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The increasing incidence of oropharyngeal squamous cell carcinoma (OPSCC) is primarily due to human papillomavirus, and understanding the tumor biology caused by the virus is crucial. Our goal was to investigate the proteins present in the serum of patients with OPSCC, which were not previously studied in OPSCC tissue. We examined the difference in expression of these proteins between HPV-positive and -negative tumors and their correlation with clinicopathological parameters and patient survival. The study included 157 formalin-fixed, paraffin-embedded tissue samples and clinicopathological data. Based on the protein levels in the sera of OPSCC patients, we selected 12 proteins and studied their expression in HPV-negative and HPV-positive OPSCC cell lines. LRG1, SDR16C5, PIP4K2C and MVD proteins were selected for immunohistochemical analysis in HPV-positive and -negative OPSCC tissue samples. These protein´s expression levels were compared with clinicopathological parameters and patient survival to investigate their clinical relevance. LRG1 expression was strong in HPV-negative whereas SDR16C5 expression was strong in HPV-positive tumors. Correlation was observed between LRG1, SDR16C5, and PIP4K2C expression and patient survival. High expression of PIP4K2C was found to be an independent prognostic factor for overall survival and expression correlated with HPV-positive tumor status. The data suggest the possible role of LRG1, SDR16C5 and PIP4K2C in OPSCC biology. [ABSTRACT FROM AUTHOR]

Treatment of oral tongue squamous cell carcinoma (OTSCC) frequently includes surgery with postoperative radiotherapy (RT) or chemoradiotherapy (CRT). Resistance to RT or CRT remains a major clinical challenge and highlights the need to identify predictive markers for it. We included 71 OTSCC patients treated with surgery combined with RT or CRT. We evaluated the association between tumor budding, tumor–stroma ratio (TSR), depth of invasion (DOI), tumor‐infiltrating lymphocytes (TILs), hypoxia‐inducible factor‐1alpha (HIF‐1alpha) expression, octamer‐binding transcription factor 4 (OCT4) expression, high‐endothelial venules (HEVs), and disease‐free survival (DFS) using uni‐ and multivariate analyses. No significant association was observed between the different histological and molecular markers (TSR, DOI, TILs, HEV, HIF‐1alph, OCT4) and DFS. However, an associative trend between DOI, budding, and DFS was noted. Further studies with larger cohorts are needed to explore the prognostic value of DOI and budding for OTSCC patients treated with postoperative RT or CRT. [ABSTRACT FROM AUTHOR]

Background: The clinical significance of tertiary lymphoid structures (TLSs) is not well-documented in early oral tongue squamous cell carcinoma (OTSCC).Methods: A total of 310 cases of early (cT1-2N0) OTSCC were included in this multicenter study. Assessment of TLSs was conducted on hematoxylin and eosin-stained sections. TLSs were assessed both in the central part of the tumor and at the invasive front area.Results: The presence of TLSs associated with improved survival of early OTSCC as presented by Kaplan-Meier survival analyses for disease-specific survival (P = 0.01) and overall survival (P = 0.006). In multivariable analyses, which included conventional prognostic factors, the absence of TLSs associated with worse disease-specific survival with a hazard ratio (HR) of 1.96 (95% CI 1.09-3.54; P = 0.025) and poor overall survival (HR 1.66, 95% CI 1.11-2.48; P = 0.014).Conclusion: Histological evaluation of TLSs predicts survival in early OTSCC. TLSs showed superior prognostic power independent of routine WHO grading and TNM staging system. [ABSTRACT FROM AUTHOR]

Background: Insufficient preoperative work-up and consequent intralesional or marginal resection of soft-tissue sarcomas of the head and neck (STSHNs) is common. Methods: This retrospective cohort study comprised 63 patients with STSHN treated at the Helsinki University Hospital between 2005 and 2017. We assessed the effect of pretreatment tumor sampling on surgical margin status and need for supplemental surgery, as well as prognostic factors and survival. Results: The lack of representative pretreatment biopsy specimen was associated with unfavorable margin status. Primary surgery at a non-academic center was associated with need for supplemental surgery. The 3-year overall survival (OS) was 68%, disease-specific survival (DSS) 71%, and recurrence-free survival (RFS) 61%. Higher tumor grade and primary tumor size over 5 cm were associated with reduced DSS. Conclusions: Diagnosis and management of STSHNs should be centralized to experienced academic centers. Decision-making between needle biopsy, open biopsy, or upfront radical surgery depends on tumor location and size. [ABSTRACT FROM AUTHOR]

Although there are many histopathologic prognosticators, grading of early oral tongue squamous cell carcinoma (OTSCC) is still based on morphological cell differentiation which has low prognostic value. Here we summarize the emerging histopathological markers showing powerful prognostic value, but are not included in pathology reports. Using PubMed, Scopus, Ovid Medline, and Web of Science databases, a systematic literature search was preformed to identify early OTSCC studies that investigated the prognostic significance of hematoxylin–eosin‐based histopathologic markers. Our meta‐analysis showed that tumor budding was associated with overall survival (hazard ratio [HR] 2.32; 95% CI 1.40–3.84; p < 0.01) and disease‐specific survival (DSS) (1.89; 95% CI 1.13–3.15; p = 0.02). Worst pattern of invasion was associated with disease‐free survival (DFS) (1.95; 95% CI 1.04–3.64; p = 0.04). Tumor–stroma ratio was also associated with DFS (1.75, 95% CI 1.24–2.48; p < 0.01) and DSS (1.69; 95% CI 1.19–2.42; p < 0.01). Tumor budding, worst pattern of invasion, and tumor–stroma ratio have a promising prognostic value in early OTSCC. The evaluation and reporting of these markers is cost‐effective and can be incorporated in daily practice. [ABSTRACT FROM AUTHOR]

Background: The evaluation of immune response can aid in prediction of cancer behaviour. Here, we assessed the prognostic significance of tumour-infiltrating lymphocytes (TILs) in oropharyngeal squamous cell carcinoma (OPSCC).Methods: A total of 182 patients treated for OPSCC were included in this study. Assessment of TILs was conducted on tumour sections stained with standard haematoxylin and eosin (HE) staining. We used the scoring criteria proposed by the International Immuno-Oncology Biomarker Working Group.Results: The multivariable analysis showed that TILs associated with disease-specific survival with a hazard ratio (HR) of 2.13 (95% CI 1.14-3.96; P = 0.017). Similarly, TILs associated significantly with overall survival with HR of 1.87 (95% CI 1.11-3.13; P = 0.018). In a sub-analysis of HPV-positive and HPV-negative cases separately, TILs showed a significant prognostic value in both groups (P < 0.05).Conclusion: The evaluation of TILs as proposed by the International Immuno-Oncology Biomarker Working Group is a simple and promising method in prediction of survival of OPSCC. It is easily applicable and after further validation can be implemented in the routine pathological report as a basic immune parameter. [ABSTRACT FROM AUTHOR]

P‐cadherin (CDH3) is a cell‐to‐cell adhesion molecule that regulates several cellular homeostatic processes in normal tissues. Lack of CDH3 expression is associated with aggressive behavior in oral squamous cell carcinoma (OSCC). Previous studies have shown that CDH3 is downregulated in high‐grade OSCC and its reduced expression is predictive for poorer survival. The aim of this study was to evaluate the expression and prognostic relevance of CDH3 in tongue squamous cell carcinoma (TSCC). A retrospective series of 211 TSCC and 50 lymph node samples were stained immunohistochemically with polyclonal antibody (anti‐CDH3). CDH3 expression was assessed semi‐quantitatively with light microscopy. Fisher's exact test was used to compare patient and tumor characteristics, and the correlations were tested by Spearman correlation. Survival curves were drawn by the Kaplan–Meier method and analyzed by the log‐rank test. Univariate and multivariate Cox regression was used to estimate the association between CDH3 expression and survival. CDH3 expression did not affect TSCC patient's disease‐specific survival or overall survival. Strong CDH3 expression in the primary tumor predicted poor disease‐specific and overall survival in patients with recurrent disease. CDH3 expression in lymph nodes without metastasis was negative in all cases. CDH3 expression was positive in all lymph node metastases with extranodal extension. In contrast to previous report about the prognostic value of CDH3 in OSCC, we were not able to validate the result in TSCC. [ABSTRACT FROM AUTHOR]

Nonsurgical primary treatment of early and advanced laryngeal squamous cell carcinoma, employing radiotherapy with or without chemotherapy, is considered a standard of care in many centers throughout the world. When patients have persistent or recurrent disease after non-surgical treatment, salvage surgery is frequently the only remaining potentially curative treatment. Depending on the extent of the residual/recurrent disease, different surgical salvage options are at the surgeon's disposal. In selected cases with limited local disease, salvage transoral laser microsurgery, transoral robotic surgery and open partial laryngectomies can be employed to achieve cure while preserving laryngeal function. For more advanced cases total laryngectomy is necessary. Identifying situations with unacceptable results from surgical salvage may guide future therapies. [ABSTRACT FROM AUTHOR]

The key regulator of the polyamine biosynthetic pathway is ornithine decarboxylase (ODC). ODC is activated by antizyme inhibitor 1 (AZIN1) and 2 (AZIN2). AZIN1 and recently AZIN2 have been related to cancer; however, their functions in adenoid cystic carcinoma (ACC) have not been studied. We performed immunohistochemical study on minor salivary and mucous gland ACC tissue samples of patients treated at the Helsinki University Hospital (Helsinki, Finland) during 1974–2012. We scored AZIN1 and 2 immunoexpression in 42 and 45 tumor tissue samples, respectively, and correlated them with clinicopathological factors and survival. Enhanced AZIN2 expression was associated with better survival. In addition, both AZINs were seen more commonly in cribriform and tubular than in solid growth patterns. AZIN1 expression did not correlate with the studied clinicopathological factors. It seems that AZIN2 expression is higher in cancer tissue with secretory functions. In ACC tissue, high AZIN2 expression could be related to well‐differentiated histological type which still has a functioning vesicle transportation system. Thus, AZIN2 could be a prognostic factor for better survival of ACC patients. [ABSTRACT FROM AUTHOR]

Up to 85% of the patients with nasopharyngeal carcinoma present with regional nodal metastasis. Although excellent nodal control is achieved with radiotherapy, a thorough understanding of the current TNM staging criteria and pattern of nodal spread is essential to optimize target delineation and minimize unnecessary irradiation to adjacent normal tissue. Selective nodal irradiation with sparing of the lower neck and submandibular region according to individual nodal risk is now emerging as the preferred treatment option. There has also been continual refinement in staging classification by incorporating relevant adverse nodal features. As for the uncommon occurrence of recurrent nodal metastasis after radiotherapy, surgery remains the standard of care. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) forms a major health problem in many countries. For several decades the management of OSCC consisted of surgery with or without radiotherapy or chemoradiotherapy. Aiming to increase survival rate, recent research has underlined the significance of harnessing the immune response in treatment of many cancers. The promising finding of checkpoint inhibitors as a weapon for targeting metastatic melanoma was a key event in the development of immunotherapy. Furthermore, clinical trials have recently proven inhibitor of PD-1 for treatment of recurrent/metastatic head and neck cancer. However, some challenges (including patient selection) are presented in the era of immunotherapy. In this mini-review we discuss the emergence of immunotherapy for OSCC and the recently introduced biomarkers of this therapeutic strategy. Immune biomarkers and their prognostic perspectives for selecting patients who may benefit from immunotherapy are addressed. In addition, possible use of such biomarkers to assess the response to this new treatment modality of OSCC will also be discussed. [ABSTRACT FROM AUTHOR]

Background: The prognostic importance of intraparotid lymph node metastasis (P+) in patients with primary parotid gland carcinoma is unclear. Methods: Nineteen retrospective and noncomparative cohort studies, published between 1992 and 2020, met the inclusion criteria and included 2202 patients for this systematic review. Results: The pooled prevalence of the P in adult patients in the unselected studies was 24.10% (95% confidence interval = 17.95‐30.25). The number of P+ lymph nodes per patient was counted in only three studies and ranged from 1 to 11. The 5‐year recurrence‐free survival rate based on Kaplan‐Meier analysis varied from 83% to 88% in P− patients compared to 36% to 54% in P+ patients. The average hazard ratio for tumor recurrence in patients with P+ compared to P− was 2.67 ± 0.58. Conclusions: P+ is an independent negative prognostic factor in primary parotid gland cancer and should be included into the treatment planning. [ABSTRACT FROM AUTHOR]

Tumour budding has emerged as a promising prognostic marker in many cancers. We systematically reviewed all studies that evaluated tumour budding in diagnostic biopsies. We conducted a systematic review of PubMed, MEDLINE, Scopus, Web of Science and Cochrane library for all articles that have assessed tumour budding in diagnostic (i.e. pretreatment or pre‐operative) biopsies of any tumour type. Two independent researchers screened the retrieved studies, removed duplicates, excluded irrelevant studies and extracted data from the eligible studies. A total of 13 reports comprising 11 cohorts were found to have studied tumour budding in diagnostic biopsies. All these reports showed that evaluation of tumour budding in diagnostic biopsies was easily applicable. A strong association was observed between tumour budding score in diagnostic biopsies and corresponding surgical samples. Evaluation of tumour budding in diagnostic biopsies had a significant prognostic value for lymph node metastasis and patient survival. In all studies, tumour budding was a valuable marker of tumour aggressiveness and can be evaluated in technically satisfactory diagnostic biopsies. Thus, the assessment of tumour budding seems to identify the behaviour of cancer, and therefore to facilitate treatment planning. [ABSTRACT FROM AUTHOR]

Background: Laryngeal squamous cell carcinoma (LSCC) is rare in the young. Objectives: We characterized the clinical behavior of LSCC and assessed the presentation of second primary tumors (SPCs) in this patient population. Materials and methods: Data from the Finnish Cancer Registry (FCR) were used to identify an epidemiological series of LSCC patients diagnosed at the age of 40 years or under, during 1953-2012 in Finland. Data regarding primary treatment, survival, and SPCs were available. To further characterize the comorbidity and lifestyle factors of young patients with LSCC, institutional data were collected of patients treated at the Helsinki University Hospital during 1967-2012. Results: We identified 151 patients, with a mean follow-up of 252 months. The 10-year overall survival (OS) was 75% and the disease-specific survival was 84%. SPCs were diagnosed in 26% (n = 39), with a median delay of 28 years. Of the 35 patients in the institutional series from Helsinki, 22 (63%) were current or former smokers. LSCC recurred in 28% of patients. Conclusions and Significance: The delay to SPCs in young patients was significantly longer compared with the general LSCC population. As factors underlying this phenomenon cannot be identified by this retrospective study, further studies are warranted. [ABSTRACT FROM AUTHOR]

Background: Various detection methods to identify the primary in head and neck cancer of unknown primary (HN-CUP) require evaluation to improve and standardize management. Objectives: To evaluate the use of different diagnostic methods, which aim at decreasing the incidence of HN-CUP. Material and methods: We conducted a retrospective analysis of patients with HN-CUP at the Helsinki University Hospital during 1995-2011. We evaluated clinical assessment, definitive treatment, histopathology, and follow up. We analyzed the success in identifying the primary site to show any changes in diagnostic methods over time. Results: Frequency of HN-CUP and success in identifying the primary site have remained constant despite the addition of PET-CT and determination of human papilloma virus (HPV) status in diagnostics. Among 133 patients, the diagnostic work up identified the primary site in 53% and the oropharynx predominated (69%). This left 85 patients with HN-CUP and 5-year overall and disease-free survival rates were 71 and 69%, respectively. Conclusions: Panendoscopy including tonsillectomy should not be omitted in the work up. Significance: We demonstrate a steady frequency of HN-CUP and constant success in identifying the primary site. Detection of a primary later in the follow up did not impact the survival. [ABSTRACT FROM AUTHOR]

Aims: Oral tongue squamous cell carcinoma (OTSCC) has a relatively poor outcome, and there is a need to identify better prognostic factors. Recently, tumour–stroma ratio (TSR) has been associated with prognosis in several cancers. The aim of this multi‐institutional study was to evaluate the prognostic value of TSR from original haematoxylin and eosin (HE)‐stained tumour‐resection slides in a series of early‐stage (cT1‐2N0) OTSCC patients. Methods and results: A TSR cutoff value of 50% was used to divide the patients into stroma‐rich (≥50%) and stroma‐poor (<50%) groups. The relationships between TSR and clinicopathological characteristics of 311 early‐stage OTSCC cases were analysed. The prognostic value of TSR in OTSCC was calculated separately and in combination with a previously published cancer cell budding and depth of invasion (BD) prognostic model. A total of 89 cases (28.6%) belonged to the stroma‐rich group. In a multivariate analysis, the stroma‐rich group had worse disease‐free survival, with a hazard ratio (HR) of 1.81 [95% confidence interval (CI) 1.17–2.79, P = 0.008], and higher cancer‐related mortality (HR 1.71, 95% CI 1.02–2.86, P = 0.03). The combination of the highest‐risk parameter scores of TSR and the BD model showed significant correlations with recurrence rate (HR 3.42, 95% CI 1.71–6.82, P = 0.004) and cancer‐related mortality (HR 11.63, 95% CI 3.83–35.31, P < 0.001). Conclusions: We conclude that TSR is a simple histopathological feature that is useful for prognostication of early‐stage OTSCC, and suggest that TSR analyses in association with BD score could be included in routine clinical pathology reports for HE‐stained slides. [ABSTRACT FROM AUTHOR]

Background: Treatment for oropharyngeal squamous cell carcinoma (OPSCC) has changed, as the proportion of human papilloma virus (HPV)-related disease has increased. We evaluated nationwide information on its management and outcome during the treatment paradigm change period. Methods: We included all patients diagnosed and treated for OPSCC at the five Finnish university hospitals from 2000 to 2009. Patient records and pathology registries provided the clinicopathological data. p16 staining was performed on primary tumor samples of patients who had received treatment with curative intent. Results: A total of 674 patients were diagnosed and treated for OPSCC and the incidence increased along the study period. Of the evaluable tumors 58.5% were p16-positive and the number of p16-positive tumors increased along the years. The treatment was given with curative intent for 600 patients and it was completed in 564. Of them, 47.9% underwent primary surgery and 52.1% received definitive oncological treatment. Also, the treatment protocol changed towards a more oncological approach. Among patients treated with curative intent the five-year overall, disease-specific and disease-free survival rates were 60.1, 71.5 and 57.0%. In multivariate analysis, p16-positivity seemed to relate to reduced disease mortality in lateral and anterior-wall disease. Depending on primary tumor localization, also sex, classes T3-4, presence of regional metastasis and radiotherapy modality had an association with disease mortality. Conclusion: The incidence of p16-positive OPSCC and delivery of definitive oncological treatment increased in Finland during the study period. An improved survival outcome compared with the previous nationwide investigation was observed in this subset of patients. [ABSTRACT FROM AUTHOR]

The vast majority of head and neck cancers (HNCs) are sporadic squamous cell carcinomas, smoking and heavy drinking being the main risk factors. However, little is known about the possible role of family history and the importance of inherited factors versus shared environment. We used Swedish population-based registries to study the family history of HNC. In order to estimate the risk for family members to get the same cancer, and the risk for cancer-specific death in patients with a family history of HNC compared with patients without a family history, multivariate Cox proportional hazards analyses were performed. A 1.43-fold increased risk for developing HNC in the first-degree relatives (FDRs) of HNC patients [hazard ratio (HR), 1.43; 95% CI, 1.28-1.61] was found, when compared with relatives of healthy controls. In spouses of patients with HNC, the risk for developing any HNC was moderately increased (HR, 1.25; 95% CI, 1.01-1.53), compared with spouses of healthy controls. In addition, a 1.34-fold increased risk for death of HNC was found in HNC patients with a family history of HNC (HR, 1.34; 95% CI, (1.03-1.73) compared with HNC patients without a family history. We found an increased risk for HNC in relatives and spouses of HNC patients, when compared with family members of healthy controls. This suggests that in addition to inherited factors, shared environmental factors have a significant role in the development of the cancer. Family history of HNC was associated with worse survival in a newly diagnosed HNC patient. [ABSTRACT FROM AUTHOR]

Conclusions: One third of the patients had cachexia with an association of significantly shorter survival. These results suggest that combining HGS and MAMA seems to be a practical method to screen cachexia in patients with head and neck cancer and may also be used when assessing their prognosis. Objectives: The aim of this study was to analyze the hypothesis that cachexia defined as both low mid-arm muscle area (MAMA) and handgrip strength (HGS) is associated with decreased survival in patients with head and neck squamous cell carcinoma (HNSCC). Methods: Sixty-five consecutive patients with primary HNSCC were enrolled prior to cancer therapy. Cachexia was defined as low handgrip strength (HGS) and low mid-arm muscle area (MAMA). Nutritional status was assessed by patient-generated subjective global assessment (PG-SGA) and sarco-penia by low MAMA. Biochemical parameters reflecting nutritional status and S-25-OHD were measured. Results: Cachexia was seen in 31% and sarcopenia in 46% of patients. Altogether, 34% of patients were malnourished. Disease-free survival was 13 months (3-62) in cachectic patients, compared with 66 months (31-78) in non-cachectic patients (p - 0.009). S-25-OHD was 28 nmol/l in cachectic patients, compared with 46nmol/l in non-cachectic patients (p - 0.009) and prealbumin 187mg/l and 269mg/l, respectively (p < 0.001 ). [ABSTRACT FROM AUTHOR]

Background Up to 30% of patients with laryngeal squamous cell carcinoma (SCC) present with recurrence after treatment. We analyzed factors associated with the risk of cancer recurrence and prognosis after recurrence. Methods A nationwide laryngeal SCC cohort from Finnish university hospitals during 2001 to 2005 with initial successful therapy ( n = 316) was analyzed. Results Laryngeal SCC recurred in 22% of patients. The median time to recurrence was 9 months, with 90% occurring within 36 months after treatment. The World Health Organization (WHO) performance status >0, neck metastasis at presentation, and nonsurgical treatment were independent prognostic factors for recurrence. Patients with local recurrence had a 5-year overall survival (OS) of 53% compared with 5% in patients with regional/distant recurrences. OS for glottic and nonglottic laryngeal SCC recurrence was 45% and 0%, respectively. Conclusion The type of treatment affected the risk of recurrence in this retrospective series. Local recurrences carried a chance for successful salvage treatment. Routine follow-up beyond 36 months remains controversial. © 2016 Wiley Periodicals, Inc. Head Neck 39: 555-563, 2017 [ABSTRACT FROM AUTHOR]

Conclusions BMI-1 is an upstream repressor of tumor suppressor p16 and their inverse expression patterns have been linked with patient survival in OPSCC. In this material only p16 remained a relevant prognostic marker in OPSCC. Objectives HNSCC tumors carry variable phenotypes and clinical outcomes depending on their anatomical location. In OPSCC, expression of tumor suppressor p16 is used as a surrogate marker of HPV infection and has prognostic value. There are no good prognostic biomarkers for HNSCC tumors of other anatomical locations. Aim To study the expression patterns of p16 and BMI-1 in not only oropharyngeal but also oral, hypopharyngeal, and laryngeal squamous cell carcinomas and to clarify their putative connections with clinical parameters, survival, and each other. Method Hospital records on 130 patients (59 OPSCC, 18 OSCC, 20 HPSCC, and 33 LSCC) diagnosed between 1997–2008 at the Helsinki University Hospital, Finland, were reviewed. BMI-1 and p16 expressions were studied by immunohistochemistry. Results Sixty-eight per cent of OPSCC expressed p16 and expression correlated with lower age, lower T- and higher N-category, and with improved OS and DFS. BMI-1 expression was most prevalent in OPSCC and LSCC, but had no clinical correlations. No correlation between p16 and BMI-1 expression was found. [ABSTRACT FROM AUTHOR]

The purpose of this study was to acquire nationwide data on the management and outcome of laryngeal squamous cell carcinoma (SCC) in Finnish university hospitals over a 5-year posttreatment follow-up. Methods All records of patients diagnosed and treated for primary laryngeal SCC during 2001 to 2005 were reviewed. Results Three hundred sixty-six patients with laryngeal cancer were identified, 360 of whom had laryngeal SCC. Three hundred forty-two patients with laryngeal SCC (95%) were treated with curative intent. Five-year disease-specific survival (DSS) for T1a, T1b, T2, T3, and T4 glottic SCC was 100%, 95%, 78%, 79%, and 53%, respectively. The corresponding figures for T1 to T4 supraglottic SCC were 68%, 54%, 72%, and 59%. Conclusion Results of this nationwide study give a general overview of the outcome of unselected patients treated with unified guidelines. Patients with T2 tumors, usually treated with radiotherapy (RT), had a worse prognosis than expected. This patient group warrants further investigation and possibly treatment intensification. [ABSTRACT FROM AUTHOR]

Background Predicting the clinical course of early-stage oral tongue squamous cell carcinoma (SCC) is challenging. As matrix metalloproteinases (MMPs) are enzymes associated with invasion, metastasis, and poor survival in many cancers, we examined MMP-7 and MMP-25 in oral tongue SCC. Methods We used tissue microarray (TMA) technique and immunohistochemistry to study the expression of MMP-7 and MMP-25 in 73 patients with stage I to II oral tongue SCC and compared their immunoexpressions with clinical data. Results Immunohistochemistry revealed MMP-7 and MMP-25 expression in 90% ( n = 63 of 70) and 90% ( n = 64 of 71) of the tumors, respectively. MMP-7 protein expression was associated with presence of occult cervical metastases (odds ratio [OR], 3.67; p = .013), increased invasion depth (OR, 4.60; p = .005), and higher tumor grade (OR, 3.30; p = .007). MMP-7 expression was predictive for poor outcome ( p = .021). Immunostaining of MMP-25 did not correlate with any clinical parameters. Conclusion We conclude that MMP-7, but not MMP-25, expression may have prognostic significance in early-stage oral tongue SCC. © 2014 Wiley Periodicals, Inc. Head Neck 36: 1783-1788, 2014 [ABSTRACT FROM AUTHOR]

The original article can be found online at https://doi.org/10.1007/s00405-021-07162-0. Correction to: European Archives of Oto-Rhino-Laryngology https://doi.org/10.1007/s00405-021-... In the original publication of the article, affiliation 1 was published incorrectly and the correct affiliation 1 should read as below, Department of Otolaryngology, Head and Neck Surgery, University of Helsinki and HUS Helsinki University Hospital, Helsinki, Finland In addition, under funding section, the university name should read as "Helsinki University Hospital" instead "Helsinki University Central Hospital". [Extracted from the article]

Background Mucoepidermoid carcinoma ( MEC) is the most common salivary gland malignancy. Although several biomarkers have been evaluated, histological grade remains the most valuable prognostic marker. Toll-like receptor 9 ( TLR9) is an immune receptor recognizing microbial DNA. Its expression associates with prognosis or cancer properties in several cancers. This study examined the role of TLR9 in MEC. Methods Sixty patients with salivary gland MEC were collected from two Finnish university hospitals, and tumor samples were stained for TLR9. Salivary gland high-grade MEC cell line ( UT- MUC-1) was cultured to assess TLR9 and MMP-13 expression. The function of TLR9 was studied in vitro using traditional Matrigel® invasion assay and novel human myoma organotypic model. Results Cancer-specific survival was related with tumor grade ( P = 0.01), and there were no deaths in patients with low-grade MEC. TLR9 was expressed in 56 of 60 (93%) tumors. High TLR9 expression indicated better survival in the patient series ( P = 0.002) and showed a trend for association with lower disease stage ( P = 0.06) and higher differentiation grade ( P = 0.068). In multivariate analysis, TLR9 expression was prognostically insignificant due to heavy correlation to disease stage and higher gradus. Treating UT- MUC-1 cells with TLR9 ligand CpG in vitro induced MMP-13 expression and invasion in Matrigel® invasion assay, whereas decreased invasion was seen in myoma organotypic model. Conclusion Functional TLR9 is present in salivary MEC, and high level of expression may indicate good prognosis. However, more studies are needed to evaluate biological consequences of TLR9 interaction in tumor cells. [ABSTRACT FROM AUTHOR]

Conclusion: Transforming growth factor β1 gene ( TGFβ1) genotype is a potential p16 independent prognostic factor predicting response to chemoradiotherapy in head and neck squamous cell carcinoma (HNSCC). Objectives: Expression of p16 and epidermal growth factor receptor (EGFR) has been reported to be associated with survival in HNSCC. We have previously reported that genetic polymorphism of TGFβ1 is linked with survival in HNSCC patients who have undergone chemoradiotherapy. We evaluate here whether TGFB1 genotype can serve as a prognostic factor independent of tumor p16 and EGFR expression. Methods: Expression of p16 and EGFR was studied by immunohistochemistry in tumors from 130 HNSCC patients. Peripheral blood DNA was used to genotype 95 patients for single nucleotide polymorphism rs1800470 within the TGFβ1 gene. The minimum follow-up time was 31 months. Results: p16 overexpression was associated with an improved disease-free survival (hazard ratio (HR) = 0.39, 95% CI 0.19-0.78), whereas no evident association was observed between EGFR expression and disease-free survival (HR = 0.90, 95% CI 0.68-1.19). Among the 37 patients who had received chemoradiotherapy, TGFβ1 genotype was associated with disease-free (HR = 0.44, 95% CI 0.19-1.02) and overall survival (HR = 0.31, 95% CI 0.12-0.80) independent of tumor p16 expression. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: The first International Union Against Cancer (UICC) TNM classification for aerodigestive malignant mucosal melanoma was not published until 2009, and since then, only a few studies have evaluated the accuracy of this staging system. Our aim was to evaluate the accuracy of this UICC staging system for sinonasal malignant mucosal melanoma (SMMM) in a nationwide survey. Study Design: Retrospective, population-based, multicenter study. Methods: The hospital surgical and discharge registries were used to identify the patients. A database including demographic and clinicopathologic variable was created. Results: Altogether, 50 SMMM patients diagnosed in Finland from 1990 to 2004 were evaluated. Three- and 5-year overall survival rates were 44% and 27%, respectively. Significant differences in overall survival according to T classification ( P = .028, log rank) and stage ( P = .02, log rank) were found. Tumor extension to the sphenoid sinus had a significant negative impact on survival (n = 11, P = .03, log rank). Conclusions: The current UICC staging system for mucosal melanoma provides a useful format for staging SMMMs in clinical settings. Laryngoscope, 2012 [ABSTRACT FROM AUTHOR]

J Oral Pathol Med (2012) 41: 394-399 Background: Oral tongue squamous cell carcinoma (OTSCC) often metastasizes to cervical lymph nodes. Mechanisms of this disease progression are not fully known. We aimed at finding new predictive markers for diagnosis and disease monitoring. Methods: Seventy-three consecutive T1N0M0 and T2N0M0 OTSCC patients treated at Helsinki University Central Hospital, Helsinki, Finland, in 1992-2002 were included. Tissue array blocks were prepared from primary tumors and immunostained. Immunoexpression of matrix metalloproteinase (MMP)-2, -8, -9, and -13 was compared with patient characteristics and outcome. Results: Nuclear expression of MMP-13, but not cytoplasmic expression of MMP-2, -8, and -9, was associated with invasion depth ( P = 0.017) and tumor size ( P = 0.008). Furthermore, high nuclear MMP-13 expression was predictive of poor outcome ( P = 0.042). Conclusion: Our results suggest that especially MMP-13 may be regarded as a prognostic biomarker in OTSCC. [ABSTRACT FROM AUTHOR]

Background. Fast and accurate work-up is crucial to ensure the best possible treatment and prognosis for patients with head and neck cancer. The presence or absence of neck lymph node metastases is important for the prognosis and the choice of treatment. Clinical lymph node (N)-staging is done by palpation and diagnostic imaging of the neck. We investigated the current practice of the initial radiological work-up of patients with oral squamous cell carcinomas (OSCC) in the Nordic countries. Methods. A questionnaire regarding the availability and use of guidelines and imaging modalities for radiological N-staging in OSCC was distributed to 21 Head and Neck centres in Denmark (n == 4), Finland (n == 5), Iceland (n == 1), Norway (n == 4) and Sweden (n == 7). We also asked for a description of the radiological criteria for determining the lymph nodes as clinical positive (cN++) or negative (cN0). Results. All 21 Head and Neck centres responded to the questionnaire. Denmark and Finland have national guidelines, while Norway and Sweden have local or regional guidelines. Seventeen of the 19 centres with available guidelines recommended computed tomography (CT) of the cN0 neck. The waiting time may influence the imaging modalities used. Lymph node size was the most commonly used criteria for radiological cN++, but the cut-off measures vary from 0.8 to 2.0 cm. Conclusion. Overall, CT is the most commonly recommended and used imaging modality for OSCC. Despite availability of national guidelines the type and number of radiological examinations vary between centres within a country, but the implementation of a fast-track programme may facilitate fast access to imaging. The absence of uniform criteria for determining the lymph nodes of the neck as cN++ complicates the comparison of the accuracy of the imaging modalities. Well-defined radiological strategies and criteria are needed to optimise the radiological work-up in OSCC. [ABSTRACT FROM AUTHOR]

Sinonasal cancer is still a somewhat controversial entity because most series are single-center studies. The aim of this study was to give more accurate and generalisable information about treatment of the neck and prognosis of sinonasal cancer. Retrospective, population-based, multicentre study. Altogether 244 patients diagnosed in 1990-2004 were evaluated. The 3- and 5-year disease-specific survival (DSS) rates after treatment with curative intent were 68 and 57%, respectively. Regional status at the time of the diagnosis ( P < 0.001, log rank) and local recurrence ( P = 0.02, log rank) during the follow-up had a statistically significant effect on DSS. Initially 13% of the patients were diagnosed with neck metastasis. The proportion of regional recurrences during the follow-up was 9%, but it did not have a statistically significant impact on DSS ( P = 0.68, log rank). Histopathology had no statistically significant impact on survival in this material of 244 patients. In conclusion, routine elective neck treatment of all sinonasal cancer patients is not recommended, but the importance of the treatment of the primary location is emphasised. [ABSTRACT FROM AUTHOR]

The diagnosis is the art of determining the nature of a disease, and an accurate diagnosis is the true cornerstone on which rational treatment should be built. Within the workflow in the management of head and neck tumours, there are different types of diagnosis. The purpose of this work is to point out the differences and the aims of the different types of diagnoses and to highlight their importance in the management of patients with head and neck tumours. Qualitative diagnosis is performed by a pathologist and is essential in determining the management and can provide guidance on prognosis. The evolution of immunohistochemistry and molecular biology techniques has made it possible to obtain more precise diagnoses and to identify prognostic markers and precision factors. Quantitative diagnosis is made by the radiologist and consists of identifying a mass lesion and the estimation of the tumour volume and extent using imaging techniques, such as CT, MRI, and PET. The distinction between the two types of diagnosis is clear, as the methodology is different. The accurate establishment of both diagnoses plays an essential role in treatment planning. Getting the right diagnosis is a key aspect of health care, and it provides an explanation of a patient's health problem and informs subsequent decision. Deep learning and radiomics approaches hold promise for improving diagnosis. [ABSTRACT FROM AUTHOR]

Knowledge on the role of matrix metalloproteinases (MMPs) in adenoid cystic carcinoma (ACC) is limited. MMPs are capable of degrading almost all extracellular and pericellular components to promote invasion and metastasis. This study aimed to evaluate the immunohistochemical expression of MMP-7, -8, -9, -15, and -25 in ACC and to relate the results with clinicopathological factors and survival. The study included 68 patients with minor salivary gland ACC treated at the Helsinki University Hospital (Helsinki, Finland) in 1974–2012. Samples from 52 patients were available, consisting of 44 primary tumours and eight recurrent tumours. We scored immunostaining of MMP-7, -8, -9, -15, and -25 and analysed the immunoscore against clinical and pathological parameters using statistical correlation test. MMP-9 immunoexpression in pseudocysts of ACC and in peritumoural inflammatory cells associated with better survival and fewer treatment failures. High tumoural MMP-7 and -25 associated with better survival. High tumoural MMP-15 associated with poorer survival and high tumoural MMP-9 with advanced stage and regional recurrences. Tumour cells did not show MMP-8 immunopositivity. These results suggest that MMP-9 may contribute to ACC carcinogenesis in different roles. MMP-7, -8, and -9 can stimulate signalling pathways that may promote tissue modulation and metastatic potential. MMP-15 and -25 may reflect prognosis. [ABSTRACT FROM AUTHOR]

Background: Cell-in-cell structures (caused by cell cannibalistic activity) have been related to prognosis of many cancers. This is the first multi-institutional study to assess the prognostic impact of cell-in-cell structures in a large cohort of early oral tongue squamous cell carcinomas (OTSCC).Methods: A total of 308 cases from five Finnish University Hospitals and from the A.C. Camargo Cancer Center, São Paulo, Brazil, were included in this study. Cell-in-cell structures were evaluated on surgical postoperative sections that stained with hematoxylin and eosin staining.Results: We found that cell-in-cell structures associated with cancer-related mortality in univariable analysis with a hazard ratio (HR) of 2.99 (95%CI 1.52-5.88; P = 0.001). This association was confirmed in multivariable analysis (HR 2.22, 95%CI 1.12-4.44; P = 0.024). In addition, statistically significant associations were observed between the cell-in-cell structures and other adverse histopathologic characteristics including deep invasion (P <  0.001), high index of tumor budding (P = 0.007), worst pattern of invasion (P <  0.001), perineural invasion (P = 0.01), and stroma-rich pattern (P = 0.001).Conclusions: Our findings demonstrate a significant relationship between cell-in-cell formation and aggressive characteristics of early OTSCC. Cell-in-cell structures have a distinct impact as a novel prognostic indicator in early OTSCC and they can be easily assessed during routine pathology practice. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) is a common malignancy of the head and neck region. OSCC has a relatively low survival rate and the incidence of the disease is increasing in some geographic areas. Staging and grading of OSCC are established prerequisites for management, as they influence risk stratification and are the first step toward personalized treatment. The current AJCC/UICC TNM staging (8th edition, 2017) of OSCC has included significant modifications through the incorporation of depth of invasion in the T stage and extracapsular spread/extranodal extension in the N stage. Further modifications for AJCC 8 have been suggested. On the other hand, the World Health Organization (WHO) classification (4th edition, 2017) still endorses a simple, differentiation-based histopathologic grading system of OSCC (despite its low prognostic value) and ignores factors such as tumor growth pattern and dissociation, stromal reactions (desmoplasia, local immune response), and tumor-stroma ratio. The various controversies and possible developments of the current staging and grading criteria of OSCC are briefly discussed in this update together with possible applications of artificial intelligence in the context of screening and risk stratification. [ABSTRACT FROM AUTHOR]