A descriptive study on diagnostic timelines, and factors influencing delayed diagnosis among adult head and neck cancer patients at Uganda cancer institute.

BACKGROUND: Many patients with head and neck cancer (HNC) often present with advanced disease. This may result from delay in deciding to seek care, delay in reaching the healthcare facility and or delay in accessing care in the healthcare facility. We therefore set out to determine the time to definitive diagnosis and factors associated with delayed diagnosis among patients with HNC at the Uganda Cancer Institute (UCI). METHODS: A cross-sectional study was conducted at UCI, patients with HNC were recruited. An interviewer administered questionnaire was used to collect data on sociodemographic factors and clinical characteristics, including timelines in months, from symptom onset to deciding to seek care, to reaching the health care facility and to definitive diagnosis. Multivariate Poisson regression analysis was used to calculate odds ratios (ORs) for the factors of association with delayed diagnosis. RESULTS: We recruited 160 HNC patients, and 134 patients were analyzed. The median age was 49.5 years (IQR 26.5), 70% (94 of 134) were male, 48% (69 of 134) had below secondary school education, 49% (65 of 134) had a household income < 54 USD. 56% (76 of 134) were sole bread winners, 67% (89 of 134) had good access road condition to the nearest health unit and 70% (91 of 134) presented with tumor stage 4. Median time from onset of symptoms to definitive diagnosis was 8.1 months (IQR 15.1) and 65% (87 of 134) of patients had delayed diagnosis. Good access roads (aOR: 0.26, p = 0.006), secondary school education (aOR: 0.17, p = 0.038), and household income > 136 USD (aOR: 0.27, p = 0.043) were associated with lower odds of delayed diagnosis. Being the sole bread winner (aOR: 2.15, p = 0.050) increased the odds of delayed diagnosis. CONCLUSION: Most of HNC patients (65%) at UCI had delayed diagnosis. A national care pathway for individuals with suspected HNC should be established and consider rotation of Ear, Nose and Throat surgeons to underserved regions, to mitigate diagnostic delay.

Utility of UV Signature Mutations in the Diagnostic Assessment of Metastatic Head and Neck Carcinomas of Unknown Primary.

BACKGROUND: Metastatic carcinoma of unknown primary origin to the head and neck lymph nodes (HNCUP) engenders unique diagnostic considerations. In many cases, the detection of a high-risk human papillomavirus (HR-HPV) unearths an occult oropharyngeal squamous cell carcinoma (SCC). In metastatic HR-HPV-independent carcinomas, other primary sites should be considered, including cutaneous malignancies that can mimic HR-HPV-associated SCC. In this context, ultraviolet (UV) signature mutations, defined as ≥ 60% C→T substitutions with ≥ 5% CC→TT substitutions at dipyrimidine sites, identified in tumors arising on sun exposed areas, are an attractive and underused tool in the setting of metastatic HNCUP. METHODS: A retrospective review of institutional records focused on cases of HR-HPV negative HNCUP was conducted. All cases were subjected to next generation sequencing analysis to assess UV signature mutations. RESULTS: We identified 14 HR-HPV negative metastatic HNCUP to either the cervical or parotid gland lymph nodes, of which, 11 (11/14, 79%) had UV signature mutations, including 4 (4/10, 40%) p16 positive cases. All UV signature mutation positive cases had at least one significant TP53 mutation and greater than 20 unique gene mutations. CONCLUSION: The management of metastatic cutaneous carcinomas significantly differs from other HNCUP especially metastatic HR-HPV-associated SCC; therefore, the observation of a high percentage of C→T with CC →TT substitutions should be routinely incorporated in next generation sequencing reports of HNCUP. UV mutational signatures testing is a robust diagnostic tool that can be utilized in daily clinical practice.

A novel remote assessment pathway to streamline the management of two-week-wait suspected head and neck cancer referrals: a prospective analysis of 660 patients.

OBJECTIVE: This study analyses outcomes for 660 patients managed via a novel telescopic pathway for suspected head and neck cancer referrals. METHOD: Data were collected prospectively between January 2021 and December 2022, capturing all two-week-wait referrals triaged as low risk and managed via a nurse-led clinic for nasendoscopic examination and consultant-led remote assessment. RESULTS: In total, 660 patients were included. There were six head and neck cancers diagnosed, giving a conversion rate of 0.9 per cent. Mean (standard deviation) time to informing the patient whether they did or did not have cancer (28-day faster diagnosis standard) was 28.6 days (20.2), with no significant difference observed in patients imaged prior to review (p = 0.63). No missed cancers were detected in the follow-up period. CONCLUSION: Low-risk head and neck cancer referrals can be safely managed in a nurse-led clinic for recorded examination with asynchronous consultant-led management. Further work is required to ensure adherence to the new faster diagnosis standard.

Assessment of the prevalence of types of head and neck cancer in a tertiary cancer center at Madurai, Tamil Nadu: A cross-sectional study.

AIM: The aim of the study was to assess the prevalence of types of head and neck cancer in Madurai, Tamil Nadu. OBJECTIVES: The objectives of the study were to assess the prevalence of types of head and neck cancer in Madurai, Tamil Nadu using a questionnaire. MATERIALS AND METHODS: A descriptive cross-sectional study was carried out for two months among 300 head and neck cancer patients at a tertiary cancer center in Madurai. A convenience sampling technique was used. The data were collected using a pretested, self-structured questionnaire. The data were analyzed using the Statistical Package for the Social Sciences (SPSS) version 20.0 software. RESULTS: Of 300 head and neck cancer patients, the mean age of the patients was about 51.04 ± 16.49 years. The majority of the patients were male (80%), employed (85%), and literate (65%). Among the head and neck cancer patients, 65% were tobacco users and 42.4% were alcohol consumers. Squamous cell carcinoma was the most common type of head and neck cancer, and 79.7% were diagnosed at an advanced stage of said cancer, such as stages III and IV. CONCLUSION: Lack of knowledge and awareness is a major cause of increasing prevalence of head and neck cancer in our country. It is most important to increase the knowledge and awareness of early symptom recognition and its seriousness among the general population.

Frailty assessment by two screening instruments in non-elderly patients with head and neck cancer.

PURPOSE: Frailty assessment is often overlooked in non-elderly patients with cancer, possibly due to the lack of an effective frailty screening tool. This study aimed to evaluate the performance of two modern frailty screening tools, the Flemish version of the Triage Risk Screening Tool (fTRST) and the modified 5-Item Frailty Index (mFI-5), compared to the gold standard comprehensive geriatric assessment (GA) among non-elderly patients with head and neck cancer (HNC). METHODS: We prospectively included 354 consecutive patients aged < 65 years with newly diagnosed HNC scheduled for definitive concurrent chemoradiotherapy (CCRT) at three academic hospitals in Taiwan between January 2020 and December 2022. Frailty assessment using the GA, fTRST, and mFI-5 was performed in all patients to evaluate the relationship between frailty and treatment outcomes. RESULTS: The prevalence of frailty was 27.1%, 37.0%, and 42.4% based on GA, mFI-5, and fTRST, respectively. mFI-5 and fTRST demonstrated good predictive value in identifying frail patients compared to the GA. Patients with frailty, as defined by GA, mFI-5, and fTRST, exhibited higher risks of treatment-related complications, incomplete treatment, and poorer baseline quality of life (QoL). However, only GA showed significant prognostic value for overall survival. CONCLUSIONS: Frailty assessment using fTRST and mFI-5 is valuable for predicting treatment-related adverse events, treatment tolerance, and QoL in non-elderly patients with HNC. Incorporating frailty assessment into the management of non-elderly cancer patients can aid in the identification of high-risk individuals. However, the performance of these tools varies, highlighting the need for further validation and refinement.

[Patient-reported outcomes in head and neck cancer treatment: relevance, challenges, and benefit]. / Patientenberichtete Endpunkte in der Kopf-Hals-Tumortherapie: Relevanz, Herausforderungen und Nutzen.

Next to overall survival, quality of life is becoming more and more pivotal for cancer patients. The various domains of quality of life are complex and have different value to each patient. However, not only patients but also health care professionals, the pharmaceutical industry, and regulatory bodies ask: How can quality of life be reliably ascertained in clinical trials? For this purpose, carefully developed and validated specific questionnaires are needed: the patient-reported outcome measures (PROMs). A key challenge is to define how results based on PROMs can be used for shared decision-making. Next to clinical factors such as health and nutritional status, quality of life acts as a prognostic factor for overall survival in cancer. Thus, it is crucial to take quality of life into account in daily clinical practice.

Diagnostic accuracy of intraoperative margin assessment techniques in surgery for head and neck squamous cell carcinoma: A meta-analysis.

BACKGROUND: Positive margins following head and neck squamous cell carcinoma (HNSCC) surgery lead to significant morbidity and mortality. Existing Intraoperative Margin Assessment (IMA) techniques are not widely used due to limitations in sampling technique, time constraints and resource requirements. We performed a meta-analysis of the diagnostic performance of existing IMA techniques in HNSCC, providing a benchmark against which emerging techniques may be judged. METHODS: The study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. Studies were included if they reported diagnostic metrics of techniques used during HNSCC surgery, compared with permanent histopathology. Screening, manuscript review and data extraction was performed by multiple independent observers. Pooled sensitivity and specificity were estimated using the bivariate random effects model. RESULTS: From an initial 2344 references, 35 studies were included for meta-analysis. Sensitivity (Sens), specificity (Spec), diagnostic odds ratio (DOR) and area under the receiver operating characteristic curve (AUROC) were calculated for each group (n, Sens, Spec, DOR, AUROC): frozen section = 13, 0.798, 0.991, 309.8, 0.976; tumour-targeted fluorescence (TTF) = 5, 0.957, 0.827, 66.4, 0.944; optical techniques = 10, 0.919, 0.855, 58.9, 0.925; touch imprint cytology = 3, 0.925, 0.988, 51.1, 0.919; topical staining = 4, 0.918, 0.759, 16.4, 0.833. CONCLUSIONS: Frozen section and TTF had the best diagnostic performance. Frozen section is limited by sampling error. TTF shows promise but involves administration of a systemic agent. Neither is currently in widespread clinical use. Emerging techniques must demonstrate competitive diagnostic accuracy whilst allowing rapid, reliable, cost-effective results.

Examining the effect of Medicaid expansion on early detection of head and neck cancer of the oral cavity and pharynx by HPV-type and generosity of dental benefits.

BACKGROUND: Over a decade of evidence supports the claim that increased access to insurance through Medicaid expansions improves early detection of cancer. Yet, evidence linking Medicaid expansions to early detection of head and neck cancers (HNC) of the oral cavity and pharynx, specifically, may be limited by the lack of attention to Human Papillomavirus (HPV) etiology, generosity of dental coverage, and valid inference analyzing state cancer registry data. AIMS: This study reexamined the effect of Medicaid expansion on early detection of HPV+/- HNC in states offering extensive dental benefits. MATERIALS AND METHODS: Specialized data from the Surveillance, Epidemiology, and End Results (SEER) program was analyzed to account for, previously unmeasurable, differential detection patterns of HNCs associated with HPV. Then, to identify the effect of increasing Medicaid eligibility on staging patterns in states offering extensive benefits amidst potentially non-common trends between states, a "Triple Differences" design identifies the differential effect of Medicaid Expansion (with dental coverage) on HPV-negative HNCs relative to the change in HPV-positive HNCs. For valid inference analyzing a small number of state clusters (12) in cancer registry data, each regression model applies a Wild Cluster Bootstrap. RESULTS: Expanding Medicaid eligibility was found to be associated with a decrease in the proportion of distant-stage diagnoses of HPV(-) HNCs, but only among states which increased Medicaid dental generosity at the time of Medicaid expansion. CONCLUSIONS: These results suggest that adding extensive Medicaid dental benefits was the primary mechanism impacting HNC detection. This study highlights the potential positive spillover effects of policies which increase access to public dental coverage for low-income adults, while also showing the limitation of access to dental services for improving early detection of HPV+ HNCs.

The "Medicare effect" on head and neck cancer diagnosis and survival.

BACKGROUND: Uninsured individuals age 55-64 experience disproportionately poor outcomes compared to their insured counterparts. Adequate coverage may prevent these delays. This study investigates a "Medicare-effect" on head and neck squamous cell carcinoma (HNSCC) diagnosis and treatment. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was queried for persons ages 60-70 years in the United States from 2000 to 2016 with HNSCC. A "Medicare effect" was defined as an increase in incidence, reduction in advanced stage presentation, and/or decrease in cancer-specific mortality (CSM). RESULTS: Compared to their Medicaid or uninsured counterparts, patients age 65 have an increased incidence of HNSCC diagnosis, reduction in advanced stage presentation, decrease in cancer-specific mortality, and higher likelihood of receiving cancer-specific surgery. CONCLUSIONS: Patients age 65 with Medicare have decreased incidence of HNSCC, less hazard of late-stage diagnosis, and lower cancer-specific mortality than their Medicaid or uninsured counterparts, supporting the idea of a "Medicare effect" in HNSCC.

Sentinel lymph node biopsy for head and neck cutaneous squamous cell carcinoma using the Brigham and Women's staging system: a cost analysis.

The objective is to determine the cost-effectiveness of sentinel lymph node biopsy (SLNB) for cutaneous squamous cell carcinoma (CSCC) according to the Brigham and Women's Hospital (BWH) Tumor Staging system. A decision analysis was utilized to examine costs and outcomes associated with the use of SLNB in patients with high-risk head and neck CSCC. Decision tree outcome probabilities were obtained from published literature. Costs were derived from Medicare reimbursement rates (US$) and effectiveness was represented by quality-adjusted life-years (QALYs). The primary outcome was the incremental cost-effectiveness ratio (ICER), with a willingness-to-pay set at $100,000 per QALY gained. SLNB was found to be a cost-effective tool for patients with T3 tumors, with an ICER of $18,110.57. Withholding SLNB was the dominant strategy for both T2a and T2b lesions, with ICERs of - $2468.99 and - $16,694.00, respectively. Withholding SLNB remained the dominant strategy when examining immunosuppressed patients with T2a or T2b lesions. In patients with head and neck CSCC, those with T3 or T2b lesions with additional risk factors not accounted for in the staging system alone, may be considered for SLNB, while in other tumor stages it may be impractical. SLNB should only be offered on an individual patient basis.

An ion-channel-gene-based prediction model for head and neck squamous cell carcinoma: Prognostic assessment and treatment guidance.

Purpose: Head and neck squamous cell carcinoma (HNSCC) is a very diverse malignancy with a poor prognosis. The purpose of this study was to develop a new signature based on 12 ion channel genes to predict the outcome and immune status of HNSCC patients. Methods: Clinicopathological information and gene sequencing data of HNSCC patients were generated from the Cancer Genome Atlas and Gene Expression Omnibus databases. A set of 323 ion channel genes was obtained from the HUGO Gene Nomenclature Committee database and literature review. Using univariate Cox regression analysis, the ion channel genes related to HNSCC prognosis were identified. A prognostic signature and nomogram were then created using machine learning methods. Kaplan-Meier analysis was used to explore the relevance of the risk scores and overall survival (OS). We also investigated the association between risk scores, tumor immune infiltration, and gene mutational status. Finally, we detected the expression levels of the signature genes by quantitative real-time polymerase chain reaction, western blotting, and immunohistochemistry. Results: We separated the patients into high- and low-risk groups according to the risk scores computed based on these 12 ion channel genes, and the OS of the low-risk group was significantly longer (p<0.001). The area under the curve for predicting 3-year survival was 0.729. Univariate and multivariate analyses showed that the 12-ion-channel-gene risk model was an independent prognostic factor. We also developed a nomogram model based on risk scores and clinicopathological variables to forecast outcomes. Furthermore, immune cell infiltration, gene mutation status, immunotherapy response, and chemotherapeutic treatment sensitivity were all linked to risk scores. Moreover, high expression levels of ANO1, AQP9, and BEST2 were detected in HNSCC tissues, whereas AQP5, SCNN1G, and SCN4A expression was low in HNSCC tissues, as determined by experiments. Conclusion: The 12-ion-channel-gene prognostic signatures have been demonstrated to be highly efficient in predicting the prognosis, immune microenvironment, gene mutation status, immunotherapy response, and chemotherapeutic sensitivity of HNSCC patients.

Cell-free DNA hypermethylated genes may have a limited role in cancer screening but a potential role in risk assessment of head and neck cancer.

Cell-free DNA (cfDNA) hypermethylation in blood-based liquid biopsy is an attractive, minimally invasive biomarker for head and neck cancer (HNC) diagnosis and risk assessment. Yet, there is a lack of adequate description and discussion on this issue. A total of 10 eligible case-control studies containing 26 different hypermethylated genes in cfDNA were retrieved. There were 2026 HNC patients and 3149 healthy individuals for determining various hypermethylated genes in cfDNA. The pooled diagnostic parameter of sensitivity, specificity, and diagnostic accuracy value (95% confidence interval) was 33.2% (31.2-35.3%), 93.3% (92.3-94.1%), and 69.8% (68.5-71.0%), respectively. Odds ratios analysis revealed that SHOX2, SEPT, HIC1, CDKN2A, and CALML5 were significantly associated with increased risk of HNC development. Collectively, cfDNA hypermethylation biomarkers had a high specificity but accompanied by a low sensitivity for HNC detection, which might have a limited role in cancer screening but a potential role in risk assessment of HNC.

Development of the remote 100 ml water swallow test versus clinical assessment in patients with head and neck cancer: Do they agree?

BACKGROUND: The 100 ml water swallow test (WST) is a validated swallow assessment used in head and neck cancer (HNC). We aimed to determine the level of agreement when completing the 100 ml WST via clinician-graded video-testing or patient self-testing compared to standard face-to-face assessment (FTF). METHODS: Convenience sampling from four UK centers. INCLUSION CRITERIA: patients with HNC treated with any modality prior to, or within 5 years of treatment. Participants were recruited to complete the 100 ml WST by video-testing or self-testing and compared with FTF. RESULTS: Sixty-three patients were recruited; 1 was unable to perform the task; 30 in video-testing; and 32 in self-testing. There was no difference in swallow capacity (p = 0.424) and volume (p = 0.363) for the video-testing or the self-testing swallow capacity (p = 0.777) and volume (p = 0.445). CONCLUSIONS: This study demonstrates that video-testing and self-testing are reliable methods of completing the 100 ml WST for this sample of patients with HNC.

Symptom-based remote assessment in post-treatment head and neck cancer surveillance: A prospective national study.

OBJECTIVES: To report the incidence of locoregional recurrence in head and neck cancer (HNC) patients under surveillance following treatment undergoing symptom-based remote assessment. DESIGN: A 16-week multicentre prospective cohort study. SETTING: UK ENT departments. PARTICIPANTS: HNC patients under surveillance following treatment undergoing symptom-based telephone assessment. MAIN OUTCOME MEASURES: Incidence of locoregional recurrent HNC after minimum 6-month follow-up. RESULTS: Data for 1078 cases were submitted by 16 centres, with follow-up data completed in 98.9% (n = 1066). Following telephone consultation, 83.7% of referrals had their face-to-face appointments deferred (n = 897/1072). New symptoms were reported by 11.6% (n = 124/1072) at telephone assessment; 72.6% (n = 90/124) of this group were called for urgent assessments, of whom 48.9% (n = 44/90) came directly for imaging without preceding clinical review. The sensitivity and specificity for new symptoms as an indicator of cancer recurrence were 35.3% and 89.4%, respectively, with a negative predictive value of 99.7% (p = .002). Locoregional cancer identification rates after a minimum of 6 months of further monitoring, when correlated with time since treatment, were 6.0% (n = 14/233) <1 year; 2.1% (n = 16/747) between 1 and 5 years; and 4.3% (n = 4/92) for those >5 years since treatment. CONCLUSIONS: Telephone assessment, using patient-reported symptoms, to identify recurrent locoregional HNC was widely adopted during the initial peak of the COVID-19 pandemic in the United Kingdom. The majority of patients had no face-to-face reviews or investigations. New symptoms were significantly associated with the identification of locoregional recurrent cancers with a high specificity, but a low sensitivity may limit symptom assessment being used as the sole surveillance method.

A Daily Assessment Study of Smoking Cessation After a Head and Neck Cancer Diagnosis.

INTRODUCTION: This intensive longitudinal study describes key events in the process of smoking cessation after a new head and neck cancer (HNC) diagnosis. Prior longitudinal studies show some cancer patients quit, while others continue to smoke, but details about the pattern in which these discrete outcomes arise are scarce. This study is meant to help rectify this gap in the literature. AIMS AND METHODS: Participants were 42 HNC patients who reported current smoking at enrollment. Participants were recruited from an outpatient oncology clinic and completed a baseline questionnaire prior to begin a 30-day daily assessment. RESULTS: Few participants (9.52%) achieved 30-day continuous abstinence from smoking. On average, participants reported 9.64 ± 11.93 total days of abstinence. Nearly, all (94.44%, n = 34) participants made at least one quit attempt, with an average of 16.94 ± 11.30 quit attempt days. Fewer participants were able to achieve a 24-hour quit attempt (52.78%, n = 19), with a corresponding average of 5.50 ± 8.69 24-hour days. The median time to first 24-hour quit attempt was 13 days after enrollment. Based on smoking behavioral patterns, participants were categorized into five groups, the most common being "persistent attempters," which involved unsuccessful quit attempts throughout the study. Only 45% of participants (n = 19) used evidence-based treatment, the most common being cessation medication. CONCLUSIONS: This intensive longitudinal study found that cancer diagnosis can spur a lot of efforts to quit smoking. Unfortunately, this study suggests that many quit attempts are short lived, possibly a result of an absence or insufficient use of evidence-based treatments. IMPLICATIONS: For adults who are current smokers at the time of cancer diagnosis, there is a high likelihood of persistent cigarette smoking and use of other tobacco products in the weeks and months after a cancer diagnosis. Furthermore, this study shows that while a lot of quit attempts may occur, few are successful, which may be partly attributable to the low use of evidence-based tobacco treatment. Future research with cancer patients should aim to identify predictors of quit attempts and abstinence as well as treatment utilization.

A systematic review: impact of in-office biopsy on safety and waiting times in head and neck cancer.

OBJECTIVE: This study aimed to assess the current literature on the safety and impact of in-office biopsy on cancer waiting times as well as review evidence regarding cost-efficacy and patient satisfaction. METHOD: A search of Cinahl, Cochrane Library, Embase, Medline, Prospero, PubMed and Web of Science was conducted for papers relevant to this study. Included articles were quality assessed and critically appraised. RESULTS: Of 19 741 identified studies, 22 articles were included. Lower costs were consistently reported for in-office biopsy compared with operating room biopsy. Four complications requiring intervention were documented. In-office biopsy is highly tolerated, with a procedure abandonment rate of less than 1 per cent. When compared with operating room biopsy, it is associated with significantly reduced time-to-diagnosis and time-to-treatment initiation. It is linked to improved overall three-year survival. CONCLUSION: In-office biopsy is a safe procedure that may help certain patients avoid general anaesthetic. It was shown to significantly reduce time-to-diagnosis and time-to-treatment initiation when compared with operating room biopsy. This may have important implications for oncological outcomes. In-office biopsy requires fewer resources and is likely to be cost-saving five-years following introduction. With high rates of sensitivity and specificity, in-office biopsy should be considered as the first-line procedure to achieve tissue diagnosis.

The Edmonton Symptom Assessment System: A narrative review of a standardized symptom assessment tool in head and neck oncology.

OBJECTIVE: Symptom burden is common in head and neck cancer patients though it frequently remains undetected and untreated. The Edmonton Symptom Assessment System - revised version (ESAS-r) is a generic symptom scale deployed in many outpatient settings worldwide. The ESAS-r is meant to improve symptom detection and management. We sought to review the ESAS-r and its psychometric properties in a head and neck oncology population. METHODS: Narrative Review. RESULTS: Over the past 30 years, the ESAS-r has emerged as one of the most used symptom scales for cancer patients. Its psychometric properties in a heterogenous cancer population are well supported, proving to be reliable and valid in a variety of settings. The linking of ESAS-r scores with Ontario administrative health data has led to a detailed assessment of validity in head and neck cancer. The ESAS-r can discriminate between high and low levels of symptom burden and is responsive to change over time in this patient population. ESAS-r scores have also been shown to be a strong predictor of future emergency department use and unplanned hospitalization in head and neck cancer patients. CONCLUSIONS: The ESAS-r is reliable and valid in the head and neck cancer population and may serve as a useful clinical endpoint in research studies.