the primary treatment approach was non-surgical in 89% of the patients. However, the survival figures have not changed and remain dismal, but most of the few surviving patients now can retain their larynx.