A phase 1, single centre, open label, escalating dose study to assess the safety, tolerability and immunogenicity of a therapeutic human papillomavirus (HPV) DNA vaccine (AMV002) for HPV-associated head and neck cancer (HNC).

BACKGROUND: We conducted a phase 1 dose escalation study (ACTRN12618000140257 registered on 30/01/2018) to evaluate the safety, tolerability and immunogenicity of a therapeutic human papillomavirus (HPV) DNA vaccine (AMV002) in subjects previously treated for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). METHODS: Eligible subjects had to have no evidence of recurrent and/or metastatic disease at least 12 weeks following the completion of treatment. Three dosing cohorts each consisted of four subjects: group 1: 0.25 mg/dose, group 2: 1 mg/dose, group 3: 4 mg/dose. AMV002 was delivered intradermally on days 0, 28 and 56. Incidence and severity of treatment-emergent adverse events (TEAE) including local reaction at the injection site, and vaccination compliance were recorded. T cell and antibody responses to HPV16 E6 and E7 were measured by interferon gamma (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) assay and enzyme-linked immunosorbent assay (ELISA). RESULTS: All subjects completed the vaccination programme and experienced mild discomfort at the injection site(s). Pre-immunisation, cell-mediated responses to HPV16 E6 and E7 were evident in all subjects, and E7-specific antibodies were detected in 11 (91.7%), reflecting previous exposure to HPV. Post-vaccination, 10 of 12 (83.3%) subjects responded to one or more of the E6 and/or E7 peptide pools, while 2 (16.7%) did not show additional vaccine-induced cell-mediated responses. Vaccination resulted in a ≥ 4-fold increase in anti-HPV16 E7 antibody titre in one subject in group 3. CONCLUSIONS: AMV002 was well tolerated at all dose levels and resulted in enhanced specific immunity to virus-derived tumour-associated antigens in subjects previously treated for HPV-associated OPSCC.

Recommendations for head and neck surgical oncology practice in a setting of acute severe resource constraint during the COVID-19 pandemic: an international consensus.

The speed and scale of the global COVID-19 pandemic has resulted in unprecedented pressures on health services worldwide, requiring new methods of service delivery during the health crisis. In the setting of severe resource constraint and high risk of infection to patients and clinicians, there is an urgent need to identify consensus statements on head and neck surgical oncology practice. We completed a modified Delphi consensus process of three rounds with 40 international experts in head and neck cancer surgical, radiation, and medical oncology, representing 35 international professional societies and national clinical trial groups. Endorsed by 39 societies and professional bodies, these consensus practice recommendations aim to decrease inconsistency of practice, reduce uncertainty in care, and provide reassurance for clinicians worldwide for head and neck surgical oncology in the context of the COVID-19 pandemic and in the setting of acute severe resource constraint and high risk of infection to patients and staff.

Economic Analysis of a Three-Arm RCT Exploring the Delivery of Intensive, Prophylactic Swallowing Therapy to Patients with Head and Neck Cancer During (Chemo)Radiotherapy.

Research advocates for the use of intensive, prophylactic swallowing therapy to help reduce the severity of dysphagia in patients receiving (chemo)radiotherapy ([C]RT) for head/neck cancer (HNC). Unfortunately, the intensity of this therapy, coupled with growing patient numbers and limited clinical resources, provides challenges to many international cancer facilities. Telepractice has been proposed as a potential method to provide patients with greater support in home-practice, whilst minimising burden to the health service. This study investigated the clinical and patient-attributable costs of delivering an intensive, prophylactic swallowing therapy protocol via a new telepractice application "SwallowIT" as compared to clinician-directed FTF therapy and independent patient self-directed therapy. Patients (n = 79) with oropharyngeal HNC receiving definitive (C)RT were randomised to receive therapy via a: clinician-directed (n = 26), patient-directed (n = 27), or SwallowIT-assisted (n = 26) model of care. Data pertaining to health service costs (service time, consumables, therapy resources), patient-attributable costs (travel and wages) and patient-reported health-related quality of life (QoL) (AQoL-6D) were collected. SwallowIT provided a cost-efficient model of care when compared to the clinician-directed model, with significant cost savings to both the health service and to HNC consumers (total saving of $1901.10 AUD per patient; p < 0.001). The SwallowIT model also proved more cost-effective than the patient-directed model, yielding clinically significantly superior QoL at the end of (C)RT, for comparable costs. Overall, when compared to the alternate methods of service-delivery, SwallowIT provided a financially viable and cost-effective method for the delivery of intensive, prophylactic swallowing therapy to patients with HNC during (C)RT.

Sexual behaviour, HPV status and p16INK4a expression in oropharyngeal and oral cavity squamous cell carcinomas: a case-case comparison study.

A significant proportion of mucosal squamous cell carcinomas of the head and neck (HNSCC; particularly of the oropharynx) are directly attributable to the human papillomavirus (HPV). The increase in the incidence of HPV-related tumours has been postulated to be due to changing sexual practices in the community. We analysed 136 formalin-fixed paraffin-embedded squamous cell carcinomas from the oral cavity (n=40) and oropharynx (n=96) recruited from the Princess Alexandra Hospital (Brisbane, Australia). Samples were analysed for the presence of HPV DNA using a combination of mucosal HPV general primer GP+ PCR and sequencing; p16INK4a expression was assessed by immunohistochemistry. Each patient completed a questionnaire detailing their lifestyle factors, such as tobacco smoking and alcohol consumption, marital status, and sexual behaviour and history. The HPV DNA prevalence was 5 % in the oral cavity cancers and 72 % in the oropharyngeal cancers (P<0.0001). HPV-16 was the most commonly detected HPV type (found in 91 % of all HPV-positive tumours). There was a strong correlation between HPV DNA positivity and positive p16INK4a staining in oropharyngeal tumours (P<0.0001). Having an HPV-related tumour was associated with being married or having been married previously (P=0.046), an increasing number of passionate kissing partners (P=0.046), ever having given oral sex (P=0.0007) and an increasing number of oral sex partners (P=0.0015). This study found a higher prevalence of HPV in oropharyngeal compared to oral cavity tumours, with a strong association being identified between oral sex behaviours and HPV-positive tumours. Further research is needed to establish that vaccines will reduce the transmission and carriage of oropharyngeal HPV infections.

Management of elderly patients with locoregionally confined head and neck cancer.

Head and neck cancer in elderly patients represents a major health burden because its management provides unique and complex challenges for multidisciplinary teams, such as reduced treatment tolerance, multiple comorbidities, and altered pharmacokinetics and pharmacodynamics. Despite the prominent challenges involved, high-level evidence for the management of this group of patients is scarce. Substantial advances in treatment, such as robotic surgery, dynamic intensity-modulated radiation therapy, immunotherapy, and de-escalation trials, might allow for improved treatment tolerance in this patient population. Advanced age alone does not appear to be a contraindication to curative treatment. Evaluation of age-specific factors such as life expectancy, impaired functional status, and cognitive decline warrant consideration as part of the management decision process. In this Review, we provide an update of the available evidence on the management of locoregionally confined head and neck cancer in elderly patients and propose a practical treatment algorithm for clinicians to help manage this patient population.

Past sexual behaviors and risks of oropharyngeal squamous cell carcinoma: a case-case comparison.

The incidence of oropharyngeal squamous cell carcinomas (SCCs) is increasing and is believed to reflect changing sexual practices in recent decades. For this case-case comparative study, we collected medical and life-style information and data on sexual behavior from 478 patients treated at the head and neck clinic of a tertiary hospital in Brisbane, Australia. Patients were grouped as (i) oropharyngeal SCC (n = 96), (ii) oral cavity, larynx and hypopharynx SCC ("other HNSCCs," n = 96), (iii) other SCCs (n = 141), and (iv) other diagnoses (n = 145). We fitted multivariable logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) associated with lifestyle factors and sexual behaviors. Compared to the other three patient groups, the oropharyngeal SCC patients had overall more sexual lifetime partners (kissing, oral sex and sexual intercourse). Oropharyngeal SCC patients were significantly more likely to have ever given oral sex compared to the other three patient groups-93% of oropharyngeal SCC patients, 64% of other HNSCC patients, and 58% of patients with other SCC or other diagnoses. Oropharyngeal SCC patients were significantly more likely to have given oral sex to four or more partners when compared to patients with other HNSCC (odds ratio [OR] 11.9; 95% CI 3.5-40.1), other SCC (OR 16.6; 95% CI 5.3-52.0) or patients with other diagnoses (OR 25.2; 95% CI 7.8-81.7). The very strong associations reported here between oral sex practices and risks of oropharyngeal SCC support the hypothesis that sexually transmitted HPV infections cause some of these cancers.

Adherence to a Prophylactic Swallowing Therapy Program During (Chemo) Radiotherapy: Impact of Service-Delivery Model and Patient Factors.

Intensive, prophylactic swallowing therapy programs have been developed to improve dysphagia outcomes for patients with head/neck cancer (HNC) receiving (chemo)radiotherapy ([C]RT). Across studies, variable therapy adherence rates have been reported. Preliminary research suggests that service-delivery mode and demographic factors may influence adherence. This study examined patient adherence to a prophylactic swallowing therapy protocol across three service-delivery models: (1) clinician-directed face-to-face therapy, (2) technology-assisted therapy using the telepractice application, SwallowIT and (3) independent patient-directed therapy. The secondary aim explored the impact of patient factors on adherence. Patients with oropharyngeal HNC receiving definitive (C)RT were randomised to receive the Pharyngocise exercise protocol via clinician-directed (n = 26), patient-directed (n = 27) or SwallowIT-assisted (n = 26) models. Adherence was calculated as the percentage of prescribed exercise completed. Multiple patient factors were recorded at baseline. Adherence across the 6 weeks in all groups was low (27%), and declined from week 4 of (C)RT. The clinician-directed model yielded significantly (p = 0.014) better adherence than patient-directed therapy in weeks 1-3. There was also a trend for higher adherence in the SwallowIT group compared to patient-directed in weeks 1-3 (p = 0.064). Multivariable linear modelling identified active smoking at baseline (p < 0.001) and concomitant chemotherapy (p = 0.040) as significant negative predictors of adherence, with baseline reduced motivation trending towards significance. Although (C)RT-related toxicities will impact adherence, adopting service-delivery models with greater structure/support and providing extra assistance to patients with known risk factors may help optimise therapy adherence to prophylactic therapy programs. Telepractice may provide an alternate model to support adherence where service constraints limit intensive clinician-directed therapy.

Variants of EVER1 and EVER2 (TMC6 and TMC8) and human papillomavirus status in patients with mucosal squamous cell carcinoma of the head and neck.

PURPOSE: There is a growing association of human papillomavirus (HPV) with some cases of mucosal squamous cell carcinoma of the head and neck (HNSCC), particularly of the oropharynx. Persistent oral HPV infection is believed to increase the likelihood of malignancy, and it is possible that host genetic factors can determine susceptibility to persistent HPV infection. Polymorphisms in the two EV genes (EVER1 and EVER2, also known as transmembrane channel protein (TMC) 6 and 8) have been identified as strong candidate genes, since a small number of critical mutations in these genes have been shown to cause profound and florid skin HPV infections, and some of them have been linked to susceptibility to cervical cancer. METHODS: We sought to determine whether there was a difference in the frequency of single nucleotide polymorphisms (SNPs) in EVER1 (rs2613516, rs12449858) and EVER2 (rs7205422, rs12452890) between HNSCC patients with HPV-positive and HPV-negative tumors, and healthy controls. We used logistic regression to analyze SNPs in 219 patients with histologically confirmed primary SCC of the oropharynx, oral cavity, hypopharynx, or larynx, and 321 healthy controls. RESULTS: We did not find any associations with the EVER1/EVER2 SNPs and HPV status or being a HNSCC case or a control. CONCLUSIONS: The present data do not provide evidence for a role of genetic variations in EVER1 or EVER2 for HPV status of mucosal HNSCC or between HNSCC patients and controls.

Evaluation of a weekly speech pathology/dietetic service model for providing supportive care intervention to head and neck cancer patients and their carers during (chemo)radiotherapy.

PURPOSE: Dysphagia is a common and debilitating side effect for head and neck cancer (HNC) patients undergoing radiotherapy (RT) with or without chemotherapy ([C]RT) and is associated with nutritional and emotional comorbidities. Emotional sequelae and distress are also known to affect carers of HNC patients. A weekly, joint speech pathology/dietetic (SP/DN) service-delivery model has been employed to manage swallowing/nutritional and associated emotional issues during (C)RT. This study aimed to conduct a service evaluation of the weekly SP/DN clinical model. METHODS: Cross-sectional sampling of core service metrics and perceptions of key stakeholders (70 HNC patients, 30 carers, and 10 clinicians) were collated from the Metro South Radiation Oncology Service in Brisbane, Australia. Data from each source was examined separately and then triangulated. RESULTS: An average of 28 patients (SD = 5.54) attended SP/DN appointments per week, with 58% reporting swallowing and/or nutritional issues. Distress was reported by 27% of patients and 30% of carers. Clinicians felt able to adequately identify and manage swallowing and nutrition 90% of the time but only 10% of the time for distress. Seventy-six percent of scheduled SP/DN sessions were perceived as necessary by either patients, clinicians or both. CONCLUSIONS: Findings demonstrated a third of patients and their carers had a high level of distress during HNC [C]RT, supporting need for the provision of a weekly SP/DN service in a select cohort. However, the routine weekly SP/DN assessment model for all patients undergoing HNC treatment demonstrates the potential for over-servicing. Alternative service-delivery models warrant further evaluation.

Application of the International Classification of Functioning, Disability and Health (ICF) to people with dysphagia following non-surgical head and neck cancer management.

The International Classification of Functioning, Disability, and Health (ICF) is an internationally recognized framework which allows its user to describe the consequences of a health condition on an individual in the context of their environment. With growing recognition that dysphagia can have broad ranging physical and psychosocial impacts, the aim of this paper was to identify the ICF domains and categories that describe the full functional impact of dysphagia following non-surgical head and neck cancer (HNC) management, from the perspective of the person with dysphagia. A secondary analysis was conducted on previously published qualitative study data which explored the lived experiences of dysphagia of 24 individuals with self-reported swallowing difficulties following HNC management. Categories and sub-categories identified by the qualitative analysis were subsequently mapped to the ICF using the established linking rules to develop a set of ICF codes relevant to the impact of dysphagia following HNC management. The 69 categories and sub-categories that had emerged from the qualitative analysis were successfully linked to 52 ICF codes. The distribution of these codes across the ICF framework revealed that the components of Body Functions, Activities and Participation, and Environmental Factors were almost equally represented. The findings confirm that the ICF is a valuable framework for representing the complexity and multifaceted impact of dysphagia following HNC. This list of ICF codes, which reflect the diverse impact of dysphagia associated with HNC on the individual, can be used to guide more holistic assessment and management for this population.

Carers' experiences of dysphagia in people treated for head and neck cancer: a qualitative study.

The implication of dysphagia for people treated nonsurgically for head and neck cancer (HNC) and its detrimental effects on functioning and quality of life has been well documented. To date, however, there has been a paucity of research on the effects of dysphagia following HNC on carers, independent of the consequences of a gastrostomy. The objective of this qualitative study was to report on the experiences of carers of people with dysphagia (non-gastrostomy dependent) following nonsurgical treatment for HNC and to identify the support needs of this group. A purposive, maximum-variation sampling technique was adopted to recruit 12 carers of people treated curatively for HNC since 2007. Each participated in an in-depth interview, detailing their experience of caring for someone with dysphagia and the associated impact on their life. Thematic analysis was adopted to search the transcripts for key phases and themes that emerged from the discussions. Analysis of the transcripts revealed four themes: (1) dysphagia disrupts daily life, (2) carers make adjustments to adapt to their partner's dysphagia, (3) the disconnect between carers' expectations and the reality of dysphagia, and (4) experiences of dysphagia-related services and informal supports. Carers generally felt ill-prepared for their role in dysphagia management. The qualitative methodology successfully described the impact of dysphagia on the everyday lives of carers, particularly in regard to meal preparation, social events, and family lifestyle. Clinicians should provide adequate and timely training and support to carers and view carers as copartners in dysphagia management.

Survivors' experiences of dysphagia-related services following head and neck cancer: implications for clinical practice.

BACKGROUND: It is known that people with dysphagia experience a number of negative consequences as a result of their swallowing difficulties following head and neck cancer management (HNC). However their perceptions and experiences of adjusting to dysphagia in the post-treatment phase, and the services received to assist this process, has not been studied. AIMS: To explore the lived experience of people with dysphagia following non-surgical treatment for HNC and examine their perceptions of service needs. METHODS & PROCEDURES: A demographically diverse group of 24 people who had received radiotherapy for HNC in the past five years, and experienced dysphagia as a result of treatment, were recruited using maximum variation sampling. Each participant took part in a semi-structured, in-depth interview, where they reflected on their adjustment to, and recovery from dysphagia following treatment for HNC, as well as the dysphagia-related services they received during their treatment. Thematic analysis was used to analyse the transcripts and to identify key themes that emerged from the data. RESULTS: The main integrative theme was the desire for ongoing access to dysphagia-related services in order to adequately manage dysphagia. Within this integrative theme were five additional themes including: (1) entering the unknown: life after treatment for HNC; (2) making practical adjustments to live with dysphagia; (3) making emotional adjustments to live with dysphagia; (4) accessing support outside the hospital services; and (5) perceptions of dysphagia-related services. CONCLUSIONS & IMPLICATIONS: The interviews revealed the need for both greater access to services and a desire for services which address the multitude of issues faced by people with dysphagia following HNC in the post-treatment period. Speech and language therapists managing this caseload need to ensure post-treatment services are available and address not only the physical but also the emotional and psychosocial changes impacting people with dysphagia in order to assist them to adjust to, and live successfully with dysphagia. Further research should be conducted to support the development of innovative services and to highlight dysphagia-related survivorship issues to governing bodies/policy makers.

Characterising B cell expression and prognostic significance in human papillomavirus positive oropharyngeal cancer.

OBJECTIVES: The incidence of human papillomavirus positive oropharyngeal cancer (HPV+OPC) is increasing, and new biomarkers are required to better define prognostic groups and guide treatment. Infiltrating T cells have been well studied in head and neck cancer, however the presence and role of B cells and tertiary lymphoid structures (TLS) in the tumor microenvironment has not, even though the interplay between T and B cells is increasingly being recognised. MATERIALS AND METHODS: Using CD20 immunohistochemistry (IHC) to identify B cells and TLS in a cohort of 159 HPV + OPC patients, we semi-quantitatively scored abundance and location (intra-tumoral or stromal) and correlated findings with patient survival. RESULTS: 32% (51/157) of patients had high intra-tumoral (IT) abundance of CD20+ B cells (≥5%) and this was prognostic for improved overall survival (OS) with an adjusted hazard ratio (HR) of 0.2 (95 % CI 0.0-0.7, p = 0.014). We validated our results in an independent cohort comprising 171 HPV + OPC where 14% (23/171) were IT CD20+ high, again showing improved survival with an adjusted HR for OS of 0.2 (95 % CI 0.0-1.4, p = 0.003). Neither stromal abundance nor the presence of TLS were prognostic in either cohort. B cells were subtyped by multispectral IHC, identifying CD20+CD27+ cells, consistent with memory B cells, as the predominant subtype. Combined with validated biomarker CD103, a marker of tissue-resident memory T cells, IT CD20+ B cells abundance was able to prognostically stratify patients further. CONCLUSIONS: CD20+ B cell abundance has the potential to be used as a biomarker to identify good and poor prognosis HPV + OPC patients.

Human papillomavirus associated oropharyngeal cancer now the most common mucosal head and neck cancer in Queensland.

INTRODUCTION: The profile and outcomes of head and neck cancer throughout Australia has changed over the past decade. The aim of this study was to perform a population-based analysis of incidence, demographics, stage, treatments and outcomes of patients diagnosed with oropharyngeal squamous cell carcinoma (OPSCC), with a particular focus on HPV-associated disease. METHODS: This was a retrospective analysis of prospectively collected data within the Queensland Oncology Repository (QOR) and analysed by the Queensland Cancer Control Analysis Team. The cohort included patients diagnosed in Queensland between 1 January 2015 and 31 December 2019. Outcome measures included incidence of new OPSCC cases, age-standardised rates (ASR) (3-year average), demographics, p16 status, stage (8th Edition American Joint Commission on Cancer), treatments, and 2- and 5-year overall survival. RESULTS: There were 1527 newly diagnosed OPSCC, representing 96% (1527/1584) of all oropharyngeal cancers. It was the most common head and neck cancer diagnosed, with oral cavity cancer being the second most common (n = 1171). Seventy-seven percent were p16 positive (1170/1527), of which 87% (1019/1170) were male. The median age was 61 years and 49% (568/1170) presented with Stage I disease. The ASR was 6.3/100,000, representing a 144% incidence increase since 1982 (2.6/100,000). Radiotherapy was utilised in 91% of p16+ cases with 2- and 5- year overall survival of 89% and 79%, respectively. CONCLUSION: OPSCC is now the most common mucosal head and neck cancer diagnosed in Queensland, having surpassed oral cavity cancer. The majority are HPV-associated (p16+), presenting with early-stage disease with a favourable prognosis.

The Current Treatment Landscape of Cutaneous Squamous Cell Carcinoma.

Non-melanoma skin cancers (NMSCs) are the most common form of skin cancer worldwide. The global incidence of cutaneous squamous cell carcinoma (CSCC) is rising, with an estimated 2.4 million cases diagnosed in 2019. Chronic exposure to ultraviolet (UV) radiation is a major risk factor for developing CSCC. Most early-stage CSCCs are treated successfully with surgery or radiotherapy; however, locally advanced or metastatic disease can be associated with significant morbidity or mortality. Recently, the treatment paradigm for advanced CSCC has been revolutionised by the introduction of immunotherapy, which can achieve a response rate of approximately 50% with durable cancer control, and significant improvement in quality of life. With the regulatory approval of programmed death-1 (PD-1)-targeting drugs since 2018, immunotherapy is now recognised as the standard of care for first-line systemic therapy in advanced or metastatic CSCC.

Facial nerve perineural spread from cutaneous squamous cell carcinoma of the head and neck: A single institution analysis of epidemiology, treatment, survival outcomes, and prognostic factors.

BACKGROUND: This study aimed to examine patients with facial nerve (VII) perineural spread (PNS) from cutaneous squamous cell carcinoma of the head and neck. METHODS: Retrospective analysis of patients managed by an Australian tertiary center between 2000 and 2019. RESULTS: Seventy three patients were included. Most presented with recurrent disease (89.0%) and simultaneous trigeminal nerve (V) involvement (67.1%). Of the 55 patients (75.3%) who received curative intent treatment, 48 received surgery plus/minus post-operative radiotherapy. In these patients, 5-year disease-free survival, disease-specific survival, and overall survival was 50.7%, 68.7%, and 58.1%, respectively. Pathological nodal disease, involved margins, increasing VII zonal extent, and concurrent zone 2 V PNS significantly worsened outcomes. CONCLUSION: High rates of recurrent disease reflects the importance of adequate treatment of the primary. Surgery and post-operative radiotherapy remains the mainstay treatment. Outcomes are improved in early-stage disease and with clear surgical margins, reinforcing the need for prompt diagnosis and intervention.

Epidemiology and treatment outcomes of cutaneous squamous cell carcinoma extending to the temporal bone.

BACKGROUND: Accurate epidemiological and outcomes data regarding cutaneous squamous cell carcinoma (cSCC) extending to the temporal bone is lacking. METHODS: Retrospective analysis of 167 Australian patients with primary and peri-temporal bone cSCC. RESULTS: cSCC extending from secondary subsites (93.4%) was 14 times more frequent than primary temporal bone SCC (6.6%). For patients who underwent curative surgery ± post-operative radiotherapy (n = 146, 87.4%), 5-year disease-free survival, locoregional recurrence-free survival, disease-specific survival, and overall survival was 53.0%, 59.4%, 67.9%, and 44.7%, respectively. External ear and pre-auricular tumors, salvage surgery, tumor size (≥40 mm medial-lateral), nodal disease, and involved margins were negative predictors of survival in multivariable analysis. CONCLUSION: In regions of high sun exposure, cSCCs extending to the temporal bone are more common than primary cancers. Outcomes are improved with clear margins, justifying the need for radical resection. Further research regarding pre-auricular cancers is required given poorer associated survival outcomes.

Indications and limits of postoperative radiotherapy for skin malignancies.

PURPOSE OF REVIEW: To provide a summary of the current evidence, with a focus on recent publications, pertaining to indications for postoperative radiation therapy for cutaneous squamous-cell carcinoma (cSCC), basal-cell carcinoma, Merkel-cell carcinoma and melanoma of the head and neck. RECENT FINDINGS: Meta-analyses in cSCC and Merkel-cell carcinoma have shown an association between postoperative radiation therapy and overall survival. Prospective phase III data in head and neck cSCC has shown excellent locoregional control following surgery and postoperative radiation therapy. The addition of concurrent cytotoxic chemotherapy to postoperative radiation therapy has not improved outcomes in either of these two entities. Postoperative immune checkpoint inhibition or combined BRAF and MEK blockade in stage-III melanoma improves progression-free survival whereas postoperative radiation therapy does not. SUMMARY: Further improvement in outcomes with high-risk cSCC and Merkel-cell carcinoma might be achieved with concurrent or sequential immune checkpoint inhibition and postoperative radiation therapy. Postoperative radiation therapy for cutaneous melanoma should be reserved for patients in whom novel systemic therapies are not a treatment option.