To Örebro University

OBJECTIVES: HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) and head and neck carcinoma of unknown primary (HNCUP) are increasing. Despite good prognosis, recurrence rates range from 10% to 25%. Surveillance with clinical controls and imaging is not always reliable. Circulating tumour human papillomavirus DNA (ctHPV-DNA) has emerged as a potential biomarker for treatment evaluation and detection of recurrence. We aimed to investigate the correlation between ctHPV-DNA in HPV+ OPSCC/HNCUP and radiologic tumour burden. Additionally, we sought to assess whether ctHPV-DNA could serve as a tool in treatment evaluation.

DESIGN: A prospective observational cohort study.

SETTING: This multicenter study involved three otolaryngology units located in central Sweden. We utilised HPV genotype-specific assays for droplet digital PCR (ddPCR) to detect ctHPV-DNA in plasma at diagnosis and follow-up. ctHPV-DNA levels were correlated to radiological tumour burden and radiological response using the Kendall Rank correlation coefficient and the Kruskal-Wallis test.

PARTICIPANTS: Patients with HPV+ OPSCC/HNCUP undergoing definitive (chemo)radiotherapy and enrolled in the CIRCOS study. RESULTS: Out of 54 patients, 51 were eligible for analyses. At baseline, ctHPV-DNA was detectable in 88%. A majority of patients with a favourable radiological evaluation according to RECIST had a corresponding undetectable ctHPV-DNA at follow-up. The levels of ctHPV-DNA at baseline correlated with total tumour volume and nodal volume (rτ = 0.39, p < 0.01, respectively rτ = 0.26, p < 0.01).

CONCLUSION: ctHPV-DNA shows correlation with tumour burden. This study strengthens the role of ctHPV-DNA as a promising biomarker for treatment evaluation in HPV-related OPC/HNCUP. With further research on serial plasma sampling, ctHPV-DNA could complement radiological treatment evaluation in HPV+ OPSCC/HNCUP.

TRIAL REGISTRATION: NCT05904327 [ClinicalTrials.gov].

BACKGROUND: In oral cancers, tumour borders are typically defined by white light (WL). Narrow-band imaging (NBI) is an optical endoscopic technique commonly used for the larynx and for cancers of unknown primary. However, evidence for using NBI in oral cancers is insufficient.

AIMS/OBJECTIVES: We investigated whether NBI is a better predictor of the true mucosal tumour borders than WL in oral cancers. Additionally, we examined the agreement between NBI-based Takano intrapapillary capillary loop classifications and pathology reports.

MATERIALS AND METHODS: In this prospective study, the tumour borders were assessed by both NBI and WL at the time of surgical resection and then compared. Pathology reports of the examined areas were used as gold standard.

RESULTS: Forty-nine participants were included. After exclusion of 15 patients due to missing data, 34 were included in analyses. In 26.5% of the assessments, the tumour borders defined by NBI were outside the borders defined by WL. However, 55.5% of these were false-positives.

CONCLUSIONS AND SIGNIFICANCE: The delineation of mucosal tumour borders in oral cancers by NBI was not better than that by WL in this study. Several methodological challenges may have influenced the findings of this study, similar to the limitations reported in previous studies.

Surgery is the first line of treatment in gingival cancers of the mandible, and bone resection is necessary in the majority of cases. In the less extensive surgical option, marginal mandibulectomy (MM), the mandibular base is preserved. In contrast, in a segmental mandibulectomy (SM) the mandible is divided and the continuity is not preserved. If MM can be performed with comparable oncological results to SM, it is the preferred method. The aim of the present study was to identify preoperative predictors for local recurrence (LR), to support the selection of candidates for MM. Outcome measures were local recurrence free survival (LRFS) and disease specific survival (DSS). 67 patients treated with MM between 2008 and 2021 were included. Cox regression analyses of LR with hazard ratios and adjustments for postoperative radiotherapy, pathological T-stage (pT) and soft tissue margins were performed. 5-years LRFS was 63% (95% CI 46.9-75.5) and DSS 80.6% (95% CI 64.7-89.9). In conclusion we found that edentulous patients, more advanced pT-stage and positive soft tissue margins had increased risk for LR. Future studies of the correlation between cT and pT would be important to provide more robust preoperative support in the selection between MM and SM.

BACKGROUND: Base of tongue cancer incidence and patient survival is increasing why treatment sequelae becomes exceedingly important. Osteoradionecrosis (ORN) is a late adverse effect of radiotherapy and brachytherapy (BT) could be a risk factor. Brachytherapy is used in three out of six health care regions in Sweden.

AIMS: Investigate if patients treated in regions using BT show an increased risk for ORN and whether brachytherapy has any impact on overall survival. MATERIAL AND METHODS: We used data from the Swedish Head and Neck Cancer Register between 2008-2014. Due to the nonrandomized nature of the study and possible selection bias we compared the risk for ORN in brachy vs non-brachy regions.

RESULTS: Fifty out of 505 patients (9.9%) developed ORN; eight of these were treated in nonbrachy regions (16%), while 42 (84%) were treated in brachy regions. Neither age, sex, TNM-classification/stage, p16, smoking, neck dissection, or chemotherapy differed between ORN and no-ORN patients. The risk for ORN was significantly higher for patients treated in brachy regions compared to non-brachy regions (HR = 2,63, p = .012), whereas overall survival did not differ (HR = 0.95, p = .782).

CONCLUSIONS AND SIGNIFICANCE: Brachytherapy ought to be used cautiously for selected patients or within prospective randomized studies.

Background: Optimum management of the N0 neck is unresolved in parotid salivary gland cancer. Sentinel node biopsy (SNB) can reliably detect microscopic lymph node metastasis and its ' clinical use is increasing for head and neck tumors. The object of this study was to establish whether the technique is applicable to detect distribution of sentinel nodes for parotid tumors.

Materials and Methods: Prosepective observational study in 30 patients with benign or low-grade T1-T2N0 malignant tumors in the parotid gland planned for surgical treatment. Distribution of SN was detected with a preoperative ultrasound-guided peritumoral injection with a technetium-99 (Tc-99 m) laballed tracer followed by a SPECT-CT and intraoperative measurement in the neck and parotidal tissue. In patients with cytologically suspected malignant tumor or highly unclerar cytology, SNB was also performed.

Results: Sentinel nodes (SNs) were detected in 26/30 cases. Out of these, 7 presented with only one SN, whereas multiple sentinel nodes where detected in 19 cases. No SNs were found in neck level 1. SN was detected in level 5 independent of tumor location within the parotid gland. An intraparotidal distribution of SNs was more frequent in larger tumors.

Conclusions: The use of SN-technique in the planning of surgical treatment of parotid tumors seems feasible. It may be of clinical value for patients with parotid cancer to enable a more accurate staging and to detect occult metastasis in the SNs within the parotid as well as in the neck, enabaling the possibility to surgically remove all positive SNs at primary surgery and with reduced surgical morbidity.

Background: Depth of invasion (DOI) is important for the T-classification of squamous cell carcinoma of the oral tongue (SCCOT) and incorporated in the TNM 8 classification of oral cavity cancer. To determine DOI clinical palpation is performed, but the preferred radiological modality remains controversial. The aim of this study was to investigate the assessment of DOI using ultrasound (US-DOI).

Methods: The DOI was assessed in 40 patients with T1-T3 SCCOT by ultrasound, palpation, computed tomography and magnetic resonance imaging (MRI). Histopathological DOI (H-DOI) was gold standard. Bland-Altman analysis was used to compare mean difference and 95% limits of agreement (LOA). Results The mean difference of US-DOI was -0.5 mm (95% LOA -4.9-4.0) compared to H-DOI and the mean difference for MRI was 3.9 mm (95% LOA -2.3-10.2). In the subgroup analysis of cT1-T2 the US-DOI mean difference was 0.1 mm and the 95% LOA limits -2.5-2.7.

Conclusions: Ultrasound seems to be the most accurate method to assess DOI in T1-T2 SCCOT. MRI overestimates DOI and cannot assess a substantial proportion of the tumors. Level of Evidence 2c.

BACKGROUND: In surgical resection of squamous cell carcinoma of the oral tongue (SCCOT), achieving clear margins is important for prognosis. Insufficient histopathological margins are common, particularly deep margins.

AIMS/OBJECTIVES: The aim of the present study was to determine whether ultrasound (US)-assisted resection could decrease the proportion of insufficient histopathological deep margins in SCCOT.

MATERIAL AND METHODS: 34 patients with SCCOT undergoing US-assisted resection (study group) were compared to 76 whose resections were performed without US (conventional group). Outcome measures were insufficient deep histopathological resection margins and mean difference in deep margins.

RESULTS: Insufficient deep resection margins (<5.0 mm) were seen in 8 of 34 (23.5%) in the study group, compared to 31 of 76 (40.8%) in the conventional group, unadjusted RR 0.58 [95% CI 0.30-1.12; p = .11], adjusted RR 0.82 [95% CI 0.35-1.92; p = .64]. Unadjusted mean difference was 1.4 mm (95% CI 0.1-2.7, p = .04), adjusted mean difference 1.1 mm (95% CI -2.7 to 0.5, p = .19).

CONCLUSIONS: Intraoperative US can visualize the deep resection margins in T1/T2 SCCOT. US-assisted resection seems to decrease the number of insufficient histopathological deep margins, though the results are not statistically significant. Comparatively good results in the conventional group is one explanation for the lack of significance.

CLINICALTRIALS.GOV ID: NCT04059861.

OBJECTIVE: Upper airway dyspnea is a challenging condition in which assessing the discomfort experienced by the patient is essential. There are three patient-reported outcome (PRO) instruments developed particularly for this patient group, none of which is available in Swedish. The aim of this study was to translate the Dyspnea Index (DI) into Swedish and validate the instrument for use in the Swedish-speaking population by investigating its basic psychometric properties.

DESIGN: A prospective instrument validation study.

SETTING: Tertiary referral center.

PARTICIPANTS: Fifty-three (n=53) patients with upper airway dyspnea and 19 healthy controls.

MAIN OUTCOME MEASURES: The questionnaire was translated into Swedish (swDI) with a forward-backward method. Reliability, repeatability, responsiveness and construct validity were assessed by asking the subjects to complete the swDI, a visual analog scale (VAS) at exertion and at rest and the Voice Handicap Index (VHI).

RESULTS: The swDI showed excellent internal consistency (Cronbach's α: 0.85) and repeatability (interclass correlation coefficient: 0.87 and Pearson's r: 0.89) in the patient group. No ceiling effect was observed (maximum score achieved was 39; 85% of the patients scored ≤36). SwDI scores moderately correlated with VAS at exertion (r: 0.59) and at rest (r: 0.42), yet poorly with the VHI (r: 0.36). The effect size (ES) was 3.8.

CONCLUSIONS: The swDI is a valid, robust and reliable questionnaire for self-assessment in Swedish-speaking patients with upper airway obstruction. A future anchor-based longitudinal study is needed to assess the smallest detectable change (SDC) and minimum important change (MIC) that were not estimated in our study.

BACKGROUND: A peritonsillar abscess (PTA) is a common complication to acute tonsillitis. Needle aspiration (NA) is the gold standard for diagnosis of PTA. NA is usually painful and not risk-free. Ultrasound (US) is a noninvasive, portable radiological modality that could potentially be used in the diagnosis of PTA and selection of patients for NA. The reliability of US is dependent on the experience of the examiner which limits is usefulness.

AIM: To evaluate the reliability of US in the diagnosis of PTA by an inexperienced examiner.

METHODS: Thirty patients with suspected PTA were included. They were first examined with trans-cervical US by a medical student then clinically examined by a physician that performed a NA if clinically motivated. They were then followed for at least two days.

RESULTS: Three patients were excluded from analysis because no NA was performed. In these patients, US correctly classified them as negative for PTA. In the remaining 27 patients, the sensitivity and negative predictive value was 100%. The specificity was 64.3% and the positive-predictive value was 72.2%.

CONCLUSION: US can be very useful in the diagnosis of PTA and the selection for NA even with an inexperienced examiner.

SIGNIFICANCE: The results highlight the usefulness of ultrasound in otolaryngology.

Introduction: Head and neck cancer of unknown primary (HNCUP) is a rare condition whose prognostic factors that are significant for survival vary between studies. No randomized treatment study has been performed thus far, and the optimal treatment is not established.

Objective: The present study aimed to explore various prognostic factors and compare the two main treatments for HNCUP: neck dissection and (chemo) radiation vs primary (chemo) radiation.

Methods: A national multicenter study was performed with data from the Swedish Head and Neck Cancer Register (SweHNCR) and from the patients' medical records from 2008 to 2012.

Results: Two-hundred and sixty HNCUP patients were included. The tumors were HPVpositive in 80%. The overall 5-year survival rate of patients treated with curative intent was 71%. Age (p < 0.001), performance status (p = 0.036), and N stage (p = 0.046) were significant factors for overall survival according to the multivariable analysis. Treatment with neck dissection and (chemo) radiation (122 patients) gave an overall 5-year survival of 73%, and treatment with primary (chemo) radiation (87 patients) gave an overall 5-year survival of 71%, with no significant difference in overall or disease-free survival between the 2 groups.

Conclusions: Age, performance status, and N stage were significant prognostic factors. Treatment with neck dissection and ( chemo) radiation and primary (chemo).