Circulating Tumor DNA in Head and Neck Squamous Cell Carcinoma: Association with Metabolic Tumor Burden Determined with FDG-PET/CT.

BACKGROUND: The detection of circulating tumor DNA (ctDNA) with next-generation sequencing (NGS) in venous blood is a promising tool for the genomic profiling of head and neck squamous cell carcinoma (HNSCC). The association between ctDNA findings and metabolic tumor burden detected with FDG-PET/CT imaging is of particular interest for developing prognostic and predictive algorithms in HNSCC. METHODS: Twenty-six prospectively enrolled HNSCC patients were eligible for further analysis. All patients underwent tumor tissue and venous liquid biopsy sampling and FDG-PET/CT before definitive oncologic treatment. An NGS-based commercial panel was used for a genomic analysis of the samples. RESULTS: Maximum variant allele frequency (VAF) in blood correlated positively with whole-body (WB) metabolic tumor volume (MTV) and total lesion glycolysis (TLG) (r = 0.510, p = 0.008 and r = 0.584, p = 0.002, respectively). A positive liquid biopsy was associated with high WB-TLG using VAF ≥ 1.00% or ≥5.00% as a cut-off value (p = 0.006 or p = 0.003, respectively). Additionally, ctDNA detection was associated with WB-TLG when only concordant variants detected in both ctDNA and tissue samples were considered. CONCLUSIONS: A high metabolic tumor burden based on FDG imaging is associated with a positive liquid biopsy and high maximum VAF. Our findings suggest a complementary role of metabolic and genomic signatures in the pre-treatment evaluation of HNSCC.

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.

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.

The continuous laryngoscopy exercise test in severe or in difficult-to-treat asthma in adults: a systematic review.

OBJECTIVE: A systematic review was performed to determine if the continuous laryngoscopy exercise test (CLE) has been used in the diagnostics of exercise dyspnea in adults with asthma, and whether inducible laryngeal obstruction (ILO) is found in those with asthma or with severe or difficult-to-treat asthma. DATA SOURCES: We used Scopus and PubMed databases. The articles published up to 13 August 2019 were considered. STUDY SELECTIONS: We excluded manuscripts that did not contain information about adult patients with asthma. We included six studies from 59 search results in Scopus and none from the 17 search results in PubMed. RESULTS: The articles included 455 study individuals. Of these, 229 (50.3%) had diagnosed asthma or were treated with asthma medication. Altogether 31/229 (13.5%) subjects with diagnosis of asthma or previous asthma treatment had exercise-induced laryngeal obstruction (EILO) as comorbidity. The CLE test was performed on 229 patients with asthma. The method was used only for differential diagnosis of exercise-induced dyspnea to confirm EILO. At least 10/455 (2.2%) out of the 455 subjects experienced adverse events. CONCLUSIONS: This systematic review revealed that only a small proportion of patients with asthma had undergone the CLE test to assess exercise-induced dyspnea. None of the selected manuscripts reported severity of asthma. Whether CLE provides a valuable diagnostic tool for patients with severe or difficult-to-treat asthma cannot be determined according to this review.

Otorhinolaryngology Virtual Visits During the COVID-19 Pandemic: A 2-Year Follow-Up Study.

Objective: To clarify how successful virtual visits were in different age groups and subspecialties of otorhinolaryngology during the COVID-19 pandemic, with a 2-year follow-up. Methods: We examined the progress of treatment and need for face-to-face follow-ups in a retrospective setting. Case records of all the visits marked as virtual between March and June 2020 in Helsinki University Hospital Department of Otorhinolaryngology-Head and Neck Surgery (ORL-HNS) were reviewed. Results: Among 865 virtual visits, 71.2% (n = 616) clearly advanced treatment, 53.8% (n = 465) needed no face-to-face follow-up, and only 9.0% (n = 78) were followed by an unplanned visit within 6 months. Statistically significant differences were detected among different subspecialties and age groups. Virtual visits achieved clear progress of treatment most frequently in laryngology (119/149 visits, 79.9%) and in head and neck surgery (69/83 visits, 83.1%). Laryngology patients required the least face-to-face follow-ups (n = 38 scheduled, 25.5% of laryngology visits). Most visits with clear progress involved 18-29-year-olds (n = 100, 80.0%) and they also required least face-to-face follow-ups (n = 39, 31.2%). During the 6-month to 2-year follow-up, 82 patients (9.6%) contacted our clinic directly for outpatient treatment, 28 patients (3.3%) called or visited the emergency department, and 37 patients (4.3%) were referred to the ORL-HNS clinic again for the same issue. Conclusion: Virtual visits were beneficial for treatment of otorhinolaryngology patients, and unplanned visits afterward were rare. Differences in effectiveness among subspecialties suggest that the utility of telemedicine applications can be enhanced by examining more closely which patient and ailment characteristics favor virtual visits.

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.

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.

Persistence of Human Bocavirus 1 in Tonsillar Germinal Centers and Antibody-Dependent Enhancement of Infection.

Human bocavirus 1 (HBoV1), a nonenveloped single-stranded DNA parvovirus, causes mild to life-threatening respiratory tract infections, acute otitis media, and encephalitis in young children. HBoV1 often persists in nasopharyngeal secretions for months, hampering diagnosis. It has also been shown to persist in pediatric palatine and adenoid tonsils, which suggests that lymphoid organs are reservoirs for virus spread; however, the tissue site and host cells remain unknown. Our aim was to determine, in healthy nonviremic children with preexisting HBoV1 immunity, the adenotonsillar persistence site(s), host cell types, and virus activity. We discovered that HBoV1 DNA persists in lymphoid germinal centers (GCs), but not in the corresponding tonsillar epithelium, and that the cell types harboring the virus are mainly naive, activated, and memory B cells and monocytes. Both viral DNA strands and both sides of the genome were detected, as well as infrequent mRNA. Moreover, we showed, in B-cell and monocyte cultures and ex vivo tonsillar B cells, that the cellular uptake of HBoV1 occurs via the Fc receptor (FcγRII) through antibody-dependent enhancement (ADE). This resulted in viral mRNA transcription, known to occur exclusively from double-stranded DNA in the nucleus, however, with no detectable productive replication. Confocal imaging with fluorescent virus-like particles moreover disclosed endocytosis. To which extent the active HBoV1 GC persistence has a role in chronic inflammation or B-cell maturation disturbances, and whether the virus can be reactivated, will be interesting topics for forthcoming studies.IMPORTANCE Human bocavirus 1 (HBoV1), a common pediatric respiratory pathogen, can persist in airway secretions for months hampering diagnosis. It also persists in tonsils, providing potential reservoirs for airway shedding, with the exact location, host cell types, and virus activity unknown. Our study provides new insights into tonsillar HBoV1 persistence. We observed HBoV1 persistence exclusively in germinal centers where immune maturation occurs, and the main host cells were B cells and monocytes. In cultured cell lines and primary tonsillar B cells, we showed the virus uptake to be significantly enhanced by HBoV1-specific antibodies, mediated by the cellular IgG receptor, leading to viral mRNA synthesis, but without detectable productive replication. Possible implications of such active viral persistence could be tonsillar inflammation, disturbances in immune maturation, reactivation, or cell death with release of virus DNA, explaining the long-lasting HBoV1 airway shedding.

European white paper: oropharyngeal dysphagia in head and neck cancer.

PURPOSE: To develop a European White Paper document on oropharyngeal dysphagia (OD) in head and neck cancer (HNC). There are wide variations in the management of OD associated with HNC across Europe. METHODS: Experts in the management of specific aspects of OD in HNC across Europe were delegated by their professional medical and multidisciplinary societies to contribute to this document. Evidence is based on systematic reviews, consensus-based position statements, and expert opinion. RESULTS: Twenty-four sections on HNC-specific OD topics. CONCLUSION: This European White Paper summarizes current best practice on management of OD in HNC, providing recommendations to support patients and health professionals. The body of literature and its level of evidence on diagnostics and treatment for OD in HNC remain poor. This is in the context of an expected increase in the prevalence of OD due to HNC in the near future. Contributing factors to increased prevalence include aging of our European population (including HNC patients) and an increase in human papillomavirus (HPV) related cancer, despite the introduction of HPV vaccination in various countries. We recommend timely implementation of OD screening in HNC patients while emphasizing the need for robust scientific research on the treatment of OD in HNC. Meanwhile, its management remains a challenge for European professional associations and policymakers.

Overstay and Readmission in Ear, Nose, and Throat Day Surgery-Factors Affecting Postanesthesia Course.

AIMS: Many procedures in ear, nose, and throat (ENT) day surgery are carried out under local anesthesia in Finland, whereas many other countries use general anesthesia. We investigated overstay and readmission rates in local and general anesthesia at Helsinki University Hospital. MATERIAL AND METHODS: We conducted a retrospective study on ENT (n = 1011) day surgery patients within a 3-month period using the hospital's surgery database to collect data pertaining to anesthesia, overstays, readmissions, and contacts within 30 days of surgery. OBJECTIVES: We examined the effect of American Society of Anesthesiologists (ASA) class, age, sex, type of procedure, and anesthesia type on overstay, contact, and readmission rates. RESULTS: A multivariable logistic regression model included ASA class, age, sex, type of procedure, and anesthesia (local vs general). Sex, age, and type of procedure had an effect on the outcomes of overstay, readmission, or contact. With general anesthesia, 3.2% (n = 23) had an overstay or readmission compared to 1.4% (n = 4) after local anesthesia. This was mainly explained by the number of study outcomes in tonsillar surgery that was performed only in general anesthesia. CONCLUSIONS: Day surgery could be done safely using local anesthesia, as the number of study outcomes was no greater than in general anesthesia. Sex, type of procedure, and age affected the rate of study outcomes, but ASA class and anesthesia form did not. Our overstay, contact, and readmission rates are on the same level, or lower, than in international studies.

Analysis of weekend effect on mortality by medical specialty in Helsinki University Hospital over a 14-year period.

BACKGROUND: The weekend effect, the phenomenon of patients admitted at the weekend having a higher mortality risk, has been widely investigated and documented in both elective and emergency patients. Research on the issue is scarce in Europe, with the exception of the United Kingdom. We examined the situation in Helsinki University Hospital over a 14-year period from a specialty-specific approach. MATERIALS AND METHODS: We collected the data for all patient visits for 2000-2013, selecting patients with in-hospital care in the university hospital and extracting patients that died during their hospital stay or within 30 days of discharge. These patients were categorized according to urgency of care and specialty. RESULTS: A total of 1,542,230 in-patients (853,268 emergency patients) met the study criteria, with 47,122 deaths in-hospital or within 30 days of discharge. Of 12 specialties, we found a statistically significant weekend effect for in-hospital mortality in 7 specialties (emergency admissions) and 4 specialties (elective admissions); for 30-day post-discharge mortality in 1 specialty (emergency admissions) and 2 specialties (elective admissions). Surgery, internal medicine, neurology, and gynecology and obstetrics were most sensitive to the weekend effect. CONCLUSIONS: The study confirms a weekend effect for both elective and emergency admissions in most specialties. Reducing the number of weekend elective procedures may be necessary. More disease-specific research is needed to find the diagnoses most susceptible.

Root causes of extended length of stay and unplanned readmissions after orthopedic surgery and hand surgery: a retrospective observational cohort study.

BACKGROUND: While previous studies have evaluated the effect of some patient characteristics (e.g. gender, American Society of Anesthesiologists (ASA) class and comorbidity) on outcome in orthopedic and hand day surgery, more detailed information on anesthesia related factors has previously been lacking. Our goal was to investigate the perioperative factors that affect overstay, readmission and contact after day surgery in order to find certain patient profiles more prone to problemed outcomes after day surgery. METHODS: We examined orthopedic and hand day surgery at an orthopedic day surgery unit of Helsinki University Hospital. Patient data of all adult orthopedic and hand day surgery patients (n = 542) over a 3-month period (January 1 - March 31, 2015) operated on at the unit were collected retrospectively using the hospital's surgery database. These data comprised anesthesia and patient records with a follow-up period of 30 days post-operation. Patients under the age of 16 and patients not eligible for day surgery were excluded. Patient records were searched for an outcome of overstay, readmission or contact with the emergency room or policlinic. Pearson chi-square test, Fischer's exact test and multivariable logistic regression were used to analyze the effect of various perioperative factors on postoperative outcome. RESULTS: Various patient and anesthesia related factors were examined for their significance in the outcomes of overstay, readmission or contact. Female gender (p = 0.043), total amount of fentanyl (p = 0.00), use of remifentanil (p = 0.036), other pain medication during procedure (p = 0.005) and administration of antiemetic medication (p = 0.048) emerged as statistically significant on outcome after day surgery. CONCLUSIONS: Overstay and readmission in orthopedic and hand day surgery were clearly connected with female patients undergoing general anesthesia and needing larger amounts of intraoperative opioids. By favoring local and regional anesthesia, side effects of general anesthesia, as well as recovery time, will decrease.

Weekend effect on mortality by medical specialty in six secondary hospitals in the Helsinki metropolitan area over a 14-year period.

BACKGROUND: The weekend effect is the phenomenon of a patient's day of admission affecting their risk for mortality. Our study reviews the situation at six secondary hospitals in the greater Helsinki area over a 14-year period by specialty, in order to examine the effect of centralization of services on the weekend effect. METHODS: Of the 28,591,840 patient visits from the years 2000-2013 in our hospital district, we extracted in-patients treated only in secondary hospitals who died during their hospital stay or within 30 days of discharge. We categorized patients based on the type of each admission, namely elective versus emergency, and according to the specialty of their clinical service provider and main diagnosis. RESULTS: A total of 456,676 in-patients (292,399 emergency in-patients) were included in the study, with 17,231 deaths in-hospital or within 30 days of discharge. A statistically significant weekend effect was observed for in-hospital and 30-day post-discharge mortality among emergency patients for 1 of 7 specialties. For elective patients, a statistically significant weekend effect was visible in in-hospital mortality for 4 of 8 specialties and in 30-day post-discharge mortality for 3 of 8 specialties. Surgery, internal medicine, and gynecology and obstetrics were most susceptible to this phenomenon. CONCLUSIONS: A weekend effect was present for the majority of specialties for elective patients, indicating a need for guidelines for these admissions. More disease-specific research is necessary to find the diagnoses, which suffer most from the weekend effect and adjust staffing accordingly.

Patient injuries in pediatric otorhinolaryngology.

OBJECTIVES: Patient injuries in children can have lifelong effects on the patient and a marked impact on the whole family. The aim of this study was to identify the errors and incidents leading to patient injuries in pediatric otorhinolaryngology (ORL) by evaluating accepted patient injury claims. METHODS: The records of all accepted patient injury claims in ORL between 2001 and 2011 were searched from the nationwide Patient Insurance Centre registry. Pediatric injuries were reviewed and evaluated in detail, and factors contributing to injury were identified. RESULTS: In the 10-year study period, 17 (7.6%) of the 223 patient injuries occurred in children, and of these, 15 (88%) were considered operative care. The median age of the patients was 8 years (range 3-16 years). All operations were performed as daytime elective surgery and by a fully trained specialist in 93% of the cases. One-half of the cases were routine surgeries for common ORL diseases. The most common incidences were incomplete surgery, retained gauze or foreign body, injury to adjacent anatomic structure, and insufficient charts or instructions (each occurred in 3 cases). The most frequent consequence was burn (n = 4). One child died because of post-tonsillectomy hemorrhage. CONCLUSIONS: Patient injuries in pediatric ORL are strongly related to surgery. Most injuries occurred after routine operations by a fully trained specialist. Clinicians should be aware of the most likely scenarios resulting in claims.

Symptom relief and health-related quality of life in globus patients: a prospective study.

Globus may be a persistent symptom impairing patients' quality of life. Diagnostics and treatment are controversial but some globus patients may benefit from reassurance and attention. We investigated how globus symptoms change during a short-term follow-up without any treatment after an examination by an ear, nose and throat (ENT) physician and further diagnostic procedures. We also surveyed whether patients with persistent globus suffer from simultaneous voice problems. The study comprised 30 consecutive globus patients referred to Helsinki University Hospital, Department of Otorhinolaryngology - Head and Neck Surgery. We performed an ENT examination and scored patients' videolaryngostroboscopies using the Reflux Finding Score (RFS). Patients filled in three questionnaires: the Reflux Symptom Index (RSI), the Deglutition Handicap Index (DHI) and the 15-Dimensional Measure of Health-Related Quality of Life (15-D HRQoL). Patients underwent transnasal esophagoscopy, high-resolution manometry, and 24-hour multichannel intraluminal impedance and pH monitoring. After a four-month follow-up, patients re-answered the same questionnaires and a speech and language pathologist (SLP) examined the patients. Baseline and follow-up questionnaires were available from 27 (90%) patients. According to the RSI (p = .001) and the DHI (p = .003), patients' symptoms diminished after four months. The 15-D showed improvement in one subscale measuring discomfort and symptoms (p = .023). The SLP examined 23 (77%) patients, finding functional voice problems in six (26%). The study showed that most globus patients felt their symptoms diminished without any treatment during four months. In some patients, coexisting voice problems may be associated with persistent globus.

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.