Publications by authors named "Timo Atula"

60 Publications

Additive Manufacturing of Resected Oral and Oropharyngeal Tissue: A Pilot Study.

Int J Environ Res Public Health 2021 Jan 21;18(3). Epub 2021 Jan 21.

Department of Otorhinolaryngology-Head and Neck Surgery, HUS Helsinki University Hospital, University of Helsinki, P.O.Box 263, FI-00029 HUS Helsinki, Finland.

Better visualization of tumor structure and orientation are needed in the postoperative setting. We aimed to assess the feasibility of a system in which oral and oropharyngeal tumors are resected, photographed, 3D modeled, and printed using additive manufacturing techniques. Three patients diagnosed with oral/oropharyngeal cancer were included. All patients underwent preoperative magnetic resonance imaging followed by resection. In the operating room (OR), the resected tissue block was photographed using a smartphone. Digital photos were imported into Agisoft Photoscan to produce a digital 3D model of the resected tissue. Physical models were then printed using binder jetting techniques. The aforementioned process was applied in pilot cases including carcinomas of the tongue and larynx. The number of photographs taken for each case ranged from 63 to 195. The printing time for the physical models ranged from 2 to 9 h, costs ranging from 25 to 141 EUR (28 to 161 USD). Digital photography may be used to additively manufacture models of resected oral/oropharyngeal tumors in an easy, accessible and efficient fashion. The model may be used in interdisciplinary discussion regarding postoperative care to improve understanding and collaboration, but further investigation in prospective studies is required.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijerph18030911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7908081PMC
January 2021

Three-Dimensional Presentation of Tumor Histopathology: A Model Using Tongue Squamous Cell Carcinoma.

Diagnostics (Basel) 2021 Jan 12;11(1). Epub 2021 Jan 12.

Department of Otorhinolaryngology-Head and Neck Surgery, Helsinki University Hospital and University of Helsinki, 00029 HUS Helsinki, Finland.

Medical imaging often presents objects in three-dimensional (3D) form to provide better visual understanding. In contrast, histopathology is typically presented as two-dimensional (2D). Our objective was to present the tumor dimensions in 3D by creating a 3D digital model of it and so demonstrate the location of the tumor and the histological slices within the surgical soft tissue resection specimen. We developed a novel method for modeling a tongue squamous cell carcinoma using commonly available instruments. We established our 3D-modeling method by recognizing and solving challenges that concern the selection of the direction of histological slices. Additional steps to standard handling included scanning the specimen prior to grossing and modeling the carcinoma, which required only a table scanner and modeling software. We present challenges and their solutions in modeling the resection specimen and its histological slices. We introduce a finished 3D model of a soft tissue resection specimen and the actual tumor as well as its histopathological grossing sites in 3D digital and printed form. Our novel method provides steps to create a digital model of soft tissue resection specimen and the tumor within. To our knowledge, this is the first attempt to present histopathological margins of a tongue tumor in 3D form, whereas previously, only 2D has been available. The creation of the 3D model does not call for predetermined grossing directions for the pathologist. In addition, it provides a crucial initiative to enhance oncological management. The method allows a better visual understanding of tumor margins, topography, and orientation. It thus provides a tool for an improved postoperative assessment and aids, for example, in the discussion of the need for additional surgery and adjuvant therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/diagnostics11010109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827352PMC
January 2021

Preoperative evaluation and treatment consideration of parotid gland tumors.

Laryngoscope Investig Otolaryngol 2020 Aug 20;5(4):694-702. Epub 2020 Jul 20.

Department of Otorhinolaryngology-Head and Neck Surgery University of Helsinki and Helsinki University Hospital Helsinki Finland.

Background: The nature of parotid tumors often remains unknown preoperatively and final histopathology may reveal unexpected malignancy. Still, the use of fine-needle aspiration cytology (FNAC) and imaging varies in the management of these tumors.

Methods: We evaluated the preoperative examinations and management of all 195 parotid gland tumors diagnosed within our catchment area of 1.6 million people during 2015.

Results: Altogether 171 (88%) tumors were classified as true salivary gland neoplasms. FNAC showed no false malignant findings, but it was false benign in 5 (2.6%) cases. Preoperative MRI was utilized in 48 patients (25%). Twenty (10%) malignancies included 16 salivary gland carcinomas. Pleomorphic adenomas accounted for 52% of all adenomas. For 24 (40%) Warthin tumors, surgery was omitted.

Conclusion: The proportion of malignancies was lower than generally presented. Our proposed guidelines include ultrasound-guided FNAC with certain limitations. MRI is warranted in selected cases, but seems unnecessary routinely.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lio2.433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444776PMC
August 2020

Expression and Role of E-Cadherin, β-Catenin, and Vimentin in Human Papillomavirus-Positive and Human Papillomavirus-Negative Oropharyngeal Squamous Cell Carcinoma.

J Histochem Cytochem 2020 09 14;68(9):595-606. Epub 2020 Aug 14.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Oropharyngeal squamous cell carcinoma (OPSCC) is subclassified by the World Health Organization into two different entities: human papillomavirus (HPV)-positive and HPV-negative tumors. HPV infection promotes the epithelial-to-mesenchymal transition (EMT) and transformation of keratinocyte stem cells into cancer stem cells. EMT is a crucial process in the carcinogenesis of epithelial-derived malignancies, and we aimed to study the role of its markers in OPSCC. This study consists of 202 consecutive OPSCC patients diagnosed and treated with curative intent. We examined E-cadherin, β-catenin, and vimentin expression using immunohistochemistry and compared these with tumor and patient characteristics and treatment outcome. We found that the cell-membranous expression of β-catenin was stronger in HPV-positive than in HPV-negative tumors, and it was stronger in the presence of regional metastasis. The stromal vimentin expression was stronger among HPV-positive tumors. A high E-cadherin expression was associated with tumor grade. No relationship between these markers and survival emerged. In conclusion, β-catenin and vimentin seem to play different roles in OPSCC: the former in the tumor tissue itself, and the latter in the tumor stroma. HPV infection may exploit the β-catenin and vimentin pathways in carcinogenic process. More, β-catenin may serve as a marker for the occurrence of regional metastasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1369/0022155420950841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469711PMC
September 2020

Challenges in diagnosing head and neck cancer in primary health care.

Ann Med 2021 12 5;53(1):26-33. Epub 2020 Aug 5.

Department of Otorhinolaryngology - Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Background: Early diagnosis of head and neck cancer (HNC) will improve patient outcomes. The low incidence of HNC renders its detection challenging for a general practitioner (GP) in primary health care (PHC).

Patients And Methods: To examine these challenges, our cohort consisted of all patients visiting PHC centres in the City of Helsinki in 2016. We chose 57 ICD-10 codes representing a sign or symptom resulting from a possible HNC and compared data for all new HNC patients.

Results: A total of 242,211 patients (499,542 appointments) visited PHC centres, 11,896 (5%) of whom presented with a sign or symptom possibly caused by HNC. Altogether, 111 new HNCs were diagnosed within the Helsinki area, of which 40 (36%) were referred from PHC. The median delay from the initial PHC visit to the referral to specialist care was 5 days, whereby 88% of patients were referred within one month.

Conclusions: Despite the low incidence of HNC and the large number of patients presenting with HNC-related symptoms, GPs working in PHC sort out potential HNC patients from the general patient group in most cases remarkably effectively. KEY MESSAGES For every head and neck cancer (HNC) patient encountered in the primary health care, a general practitioner (GP) will meet approximately 6000 other patients, 100 of whom exhibit a sign or a symptom potentially caused by a HNC. Despite the low incidence of HNC, GPs referred patients to specialist care effectively, limiting the median delay from the initial appointment to referral to only 5 days.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/07853890.2020.1802060DOI Listing
December 2021

In HPV-negative oropharyngeal squamous cell carcinoma, elevated toll-like receptor 2 immunoexpression may increase the risk of disease-specific mortality.

Oral Oncol 2020 08 11;107:104778. Epub 2020 May 11.

Department of Pathology, University of Helsinki, HUSLAB and Helsinki University Hospital, P.O. Box 21, 00014 Helsinki, Finland; Research Programs Unit, Translational Cancer Medicine, University of Helsinki, P.O. Box 63, 00014 Helsinki, Finland; Department of Oral Pathology and Radiology, Institute of Dentistry, Faculty of Medicine, University of Turku, Turku, Finland.

Objectives: In oropharyngeal squamous cell carcinoma (OPSCC), toll-like receptors (TLR) 5 and 7 associate with the tumor's human papilloma virus (HPV) status (Jouhi et al., 2017). TLR 2, on the other hand, has been linked to head and neck squamous cell carcinoma (HNSCC), and to oral carcinogenesis (Farnebo et al., 2015; Binder Gallimidi et al., 2015). Here we investigated the presence of TLR 2 and 4 in HPV-positive and HPV-negative OPSCC, and their relationship to opportunistic oral pathogen Treponema denticola chymotrypsin-like protease (Td-CTLP) immunoexpression, clinical parameters, and patient outcome.

Materials And Methods: Clinicopathological data of 198 unselected consecutive OPSCC patients came from hospital registries. Immunoexpression of TLRs 2 and 4 we evaluated by immunohistochemistry, and earlier in this patient series we studied immunoexpression of Td-CTLP and HPV DNA, HPV mRNA, and p16 status.

Results: Immunoexpression of both TLRs 2 and 4 showed a significant association with HPV-status. Strong expression was associated with HPV-positivity and mild expression with HPV-negativity. Patients with strong TLR 2 immunoexpression in the HPV negative subgroup had significantly poorer 5-year DSS (58%) than did patients with mild TLR 2 expression (77%), and strong TLR 2 immunoexpression remained as an independent factor linked to increased disease mortality in the multivariable setting (P = 0.019). No association existed between TLR 2 or 4 and Td-CTLP expression.

Conclusion: Our results support the role of TLR 2 receptor as a possible target for development of therapeutics as earlier proposed (Farnebo et al., 2015). The involvement of Td and other oral pathogens in carcinogenesis of OPSCC, remains open and calls for further study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.oraloncology.2020.104778DOI Listing
August 2020

Factors influencing patient and health care delays in Oropharyngeal Cancer.

J Otolaryngol Head Neck Surg 2020 Apr 23;49(1):22. Epub 2020 Apr 23.

Department of Otorhinolaryngology - Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, PO Box 263, FI-00029 HUS, Helsinki, Finland.

Background: The incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is increasing. Patients with HPV-associated and HPV-unassociated OPSCC differ in many aspects, which may also impact their diagnostic and management timelines. This study aims at studying the patient, primary health care (PHC) and specialist-care (SC) delays and possible differences between these two patient groups in seeking medical care.

Methods: We reviewed all new patients with OPSCC treated between 2016 and 2018 at our institute, which covers a referral area of 1.6 million people. We collected data on patients' symptoms and factors influencing why they sought medical care using a patient-reported questionnaire and hospital records. We compared delays based on patient and tumor characteristics.

Results: In our study population of 83 patients, the median patient delay was 30 days (range, 0-366), with a median PHC delay of 15 days (range, 0 days-2.5 years), and a median SC delay of 54 days (range, 12-231). The SC delay was further divided into diagnostic hospital delay and treatment delay, each with a median length of 16 days (range, 0-237) and 29 days (range, 0-73), respectively. Furthermore, we found that p16 status did not associate with delays. A longer patient delay associated with specific tumor factors, such as a larger primary tumor and a lower UICC 7th edition stage. Patients that had multiple visits or did not have a follow-up visit scheduled at the initial appointment had longer PHC delays. Treatment delay was significantly longer for patients scheduled for (chemo-)radiotherapy than for those undergoing surgery with or without (chemo-)radiotherapy.

Conclusions: Although delays remained short for the majority of OPSCC patients, long delays require further evaluation and improvement of management. Awareness of presenting symptoms among cancer risk patients and prompt referral practice or a follow-up visit at PHC represent key factors to shortening these delays. Ultimately, the causes for delays in SC appear multifactorial and require institutional quality control.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40463-020-00413-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181590PMC
April 2020

Sclerosing sialadenitis of the submandibular gland is rarely an immunoglobulin G4-related disease in the Finnish population.

Mod Pathol 2020 04 3;33(4):551-559. Epub 2019 Nov 3.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, PO Box 263, FI-00029, Helsinki, Finland.

Chronic sclerosing sialadenitis may represent one of many manifestations of an immunoglobulin G4-related disease. However, existing studies typically consist of small patient cohorts rarely conducted in Western populations. The clinical behavior of chronic sclerosing sialadenitis, including follow-up data, warrants further study. Thus, we aimed to determine whether chronic sclerosing sialadenitis always presents as IgG4-related disease or associates with autoimmune diseases and to determine which additional examinations patients may require. Between 2000 and 2017, 51 patients undergoing submandibular gland resection within the Helsinki University Hospital area were diagnosed with chronic sclerosing sialadenitis. We re-evaluated all specimens and performed immunostaining for IgG4. IgG and CD31 stainings were performed for IgG4-positive specimens. IgG4-related disease diagnosis was defined by the Boston consensus statement criteria. We revised clinical data, distributing a follow-up questionnaire to patients to register symptoms of IgG4-related disease or autoimmune disease during follow-up. The chronic sclerosing sialadenitis criteria were fulfilled in 34 patients, whereby 17 were diagnosed as non-sclerosing chronic sialadenitis. In 19 cases, a sialolith associated with a salivary gland lesion. In total, 12 of 51 cases were recognized as IgG4-positive, while two met the criteria for IgG4-related disease. These two cases belonged to the non-sclerosing chronic sialadenitis group, and both involved other organs. The histopathological features between chronic sclerosing sialadenitis and non-sclerosing chronic sialadenitis overlapped regarding the degree of fibrosis and inflammatory infiltrates. In the Finnish population, chronic sclerosing sialadenitis of the submandibular gland does not appear to present as IgG4-related disease. Non-sclerosing chronic sialadenitis can associate with IgG4-related disease. A histopathological distinction between chronic sclerosing sialadenitis and non-sclerosing chronic sialadenitis is not always unequivocal and the presence of a sialolith does not exclude IgG4-positivity. Therefore, immunostaining for IgG4 should be performed when dense plasma cell infiltration is present in either non-sclerosing chronic sialadenitis or chronic sclerosing sialadenitis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41379-019-0395-5DOI Listing
April 2020

Reply to "Do not de-escalate oncology care in oropharyngeal cancer routinely".

Head Neck 2020 01 12;42(1):145-146. Epub 2019 Sep 12.

Department of Otorhinolaryngology - Head and Neck Surgery, Helsinki University Hospital, Helsinki, Finland.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hed.25959DOI Listing
January 2020

Total laryngopharyngectomy with circumferential reconstruction: Helsinki institutional study.

Eur Arch Otorhinolaryngol 2019 Sep 25;276(9):2577-2584. Epub 2019 Jun 25.

Department of Otorhinolaryngology, Head and Neck Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Purpose: Surgical complications after total laryngopharyngectomy (TLP) are common, reconstruction is challenging, and patients often lose their ability to swallow and speak. To evaluate these aspects, we analysed outcome after TLP.

Methods: We reviewed all patients who underwent TLP and subsequent circumferential pharyngeal reconstruction through 2004-2017 at the Helsinki University Hospital.

Results: For the 26 eligible patients, TLP was the primary treatment for 11 and salvage surgery for 15, followed by reconstruction with free flaps in 22 patients and pedicled flaps in 4. An early (≤ 30 days) pharyngocutaneous fistula developed in seven patients (27%; median time 13 days; range 6-26), and a late (> 30 days) fistula in five patients (19%; median time 370 days; range 46-785). In addition, ten patients (39%) developed an oesophageal stricture. Four patients (15%) resumed full oral feeding. A speech prosthesis was inserted for 15 patients (58%) and most of them could produce intelligible speech. We found acceptable survival figures for patients undergoing TLP both as a primary treatment and as salvage procedure: the overall survival at 1 year was 82% and 67%, and at 5 years 33% and 27%, respectively. Disease-specific survival at 1 year was 90% and 70%, and that at 5 years was 45% and 43%, respectively.

Conclusions: Despite fair survival, TLP carries a high risk for postoperative complications with limited functional outcome, thus necessitating cautious patient selection and surgical experience.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00405-019-05526-1DOI Listing
September 2019

The expression and prognostic value of stem cell markers Bmi-1, HESC5:3, and HES77 in human papillomavirus-positive and -negative oropharyngeal squamous cell carcinoma.

Tumour Biol 2019 Mar;41(3):1010428319840473

3 Translational Cancer Medicine Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

Human papillomavirus is detected in over 50% of oropharyngeal squamous cell carcinomas. Human papillomavirus-positive oropharyngeal squamous cell carcinomas differ from human papillomavirus-negative tumors, and both expression patterns are classified as distinct entities. The Bmi-1 oncogene is a well-known member of the mammalian polycomb-group family. HESC5:3 and HES77 are newly developed monoclonal antibodies produced against undifferentiated embryonic stem cells. Our aim was to explore their roles in both human papillomavirus-positive and -negative oropharyngeal squamous cell carcinomas. Our cohort comprised 202 consecutive oropharyngeal squamous cell carcinoma patients diagnosed and treated with curative intent. We used tissue microarray tumor blocks to study the immunohistochemical expression of Bmi-1, HESC5:3, and HES77. We compared the expressions of these stem cell markers with p16 immunoexpression and human papillomavirus status, as well as with other characteristics of the tumor, and with patients' clinical data and follow-up data. Human papillomavirus- and p16-positive tumors expressed less Bmi-1 and more HESC5:3 than the negative tumors. HES77 expression was high in human papillomavirus-positive oropharyngeal squamous cell carcinoma, but it did not correlate with p16 positivity. In our multivariable model, Bmi-1 and HESC5:3 were still associated with human papillomavirus, but the association between human papillomavirus and HES77 remained absent. In conclusion, Bmi-1, HESC5:3, and HES77 may have a different role in human papillomavirus-positive and human papillomavirus-negative tumors. There was no correlation between Bmi-1, HESC5:3, and HES77 expression and survival.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1010428319840473DOI Listing
March 2019

Management of clinically N0 neck in oropharyngeal carcinoma.

Eur Arch Otorhinolaryngol 2019 Apr 7;276(4):1205-1210. Epub 2019 Feb 7.

Department of Otorhinolaryngology - Head and Neck Surgery, Helsinki University Hospital, University of Helsinki, P.O. Box 263, 00029 HUS, Helsinki, Finland.

Purpose: Only a minority of patients with oropharyngeal squamous cell carcinoma (OPSCC) are diagnosed without regional metastasis (cN0). Studies focusing on the management of cN0 neck in OPSCC are scarce.

Methods: We reviewed all OPSCC patients treated at our institution with cN0 neck between 2000 and 2009. The treatment of neck and pattern of regional control was analyzed. Median follow-up was 5 years (range 3.5-9.0) or until death.

Results: Of the total 313 OPSCC patients treated within the period, 56 (18%) presented with cN0 neck. Of them, 51 (91%) received completed treatment with curative intent: 46 (90%) underwent elective neck treatment with either neck dissection ± (chemo)radiotherapy (C)RT (n = 23) or (C)RT (n = 23). A regional recurrence occurred in three patients (6%) and they all had a p16-negative soft palate midline primary tumor. Two of these patients had received RT on the neck.

Conclusions: While the overall prognosis of OPSCC is generally favorable and regional recurrences are infrequent, soft palate tumors, that are usually p16 negative, may form an subgroup warranting more aggressive treatment despite the clinical appearance of early stage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00405-019-05314-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6426801PMC
April 2019

De-escalation of post-treatment surveillance in oropharyngeal cancer.

Head Neck 2019 05 23;41(5):1457-1462. Epub 2018 Dec 23.

Department of Otorhinolaryngology - Head and Neck Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Background: The majority of new oropharyngeal squamous cell carcinoma (OPSCC) cases are associated with human papillomavirus and favorable prognosis. Post-treatment follow-up should be targeted to patients at greatest risk for disease recurrence.

Methods: To assess the benefits of routine clinical surveillance in OPSCC, we reviewed all follow-up visits conducted in 2014 at Helsinki University Hospital Department of Otorhinolaryngology.

Results: Of 366 visits, 26 (7%) were from patients presenting with a new symptom, and disease recurrence was detected in four. The presence of a new symptom was significantly associated with disease recurrence (P < 0.001). Of 366 visits, 340 (93%) were from patients presenting without new symptoms, and not a single recurrence was found during these visits.

Conclusions: Based on our findings, and previous studies assessing the prognosis and pattern of recurrent OPSCC, we concluded that the number of routine post-treatment visits can be reduced. Follow-up should rather focus on symptom-directed examinations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hed.25593DOI Listing
May 2019

Multiple cranial nerve injuries and neck abscesses caused by a transorally penetrating organic stick.

BMJ Case Rep 2018 Jul 24;2018. Epub 2018 Jul 24.

Head and Neck Center, Otorhinolaryngology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Foreign bodies cause a remarkable number of otolaryngological emergency visits and occasionally result in life-threatening conditions and later-emerging complications. Patient recovery depends on the detection and proper extraction of all foreign materials. Despite various obtainable diagnostic tools, adequate anamnesis forms the basis of clinical reasoning and should direct later examinations and radiological imaging. This case report describes a challenging patient with a unique trauma mechanism: many pieces of a fragmented organic foreign body emerged within 1 year of the initial injury, leading to repeated operations, a long period in an intensive care unit and a long-term swallowing and speech dysfunction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bcr-2017-224021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6059225PMC
July 2018

Treponema denticola chymotrypsin-like protease as associated with HPV-negative oropharyngeal squamous cell carcinoma.

Br J Cancer 2018 07 22;119(1):89-95. Epub 2018 Jun 22.

Department of Pathology, University of Helsinki, HUSLAB and Helsinki University Hospital, P.O. Box 21, 00014, Helsinki, Finland.

Background: An opportunistic oral pathogen, Treponema denticola (Td), has been linked to orodigestive carcinogenesis, but its role in oropharyngeal squamous cell carcinoma (OPSCC) has remained open. We evaluated the presence of Td chymotrypsin-like protease (Td-CTLP) in a series of 201 unselected consecutive OPSCC patients, and the relation of the Td-CTLP to human papillomavirus (HPV) status, to expression of toll-like receptors (TLR) 5, 7, and 9, and to clinical parameters and patient outcome.

Methods: Clinicopathological data came from hospital registries. The expression of cell surface-bound Td-CTLP was evaluated by immunohistochemistry. Immunoexpression of TLRs 5, 7, and 9, and HPV status we studied earlier in this patient series.

Results: We detected Td-CTLP in 81% of the OPSCC, and especially in HPV-negative tumours (48% of all OPSCCs). Among the HPV-positive tumours (52% of all OPSCCs), low Td-CTLP expression associated with low TLR 5 and high TLR 7 expression. Among those HPV-negative, higher TLR 5 and lower TLR 7 expression associated with high Td-CTLP expression. Strong Td-CTLP expression associated with poor disease-specific survival, but no similar association among HPV-positive and HPV-negative subgroups emerged.

Conclusions: Td-CTLP was highly expressed in OPSCC and was associated with the HPV status of tumour tissue.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41416-018-0143-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6035174PMC
July 2018

MMP-7 expression may influence the rate of distant recurrences and disease-specific survival in HPV-positive oropharyngeal squamous cell carcinoma.

Virchows Arch 2018 Jun 2;472(6):975-981. Epub 2018 May 2.

Department of Otorhinolaryngology - Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, P.O. Box 263, 00029 HUS, Helsinki, Finland.

The objective of this study was to determine if matrix metalloproteinase-7 (MMP-7) expression is related to human papilloma virus (HPV) status, clinical parameters, and outcome in oropharyngeal squamous cell carcinoma (OPSCC). Tumor tissue specimens from 201 OPSCC patients treated with curative intent were available for immunohistochemistry, and the samples were stained with monoclonal MMP-7 antibody. All the patients were followed up at least 3 years or until death. MMP-7 expression did not differ between HPV-positive and HPV-negative patients. MMP-7 was not prognostic among patients with HPV-negative OPSCC. In the HPV-positive subgroup, patients with moderate, high, or very high MMP-7 expression had significantly worse 5-year disease-specific survival (DSS) (56.6%) than patients with absent, or low MMP-7 expression (77.2%), and MMP-7 expression appeared as a prognostic factor in the multivariate analysis. In addition, among HPV-positive OPSCC with moderate, high, or very high MMP-7 expression, the 5-year distant recurrence-free survival was significantly lower (69.6%) than in those who had low or absent MMP-7 expression (97.5%). Our results suggest that among HPV-positive OPSCC patients, high MMP-7 expression is related to worse 5-year DSS and increased rate of distant recurrences.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00428-018-2365-6DOI Listing
June 2018

Expression of hormone receptors in oropharyngeal squamous cell carcinoma.

Eur Arch Otorhinolaryngol 2018 May 26;275(5):1289-1300. Epub 2018 Mar 26.

Department of Pathology, University of Helsinki, HusLab and Helsinki University Hospital, Haartmaninkatu 3, P.O. Box 21, 00014, Helsinki, Finland.

Objectives: Hormone receptors play an important role in many types of cancers. Alongside factors associated with human papillomavirus (HPV) infection, hormonal receptors may impact the tumorigenesis of oropharyngeal cancer.

Materials And Methods: This study consists of 199 consecutive oropharyngeal squamous cell carcinoma (OPSCC) patients diagnosed and treated with a curative intent. We examined androgen (AR), estrogen (ER; both alpha and beta), and progesterone receptor (PR) expressions using immunohistochemistry comparing tumor and patient characteristics.

Results: AR was expressed in 16%, PR in 27% and ER-beta in 63% of the tumors. HPV- and p16-positive tumors expressed more AR and less PR than their negative counterparts. High PR expression was associated with poor disease-specific and locoregional recurrence-free survival.

Conclusion: AR, PR, and ER-beta are expressed in OPSCC, and AR and PR expressions are associated with HPV and p16 status. Furthermore, PR appears to have prognostic significance. This may allow us to investigate the role of anti-hormone receptors in the treatment of OPSCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00405-018-4949-9DOI Listing
May 2018

Epidemiological and treatment-related factors contribute to improved outcome of oropharyngeal squamous cell carcinoma in Finland.

Acta Oncol 2018 Apr 17;57(4):541-551. Epub 2017 Nov 17.

a Department of Otorhinolaryngology-Head and Neck Surgery , University of Helsinki, Helsinki University Hospital , Helsinki , Finland.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/0284186X.2017.1400688DOI Listing
April 2018

Submandibular gland cancer: Specific features and treatment considerations.

Head Neck 2018 Jan 30;40(1):154-162. Epub 2017 Oct 30.

Department of Otorhinolaryngology - Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Background: In the absence of unified treatment protocol, we evaluated the management and outcomes of submandibular gland cancers in an unselected patient series.

Methods: We included all patients with resected submandibular gland cancer treated at the Helsinki University Hospital from 2000 to 2010 with a 5-year minimum follow-up.

Results: Twenty-five patients with cancer represented 30% of submandibular gland neoplasms, and most were adenoid cystic carcinomas (ACCs; 56%). At presentation, 3 patients showed clinical signs of probable malignancy. Of 22 neck dissection specimens, 5 patients (20%) had metastases with an occult metastasis rate of 4%. Cancer recurred in 11 patients (44%), of which 7 (28%) were only at a distant site. The 5-year disease-specific survival (DSS) and overall survival (OS) rates were 76%, and disease-free survival (DFS) was 68%.

Conclusion: Most tumors were ACCs differing from the histological pattern of parotid gland cancers. Occult metastases were rare. The rarity of submandibular gland cancer, its variable histological pattern, and varying biological behavior warrant centralized management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hed.24981DOI Listing
January 2018

Prospective experience of percutaneous endoscopic gastrostomy tubes placed by otorhinolaryngologist-head and neck surgeons: safe and efficacious.

Eur Arch Otorhinolaryngol 2017 Nov 1;274(11):3971-3976. Epub 2017 Sep 1.

Department of Otorhinolaryngology - Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, P.O. Box 263, 00029, Helsinki, Finland.

Percutaneous endoscopic gastrostomy (PEG) is often the treatment of choice in head and neck cancer (HNC) patients needing long-term nutritional support. Prospective studies on PEG tube placement in an otorhinolaryngologist service are lacking. At our hospital, otolaryngologist-head and neck (ORL-HN) surgeons-have performed PEG insertions for HNC patients since 2008. We prospectively analyzed 127 consecutive HNC patients who received their PEG tubes at the Department of Otorhinolaryngology-head and neck surgery, and evaluated the outcome of PEG tube insertions performed by ORL-HN surgeons. To compare time delays before and after, PEG placement service was transferred from gastrointestinal surgeons to ORL-HN surgeons, and we retrospectively analyzed a separate group of 110 HNC patients who had earlier received PEG tubes at the Department of Gastrointestinal Surgery. ORL-HN surgeons' success rate in PEG insertion was 97.6%, leading to a final prospective study group of 124 patients. Major complications occurred in four (3.2%): two buried bumper syndromes, one subcutaneous hemorrhage leading to an abscess in the abdominal wall, and one metastasis at the PEG site. The most common minor complication was peristomal granulomatous tissue affecting 23 (18.5%) patients. After the change in practice, median time delay before PEG insertion decreased from 13 to 10 days (P < 0.005). The proportion of early PEG placements within 0-3 days increased from 3.6 to 14.6% (P < 0.005). PEG tube insertion seems to be a safe procedure in the hands of an ORL-HN surgeon. Independence from gastrointestinal surgeons' services reduced the time delay and improved the availability of urgent PEG insertions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00405-017-4732-3DOI Listing
November 2017

Toll-like receptor 5 and 7 expression may impact prognosis of HPV-positive oropharyngeal squamous cell carcinoma patients.

Cancer Immunol Immunother 2017 Dec 30;66(12):1619-1629. Epub 2017 Aug 30.

Pathology, University of Helsinki, HUSLAB, and Helsinki University Hospital, P.O Box 21, 00014 University of Helsinki, Helsinki, Finland.

A large subset of oropharyngeal squamous cell carcinomas (OPSCCs) is associated with HPV infection and has better outcome than non-viral-related tumors. Various malignancies also carry a role for TLRs, key activators of inflammation and innate immunity. We examined the expression of TLRs in OPSCC, and their association with HPV status and treatment outcome. TLR 5, 7, 9, and p16 were studied by immunohistochemistry and HPV status was detected with in situ hybridization in 202 tumors of consecutively treated OPSCC patients using tissue microarray method. The relations between TLR expression and HPV status, p16 expression, clinicopathological factors, and survival were analyzed. TLR 5, 7, and 9 expression patterns differed between HPV-positive and -negative tumors, and they were statistically significantly associated with history of smoking, heavy drinking, tumor site, grade, size (T), metastasis (N), and stage. Moreover, in HPV-positive tumors the expression of TLR 5 and 7 correlated with tumor recurrence. After adjustment, among HPV-positive OPSCC patients, high TLR 5 and low TLR 7 expression were associated with poor disease-specific survival. Our results indicate that TLR 5 and 7 may have a role in the prognostication of HPV-positive OPSCC, however, further studies are needed to clarify the comprehensive role of these TLRs in OPSCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00262-017-2054-3DOI Listing
December 2017

Changing trends in the management of the neck in oropharyngeal squamous cell carcinoma.

Head Neck 2017 07 2;39(7):1412-1420. Epub 2017 May 2.

Department of Otorhinolaryngology - Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, P.O. Box 263, FI-00029 HUS, Helsinki, Finland.

Background: Treatment for oropharyngeal squamous cell carcinoma (SCC) has changed toward a more oncologic approach. We evaluated treatment of the neck, the incidence of regional recurrences, and factors associated with regional recurrence during the treatment approach transition period in patients with regional lymph node metastasis.

Methods: All patients with oropharyngeal SCC diagnosed at the Helsinki University Hospital during 2000-2009 were analyzed for clinicopathological factors, treatment, p16 expression, and regional recurrence.

Results: Altogether, 169 patients had a complete response, and among them regional recurrence occurred in 5 patients (4.7%) treated with surgery ± radiotherapy (RT) or chemoradiotherapy (CRT) and in 2 patients (3.2%) treated with RT or CRT ± surgery. All these 7 patients had N2b disease or higher, and 5 of them had regional recurrence in the contralateral side of the neck.

Conclusion: The incidence of regional recurrence was low, and remained unchanged despite the increased use of RT or CRT ± surgery. Treatment and follow-up of the contralateral neck warrants special attention in patients with advanced neck disease (≥N2b).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hed.24781DOI Listing
July 2017

Preoperative evaluation and surgical planning of submandibular gland tumors.

Head Neck 2017 06 28;39(6):1071-1077. Epub 2017 Mar 28.

Department of Otorhinolaryngology - Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Background: Roughly half of submandibular gland neoplasms are malignant. Because preoperative information on the nature of these tumors remains limited, both preoperative evaluation and assessment of the extent of primary surgery warrant guidelines that are more accurate.

Methods: We evaluated the preoperative examinations and management of all submandibular gland neoplasms treated surgically at the Helsinki University Hospital between 2000 and 2010.

Results: Of the 83 tumors, 58 (70%) were benign and 25 (30%) were malignant. Of the benign tumors, 54 (93%) were pleomorphic adenomas. The cytology in 8 patients (10%) was class IV or V, and in 12 patients was class III; the tumors in 9 of these 12 patients turned out to be malignant. Of all malignancies, 10 (40%) required additional more extensive surgery.

Conclusion: Ultrasound-guided fine-needle aspiration cytology (FNAC) proved useful, with limitations, in preoperative examination. Surgeons should always obtain wide margins whenever possible, even when clinical means or cytology indicates no malignancy. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1071-1077, 2017.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hed.24691DOI Listing
June 2017

Is p16 an adequate surrogate for human papillomavirus status determination?

Curr Opin Otolaryngol Head Neck Surg 2017 Apr;25(2):108-112

aDepartment of Otorhinolaryngology - Head and Neck Surgery bDepartment of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland cDivision of Ear, Nose and Throat Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.

Purpose Of Review: In head and neck cancer management, immunoexpression of protein p16 is widely used as a surrogate marker for human papillomavirus (HPV) positivity due to challenges of direct HPV testing. Previously p16 has been reported to have good sensitivity but only moderate specificity in HPV-status determination. The aim of this review is to evaluate the existing information on sensitivity and specificity of p16 immunohistochemistry (IHC) in HPV-status determination among the recent studies.

Recent Findings: We searched the time period from October 2014 to April 2016 and included 28 studies (a total of 31 analyses), which reported both p16 and HPV status in their series. The sensitivity of p16 in HPV determination ranged between 28.2 and 100.0%. The mean and median sensitivities were 90.5 and 95.4%, respectively. The specificity ranged between 31.1 and 100.0%. The mean and median specificities were 83.3 and 87.3%, respectively.

Summary: Our review presents current information on the feasibility of p16 IHC in HPV status determination, which is in line with previous studies. Patients with HPV-positive tumors can be identified with p16 IHC, but a risk for misclassification of HPV-negative tumors as HPV positive exists. This fact has to be taken into consideration if HPV status will influence treatment planning.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MOO.0000000000000341DOI Listing
April 2017

Predictive factors and treatment outcome of laryngeal carcinoma recurrence.

Head Neck 2017 03 30;39(3):555-563. Epub 2016 Nov 30.

Department of Otorhinolaryngology - Head and Neck Surgery, Oulu University Hospital, Oulu, Finland.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hed.24642DOI Listing
March 2017

Complications after surgery for benign parotid gland neoplasms: A prospective cohort study.

Head Neck 2017 01 30;39(1):170-176. Epub 2016 Apr 30.

Department of Otorhinolaryngology - Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Background: Prospective studies on procedure-specific incidences of complications after benign parotid surgery are lacking. Predictive factors for postoperative facial dysfunction remain controversial.

Methods: We conducted a prospective study on 132 patients undergoing parotid surgery for benign parotid neoplasms. We analyzed complication rates and assessed risk factors of postoperative transient facial palsy.

Results: Facial palsy rate was 40.2% on the first postoperative day, 28.3% at 2 weeks, 3.9% at 6 months, and 1.6% at 12 months. Immediate postoperative palsy rates in subgroups of partial superficial parotidectomy, superficial parotidectomy, extended parotidectomy, and ECD were 41.5%, 43.8%, 53.8%, and 6.3%, respectively. Age, duration of surgery, and use of ultrasound knife were identified as risk factors for transient facial palsy.

Conclusion: Depending on the operation type, up to half of the patients experience facial palsy after benign parotid surgery. Higher age and longer duration of operation increase the risk. The role of operative instrumentation requires further studies. © 2016 Wiley Periodicals, Inc. Head Neck 39: 170-176, 2017.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hed.24496DOI Listing
January 2017

Boron Neutron Capture Therapy in the Treatment of Recurrent Laryngeal Cancer.

Int J Radiat Oncol Biol Phys 2016 May 10;95(1):404-410. Epub 2015 Nov 10.

Department of Oncology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Purpose: To investigate the safety and efficacy of boron neutron capture therapy (BNCT) as a larynx-preserving treatment option for patients with recurrent laryngeal cancer.

Methods And Materials: Six patients with locally recurrent squamous cell laryngeal carcinoma and 3 patients with persistent laryngeal cancer after prior treatment were treated with BNCT at the FiR1 facility (Espoo, Finland) in 2006 to 2012. The patients had received prior radiation therapy with or without concomitant chemotherapy to a cumulative median dose of 66 Gy. The median tumor diameter was 2.9 cm (range, 1.4-10.9 cm) before BNCT. Boron neutron capture therapy was offered on a compassionate basis to patients who either refused laryngectomy (n=7) or had an inoperable tumor (n=2). Boronophenylalanine-fructose (400 mg/kg) was used as the boron carrier and was infused over 2 hours intravenously before neutron irradiation.

Results: Six patients received BNCT once and 3 twice. The estimated average gross tumor volume dose ranged from 22 to 38 Gy (W) (mean; 29 Gy [W]). Six of the 8 evaluable patients responded to BNCT; 2 achieved complete and 4 partial response. One patient died early and was not evaluable for response. Most common side effects were stomatitis, fatigue, and oral pain. No life-threatening or grade 4 toxicity was observed. The median time to progression within the target volume was 6.6 months, and the median overall survival time 13.3 months after BNCT. One patient with complete response is alive and disease-free with a functioning larynx 60 months after BNCT.

Conclusions: Boron neutron capture therapy given after prior external beam radiation therapy is well tolerated. Most patients responded to BNCT, but long-term survival with larynx preservation was infrequent owing to cancer progression. Selected patients with recurrent laryngeal cancer may benefit from BNCT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijrobp.2015.11.010DOI Listing
May 2016

Cancer of the tongue - early detection improves the prognosis.

Duodecim 2016;132(22):2063-70

Approximately 30 to 40% of all patients with tongue cancer still succumb to the disease in five years. Early diagnosis of the disease is of vital importance, because treatment will in that case cause considerably less harm. The diagnosis is confirmed with a histological specimen, which should be taken from every suspicious lesion, and can easily be taken under local anesthesia with a punch. Already when seeking treatment, as many as 25 % of patients with tongue cancer have neck metastases, which influence the prognosis. Heavy use of tobacco and alcohol are the most important risk factors of tongue cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
January 2018

Toll-like receptors 2, 4, and 9 in primary, metastasized, and recurrent oral tongue squamous cell carcinomas.

J Oral Pathol Med 2016 May 1;45(5):338-45. Epub 2015 Oct 1.

Department of Otorhinolaryngology - Head and Neck Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Background: Toll-like receptors (TLRs) are pattern-recognizing proteins involved in innate immunity and they seem to regulate both cancer progression and inhibition. In oral cancer, TLR activation has been linked to invasion. To define the role of TLR-2, TLR-4, and TLR-9 in oral tongue squamous cell carcinoma (OTSCC), we studied their expression in vivo in OTSCC tumor samples, as well as in vitro in cell invasion model.

Methods: We used immunohistochemistry to compare the expression of TLR-2, TLR-4, and TLR-9 in 21 primary Stage I-II OTSCCs, neck metastases, and recurrent tumors. In addition, we used myoma organotypic invasion assay to evaluate the effect of GIT27 (4,5-dihydro-3-phenyl-5-isoxasoleaceticacid) on the invasion of the HSC-3 OTSCC cell line.

Results: TLR-2, TLR-4, and TLR-9 were expressed in most tumors. Nuclear TLR-2 expression occurred more often in primary tumors than in neck metastases or recurrent tumors of the neck, whereas nuclear TLR-4 expression and cytoplasmic TLR-9 expression were higher in primary tumors than in local recurrent tumors. GIT27 did not affect the invasion of HSC-3 OTSCC cells, but a myoma organotypic invasion assay revealed that the expression of TLR-2 and TLR-4 was stronger in deeper-invading cells.

Conclusions: TLR-2, TLR-4, and TLR-9 were expressed in primary tumors, neck metastases as well as in recurrent tumors of OTSCC. Thus, these receptors seem to play a role in both the development and progression of tongue carcinoma. These TLRs may also contribute to the invasive potential of OTSCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jop.12373DOI Listing
May 2016

Expression of toll-like receptors in HPV-positive and HPV-negative oropharyngeal squamous cell carcinoma--an in vivo and in vitro study.

Tumour Biol 2015 Sep 5;36(10):7755-64. Epub 2015 May 5.

Department of Pathology and Oral Pathology, University of Helsinki and Helsinki University Hospital, Haartmaninkatu 3, P.O. Box 21, FI-00014, Helsinki, Finland.

The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has increased over the past decades in many western countries. This trend is mainly attributed to the human papillomavirus (HPV). Cancer-related actions of immunological defense systems are being intensively researched. Human toll-like receptors (TLRs) are a family of pattern recognition receptors that participate in the immunological defense against pathogens, but their actions are also linked to cancer. The expression of TLRs in cervical epithelium alters both during the clearance of HPV infection and the HPV-induced neoplasia, but the expression of TLRs has not been studied in OPSCC. Thirty-five paraffin-embedded, formalin-fixed, squamous cell carcinoma tissue specimens were analyzed for TLRs 2, 3, 4, 5, 7, and 9 and HPV and p16 statuses. The TLR 9 expression was lower in HPV-positive tumors compared with HPV-negative tumors. TLR 7 was expressed in all cancer specimens, but elevated expression was evident in HPV and/or p16-positive tumors. The majority of p16-positive tumors did not express TLR 5, whereas its expression was stronger in p16-negative tumors. The results of in vitro analysis of five human OPSCC cell lines and one human oral tongue squamous cell carcinoma cell line agree with the in vivo trends: low levels of TLR 5 and high levels of TLR 7 in p16-positive OPSCC. Overall, TLR 7 and 9 expression patterns are demonstrated here to relate to the HPV status in vivo and TLR 5 and 7 expression patterns to the p16 status in vivo and in vitro.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13277-015-3494-zDOI Listing
September 2015