Search Results (204)

Photodynamic therapy (PDT) is a cornerstone non-invasive modality for keratinocytic precancers and non-melanoma skin cancer (NMSC), leveraging selective photosensitizer accumulation, light activation, and reactive oxygen species (ROS) generation. This narrative review synthesized literature from major databases (2010–2025) to comprehensively evaluate PDT’s molecular mechanisms, innovative optimization protocols, and clinical efficacy across actinic keratosis (AK), field cancerization, Bowen’s disease (BD), basal cell carcinoma (BCC), and invasive squamous cell carcinoma (cSCC). The evidence highlights frontline clinical maturity and excellent cosmetic outcomes for superficial lesions (AK, field cancerization, superficial BCC, and BD), with daylight PDT offering a virtually painless alternative for widespread dysplasia. However, therapeutic reliability decreases in thick nodular, pigmented, or high-risk lesions due to optical barriers and tissue hypoxia. To overcome these limitations, advanced physical and chemical enhancements—such as ablative fractional lasers, iron chelators, epigenetically enhanced PDT (ePDT), and targeted nanocarriers—are actively reshaping drug delivery and cellular susceptibility. Furthermore, cyclic PDT serves as an indispensable tissue-sparing intervention for organ transplant recipients and Gorlin syndrome patients. In conclusion, while PDT is highly effective for superficial neoplasias, precise histopathological stratification and the integration of nanomedicine are critical to overcoming current biological barriers in aggressive dermatological malignancies. Full article

Ultraviolet (UV) light exposure is a recognised risk factor for dermal haemangiosarcoma (HSA) in dogs and dermal squamous cell carcinoma (SCC) in dogs and cats. These tumours cause substantial local disease and often require repeated surgery due to recurrence or de novo lesions, creating a notable welfare and financial burden. Research on preventing harmful UV exposure in pets is still in its infancy, particularly in relation to the safety of UV filters used in sunscreens. This review summarises the current evidence on UV-induced carcinogenesis, strategies to reduce UV exposure, and the safety of sunscreen ingredients in dogs and cats. UV light is strongly implicated in a range of dermatoses, from actinic keratosis to dermal HSA and SCC in dogs and cats, and the risk is likely higher in Australian pets. Indoor confinement during peak UV periods, shade, and sun-protective clothing can reduce exposure, with sunscreen an additional strategy. Sunscreen is relevant because UV-associated cancers typically develop in sparsely haired or hairless regions such as the nose and ventrum, making these areas suitable for targeted sunscreen application. Sunscreens containing non-nanoparticle zinc oxide appear safe for dogs and cats when ingestion is prevented or minimised, whereas the safety of organic UV filters remains unclear due to limited safety data in both humans and animals. Non-nanoparticle titanium dioxide is a possible alternative to zinc oxide and organic filters, but there is currently little information on its safety when ingested by dogs and cats. Overall, the available evidence supports sunscreen as a necessary component of UV-reduction strategies in pets, but substantial research is needed to determine the safety profiles of different UV filters and to establish evidence-based guidelines for their safe use. Full article

Background: Actinic keratosis (AK) is a common premalignant skin disorder associated with chronic ultraviolet exposure and a recognized risk of progression to cutaneous squamous cell carcinoma. Tirbanibulin 1% ointment is an effective short-course field therapy for AK, but its efficacy in hyperkeratotic lesions (Olsen grade II–III) may be limited by reduced drug penetration through a thickened stratum corneum. Keratolytic pretreatment may represent a plausible strategy to improve topical drug delivery in these more challenging lesions. Methods: This retrospective chart review included consecutive adults with Olsen grade II–III AK treated in routine clinical practice with either a bland emollient lead-in followed by tirbanibulin (Group A) or salicylic acid 30% ointment pre-treatment (Decapan, Sanitpharma; Milan, Italy) followed by tirbanibulin (Group B). No study-driven procedures or additional visits were implemented. The 14-day bland emollient lead-in used in Group A was part of the routine clinical management applied during the relevant treatment period and was not introduced or retrospectively constructed for the purposes of the present comparative analysis. Outcomes were extracted from de-identified medical records and photographic documentation obtained as part of standard care. For the purposes of analysis, post-treatment evaluations were grouped into predefined windows of 3–6 weeks (T1), 10–14 weeks (T2), and 22–30 weeks (T3), corresponding approximately to 1, 3, and 6 months after treatment initiation. The primary efficacy endpoints were the Actinic Keratosis Area and Severity Index (AKASI) and Total Lesion Count (TLC). Secondary endpoints included quality of life assessed by the Dermatology Life Quality Index (DLQI). Results: Both treatment regimens were associated with clinically meaningful improvements in AK severity. At T3, mean AKASI was significantly lower in Group B than in Group A (0.86 ± 0.38 vs. 1.35 ± 0.27; p < 0.001), corresponding to reductions from baseline of 60.6% and 36.9%, respectively. Similarly, mean TLC at T3 was significantly lower in Group B than in Group A (4.80 ± 1.5 vs. 6.35 ± 1.6; p < 0.001), corresponding to reductions from baseline of 46.7% and 27.0%, respectively. Quality-of-life outcomes also favored the sequential approach, with lower DLQI scores at T3 in Group B compared with Group A (2.9 ± 1.6 vs. 3.8 ± 1.9; p = 0.006). Both treatments were generally well tolerated. Although the incidence of local skin reactions (LSRs) was similar between groups, Group B showed lower retrospectively documented composite LSR scores and lower patient-reported discomfort (p < 0.001) and lower patient-reported discomfort (p < 0.001). Conclusions: Sequential keratolytic pretreatment followed by tirbanibulin was associated with greater reductions in disease burden and with lower severity of treatment-related local reactions in this retrospective cohort (Olsen grade II–III). This retrospective study suggests that keratolytic pretreatment may represent a useful adjunctive strategy in hyperkeratotic AK treated with tirbanibulin. Prospective randomized studies are warranted to confirm these findings and to define standardized treatment protocols. Full article

Background/Objectives: The early identification of skin cancer by standard RGB dermoscopy is a clinical difficulty because of the complex visual differences between impacted lesions and healthy tissue. Methods: For the biomedical challenge, a novel approach to signal processing and image reconstruction is introduced in this study, called the spectrum-aided visual enhancer (SAVE). The proposed SAVE mechanism aims at reconstructing the diagnostically relevant spectral information from the conventional RGB dermoscopic images using the principles of hyperspectral imaging (HSI) and band selection (BS). After quality control and pre-processing, the images in the ISIC2019 dataset were selected, with 865 images that contain basal cell carcinoma (BCC), seborrheic keratosis (SK), and actinic keratosis (AK) lesions. To reduce data leakage, the dataset was split into training, validation, and testing subsets of 70%, 20%, and 10%, respectively. Five supervised deep learning object detection models were trained and tested on the conventional RGB image dataset and on the SAVE-enhanced dataset. Five supervised deep learning object detection models, namely, YOLOv8, YOLOv10, YOLOv11, SSDLite, and SSD, were trained and tested on the conventional RGB image dataset and the SAVE-enhanced dataset. Additional repeated experimental assessments and statistical comparisons were also carried out to evaluate the improvement in performance. Results: The experimental results showed that the SAVE-based pre-processing always yielded better performance in terms of lesion detection than conventional RGB image processing. The SAVE framework for SSD was evaluated and compared with all other evaluated models and was found to be the most successful, with an accuracy of 96%, a precision of 97%, a recall of 96%, and an F1 score of 96%. Conclusions: The results indicate that the proposed SAVE framework could be a promising RGB-compatible spectral enhancement technique for boosting skin cancer detection and computer-aided dermatologic analysis with the aid of AI. Full article

Background: Actinic keratoses are common keratinocytic precursor lesions arising within chronically ultraviolet-damaged skin and are associated with an increased risk of progression to cutaneous squamous cell carcinoma. The concept of field cancerization has shifted therapeutic strategies from the treatment of isolated visible lesions toward broader field-directed approaches targeting both clinical and subclinical disease. Methods: This narrative review summarizes the rationale, mechanisms of action, efficacy profile, tolerability, and practical limitations of currently available field-directed therapies for actinic keratosis, including 5-fluorouracil, imiquimod, diclofenac, photodynamic therapy, and tirbanibulin. Based on their distinct biological targets, we propose a mechanism-based framework for sequential treatment strategies. Results: Available therapies act through partially non-overlapping mechanisms, including cytotoxic activity, immune activation, cyclooxygenase-2 inhibition, photodynamic oxidative damage, and tubulin/Src pathway inhibition. These complementary effects provide a biological rationale for sequential regimens aimed at addressing the heterogeneity of field cancerization. However, direct clinical evidence supporting specific treatment sequences remains limited, and proposed regimens should be interpreted as hypothesis-generating rather than as validated therapeutic protocols. Conclusions: Mechanism-based sequential field therapy may represent a rational strategy to optimize long-term control of actinic keratosis and field cancerization. Prospective comparative studies are needed to define optimal sequences, treatment intervals, patient selection criteria, and clinically meaningful endpoints, including sustained field clearance, recurrence reduction, tolerability, adherence, and prevention of progression to invasive cutaneous squamous cell carcinoma. Full article

Nicotinamide (NAM), the amide form of vitamin B3, has gained increasing attention in dermatology due to its potential role in both skin aging and non-melanoma skin cancer (NMSC) prevention. This review summarizes the biological rationale and current clinical evidence supporting the use of NAM and other NAD⁺ precursors in photoaging and cutaneous carcinogenesis. Chronic ultraviolet exposure induces DNA damage, oxidative stress, inflammation, immune dysregulation, and extracellular matrix remodeling, linking photoaged skin to increased susceptibility to actinic keratoses (AKs), squamous cell carcinoma (SCCs), and basal cell carcinoma (BCCs). Through the NAD⁺ salvage pathway, NAM contributes to the maintenance of intracellular NAD⁺ pools, thereby influencing energy metabolism, DNA repair, mitochondrial function, redox homeostasis, and the activity of NAD⁺-dependent enzymes. Preclinical studies indicate that NAM enhances DNA repair, reduces oxidative stress and inflammatory signaling, supports autophagy and mitophagy, and improves epidermal barrier function and extracellular matrix integrity. Clinically, the strongest evidence for anti-aging effects concerns topical NAM, which consistently improves wrinkles, texture irregularities, pigmentation, and barrier function. Oral NAM has demonstrated chemopreventive activity in high-risk patients with previous NMSC, particularly by reducing the incidence of new SCCs and AKs during active treatment. However, despite a strong mechanistic rationale, current evidence remains heterogeneous, and additional long-term, skin-focused clinical trials are needed to better define efficacy, safety, optimal dosing strategies, and patient selection. Full article

Background: Tirbanibulin 1% ointment has demonstrated short-term efficacy and excellent tolerability in the treatment of actinic keratosis (AK) on the face and scalp. However, data on long-term efficacy are still lacking. Materials and Methods: This prospective, single-center, 12-month extension study included patients with facial and scalp AKs previously treated with tirbanibulin 1% ointment once daily for 5 consecutive days. Long-term analysis was restricted to lesions that had achieved complete clinical and dermoscopic clearance at the 2-month follow-up. At 12 months, the treated areas were reassessed clinically and dermoscopically. High-resolution images obtained at baseline, 2 months, and 12 months were compared lesion by lesion to distinguish sustained clearance, recurrence at the same anatomical site, and the development of new AKs within the treated field. Results: Thirty-seven patients were reassessed at 12 months. Of the 228 AKs treated at baseline, 116 lesions had achieved complete clearance at 2 months and were therefore eligible for long-term evaluation. At 1 year, 70/116 lesions (60.3%) remained free of recurrence, whereas 46/116 (39.7%) relapsed. Sustained clearance was observed in 35/51 grade 1 lesions (68.6%), 32/57 grade 2 lesions (56.1%), and 3/8 grade 3 lesions (37.5%). In addition, 35 new AKs developed within the previously treated field. No delayed local or systemic adverse events and no progression to invasive cSCC were observed during follow-up. Patient-reported satisfaction was high, and 94% of patients stated they would be willing to repeat the treatment. Conclusions: Tirbanibulin was associated with sustained lesion clearance at one year, particularly in lower-grade AKs. While recurrence remains relatively common—especially in thicker lesions—the treatment was well tolerated and associated with no delayed adverse effects. Its short application regimen and excellent safety profile support tirbanibulin’s role in the long-term management of field cancerization. Full article

Background/Objectives: The efficacy of topical therapies in dermatology is often limited by the barrier function of the stratum corneum, which restricts drug penetration. Iontophoresis is a non-invasive transdermal delivery technique that uses a low-intensity electrical current to enhance the transport of charged and polar molecules across the skin. It has emerged as a strategy to improve local drug bioavailability while minimizing systemic exposure. We systematically reviewed the clinical evidence on the efficacy, safety, and pharmacologic performance of iontophoresis-assisted topical drug delivery in dermatologic diseases. Methods: This systematic review followed PRISMA guidelines and was prospectively registered in PROSPERO (CRD420251234877). PubMed, Embase, Web of Science, CENTRAL, and ClinicalTrials.gov were searched through 19 November 2025 without language restrictions. Records were screened against predefined eligibility criteria, and data were extracted on study design, participants, dermatologic indications, intervention/comparator, iontophoresis parameters, efficacy outcomes, and adverse events. The risk of bias was assessed using RoB 2 for randomized trials and the JBI checklist for non-randomized studies. Because of substantial clinical and methodological heterogeneity, the findings were synthesized narratively and no meta-analysis was performed. Results: Twenty-one studies published between 1990 and 2025 met the inclusion criteria, including 15 randomized and 6 non-randomized studies. Investigated conditions included psoriasis, eczema, melasma, post-inflammatory hyperpigmentation, herpes labialis, onychomycosis, chronic ulcers, systemic sclerosis-related digital ulcers, acne scarring, and actinic keratosis. Across studies, findings were mixed. The most consistent signals of benefit were observed in pigmentary disorders and infectious diseases, whereas results were more heterogeneous in inflammatory dermatoses and some studies did not show superiority over active comparators. Tolerability was generally favorable, with adverse events limited to mild, reversible local reactions such as erythema, tingling, burning, or transient irritation. No serious treatment-related adverse events were reported. Conclusions: Iontophoresis may represent a useful non-invasive delivery-enhancement strategy in selected dermatologic settings, particularly when topical efficacy is limited by anatomical or physicochemical barriers. However, heterogeneity in protocols, formulations, outcomes, and clinical indications limits direct comparison and does not support broad conclusions of efficacy across all dermatologic conditions. Larger, standardized trials are needed to clarify its therapeutic role, long-term efficacy, and indication-specific benefit. Full article

Background: Angiogenesis is critical for tumor progression. Microvessel density (MVD) is commonly assessed using CD31 and CD34, which detect both mature and newly formed vessels and therefore cannot distinguish active neoangiogenesis from stable, quiescent vasculature. Nestin, an intermediate filament protein expressed preferentially in proliferating endothelial cells, has been proposed as a complementary marker of active angiogenesis and has been investigated in several solid tumor types, including pancreatic, colorectal, and breast carcinomas. However, no studies have quantitatively compared nestin-positive MVD across AK, BCC, and SCC using standardized methods. Methods: Immunohistochemistry for nestin, CD31, and CD34 was performed on 118 patient samples collected in 2015–2019 and diagnosed with AK, BCC, or SCC. MVD was quantified by averaging vessel counts in three representative “hot spot” areas. Results: Nestin-positive MVD was significantly lower in patients with AK compared to patients with BCC and SCC (p < 0.001). The mean MVD of nestin-positive vessels was significantly lower in AK than in BCC and SCC (p < 0.0001). In all three groups, nestin-positive MVD demonstrated a strong, positive correlation with both CD34 and CD31. Conclusions: Nestin-positive MVD was significantly elevated in BCC and SCC compared to AK lesions and demonstrated strong correlations with standard angiogenic markers. These findings suggest that nestin may warrant further investigation as a complementary marker of angiogenesis in non-melanoma skin cancer. Whether nestin-positive MVD offers independent diagnostic or prognostic value in this context remains to be determined in larger, prospective, multicentre studies. Full article

Background and Objectives: Invasive cutaneous squamous cell carcinoma (cSCC) and actinic keratosis (AK) are growing burdens on ageing societies and mainly arise from chronic sun exposure. Distinguishing between carcinoma and carcinoma in situ is often clinically challenging but essential for decision-making with respect to targeted therapy. Ex vivo confocal laser scanning microscopy (CLSM) allows histologic examination of native tissue using tissue reflection and nuclear fluorescence staining. The digital staining process almost perfectly mimics conventional haematoxylin and eosin (HE) staining. While the use of CLSM for basal cell carcinoma (BCC) diagnosis is well described, data on cSCC remain scarce. The aim of this study was to compare CLSM with conventional histology in diagnosing and distinguishing cSCC and AK in routine clinical practice. Materials and Methods: Between August 2022 and March 2024, 63 patients with clinically suspected invasive cSCC or AK were enrolled. Biopsy or excision specimens were examined by ex vivo confocal laser scanning microscopy (VivaScope^® 2500 M-G4) followed by acridine orange staining. All samples underwent subsequent routine histopathology, which served as the reference. Two dermatologists independently compared the CLSM findings with the histopathological diagnoses. Results: Eighty-one lesions suspected to be cSCC were assessed using CLSM. The diagnostic accuracy was high across specimen types: cSCC was correctly identified in 24/26 cases (92.3%), AK/Morbus Bowen in 16/17 cases (94.1%), cSCC filia (cutaneous squamous cell carcinoma metastases) in 3/3 cases (100%), and basal cell carcinoma in 9/9 cases (100%). The absence of a tumour was correctly recognized in 19/21 cases (90.5%). In five cases (6.2%), AK and early invasive cSCC could not be differentiated, reflecting the histopathological results. Conclusions: CLSM with digital HE staining is well suited for rapid cSCC and AK diagnosis and differentiation in clinical practice. Full article

Photodynamic therapy (PDT) is a minimally invasive treatment choice whose clinical success in dermatology relies on the interaction between a photosensitizer, light of an appropriate wavelength, and tissue oxygen, leading to reactive oxygen species generation and selective cytotoxicity. This narrative review summarizes contemporary mechanisms and clinical evidence supporting PDT across neoplastic, inflammatory, infectious, and esthetic indications. A comprehensive literature search included randomized trials when available, systematic reviews, meta-analyses, and guideline and consensus documents, complemented by mechanistic and translational studies relevant to clinical outcomes. In premalignant and neoplastic disease, strongest evidence supports field-directed PDT for actinic keratosis and high efficacy in Bowen’s disease, with favorable cosmetic outcomes and acceptable recurrence patterns. PDT plays a more selective role in basal cell carcinoma, particularly superficial and selected nodular lesions, while its routine use as monotherapy in squamous cell carcinoma remains limited by higher recurrence. Beyond oncology, PDT shows expanding utility in acne via sebomodulatory and immunomodulatory effects, and in infectious dermatoses through broad antimicrobial activity and biofilm disruption with low resistance potential. Cosmetic applications, including photorejuvenation, benefit from protocol tailoring and combination strategies that enhance penetration and remodeling. Overall, PDT is evolving into an adaptable therapeutic framework best positioned within mechanism-oriented, multimodal algorithms. Full article

Background: Actinic keratoses (AKs) are considered early in situ forms of cutaneous squamous cell carcinoma (cSCC). However reliable histopathological or molecular markers for predicting the risk of progression are still lacking. The aim of this study was to investigate the relationship between immunohistochemical markers and basal proliferation patterns of AKs in order to identify histopathological associations that may be relevant for malignant transformation. Methods: A total of 97 AK samples from facial and scalp areas were retrospectively analyzed and classified according to their basal proliferation pattern (Pro I: non-proliferative and Pro III: proliferative). Immunohistochemical staining was performed for Ki-67, p53, p16 and podoplanin. In addition, histopathological parameters such as Röwert-Huber grade, inflammatory infiltrate, parakeratosis, elastosis and the presence of acantholysis were evaluated. Results: Pro III lesions were significantly more frequently associated with higher Röwert-Huber grades (AK III: 47.9% vs. 14.3%; p = 0.0004) and with acantholysis (p = 0.0004). No significant differences between the groups were found for Ki-67, p53 and p16. Podoplanin expression, however, was significantly higher in Pro III lesions (93.7% vs. 57.1%, p < 0.0001) and was predominantly localized basally. The combination of a PRO III pattern and podoplanin positivity identified a distinct histopathological subgroup associated with features linked to progression. Conclusions: Podoplanin expression, especially in combination with PRO III pattern and acantholysis, characterizes a histologically and biologically distinct AK subgroup. In contrast, Ki-67, p53 and p16 showed no additional discriminative value in this cohort. Podoplanin could therefore be a useful addition to existing classification systems and in the future support risk-adapted treatment decision. However, prospective longitudinal studies are required to determine its prognostic value. Full article

Background: In actinic keratosis (AK), clinical clearance after field-directed therapies does not necessarily correspond to histological resolution, resulting in subclinical persistence and risk of recurrence. Objective: To provide a practical, up-to-date framework for non-invasive monitoring of treatment response in AK, integrating clinical assessment and dermoscopy with high-resolution imaging techniques, reflectance confocal microscopy (RCM), line-field confocal optical coherence tomography (LC-OCT), and high-frequency ultrasound (HFUS), and to discuss emerging optical biomarkers based on Raman spectroscopy. Results: For each modality, we summarize pre- and post-treatment imaging patterns, proposed response criteria, recommended follow-up timing, and correlations with clinical outcomes (including clearance and AKASI) and, when available, histological findings. The available evidence is derived from a limited number of observational studies, predominantly involving RCM and LC-OCT, whereas data on HFUS and Raman spectroscopy remain comparatively scarce. RCM and LC-OCT allow in vivo assessment of epidermal architectural normalization and reduction of intraepidermal keratinocyte atypia. HFUS captures quantitative trajectories of superficial dermal remodeling, including changes in the subepidermal low-echogenic band (SLEB) and dermal echogenicity after photodynamic therapy and other field treatments. Dermoscopy remains the first-line tool for routine follow-up but may fail to detect minimal subclinical persistence. Finally, we discuss the potential role of in vivo Raman spectroscopy for dynamic molecular endpoints and its possible integration with artificial intelligence–based analytical approaches. Conclusions: A standardized multimodal follow-up strategy improves the accuracy of treatment-response assessment compared with clinical evaluation alone. We propose a technique-specific checklist of minimal response criteria and a pragmatic temporal assessment scheme, and outline a research roadmap to support validation and clinical implementation of non-invasive imaging-guided monitoring in actinic keratosis. Full article

Background: Accurate and timely diagnosis of skin lesions, including Melanoma (MEL), Basal Cell Carcinoma (BCC), Squamous Cell Carcinoma (SCC), Actinic Keratosis (ACK), Seborrheic Keratosis (SEK), and Nevus (NEV), is often hindered by the severe class imbalance and high morphological similarity among pathologies in clinical practice. Although multimodal learning has shown potential in resolving these issues, existing approaches often fail to address predictive uncertainty or effectively integrate heterogeneous clinical metadata. Therefore, this study proposes DermaCalibra, a robust and explainable multimodal framework optimized for small-scale, imbalanced clinical datasets. Methods: The proposed framework integrates three essential modules: First, the Attention-Based Multimodal Channel Recalibration (AMCR) module introduces a probabilistic Bayesian uncertainty estimation mechanism via Monte Carlo dropout to adjust focal loss weights, prioritizing features from underrepresented classes. Second, the Metadata-Driven Dynamic Feature Modulation and Cross-Attention Fusion (MDFM-CAF) module, designed to resolve inter-class visual ambiguity, dynamically rescales dermoscopic feature maps using non-linear clinical context transformations. Lastly, the Gradient Feature Attribution (GFA) module is implemented to provide pixel-level diagnostic heatmaps and metadata importance scores. Results: Evaluated on the PAD-UFES-20 dataset, DermaCalibra achieves a balanced accuracy (BACC) of 84.2%, outperforming current state-of-the-art (SOTA) methods by 3.6%, and a Macro Area Under the Receiver Operating Characteristic Curve (Macro AUC) of 96.9%. Extensive external validation on unseen hospital and synthetic datasets confirms robust generalizability across diverse clinical settings without the need for retraining. Conclusions: DermaCalibra effectively bridges the gap between deep learning complexity and clinical intuition through uncertainty-aware reasoning and transparent interpretability. The framework provides a reliable and scalable computer-aided diagnostic tool for early skin lesion detection, particularly in resource-limited clinical environments. Full article

Cellular senescence is a stress-induced cell-cycle arrest that constrains expansion of ultraviolet-damaged keratinocytes yet can remodel the microenvironment. This systematic review evaluated histological and genetic or epigenetic senescence markers in actinic keratosis (AK), cutaneous squamous cell carcinoma (cSCC), and basal cell carcinoma (BCC). PubMed, Scopus, and Web of Science were searched (January 2005–May 2025); 34 human studies were included. AK showed an early senescent signature with frequent cyclin-dependent kinase inhibitor p21 (p21CIP1) expression (82.1%) and DNA damage signaling, including phosphorylated histone H2AX (gamma-H2AX) positivity (77%). In invasive cSCC, p21^CIP1 fell to 43.9% and tumor suppressor p53 immunoreactivity often declined, whereas cyclin-dependent kinase inhibitor p16 (p16INK4a) commonly accumulated without arrest, including cytoplasmic staining at invasion fronts. Reported escape pathways involved c-Jun N-terminal kinase 2 activity and long noncoding RNA PVT1–dependent repression of p21. Telomerase reverse transcriptase (TERT) promoter mutations were prevalent in cSCC (about 50%) and BCC (up to 78%) but uncommon in AK, consistent with late telomerase activation. Study heterogeneity, variable antibody scoring, and limited assessment of senescence-associated beta-galactosidase and secretory mediators restricted cross-study comparability. Standardized, spatially resolved profiling may refine risk stratification and support senescence-targeted prevention and therapy in keratinocyte cancers. Full article