Emily Wenande

Keratinocyte carcinoma (KC) places a considerable and growing burden on healthcare systems. Given the KC population’s heterogeneity, tailored clinical pathways are needed to accommodate diverse management needs. This study applied machine learning (ML)-based phenomapping to identify distinct real-world subgroups within a national KC population using demographic and medical history variables. The study included KC patients treated in publicly-funded, office-based dermatology practices and registered in the Danish Skin Cancer Registry (2014–2022). In 106,490 KC patients, 7 ML-derived clusters were identified. One cluster (22.2%; n=23,590) consisted primarily of young, well educated high-income medically noncomplex females presenting with low-risk basal cell carcinomas (BCCs). Four clusters (55.2%; n=58,736) comprised patients with a greater dermatological disease burden, characterized by facial BCCs, multiple BCCs, a greater proportion of squamous cell carcinomas (SCCs), a history of skin cancer or previous actinic keratosis-related treatment. The remaining 2 clusters (22.7%; n=24,164) comprised highly comorbid patients with a greater proportion of SCCs, a high number of KCs on the head and neck and high immunosuppressive drug exposure. ML-derived phenomapping of a national KC population identified distinct, clinically relevant KC subgroups, providing a basis for tailored clinical pathways with differentiated resource needs.

Despite the rising incidence of basal cell carcinoma (BCC), few studies have compared treatment outcomes or predicted recurrences using nationwide real-world datasets. Hence, the objective was to investigate and compare recurrence rates of nodular BCC (nBCC) and superficial BCC (sBCC) following treatment with standard excision (SE), curettage, cryotherapy, photodynamic therapy and imiquimod. Additionally, we identified predictors of BCC 2 year recurrence using machine-learning. The study examined BCCs treated in state-funded, office-based dermatology practices registered in the Danish Skin Cancer Registry from 2014 to 2024. A total of 131,119 tumours were included, comprising 100,221 nBCCs and 30,898 sBCCs. For nBCC, the lowest rate of recurrence was observed for SE, with an 8-year cumulative recurrence rate (CRR) of 16.5% (95% confidence interval: 14.4–19.0%) and hazard ratio of 0.80 (0.76–0.84) compared with curettage. For sBCC, both SE and curettage had similarly low 8 year CRRs of 16.3% (12.7–20.8%) and 16.3% (15.2 17.5%), respectively, with no significant difference in hazard. The machine-learning model identified key predictors of BCC recurrence, including facial location, larger tumour size, having a high number of hospital-registered diagnoses and short distance to dermatological clinics. These findings highlight the impact of treatment selection and patient-specific factors in guiding dermatologists towards optimal BCC management.

A mainstay treatment of head and neck basal cell carcinoma (BCC) is excision with a fixed surgical margin. Large-scale evaluation of post-surgical margin status is necessary to improve outcomes. This cross-sectional study assessed margin outcomes following excision of head and neck BCCs across Danish healthcare settings, including risk factors for tumour-positive margins. Histopathology records on BCCs excised by all medical specialities between 1 January–31 December 2022 were retrieved from The Danish Pathology Bank. Cases with intraoperative microscopic margin assessment were excluded. Descriptive analyses and multivariable logistic regression determined complete excision proportions and risk factors for positive margins. Including 9,291 BCC excisions in 7,741 patients, the tumour-free proportion was 80.0% (95% CI: 79.2–80.8%). Significant variation occurred by histologic subtype, with tumour-free margins ranging from 60.6% in morpheaform to 83.6% in nodular BCCs. Multivariable analyses also identified morpheaform, micronodular, infiltrating, and superficial subtypes, auricular/postauricular locations, small specimen size, and advancing age as risk factors for tumour-positive margins. The nose was a risk factor in univariable analysis. Simple excision of head and neck BCCs shows notable variation in margin outcomes by patient, tumour, and specimen profile. To minimise recurrence and optimise resources, increased awareness of positive margins is essential.

Background: Infrared fractional lasers that target tissue water are traditionally divided into nonablative and ablative devices. The 1927 nm fractional thulium fiber laser (FTL) may, due to an intermediate water absorption coefficient, offer a range of nonablative‐to‐ablative effects.Objective: This study explored dynamic 1927 nm FTL‐tissue interactions produced by different pulse energies in in vivo human skin, using non‐invasive optical coherence tomography (OCT) and line‐field confocal OCT (LC‐OCT) imaging.Methods: FTL exposure was performed on in vivo antero‐lateral forearm skin at 0, 3, 15, or 20 mJ pulse energy using two separate laser tips (spot size: 200 μm (C1); 350 μm (C5)) at 20‐watt power. Immediately after, LC‐OCT and OCT imaging enabled qualitative description of microthermal treatment zone (MTZ) morphology, as well as semiquantitative measurement of MTZ diameter and ablation depth.Results: Ranging from nonablative subepidermal effects to frank ablation, imaging revealed a variety of MTZ morphologies depending on pulse energy and laser tip. At low 3 mJ pulse energy, effects were generally limited to the epidermis, with MTZs consisting of subepidermal clefts (C5) or disruptions through the viable epidermis (C1) under a residual stratum corneum. Rising 15–20 mJ pulse energies expanded thermal effects in the lateral and vertical plane, leading to wider MTZs (e.g., C1: 3 mJ vs. 20 mJ: 213 vs. 357 μm), more extensive stratum corneum involvement, and increasing ablation depth to the superficial dermis (e.g., C1: 3 mJ vs. 20 mJ: 93 vs. 101 μm).Conclusion: Visualized by combined LC‐OCT and OCT imaging, FTL‐tissue interactions are highly modifiable and span the nonablative to ablative spectrum depending on pulse energy and laser tip.

Background: Socioeconomic status (SES) and access to dermatological care are known to influence rates of keratinocyte carcinoma (KC). However, few studies have examined the impact of these factors on the disease burden of specific KC subtypes. Objectives: To determine the impact of SES and distance to a dermatologist on the burden of KC, determined by tumour incidence rate ratios (TIRRs) and tumour size, for nodular basal cell carcinoma (nBCC), superficial BCC (sBCC), squamous cell carcinoma (SCC) and the KC precursor, Bowen disease (BD). Methods: Using data from the nationwide Danish Skin Cancer Registry, our study included 100 705 patients with 190 468 histologically or clinically verified cases of KC/BD registered in state-funded office-based dermatology practices between 2013 and 2022. Negative binomial regression was used to calculate TIRRs; the impact on lateral tumour size was estimated with log-linear quantile regression. Results: High SES was associated with increased tumour incidence and smaller tumours for all KC subtypes. Rates of nBCC and sBCC were 2.7 times and 2.4 times higher, respectively, among the top 25% earners vs. the lowest income category [nBCC 2.74, 95% confidence interval (CI) 2.69–2.79; sBCC 2.38, 95% CI 2.30–2.47], with top earners having BCC tumours that were up to 9.7% smaller (95% CI 8.5–11.0%). The impact of distance to a dermatologist varied by KC subtype. For nBCC, increasing tumour incidence was noted with shorter distances to a dermatologist, while the opposite trend was seen for SCC and BD. Individuals living further away from a dermatologist had larger nBCC and sBCC tumours. No correlation between tumour size and distance to a dermatologist was found for SCC. Conclusions: High SES was associated with increased tumour incidence and smaller tumours for all KC subtypes, reflecting either higher rates of detection or higher rates of disease occurrence. Distance to a dermatologist was an independent predictor of KC burden, with shorter distances leading to increased tumour incidence but smaller nBCC tumours and decreased incidence of SCC.

Importance: The substantial morbidity and socioeconomic costs associated with actinic keratosis (AK) management represent major public health concerns. Anecdotal evidence suggests that human papillomavirus (HPV) vaccination may offer therapeutic and preventive effects against AK and keratinocyte carcinomas (KCs).Objective: To investigate the effect of HPV vaccination on burden of disease in immunocompetent patients with high numbers of AK.Design, Setting, and Participants: The VAXAK trial was a parallel-design, double-blind, randomized sham-controlled clinical trial with 12 months’ follow-up. This single-center trial was conducted at the Department of Dermatology, Bispebjerg University Hospital in Copenhagen, Denmark, between May 2021 and June 2024. Eligible participants were immunocompetent adults with 15 or more clinical AK lesions in a 50 cm² to 100 cm² test area on the head, trunk, or extremities.Interventions: Participants were randomized 1:1 to blinded, 9-valent alphapapillomavirus vaccine or sham vaccine (isotonic sodium chloride solution), each administered intramuscularly at 0, 2, and 6 months. Thick AKs (Olsen grade II-III) received cryotherapy at months 6 and 9; test areas were otherwise untreated during the study.Main Outcomes and Measures: The preselected primary outcome was the percentage reduction in baseline AKs assessed 2, 6, 9, and 12 months after first vaccination. Secondary outcomes included total AK number, thick lesions, new AKs, and rate of incident KCs over 12 months.Results: Participants were selected by consecutive sampling of 163 screened patients following exclusion of 93 individuals due to ineligibility or patients opting out. Among 70 enrolled participants (median [IQR] age, 75.50 [69.00-79.00] years; 47 [67%] male), 69 completed the study. Median (IQR) AK reductions were higher in the HPV-vaccinated vs sham group, shown consistently over the study period (month 2: 35% [25%-44%] vs 25% [18%-33%]; P = .03; month 6: 47% [33%-53%] vs 29% [16%-44%]; P = .01; month 9: 58% [37%-63%] vs 42% [33%-56%]; P = .09; month 12: 58% [47%-69%] vs 47% [32%-65%]; P = .05). Total AK numbers were correspondingly lower in the HPV-vaccinated group (median [IQR] at month 6: 14.00 [11.00-16.00] vs 17.00 [12.00-23.00]; P = .01; month 12: 10.00 [6.00-24.00] vs 16.00 [8.50-21.00]; P = .02). Coincidingly, fewer thick AKs were observed in the HPV-vaccinated group (median [IQR] at month 6: 5.00 [3.00-7.00] vs 6.50 [3.75-10.00]; P = .02; month 12: 3.00 [2.00-5.00] vs 5.00 [2.50-8.50]; P = .049). In contrast, no significant differences in rates of new AKs (1-2 AK[s] per month) or KC numbers overall or per participant were identified during the 12-month trial.Conclusions and Relevance: In this randomized clinical trial, standard alphapapillomavirus vaccination was found to reduce AK burden in immunocompetent individuals with multiple lesions. HPV-targeted vaccines may be useful for management of AK, a chronic, relapsing disease and the most common precancer in fair-skinned populations.Trial Registration: ClinicalTrials.gov Identifier: NCT05202860

In the United States, 1 in 5 Americans develop keratinocyte carcinoma (KC) by age 70, placing the disease among the five most expensive cancers based on Medicare expenditure. Current preventative measures have failed to stem rising KC rates, highlighting the need for alternative strategies. Evolving evidence indicates that lasers conventionally used to treat photoaging, may provide protective effects against the development of KC and precursor lesion, actinic keratosis (AK). This review first delves into existing evidence on fractional infrared laser-based KC and AK prevention. Next, the work discusses potential underlying mechanisms that might explain fractional infrared lasers’ prophylactic effects. A comprehensive literature search of PubMed and Web of Science databases was conducted from inception to April 2024 using preselected search terms. Interventional human and animal studies, epidemiological analyses, and case reports on fractional infrared laser-based prevention of KC or AK were screened according to predefined inclusion/exclusion criteria. Included evidence demonstrates that ablative fractional lasers reduce and delay development of AK/KC, shown in two controlled trials of photodamaged patients and two murine studies (i.e. Er: YSGG and CO₂ lasers). Weaker evidence of KC prevention by nonablative infrared lasers is provided by a retrospective cohort study. In the laser literature, three mechanisms are proposed to drive these prophylactic effects, including the ability of infrared lasers to (i) remove DNA-damaged epidermal cells, (ii) activate the insulin-like growth factor-1 pathway by reducing fibroblast senescence, and (iii) initiate immunomodulating effects. Based on current evidence, infrared fractional lasers show promise particularly for secondary KC prevention in photodamaged populations.

Background: Rates of keratinocyte carcinoma (KC) across Europe are impacted by population demographics and geography. Regional differences in KC occurrence exist, but few European studies investigate incidences of specific subtypes in the secondary healthcare sector on a national level.Objectives: To determine geographical differences in incidence rate and lifetime risk of KC subtypes across Denmark, including nodular and superficial basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and the KC precursor, Bowen's disease (BD), identified in office‐based dermatological practice.Methods: Based on a nationwide registry (The Danish Skin Cancer Registry), all patients in Denmark's five regions with a histologically‐ or clinically verified KC or BD registered in a state‐funded office‐based dermatology practice between 2013 and 2022 were included. Trends in national‐ and region‐specific age and sex standardised tumour incidence rates (STIR) were calculated. Further, national lifetime risk of each tumour subtype was estimated.Results: Between 2013 and 2022, the combined STIR for KC/BD rose 172% nationally from 180 to 489 per 100,000 person‐years (PY). This increase reflected rising rates of nodular BCC, SCC, and BD, while superficial BCC incidence was relatively stable. Regional differences in STIR for combined KC/BD were observed, with the Capital Region and North Jutland generally demonstrating higher rates than Zealand, Southern‐ and Central Denmark (e.g., North Jutland vs. Southern Denmark: 714 vs. 405/100,000PY). While the estimated lifetime risk of developing at least one KC or BD tumour was 21.8%, risk varied with tumour subtype, resulting in subtype‐specific risks of 16.4%, 5.1%, 1.9% and 1.3% for nodular BCC, superficial BCC, SCC, and BD, respectively.Conclusions: In Denmark's secondary dermatological care sector, incidence of nodular BCC, SCC and BD continues to rise with an overall lifetime risk nearing 22%. While KC incidence is increasing in Denmark, the study detected differences in geographical trends and rate increases of specific tumour subtypes.

Non‐invasive diagnostics like line‐field confocal optical coherence tomography (LC‐OCT) are being implemented in dermato‐oncology. However, unification of terminology in LC‐OCT is lacking. By reviewing the LC‐OCT literature in the field of dermato‐oncology, this study aimed to develop a unified terminological glossary integrated with traditional histopathology. A PRISMA‐guided literature‐search was conducted for English‐language publications on LC‐OCT of actinic keratosis (AK), keratinocyte carcinoma (KC), and malignant melanoma (MM). Study characteristics and terminology were compiled. To harmonize LC‐OCT terminology and integrate with histopathology, synonymous terms for image features of AK, KC, and MM were merged by two authors, organized by skin layer and lesion‐type. A subset of key LC‐OCT image‐markers with histopathological correlates that in combination were typical of AK, squamous cell carcinoma in situ (SCCis), invasive squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and MM in traditional histopathology, were selected from the glossary by an experienced dermatopathologist. Seventeen observational studies of AK (7 studies), KC (13 studies), MM (7 studies) utilizing LC‐OCT were included, with 117 terms describing either AK, KC, or MM. These were merged to produce 45 merged‐terms (61.5% reduction); 5 assigned to the stratum corneum (SC), 23 to the viable epidermis, 2 to dermo‐epidermal junction (DEJ) and 15 to the dermis. For each lesion, mandatory key image‐markers were a well‐defined DEJ and presence of mild/moderate but not severe epidermal dysplasia for AK, severe epidermal dysplasia and well‐defined DEJ for SCCis, interrupted DEJ and/or dermal broad infiltrative strands for invasive SCC, dermal lobules connected and/or unconnected to the epidermis for BCC, as well as single atypical melanocytes and/or nest of atypical melanocytes in the epidermis or dermis for MM. This review compiles evidence on LC‐OCT in dermato‐oncology, providing a harmonized histopathology‐integrated terminology and key image‐markers for each lesion. Further evaluation is required to determine the clinical value of these findings.