Changes in occurrence and management of laryngeal fractures at the Helsinki University Hospital during 25 years.

PURPOSE: Laryngeal fracture is a rare but potentially life-threatening trauma. Fractures vary from mild to dislocated and extensive with risk of severe complications. This study investigated the occurrence, clinical characteristics and management of laryngeal fractures in the last 15 years. MATERIAL AND METHODS: A retrospective population-based cohort study reviewing all laryngeal fractures at the Helsinki University Hospital in 2005-2019. Patient records and imaging studies were systematically reviewed for mode of injury, fracture type, secondary complications, treatment modality, possible airway management, length of stay, and mortality. Results were compared with corresponding data from 1995 to 2004. RESULTS: Overall 80 fracture patients were recorded (5.3/year); 79% were men and mean age was 42 years (range 18-78). Altogether 91% were closed and 9% open. While unintentional traumas were most common (54%), an increasing proportion were from intentional injury (10%) or Schaefer Gr IV in severity (35%). Altogether 46% had compromised airway and 21% needed airway intervention; airway narrowing was more common with cricoid (p = 0.042) and multiple fractures (p = 0.07) and correlated positively with amount of dislocation (p = 0.001) and number of fracture lines (p = 0.006). Surgery was performed for 33%, of which 46% were Schaefer Gr IV and 62% from intentional trauma. Mortality was 1.4%. CONCLUSIONS: Deliberate and violence-related laryngeal fractures have increased. These often result in more extensive injuries predisposing to compromised airway and requiring surgical intervention and longer treatment. Most fractures are still treated conservatively with good long-term outcomes. An observation period of 24 h is recommended to detect any delayed complications. Mortality remains low.

PET-CT detection of local residual laryngeal carcinoma after definitive (chemo)radiotherapy.

BACKGROUND: Positron emission tomography and computed tomography (PET-CT) is currently recommended in evaluating the treatment response after (chemo)radiotherapy ([C]RT). In the larynx, post-treatment changes and physiological uptake make image interpretation more challenging compared to other head and neck sites. Previous research has not addressed imaging factors specifically in the larynx that would help in distinguishing the residual disease and explain the unique challenges of that anatomic area. The study cohorts are small and heterogenous. Our objective was to investigate the ability of PET-CT in diagnosing local residual laryngeal carcinoma, and to uncover imaging factors that could be used in differentiating the residual disease from post-treatment and physiological changes. In the same study cohort, we also aimed to uncover prognostic factors for local residual or recurrent disease. METHODS: Our retrospective study cohort included 73 patients with T2-T4 laryngeal carcinoma undergoing (C)RT with curative intention, and post-treatment non-contrast-enhanced PET-CT at 2-6 months. Findings were compared between local residual and non-residual disease. Local residual disease was defined as a persistent tumor growth with no evidence of remission in between, confirmed by biopsy, and evident within 6 months from the end of RT. PET-CT was evaluated using a 3-step scale: negative, equivocal, and positive. RESULTS: Nine (12%) had a local residual tumor and 11 (15%) developed local recurrence, based on the biopsy. The median follow-up of surviving patients was 64 months (range, 28-174). In univariate analysis, primary tumor diameter greater than 2.4 cm (median value), and vocal cord fixation were prognostic for local residual or recurrent disease. Sensitivity, specificity, PPV, and NPV were 100%, 75%, 36%, and 100%, respectively, when the equivocal interpretation was grouped with the positive interpretation. All local residuals, and 28% (18/64) non-residuals, had a primary tumor area SUVmax of over 4.0 (p < 0.001). CT showed a persistent mass at the primary tumor area in 56% of residuals, and in 23% of non-residuals (p > 0.05). By combining SUVmax>4.0 and mass, specificity improved to 91%. CONCLUSIONS: NPV of post-treatment PET-CT in laryngeal carcinoma is high, but equivocal and positive results have low PPV and require further diagnostics. All local residuals had SUVmax over 4.0. The combination of SUVmax over 4.0 and mass on CT increased specificity, but the sensitivity was low.

Finnish Version of the Eating Assessment Tool (F-EAT-10): A Valid and Reliable Patient-reported Outcome Measure for Dysphagia Evaluation.

Our aim was to validate a Finnish version of the Eating Assessment Tool (F-EAT-10) for clinical use and to test its reliability and validity in a multicenter nationwide study. Normative data were acquired from 180 non-dysphagic participants (median age 57.0 years, 62.2% female). Dysphagia patients (n = 117, median age 69.7 years, 53.0% female) referred to fiberoptic endoscopic evaluation of swallowing (FEES) completed F-EAT-10 before the examination and after 2 weeks. Patients underwent the 100-ml water swallow test (WST) and FEES was evaluated using the following three scales: the Yale Pharyngeal Residue Severity Rating Scale, Penetration-Aspiration Scale, and the Dysphagia Outcome Severity Scale. An operative cohort of 19 patients (median age 75.8 years, 57.9% female) underwent an endoscopic operation on Zenker's diverticulum, tight cricopharyngeal muscle diagnosed in videofluorography, or both. Patients completed the F-EAT-10 preoperatively and 3 months postoperatively. The cut-off score for controls was < 3 (sensitivity 94.0%, specificity 96.1%) suggesting that ≥ 3 is abnormal. Re-questionnaires for test-retest reliability analysis were available from 92 FEES patients and 123 controls. The intraclass correlation coefficient was excellent for the total F-EAT-10 score (0.93, 95% confidence interval 0.91-0.95). Pearson correlation coefficients were strong (p < 0.001) for each of the questions and the total score. Internal consistency as assessed by Cronbach's alpha was excellent (0.95). Some correlations between findings in FEES and 100-ml WST with F-EAT-10 were observed. The change in subjective symptoms of operative patients paralleled the change in F-EAT-10. F-EAT-10 is a reliable, valid, and symptom-specific patient-reported outcome measure for assessing dysphagia among Finnish speakers.

Pretreatment tumor sampling and prognostic factors in patients with soft-tissue sarcoma of the head and neck.

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.

Enteral tube feeding of head and neck cancer patients undergoing definitive chemoradiotherapy in the Nordic Countries: Survey of the Scandinavian Society for Head and Neck Oncology.

PURPOSE: We assessed current policies and perceptions of enteral tube feeding in head and neck cancer (HNC) patients undergoing chemoradiotherapy (CRT). A web-based survey was used to compare the timing and method of tube feeding within and between the five Nordic countries, covering a population of 27 million. METHODS: From each of the 21 Nordic university hospitals, one oncologist and one otorhinolaryngology-head and neck (ORL-HN) surgeon responded to a survey. The respondents were asked whether tube insertion before the onset of CRT, or during CRT as required (prophylactic vs. reactive) was preferred. The use of a pretreatment nutritional screening tool and the choice of feeding route (nasogastric vs. gastrostomy tube) were assessed. In total, we analyzed responses from 21 oncologists and 21 ORL-HN surgeons. RESULTS: A tendency was observed towards decreasing the use of a PEG tube. Of the 21 university hospitals, only 2 (10%) reported using a prophylactic PEG tube in over half of HNC patients undergoing definitive CRT. The preferred method for reactive tube feeding was by a NG tube in 14 of 21 (67%), and by a PEG in 7 of 21 (33%). In general, both oncologists and ORL-HN surgeons were content with their current policy. CONCLUSIONS: The practices for enteral tube feeding in HNC management vary within and between the Nordic countries. We suggest that unified protocols for tube feeding should be developed for this patient population.

T1 glottic laryngeal cancer: the role of routine follow-up visits in detecting local recurrence.

PURPOSE: We assessed the treatment outcome and the benefits of routine follow-up visits in T1 glottic laryngeal squamous cell carcinoma (LSCC). METHODS: Medical records of patients diagnosed with stage T1 glottic LSCC (N = 303) in five Finnish university hospitals between 2003 and 2015 were reviewed. Moreover, data from the Finnish Cancer Registry and the Population Register Center were collected. RESULTS: Of all 38 recurrences, 26 (68%) were detected during a routine follow-up visit, and over half (21 of 38, 55%) presented without new symptoms. Primary treatment method (surgery vs. radiotherapy) was not connected with 5-year disease-specific survival (DSS) or laryngeal preservation rate. CONCLUSION: The majority of recurrences were detected on a routine follow-up visit, and local recurrences often presented without new symptoms. Routine post-treatment follow-up of T1 glottic LSCC seems beneficial. TRIAL REGISTRATION: Trial registration number and date of registration HUS/356/2017 11.12.2017.

The presence of minor salivary glands in the peritonsillar space.

Peritonsillar abscess (PTA) is traditionally considered only a purulent complication of acute tonsillitis (AT), but may be related to infection of minor salivary glands. We analysed the presence of peritonsillar minor salivary glands and inflammation patterns in 114 adult tonsils representing three patient groups: recurrent AT, chronic tonsillitis (CT), and PTA. Samples acquired from elective tonsillectomies were stored in formalin, and after preparation were microscopically examined for inflammation and fibrotic changes. Clinical features and histological characteristics were compared between the groups. Of all tonsils, the minor salivary glands were present in 77 (67.5%). Glands located near the tonsillar tissue showed signs of infection in 73 (94.8%), while only 3 (15.0%) of 20 glands located deeper in the peritonsillar space were infected. Compared to patients with recurrent AT and CT, those with PTA more often presented with periductal inflammation, p < 0.011 (PTA 82.1%, AT 42.9%, and CT 63.6%). The majority of our 114 tonsillectomy specimens, collected from patients with AT, CT, or PTA, presented with infected minor salivary glands, and inflammation of the peritonsillar space glands was evident. To further elucidate the association between these glands and PTA, tonsillar samples should be collected and analysed from patients during the acute phase of infection.

Work-up of globus: assessing the benefits of neck ultrasound and videofluorography.

Globus patients with normal ear, nose, and throat (ENT) status are a diagnostic challenge. The symptom may be long lasting and cause concern about malignancy, leading to possibly unnecessary further investigation. The aim of the study was to assess whether radiological examinations are useful in globus diagnostics, how often patients suffer from persistent globus, and whether globus patients with normal ENT status develop a malignancy during a follow-up. We reviewed medical records of all 76 globus patients referred to Helsinki University Hospital, Department of Otorhinolaryngology-Head and Neck Surgery in 2009. Patient history and findings in physical and radiological examinations were registered. A questionnaire concerning patients' present pharyngeal symptoms was sent 3 and 6 years after their initial visit. Data from the Finnish Cancer Registry revealed whether patients developed malignancies within a 3-year follow-up. Based on medical records, neck ultrasound was performed for 37 (49 %) and videofluorography for 22 patients (29 %), with nonsignificant findings. After a 3- and 6-year follow-up, half patients indicated that they were asymptomatic or had fewer symptoms, whereas the rest had persistent symptoms. The Finnish Cancer Registry data confirmed that globus patients developed no head and neck malignancies during a 3-year follow-up. In the present study, neck ultrasound and videofluorography showed no additional benefit to evaluate the globus etiology in patients whose ENT status was normal. Half the globus patients suffered from persistent symptoms after a 3- and 6-year follow-up, indicating that globus may cause discomfort chronically. However, no patients developed malignancies during a 3-year follow-up.

Efficient management of benign laryngeal symptoms in an endoscopy outpatient clinic.

Objectives: A globus and thick mucus in the throat are common reasons for referral to an ear, nose, and throat (ENT) specialist. ENT outpatient appointments focus on nasolaryngoscopy examinations, patient education, and reassurance. An endoscopic outpatient clinic (EOC) was established to efficiently manage patients with benign laryngeal symptoms. Methods: Patients referred between February 2022 and June 2023 due to a globus and/or thick mucus in the throat were immediately contacted via post. The contact letter included patient education about the potential underlying reasons for their symptoms and self-care instructions. A 15-min outpatient visit was scheduled for an ENT examination and nasolaryngoscopy. Patients completed a questionnaire about their current symptoms and whether they had followed the self-care instructions just before visiting the EOC and 1-month following their appointment. Results: In total, 203 patients examined in the EOC were included in the study. Before the EOC visit, most patients (89.2%) considered the information letter useful, it relieved concerns in 44.2% of patients, and 73.2% patients had already followed the self-care instructions. After the 1-month follow-up period, symptoms diminished significantly (p < .001). Conclusions: Instructions for self-care and encouragement relieved concerns among patients with benign laryngeal symptoms. Moreover, symptoms improved significantly after a 1-month follow-up period. Level of evidence: 4.

Sinonasal inverted papilloma - malignant transformation and non-sinonasal malignancies.

OBJECTIVES: To assess malignant transformation rate, non-sinonasal malignancies, and factors contributing to recurrence in patients treated for sinonasal inverted papilloma (SNIP). STUDY DESIGN: Retrospective study. METHODS: We retrospectively reviewed medical records of all patients treated for SNIP (n = 296) between the years 1984-2014 at Helsinki University Hospital. Data from the Finnish Cancer Registry confirmed the number of those patients with sinonasal and non-sinonasal malignancies. RESULTS: Only 2 of 296 (0.7%) patients primarily diagnosed with benign SNIP developed sinonasal cancer in a mean follow-up of 5.8 years. The most common non-sinonasal cancer sites were similar to those reported for the whole Finnish population. None of the patients presented with an HPV-associated non-sinonasal malignancy. The recurrence rate among patients who underwent attachment-oriented surgery was significantly lower compared to those operated on with other approaches (40.2% vs. 56.6%, p = 0.006). Dysplasia in SNIP was associated with a higher recurrence rate (p < 0.001). CONCLUSIONS: Malignant transformation of SNIP was rare. Patients with SNIP were not prone to HPV-associated non-sinonasal malignancies. Endoscopic resection and attachment-oriented surgery have become predominant approaches in the treatment of SNIP; meanwhile, the total number of SNIP recurrences has decreased. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:506-511, 2023.

Programmed death-ligand 1 and tumor-infiltrating lymphocytes (TILs) - low TIL density may predict poorer long-term prognosis in T1 laryngeal cancer.

We evaluated the prognostic role of programmed death-ligand 1 (PD-L1) and tumor-infiltrating lymphocytes (TILs) in T1 glottic laryngeal squamous cell carcinoma (LSCC). T1 glottic LSCC patients (n = 174) treated at five Finnish university hospitals between 2003 and 2013 were included. Tissue microarray (TMA) blocks were used for PD-L1 immunohistochemistry. TILs were scored from intratumoral and stromal regions in whole tissue sections. Of 174 patients, 92 (53%) had negative, 66 (38%) intermediate, and 16 (9%) high PD-L1 levels. Of 80 patients whose TILs were analyzed, 50 (63%) had low and 30 (38%) high stromal TIL density. Patients with a local recurrence or a new primary tumor of the larynx had lower TIL density than had other patients (p = 0.047). High PD-L1 expression with low stromal TIL density was associated with inferior 5-year disease-specific survival (85% vs. 100%, p = 0.02). In conclusion, in patients treated for T1 glottic LSCC, low stromal TIL density was associated with local recurrences and new primary tumors of the larynx. High PD-L1 expression with low stromal TIL density may be associated with worse survival in T1 glottic LSCC.

Transmission of human papillomavirus DNA from patient to surgical masks, gloves and oral mucosa of medical personnel during treatment of laryngeal papillomas and genital warts.

The risk of occupational human papillomavirus (HPV) transmission from patient to medical personnel during laser vaporization procedures remains controversial. The purpose of this study was to determine the risk of HPV transmission from the patient to the protective surgical masks, gloves and oral mucosa of medical personnel during the treatment of laryngeal papillomas and genital warts. The study involved five male patients scheduled for the surgical treatment of laryngeal papillomas, and five male patients undergoing carbon dioxide (CO(2)) laser treatment for urethral warts. Oral mucosa specimens were obtained from the study patients and the employees pre- and postoperatively. Samples were collected from the HPV-infected patient tissue, and from the surgical masks and gloves used by the employees. A total of 120 samples were analyzed for the presence of HPV DNA by PCR, using the degenerated MY09/11/HMB01 primers. After the papilloma procedures, the surgeons' gloves tested HPV positive in one of the five cases and those of the surgical nurse in three of the five cases. After the treatment of genital warts, HPV DNA corresponding to the patient tissue specimens was present in all the samples obtained from the surgical gloves of the operators. All oral mucosa samples obtained from 18 different employees tested HPV negative, as did the surgical mask specimens. According to our study, HPV may contaminate protective equipment, most of all surgical gloves, but transmission of HPV DNA to medical personnel is unlikely to occur provided that protective surgical gloves and masks are applied and disposed of properly.

ALS patients in otorhinolaryngology: A retrospective study.

Objectives: Given its rarity and the lack of clear clinical markers, amyotrophic lateral sclerosis (ALS) remains a diagnostic challenge. Because bulbar-onset ALS (buALS) presents with impaired speech or swallowing, patients are often primarily referred to an otolaryngologist (ORL) or phoniatrician. The objectives of this retrospective cohort study were to analyze the role of ORLs and phoniatricians in ALS diagnostics and treatment and the potential diagnostic delay related to initial visit to aforementioned specialists. Methods: We reviewed data for all 327 patients treated for ALS through the Hospital District of Helsinki and Uusimaa (HUS) between 2010 and 2014, focusing specifically on 110 (34%) patients presenting with bulbar nerve onset (buALS). Their presenting symptoms, referral to specialized care, and delay in referral to a neurology clinic were assessed. Indications and findings from swallowing studies were reviewed as well as the incidence of percutaneous endoscopic gastrostomy (PEG) and tracheostomy. Results: Among the 110 patients with buALS, 64 (58%) were primarily referred to a neurologist, 28 (25%) to an ORL, and five (5%) to a phoniatrician. The most common presenting symptom was dysarthria in 89 patients, (81%), followed by dysphagia in 26 (24%). In most cases, an ORL or phoniatrician suspected a neuromuscular disease; however, in eight (24%) cases, the neurological etiology of symptoms was missed. Overall, 49 (45%) patients underwent a swallowing study and 86 (78%) patients underwent PEG placement. Conclusions: Among buALS patients, 30% initially consulted an ORL or phoniatrician and 45% underwent a swallowing study. Based on our results, swallowing studies rarely lead to immediate PEG placement. An initial visit to other specialists had no impact on diagnostic delays or survival.

Survival and Larynx Preservation in Early Glottic Cancer: A Randomized Trial Comparing Laser Surgery and Radiation Therapy.

PURPOSE: The prognosis of glottic T1a laryngeal squamous cell carcinoma (LSCC) is excellent with both transoral laser surgery (TLS) and radiation therapy (RT). Our aim was to compare TLS and RT treatment results in a randomized study. METHODS AND MATERIALS: Of 56 male patients with glottic T1a LSCC, 31 were randomized for TLS and 25 for RT. Survival and larynx preservation data were collected from medical records. RESULTS: Five-year overall survival (OS) was 87%, disease-specific survival (DSS) was 97%, and recurrence-free survival (RFS) was 81% in patients treated with TLS. Five-year OS was 92%, DSS was 100%, and RFS was 88% in patients treated with RT. The primary treatment method was not associated with OS, RFS, or DSS in a log-rank test. The larynx preservation rate was similar in both groups (TLS, 97%; RT, 92%; P = .575). CONCLUSIONS: In a prospective randomized setting oncological outcomes of both treatment modalities (TLS or RT) for T1a LSCC were similar.

HPV-Positive Status Is an Independent Factor Associated With Sinonasal Inverted Papilloma Recurrence.

OBJECTIVES: The present study aimed to evaluate human papillomavirus (HPV) occurrence in sinonasal inverted papilloma (SNIP), and to assess factors associated with HPV positivity and SNIP recurrence. STUDY DESIGN: Prospective study. METHODS: We prospectively collected clinical data and fresh tissue specimens from 90 consecutive patients treated for SNIP at Helsinki University Hospital, between 2015 and 2019. Fourteen patients with recurrent SNIP underwent repeated tumor sampling. All tissue specimens were analyzed for the presence of HPV. Factors associated with SNIP recurrence and HPV positivity were assessed. RESULTS: Among 107 SNIP specimens, 14 (13.1%) were positive for low-risk HPV and 6 (5.6%) were positive for high-risk HPV. HPV positivity was associated with an increased risk of recurrence (P = .004). Smoking was significantly associated with HPV positivity in SNIP (P = .01), but a history of HPV-related diseases or patient sexual habits did not correlate with HPV positivity. The recurrence rate was lower among patients with SNIP that underwent an attachment-oriented resection, compared to patients treated without attachment-oriented resections (78.6% vs 25.8%, P < .001). CONCLUSIONS: The risk of SNIP recurrence was highly associated with 1) HPV positivity and 2) surgery without an attachment-oriented resection. Oncogenic HPV was rare in SNIP. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:1714-1718, 2022.

Exome sequencing reveals candidate mutations implicated in sinonasal carcinoma and malignant transformation of sinonasal inverted papilloma.

We explored somatic mutations in dysplastic sinonasal inverted papilloma (SNIP), SNIP with concomitant sinonasal squamous cell carcinoma (SNSCC), and SNSCC without preceding SNIP. Ten SNIP and SNSCC samples were analyzed with exome sequencing and tested for human papillomavirus. The identified mutations were compared to the most frequently mutated genes in head and neck squamous cell carcinoma (HNSCC) in the COSMIC database. Exome sequencing data were also analyzed for mutations not previously linked to SNSCC. Seven of the most commonly mutated genes in HNSCC and SNSCC in COSMIC harbored mutations in our data. In addition, we identified mutations in 23 genes that are likely to contribute to SNIP and SNSCC oncogenesis.

Acute epiglottitis after COVID-19 infection.

In patients with acute epiglottitis, the possibility of COVID-19 should be ruled out. Repeated nasofiberoscopy examinations or a tracheostomy, which may produce infectious aerosols, may be required.

Peritonsillar abscess may not always be a complication of acute tonsillitis: A prospective cohort study.

The present study aimed to specify diagnostics for peritonsillar abscesses (PTAs) and to clarify the role of minor salivary glands. This prospective cohort study included 112 patients with acute tonsillitis (AT) and PTA recruited at a tertiary hospital emergency department between February and October 2017. All patients completed a questionnaire concerning their current disease. Serum amylase (S-Amyl) and C-reactive protein (S-CRP) levels, tonsillar findings, and pus aspirate samples and throat cultures were analyzed. Eight of 58 PTA patients (13.8%) had no signs of tonsillar infection. The absence of tonsillar erythema and exudate was associated with low S-CRP (p<0.001) and older age (p<0.001). We also observed an inverse correlation between S-Amyl and S-CRP levels (AT, r = -0.519; PTA, r = -0.353). Therefore, we observed a group of PTA patients without signs of tonsillar infection who had significantly lower S-CRP levels than other PTA patients. These findings support that PTA may be caused by an etiology other than AT. Variations in the S-Amyl levels and a negative correlation between S-Amyl and S-CRP levels may indicate that minor salivary glands are involved in PTA development.

Serum matrix metalloproteinase 8 and tissue inhibitor of metalloproteinase 1: Potential markers for malignant transformation of recurrent respiratory papillomatosis and for prognosis of laryngeal cancer.

BACKGROUND: Biomarkers that could predict malignant transformation of recurrent respiratory papillomatosis (RRP) would be useful in patient follow-up. We investigated whether serum matrix metalloproteinase 8 (MMP-8) and tissue inhibitor of metalloproteinase 1 (TIMP-1) could predict malignant transformation of RRP and whether they associate with survival in laryngeal squamous cell carcinoma (LSCC) without preexisting RRP. METHODS: We analyzed serum MMP-8 (S-MMP-8) and serum TIMP-1 (s-TIMP-1) in 114 patients: 55 were treated for RRP and 59 for LSCC without preexisting RRP. Five patients with RRP developed LSCC during follow-up. RESULTS: Elevated S-MMP-8 level in RRP was associated with malignant transformation (P = .01). Compared to patients with RRP, S-MMP-8 in patients with LSCC was significantly higher (P < .001). Increased S-TIMP-1 level in LSCC was associated with poor overall survival (P = .02) and recurrence-free survival (P = .05). CONCLUSION: In RRP, high S-MMP-8 may predict malignant transformation. In LSCC, elevated S-TIMP-1 is connected to poor survival.