Development and validation of a novel TNM staging N-classification of oral cavity squamous cell carcinoma.

BACKGROUND: For oral cavity squamous cell carcinoma (OSCC), extent of extranodal extension (ENE) (minor, ≤2 mm; major, >2 mm) is differentially prognostic, whereas limitations exist with the 8th edition of American Joint Committee on Cancer/International Union Against Cancer TNM N-classification (TNM-8-N). METHODS: Resected OSCC patients at four centers were included and extent of ENE was recorded. Thresholds for optimal overall survival (OS) discrimination of lymph node (LN) features were established. After dividing into training and validation sets, two new N-classifications were created using 1) recursive partitioning analysis (RPA), and 2) adjusted hazard ratios (aHRs) and were ranked against TNM-8-N and two published proposals. RESULTS: A total of 1460 patients were included (pN0: 696; pN+: 764). Of the pN+ cases, 135 (18%) had bilateral/contralateral LNs; 126 (17%) and 244 (32%) had minor and major ENE, and two (0.3%) had LN(s) >6 cm without ENE (N3a). LN number (1 and >1 vs. 0: aHRs, 1.92 [95% confidence interval (CI), 1.44-2.55] and 3.21 [95% CI, 2.44-4.22]), size (>3 vs. ≤3 cm: aHR, 1.88 [95% CI, 1.44-2.45]), and ENE extent (major vs. minor: aHR, 1.40 [95% CI, 1.05-1.87]) were associated with OS, whereas presence of contralateral LNs was not (aHR, 1.05 [95% CI, 0.81-1.36]). The aHR proposal provided optimal performance with these changes to TNM-8-N: 1) stratification of ENE extent, 2) elimination of N2c and 6-cm threshold, and 3) stratification of N2b by 3 cm threshold. CONCLUSION: A new N-classification improved staging performance compared to TNM-8-N, by stratifying by ENE extent, eliminating the old N2c category and the 6 cm threshold, and by stratifying multiple nodes by size.

Comparing Genomic Landscapes of Oral and Cutaneous Squamous Cell Carcinoma of the Head and Neck: Quest for Novel Diagnostic Markers.

Squamous cell carcinoma is the most common head and neck malignancy arising from the oral mucosa and the skin. The histologic and immunohistochemical features of oral squamous cell carcinoma (OSCC) and head and neck cutaneous squamous cell carcinoma (HNcSCC) are similar, making it difficult to identify the primary site in cases of metastases. With the advent of immunotherapy, reliable distinction of OSCC and HNcSCC at metastatic sites has important treatment and prognostic implications. Here, we investigate and compare the genomic landscape of OSCC and HNcSCC to identify diagnostically useful biomarkers. Whole-genome sequencing data from 57 OSCC and 41 HNcSCC patients were obtained for tumor and matched normal samples. Tumor mutation burden (TMB), Catalogue of Somatic Mutations in Cancer (COSMIC) mutational signatures, frequent chromosomal alterations, somatic single nucleotide, and copy number variations were analyzed. The median TMB of 3.75 in primary OSCC was significantly lower (P < .001) than that of 147.51 mutations/Mb in primary HNcSCC. The COSMIC mutation signatures were significantly different (P < .001) between OSCC and HNcSCC. OSCC showed COSMIC single-base substitution (SBS) mutation signature 1 and AID/APOBEC activity-associated signature 2 and/or 13. All except 1 HNcSCC from hair-bearing scalp showed UV damage-associated COSMIC SBS mutation signature 7. Both OSCC and HNcSCC demonstrated a predominance of tumor suppressor gene mutations, predominantly TP53. The most frequently mutated oncogenes were PIK3CA and MUC4 in OSCC and HNcSCC, respectively. The metastases of OSCC and HNcSCC demonstrated TMB and COSMIC SBS mutation signatures similar to their primary counterparts. The combination of high TMB and UV signature in a metastatic keratinizing squamous cell carcinoma suggests HNcSCC as the primary site and may also facilitate decisions regarding immunotherapy. HNcSCC and OSCC show distinct genomic profiles despite histologic and immunohistochemical similarities. Their genomic characteristics may underlie differences in behavior and guide treatment decisions in recurrent and metastatic settings.

Whole genome duplication in oral squamous cell carcinoma in patients younger than 50 years: implications for prognosis and adverse clinicopathological factors.

INTRODUCTION: Oral squamous cell carcinoma (OSCC) in the young (<50 years), without known carcinogenic risk factors, is on the rise globally. Whole genome duplication (WGD) has been shown to occur at higher rates in cancers without an identifiable carcinogenic agent. We aimed to evaluate the prevalence of WGD in a cohort of OSCC patients under the age of 50 years. METHODS: Whole genome sequencing (WGS) was performed on 28 OSCC patients from the Sydney Head and Neck Cancer Institute (SHNCI) biobank. An additional nine cases were obtained from The Cancer Genome Atlas (TCGA). RESULTS: WGD was seen in 27 of 37 (73%) cases. Non-synonymous, somatic TP53 mutations occurred in 25 of 27 (93%) cases of WGD and were predicted to precede WGD in 21 (77%). WGD was significantly associated with larger tumor size (p = 0.01) and was frequent in patients with recurrences (87%, p = 0.36). Overall survival was significantly worse in those with WGD (p = 0.05). CONCLUSIONS: Our data, based on one of the largest WGS datasets of young patients with OSCC, demonstrates a high frequency of WGD and its association with adverse pathologic characteristics and clinical outcomes. TP53 mutations also preceded WGD, as has been described in other tumors without a clear mutagenic driver.

Electromyography in the prognostication of recovery in patients with acute peripheral facial nerve palsy: A systematic review.

OBJECTIVES: Needle electromyography (EMG) may be used to characterise the severity of the injury in acute peripheral facial nerve palsy (FNP) to predict recovery and guide management, but its prognostic value and clinical utility remain controversial. The aim of this systematic review was to evaluate the role of EMG to prognosticate the recovery of facial motor function in patients with acute peripheral FNP. DESIGN: A comprehensive search strategy was applied in PubMed, Embase, and Web of Science based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The main outcome measure was the accuracy of EMG in predicting long-term facial function at least 6 months following symptom onset. RESULTS: Eleven studies were included comprising 3837 participants, with 91.6% of these diagnosed with Bell's palsy (BP). In BP patients, the positive predictive value and negative predictive value for a good outcome based on EMG findings ranged from 82.1% to 100% and 66.7% to 80.5%, respectively, with two out of three studies finding that EMG remained a significant predictor of the outcome on multivariate analysis. Three studies addressed the role of EMG in non-idiopathic FNP with two of these studies supporting EMG to predict prognosis. CONCLUSIONS: EMG is a useful tool to gain insight into the likely outcome to guide management decisions and counsel patients on their expectations, particularly in BP. However, given inconsistencies in its application and lack of evidence around non-idiopathic FNP, it should not currently be relied on to predict recovery. Ultimately, its prognostic value and widespread adoption are dependent on the implementation of a clear and standardised protocol in future high-quality studies and routine clinical settings.

Recursive Partitioning to Determine Order of Significance of Regional Metastasis Characteristics in Head and Neck Cutaneous Squamous Cell Carcinoma.

BACKGROUND: The order of significance of clinicopathologic characteristics for the prognosis of patients with regional metastases from head and neck cutaneous squamous cell carcinoma (HNcSCC) is not well characterized. This study aimed to understand the impact of the known characteristics, including the presence of immunosuppression, number of deposits, largest deposit size, location and laterality of deposits, and presence of extranodal extension (ENE) on overall survival (OS) and disease-specific survival (DSS). METHODS: A retrospective study of 366 patients treated with curative intent for HNcSCC with regional metastatic disease was undertaken using recursive partitioning analysis (RPA). RESULTS: Using RPA modeling, the study determined that number of metastatic deposits carried the highest impact for both OS and DSS, followed by largest deposit size. The presence of ENE and immunosuppression was less significant. CONCLUSIONS: The results from this study provide new evidence for identifying and stratifying high-risk patients with metastatic HNcSCC. This information will be valuable in determining future HNcSCC staging systems.

Oral Epithelial Dysplasia: A Review of Diagnostic Criteria for Anatomic Pathologists.

Oral epithelial dysplasia (OED) represents a spectrum of histologic changes in the oral cavity mucosa that has the potential to transform into oral squamous cell carcinoma. Predicting the risk of malignant transformation is predominantly based on clinicopathologic correlation, histologic examination and grading. OED often poses a diagnostic challenge, primarily due to its histologic mimics and a large number of terminologies used in the literature. The grading system for OED is also fraught with significant interobserver variability. This review summarizes the essential clinical and histopathologic features of OED and its mimics. Practical preanalytical, analytical, and postanalytical considerations for anatomic pathologists are discussed to improve the diagnostic accuracy and increase the reproducibility in the grading of OED.

Regional Metastasis in Head and Neck Cutaneous Squamous Cell Carcinoma: An Update on the Significance of Extra-Nodal Extension and Soft Tissue Metastasis.

BACKGROUND: Soft tissue metastases (STMs) are reported to predict worse prognosis than extra-nodal extension (ENE) in metastatic head and neck cutaneous squamous cell carcinoma. This study aimed to update the authors' previous analysis of STM in a larger series. METHODS: The study analyzed 535 cases of consecutive cSCC metastatic to the parotid and/or neck treated by primary surgical resection between 1987 and 2007. A Cox proportional hazard model was used to determine the effect of STM, with adjustment for other relevant prognostic factors. Overall survival (OS) and disease-specific survival (DSS) were the primary end points. RESULTS: Of the 535 patients, 275 (51.4%) had STM. After adjustment for the effects of age, tumor location, number of metastatic deposits, and adjuvant radiotherapy, both STM (hazard ratio [HR], 1.55; 95% confidence interval [CI], 1.08-2.22; p = 0.018) and ENE (HR, 1.56; 95% CI 1.10-2.22; p = 0.013) were shown to be independent predictors of reduced OS, with similar size of effect. CONCLUSION: In metastatic cSCC of the head and neck, STM is an independent predictor of reduced survival and has an impact on survival similar to that of ENE.

Sentinel Node Biopsy in 105 High-Risk Cutaneous SCCs of the Head and Neck: Results of a Multicenter Prospective Study.

BACKGROUND: Regional nodal metastases from cutaneous squamous cell carcinoma (cSCC) is strongly associated with a poor prognosis, but these metastases are difficult to predict clinically. Sentinel node biopsy (SNB) has been used for a wide range of malignancies to assess for regional nodal metastasis, but is not widely used for cSCC. METHODS: Patients presenting with high-risk cSCC of the head and neck with clinically N0 necks were offered SNB at the time of primary cSCC excision or secondary wide local excision. Patients with positive sentinel nodes were offered completion lymph node dissection, and all the patients were followed up at regular intervals for up to 5 years. RESULTS: In this study, 105 lesions underwent SNB, and 10 sentinel nodes (9.5%) were positive. In an additional five patients, regional recurrence developed after a negative sentinel node, with a total subclinical nodal metastasis rate of 14.3%. Nodal metastases were significantly associated with reduced disease-specific survival. The significant predictors of metastasis were four or more high-risk features or tumors with a concurrent invasion deeper than 5 mm and PNI. CONCLUSION: For high-risk cSCC, SNB is a safe and feasible staging technique. The total number of high risk features and certain combinations of high-risk features predicted metastasis better than individual high-risk features.

Validation of the eighth edition AJCC staging system in early T1 to T2 oral squamous cell carcinoma.

BACKGROUND: To validate the newly proposed American Joint Committee on Cancer (AJCC) eighth edition staging in early T1 and T2 oral cavity cancers and its effect in predicting tumour control. METHODS: Retrospective analysis of treatment outcomes of 441 T1 to T2 oral squamous cell carcinoma (OSCC). Overall survival (OS), disease-specific survival (DSS), and tumour control were calculated and compared between the AJCC 7 and 8 staging systems. RESULTS: The 5-year OS was 78% and 61% for T1 and T2 tumours, respetively (P < 0.001) (AJCC 7) vs 87% and 67% (P < 0.001) (AJCC 8). The 5-year DSS was 78% and 61% for T1 and T2, respectively (P < 0.001) (AJCC 7) vs 89% and 71% (P < 0.001) (AJCC 8). For stages I and II tumours the 5-year OS was 81% and 76%, respectively (P < 0.302) (AJCC 7) vs 87% and 73% (P < 0.017) (AJCC 8). The 5-year DSS was 83% and 82% (P < 0.222) vs 89% and 77% (P < 0.016). With the AJCC eighth edition the 5-year local, regional, and distant control rates for T1 vs T2 tumours were 85% vs 74% (P = 0.003), 95% vs 77% (P = 0.001), and 95% vs 80% (P = 0.014), respectively. CONCLUSION: The AJCC 8th staging system provided for more accurate prediction of OS, DSS, and disease control in early oral cavity cancers.

Analysis of clinically relevant somatic mutations in high-risk head and neck cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma is the second most prevalent malignancy, most frequently occurring in the head and neck (head and neck cutaneous squamous cell carcinoma). Treatment of locally advanced or metastatic disease is associated with functional morbidity and disfigurement. Underlying genetic mechanisms are poorly understood. Targeted sequencing of 48 clinically relevant genes was performed on DNA extracted from formalin-fixed and paraffin-embedded high-risk primary head and neck cutaneous squamous cell carcinomas that remained non-metastatic at minimum follow-up of 24 months. Associations of somatic mutations with clinicopathologic characteristics were evaluated and compared with those described in the literature for metastatic disease. Alterations in 44 cancer-associated genes were identified. TP53 was mutated in 100% of cases; APC, ATM, ERBB4, GNAQ, KIT, RB1 and ABL1 were altered in 60% of cases. FGFR2 mutations (40%) were exclusively seen in patients with perineural invasion. MLH1 mutations were exclusively seen in the two younger patients (<45 years). Lower incidences of NOTCH1 mutations were observed compared with that described in metastatic head and neck cutaneous squamous cell carcinoma in the literature. Somatic mutations susceptible to EGFR inhibitors, and other small molecular targeted therapeutics were seen in 60% of cases. This study provides insights into somatic mutations in non-metastatic, high-risk head and neck cutaneous squamous cell carcinoma and identifies potential therapeutic targets. Alterations in FGFR2 and NOTCH1 may have roles in local and distant disease progression.

Analysis and Comparison of the 8th Edition American Joint Committee on Cancer (AJCC) Nodal Staging System in Cutaneous and Oral Squamous Cell Cancer of the Head and Neck.

BACKGROUND: The American Joint Committee on Cancer (AJCC) uses the same nodal staging system for cutaneous and mucosal squamous cell carcinoma of the head and neck in its 8th edition (AJCC 8) despite differences in the etiology, risk factors, and clinical behavior of the two diseases. This study aims to evaluate the performance of the AJCC 8 nodal staging system by direct comparison of cutaneous (cSCC) versus oral squamous cell carcinoma (oSCC) patients. METHODS: Patients with metastatic cSCC (N = 382) and oSCC (N = 325) were identified from a prospective database (years 1987-2016). Multivariable analysis was performed using Cox proportional hazards competing risk model. To assess staging system performance, an explained variation measure (proportion of variation explained, PVE) as well as a discrimination measure (Harrell's concordance index, C-index) were used. RESULTS: Inclusion of extranodal extension (ENE) in AJCC 8 increased the proportion of patients in N3b category (48.7% in cSCC, 40.3% in oSCC). AJCC 8 stratified poorly with regards to risk of death from cSCC and oSCC and showed limited monotonicity of the nodal categories. Estimates of model performance revealed modest predictive capacity for overall survival (OS) and disease-specific survival (DSS) in oSCC (Harrell's C of 0.66 in both) and weak predictive capacity in cSCC (Harrell's C of 0.58 and 0.61, respectively). CONCLUSIONS: The AJCC 8 nodal staging system performs poorly in terms of stratifying survival by N category, especially in cSCC. The data indicate that cSCC merits an independent nodal staging system from that for mucosal SCC.

Predictive value of the 8th edition American Joint Commission Cancer (AJCC) nodal staging system for patients with cutaneous squamous cell carcinoma of the head and neck.

BACKGROUND: The 8th edition American Joint Committee on Cancer (AJCC8) provides the same nodal staging system for mucosal and cutaneous squamous cell carcinoma of the head and neck (HNcSCC) and includes extranodal extension (ENE) as an adverse prognostic criterion. This study evaluates the prognostic efficacy of the AJCC8 pathologic nodal staging system (pN) for HNcSCC. METHODS: Univariate analysis of 382 patients with metastatic HNcSCC staged according to both the 7th (AJCC7) and the 8th edition staging systems. RESULTS: The AJCC7 pN3 category was associated with reduced disease specific survival (DSS HR 5.49; 95% CI: 1.83-16.53; P = 0.002) and overall survival (OS HR 3.42; 95% CI: 1.54-7.58; P = 0.002) as compared with pN1. However, no difference was observed between pN1, pN2, and pN3 categories as defined by the AJCC8. Also, when comparing Stages III and IV as defined by AJCC8, there was no difference in DSS (HR 0.75; 95% CI: 0.34-1.67; P = 0.478) or OS (HR 0.88; 95% CI: 0.51-1.51; P = 0.648). CONCLUSION: The AJCC8 performed poorly as a prognostic indicator for patients with metastatic HNcSCC in this cohort. HNcSCC would benefit from a staging system that accounts for its unique biologic characteristics distinct from mucosal SCC.

Factors Affecting Survival in Surgically Salvaged Locoregional Recurrences of Squamous Cell Carcinoma of the Tongue.

PURPOSE: To determine the factors affecting outcomes in surgically salvaged, locoregionally recurrent squamous cell carcinoma of the tongue (SCCT). MATERIALS AND METHODS: In a retrospective cohort of patients who underwent successful salvage of locoregionally recurrent SCCT, we performed this observational analytical study to determine survival and its determinants. Details extracted from our database were patient characteristics (age, gender, tobacco use), treatment characteristics, and characteristics of recurrent disease (stage and adverse pathologic features [APFs] such as grade, perineural invasion, and lymphovascular invasion). Overall survival (OS) curves were plotted using the Kaplan-Meier method. A Cox proportional hazards model was used to determine the impact of patient, disease, and treatment characteristics on OS. RESULTS: Of 52 patients with locoregional recurrences of surgically treated SCCT, 25 (48.1%) underwent surgical salvage with curative intent. The median overall OS for this cohort was 26 months. Factors predictive of worse OS were previous adjuvant therapy (P = .016) and increasing APFs in recurrent tumor histology (P = .008). Lymphovascular invasion in recurrent tumor histology and patients with a disease-free interval of less than 6 months showed worse survival (P = .008 and P = .058, respectively). CONCLUSIONS: Among patients with locoregional recurrence, the number who are eligible for curative-intent surgical salvage is small. Those who received previous adjuvant therapy and those with increasing APFs in recurrent tumors had poor outcomes despite attempts at surgical salvage, particularly patients with early recurrence.

Reconstruction of maxillary defect with musculo-adipose rectus free flap.

BACKGROUND: The rectus myocutaneous free flap (RMFF) is used for medium to large maxillectomy defects. However, in patients with central obesity the inset could be difficult due to the bulk from excessive layer of adipose tissue. We describe a modification of the RMFF for patients with excessive central obesity with a flap consisting of adipose tissue with minimal rectus muscle; the musculo-adipose rectus free flap (MARF). METHODS: Five cases of MARF reconstruction were performed between 2003 and 2013, with patients' body mass indexes ranging from 29.0 to 41.2 kg/m2 . All patients had sinonasal tumor, of which three were adenoid cystic carcinoma, one squamous cell carcinoma, and one melanoma. Four patients had Codeiro IIIb defects and one had Codeiro II defect. Using the MARF technique, the maxillectomy defect was obliterated with vascularized adipose tissue overlying the rectus muscle and was trimmed to fit the maxillectomy defect. The adipose tissue was allowed to granulate and mucosalize. RESULTS: The volume of adipose tissue harvested was between 120 and 160 mL. All flaps survived with no requirement for re-exploration. Complete oro-nasal separation was achieved in all patients. The time to commencement of oral intake ranges from 5 to 15 days. One patient developed seroma and one developed wound breakdown on the donor site. The length of stay at the hospital ranges from 9 to 22 days. On follow-up ranging 7.5-32.8 months, two patients died from their malignancies. The other three patients were able to tolerate oral soft diet. CONCLUSION: The MARF may be considered as an alternative to myocutaneous rectus free flap particularly for the reconstruction of maxillary defects in patients with central obesity. © 2015 Wiley Periodicals, Inc. Microsurgery 37:137-141, 2017.

Perineural invasion in oral squamous cell carcinoma: quantitative subcategorisation of perineural invasion and prognostication.

BACKGROUND: Evidence regarding the prognostic value of perineural invasion (PNI) in oral squamous cell carcinoma (OSCC) and whether PNI alone warrants consideration of adjuvant therapy is controversial. We evaluated whether histopathological sub-categorization of PNI improves risk stratification. METHODS: PNI was evaluated for nerve size, number of foci, and distance from the tumor in 318 OSCC patients. Univariable and multivariable analyses were performed, with local failure (LF) and disease-specific survival (DSS) as the primary endpoints. RESULTS: PNI did not influence prognosis when classified as absent versus present. In contrast, multifocal PNI was associated with LF (P = 0.049) and decreased DSS (P = 0.043) on multivariable analyses. The size of the involved nerve separated those with multifocal PNI into intermediate (<1 mm) and high-risk (≥1 mm) groups. Unifocal PNI and distance from the tumor did not influence prognosis. Multifocal PNI was associated with worse prognosis irrespective of post-operative radiotherapy (PORT). CONCLUSIONS: Multifocal PNI is associated with poor outcomes even with PORT suggesting consideration of therapeutic escalation, particularly with involved nerves ≥1 mm. Unifocal PNI did not affect prognosis even in the absence of PORT, which may not be required if this is the sole risk factor. Prospective validation and testing of these hypotheses is essential before implementation.

When should patients with T1N0 oral squamous cell carcinoma be considered for elective neck dissection?

AIMS: To identify adverse pathological features (APF) predicting nodal failure in clinically node negative T1 oral squamous cell carcinoma (OSCC). METHODOLOGY: This study evaluated patients with T1N0 (≤5 mm depth of invasion (DOI) and ≤2 cm diameter) oral cancers from a prospectively maintained database between 1988 and 2020. All patients underwent surgical excision of the primary lesion without neck dissection. Patients underwent three monthly clinical surveillance and salvage neck dissection was performed if nodal relapse was diagnosed. RESULTS: Overall, 141 patients were included. Nodal relapse was reported in 16/141 (11.3%) patients. Factors impacting regional recurrence-free survival were DOI ≥3 mm (HR: 2.4, P < 0.001), maximum tumour diameter ≥12 mm (HR: 1.1, P = 0.009), perineural invasion (PNI) (HR 7.5, P = 0.002) and poor differentiation (HR 5.3, P = 0.01). Rates of nodal relapse increased from 2% amongst patients with no APFs to 100% for those with four APFs. Patients with two or more APFs had significantly poorer 5-year regional recurrence-free survival (94.8% vs. 56.3%, P < 0.001). CONCLUSION: Patients with T1N0 OSCC with two or more APFs (DOI ≥3 mm, diameter ≥12 mm, PNI or poor differentiations) should be considered for elective neck dissection.

Surgical and health related quality of life outcomes following treatment with zygomatic implant perforated (ZIP) flaps.

BACKGROUND: The zygomatic implant perforated (ZIP) flap is a novel approach to the challenge of reconstructing the maxilla. We report on our experience using the ZIP flap technique for patients undergoing infrastructure maxillectomy at Chris O'Brien Lifehouse, Sydney, Australia. METHODS: Thirteen patients who underwent a ZIP flap reconstruction between August 2019 and August 2021 were identified. Demographic, surgical, and histopathological information was collected. Health Related Quality of Life (HRQOL) was assessed using the FACE-Q Head and Neck Cancer module, the M.D. Anderson Dysphagia Inventory, and the Speech Handicap Index. RESULTS: A total of 44 zygomatic implants were placed, of which 42 (95%) survived. The median time from surgery to dental rehabilitation was 35 days. HRQOL data was available for nine patients over 24 months, demonstrating improved speech and swallowing outcomes over the follow up period. CONCLUSIONS: The ZIP flap is a reproducible surgical technique that facilitates rapid dental rehabilitation post infrastructure maxillectomy.

Prognostic and predictive biomarkers in head and neck cancer: something old, something new, something borrowed, something blue and a sixpence in your shoe.

A biomarker is a measurable indicator of biological or pathological processes or the response to an exposure or intervention and is used to guide management decisions. In head and neck pathology, biomarkers are assessed by histological criteria and immunohistochemical and molecular studies. Surgical resection remains the mainstay of management of many head and neck malignancies. Adjuvant radiotherapy and/or systemic therapy may be administered depending on the presence of adverse prognostic factors identified on histopathological or immunohistochemical examination. In this review, we outline the clinically relevant prognostic and predictive factors in head and neck malignancies including conventionally recognised factors such as tumour size, depth of invasion, lymphovascular and perineural invasion and margin status as well as novel evolving factors such as recurrent genetic rearrangements and assessment of immune checkpoints. Practical issues are discussed to assist with recognising and reporting of these factors. A summary of useful tools such as structured pathology report formats is also included to assist with comprehensive reporting of all clinically relevant parameters, minimise risk and improve workflow efficiencies.

First Phase Development of a Patient-reported Outcome Measure for Midface Oncology.

Background: Facial cancer surgery involving the midface (comprising the lower eyelids, nose, cheeks, and upper lip) can have debilitating life-changing functional, social, and psychological impacts on the patient. Midface symptoms are inadequately captured by existing patient-reported outcome measures (PROMs). PROMs are increasingly used for individual patient care, quality improvement, and standardized reporting of treatment outcomes. This study aimed to present our findings from the first phase of the development of a midface, specifically periocular and nasal, PROM. Methods: After international guidance for PROM development, the first phase comprised identification of salient issues and item generation. Fifteen patients who had midface surgery and 10 clinicians from various specialties with more than 5 years' experience treating these patients were recruited. Semi-structured interviews explored aesthetic, functional, social, and psychological outcomes, with specific attention to deficiencies in current PROMs. Thematic analysis was used to develop an item pool, and group interviews with clinicians were carried out to create and refine PROM scales. Results: Qualitative data from patient interviews were grouped into aesthetic, functional, and psychosocial domains for the eyelids and nose. Ninety-nine draft items were generated across these domains. Following focus group discussions, the final version of the midface-specific PROM contained 31 items (13 eye-specific, 10-nose-specific, eight general midface items). Conclusions: This midface-specific PROM is valuable in assessing and comparing patient-reported outcomes in those who have undergone complex resection and reconstruction of the midface. This PROM is currently undergoing field testing.