Epigenetic studies on the role of DNA-modifying enzymes in HNSCC tumorigenesis have focused on a single enzyme or a group of enzymes. To acquire a more comprehensive insight into the expression profile of methyltransferases and demethylases, in the present study, we examined the mRNA expression of the DNA methyltransferases DNMT1, DNMT3A, and DNMT3B, the DNA demethylases TET1, TET2, TET3, and TDG, and the RNA methyltransferase TRDMT1 by RT-qPCR in paired tumor–normal tissue samples from HNSCC patients. We characterized their expression patterns in relation to regional lymph node metastasis, invasion, HPV16 infection, and CpG73 methylation. Here, we show that tumors with regional lymph node metastases (pN+) exhibited decreased expression of DNMT1, 3A and 3B, and TET1 and 3 compared to non-metastatic tumors (pN0), suggesting that metastasis requires a distinct expression profile of DNA methyltransferases/demethylases in solid tumors. Furthermore, we identified the effect of perivascular invasion and HPV16 on DNMT3B expression in HNSCC. Finally, the expression of TET2 and TDG was inversely correlated with the hypermethylation of CpG73, which has previously been associated with poorer survival in HNSCC. Our study further confirms the importance of DNA methyltransferases and demethylases as potential prognostic biomarkers as well as molecular therapeutic targets for HNSCC.

Background: Despite the widespread use of antibiotics, acute mastoiditis (AM) and related complications resulting from acute purulent otitis media continue to occur, predominantly in children. Although numerous studies have focused on the pathogenesis, aetiological agents, and treatment of AM, comprehensive investigations of the long-term outcomes of AM and the physiological consequences of surgical intervention in the temporal bone are lacking. Methods: Thirty patients who had undergone mastoidectomy for acute mastoiditis at a median age of 2.12 years were invited for evaluation at least five years postoperatively. The assessment included the Chronic Otitis Media Questionnaire 12, clinical examination with otomicroscopy, extended high-frequency pure-tone audiometry, distortion product otoacoustic emissions, middle ear impedance testing, and a newly developed protocol for noninvasive mastoid function measurement. Results were compared with a control group of 30 ears and with a group of 30 ears treated solely with tympanostomy for acute otitis media at risk of mastoiditis. Results: Although mean Chronic Otitis Media Questionnaire 12 scores were below 1 point, patients who had undergone mastoidectomy reported slightly greater difficulties with hearing in both quiet and noisy environments, along with an increased perception of tinnitus and unpleasant sensations around the ear. Otomicroscopy revealed minor structural changes in the test groups, which were absent from the control group. Pure-tone audiometry demonstrated approximately 10 dB higher thresholds at high and extended high frequencies, with similar findings observed in the distortion product otoacoustic emissions. Middle ear impedance testing indicated elevated stapedius reflex thresholds in the mastoidectomy group, while other parameters showed no statistically significant differences. Mastoid function testing demonstrated preserved pressure-buffering capacity but reduced thermal insulation of the vestibular organ under extreme thermal stimulation—an occurrence rarely encountered in daily life. Conclusions: In the long term, most patients recovering from acute mastoiditis exhibit only minor functional and structural sequelae, and the impact of mastoidectomy appears negligible compared with less invasive surgical interventions.

Background: Despite the widespread use of antibiotics, acute mastoiditis (AM) and re-lated complications resulting from acute purulent otitis media continue to occur, pre-dominantly in children. Although numerous studies have focused on the pathogenesis, aetiological agents, and treatment of AM, comprehensive investigations of the long-term outcomes of AM and the physiological consequences of surgical intervention in the temporal bone are lacking. Methods: A cohort of patients who had undergone mastoidectomy for AM were invited for evaluation at least five years postoperatively. The assessment included the COMQ-12 questionnaire, clinical examination and otomicroscopy, extended high-frequency pure-tone audiometry, DPOAE, middle ear impedance testing, and a newly developed protocol for non-invasive mastoid function measurement. Results were compared with a control group and a group treated solely with tympanostomy for acute otitis media at risk of mastoiditis. Results: In the COMQ-12 questionnaire, we found that patients who underwent mas-toidectomy experienced slightly greater difficulties with hearing in quiet environments and in noisy settings, as well as an increased perception of tinnitus and an unpleasant sensation around the ear. Otomicroscopy revealed minor structural changes in the test groups, whereas no such changes were observed in the control group. Pure-tone au-diometry demonstrated approximately 10 dB higher threshold values at high and ex-tended high frequencies, similar to findings in the DPOAE test. Middle ear impedance testing indicated an elevation in the stapedius reflex threshold, while other tests did not reveal statistically significant differences. Mastoid function testing in patients who had undergone mastoidectomy showed preserved pressure buffer function but a reduced capacity for thermal insulation of the vestibular organ under extreme thermal stimula-tion—an occurrence that is rarely encountered in daily life. Conclusions: In the long term, most patients recovering from AM exhibit only minor functional and structural sequelae. In the context of AM management, the effects of mastoidectomy are negligible compared to those of less invasive surgical interventions.

Purpose: Despite the declining incidence of acute mastoiditis (AM) due to antibiotics, complications persist, necessitating surgical intervention in severe cases. Recent studies suggest conservative treatments, avoiding mastoidectomy, show high recovery rates. However, this trend raises concerns about severe complications, prolonged treatment, increased antibiotic use, and declining surgical skills. While much research focuses on AM pathogenesis and treatment, the long-term consequences, especially post-mastoidectomy ear function, are less understood. To address this, we studied the permanent effects of surgically treated AM and mastoidectomy on ear function. Methods: A cohort of patients that received surgical treatment for AM in the form of mastoidectomy was invited to be tested after at least 5 years since the operation. Test battery included COMQ-12 questionnaire, physical exam and otomicroscopy, extended high pure tone audiogram, DPAOE and middle ear impedance testing. Results were compared with a control group and a group which received surgical treatment in the form of tympanostomy for acute otitis media with impeding mastoiditis. Results: The COMQ-12 questionnaire yielded higher scores in questions about hearing in quiet environments, hearing in noise, tinnitus, and ear discomfort. Minor structural changes were observed in the test groups during otomicroscopy, but not in the control group. Pure tone audiometry revealed a median elevation of around 10 dB in high and extended high frequencies, with similar results observed in DPAOE testing. In middle ear impedance testing, only an elevation of the stapedial reflex threshold was noted; other tests did not show any statistically significant differences. Conclusions: In the long term, the majority of patients post-AM have minor functional in structural consequences. In the context of treatment of AM, the effects of mastoidectomy are negligible when compared to less invasive surgical procedures.

Background/Objectives: Recurrent acute otitis media (AOM) in children is known to cause cumulative cochlear and vestibular injury. Whether a single fulminant episode severe enough to require surgical intervention produces an analogous long-term audiovestibular signature, and whether infection severity contributes to outcome independently of cumulative episode count, is unclear. The present study addressed this gap. Methods: In this single-centre retrospective cohort study, 65 paediatric patients who had undergone surgical treatment for acute mastoiditis—the fulminant form of AOM—between July 2001 and March 2021 were assessed a median of 11.5 years after surgery. Of these, 35 had undergone mastoidectomy with tympanostomy and 30 had undergone tympanostomy alone because their episode had not been severe enough to require mastoidectomy. Thirty-two age-matched healthy volunteers (one ear each) formed the control group, yielding 97 ears in three groups (Group TM, 35 ears; Group T, 30 ears; Group C, 32 ears). Extended high-frequency pure-tone audiometry (125–20 kHz), distortion-product otoacoustic emissions (DPOAEs), single-frequency and wideband tympanometry, ipsilateral acoustic reflex thresholds, and lateral-canal vestibulo-ocular reflex gain were measured. Results: Both operated groups showed significantly elevated audiometric thresholds in the high- and extended high-frequency ranges compared with controls (HTA: χ² = 24.25, p < 0.001), with corresponding reductions in DPOAE amplitudes (HTA: χ² = 25.04, p < 0.001). Group TM did not differ significantly from Group T at any frequency band, indicating a negligible additional contribution of mastoidectomy itself. Acoustic reflex thresholds were elevated in Group TM. Vestibulo-ocular reflex gain was within reference ranges in all groups. Conclusions: A single fulminant episode of acute middle-ear infection in childhood—whether severe enough to require mastoidectomy or treated by tympanostomy alone—was associated, more than a decade later, with significantly elevated audiometric thresholds closely resembling those reported after multiple recurrent infections, supporting an effect of infection severity independent of cumulative episode count. Long-term audiological follow-up with extended high-frequency audiometry and otoacoustic emission testing is warranted, irrespective of whether mastoidectomy was required.