Risk Of Malignant Transformation Research Articles

SATB1, senescence and senescence-related diseases.

Aging leads to an accumulation of cellular mutations and damage, increasing the risk of senescence, apoptosis, and malignant transformation. Cellular senescence, which is pivotal in aging, acts as both a guard against cellular transformation and as a check against cancer progression. It is marked by stable cell cycle arrest, widespread macromolecular changes, a pro-inflammatory profile, and altered gene expression. However, it remains to be determined whether these differing subsets of senescent cells result from unique intrinsic programs or are influenced by their environmental contexts. Multiple transcription regulators and chromatin modifiers contribute to these alterations. Special AT-rich sequence-binding protein 1 (SATB1) stands out as a crucial regulator in this process, orchestrating gene expression by structuring chromatin into loop domains and anchoring DNA elements. This review provides an overview of cellular senescence and delves into the role of SATB1 in senescence-related diseases. It highlights SATB1's potential in developing antiaging and anticancer strategies, potentially contributing to improved quality of life and addressing aging-related diseases.

Upregulation of psoriasin/S100A7 correlates with clinical severity in patients with oral lichen planus

ObjectivesThe aim of this study was to: (1) investigate the expression patterns of antimicrobial peptides (AMPs), specifically psoriasin (S100A7) and calgranulin A and B (S100A8/A9), in patients with oral lichen planus (OLP) compared to healthy individuals; (2) evaluate the oral health-related quality of life (OHrQoL) in OLP patients versus healthy controls; (3) investigate the impact of clinical severity of OLP on OHrQoL; and (4) assess the influence of AMP expression on clinical severity and OHrQoL in OLP patients.Materials and methodsOral mucosal biopsies (n = 38) were collected from healthy individuals (n = 17) and patients with OLP (n = 21). Levels of AMPs (S100A7, S100A8, S100A9) and pro-inflammatory cytokines interleukin-8 (IL-8) and tumor necrosis factor alpha (TNFα) were assessed by RT-qPCR. AMP protein localization was identified by indirect immunofluorescence analysis. OHrQoL was assessed using the OHIP-G14 questionnaire, and clinical severity was evaluated with the Oral Disease Severity Score (ODSS). Correlations between OLP manifestation, OHrQoL, and AMP expression were evaluated.Results(1) S100A7 (p < 0.001), IL-8 (p < 0.001), and TNFα (p < 0.001) mRNA levels were significantly upregulated in OLP tissue compared to healthy tissue, while S100A8 (p < 0.001) and S100A9 (p < 0.001) mRNA levels were downregulated. Immunofluorescence staining revealed an enhanced expression of S100A7 and decreased protein expression of S100A9 in OLP tissue. (2) OLP patients (9.58 ± 8.32) reported significantly higher OHIP-G14 scores compared to healthy individuals (0.67 ± 0.87; p < 0.001), particularly in the categories “physical pain” (p < 0.001) and “psychological discomfort” (p = 0.025). (3,4) Clinical severity (25.21 ± 9.77) of OLP correlated positively with OHrQoL (ρ = 0.497) and psoriasin expression (ρ = 0.402).ConclusionsThis study demonstrated differential expression patterns of AMPs in OLP and highlighted the correlation between the clinical manifestation of OLP and OHrQoL. Further research approaches should address the role of psoriasin in the risk of malignant transformation of OLP.Clinical relevancePsoriasin is a putative biomarker to monitor disease severity including malignant transformation of OLP lesions. OHIP-G14 scores can be useful to monitor OHrQoL in OLP patients.

An Update on the Use of Artificial Intelligence in Digital Pathology for Oral Epithelial Dysplasia Research.

Oral epithelial dysplasia (OED) is a precancerous histopathological finding which is considered the most important prognostic indicator for determining the risk of malignant transformation into oral squamous cell carcinoma (OSCC). The gold standard for diagnosis and grading of OED is through histopathological examination, which is subject to inter- and intra-observer variability, impacting accurate diagnosis and prognosis. The aim of this review article is to examine the current advances in digital pathology for artificial intelligence (AI) applications used for OED diagnosis. We included studies that used AI for diagnosis, grading, or prognosis of OED on histopathology images or intraoral clinical images. Studies utilizing imaging modalities other than routine light microscopy (e.g., scanning electron microscopy), or immunohistochemistry-stained histology slides, or immunofluorescence were excluded from the study. Studies not focusing on oral dysplasia grading and diagnosis, e.g., to discriminate OSCC from normal epithelial tissue were also excluded. A total of 24studies were included in this review. Nineteen studies utilized deep learning (DL) convolutional neural networks for histopathological OED analysis, and 4 used machine learning (ML) models. Studies were summarized by AI method, main study outcomes, predictive value for malignant transformation, strengths, and limitations. ML/DL studies for OED grading and prediction of malignant transformation are emerging as promising adjunctive tools in the field of digital pathology. These adjunctive objective tools can ultimately aid the pathologist in more accurate diagnosis and prognosis prediction. However, further supportive studies that focus on generalization, explainable decisions, and prognosis prediction are needed.

Asymptomatic mature intrapericardial teratoma in an adult: a case report of a rare condition

BackgroundBenign mature teratomas are the most common type of anterior mediastinal germ cell tumor. Mature intrapericardial teratomas are generally diagnosed during infancy because of symptoms of cardiac compression. In contrast, mature adult intrapericardial teratomas are extremely rare, accounting for less than 1% of mature intrapericardial teratomas. We describe herein a case of a mature intrapericardial teratoma in an asymptomatic adult.Case presentationA 52-year-old woman was found by computed tomography during a health checkup to have an anterior mediastinal mass. She was asymptomatic and hemodynamically stable with no evidence of heart failure. The preoperative provisional radiological diagnosis was a mature intrapericardial teratoma. A median sternotomy revealed an approximately 5-cm diameter protruding intrapericardial mass with a smooth surface. The mass was completely resected. Histopathological examination resulted in a diagnosis of a mature intrapericardial teratoma. The patient did well and has no evidence of recurrence 5 years after surgery.ConclusionsMature intrapericardial teratomas in adults are extremely rare. Given the risks of malignant transformation, rupture, compression of the heart, and infection, excision is indicated to prevent development of serious manifestations.

Indocyanine green (ICG)-guided robotic resection for liver adenoma: combined technologies for precision surgery.

HCA resection is crucial to prevent bleeding and malignant transformation. The aim of this study was to enhance the precision of tumor resection in hepatocellular adenoma (HCA) through the combination of intraoperative ultrasound (IOUS) and indocyanine green (ICG) fluorescence imaging. ICG was intravenously injected 24h before surgery, enabling positive staining of HCA nodules. IOUS guided the parenchymal transection performed using the RoboLap approach. IOUS combined with ICG effectively demarcated lesions, allowing precision surgery while sparing healthy liver tissue. Intraoperative frozen examination further validated the potential of ICG to identify previously undetected lesions. The study showed promising advantages of ICG in HCA resections, potentially reducing the risk of recurrence and malignant transformation. The combined robotic and laparoscopic approach improved the feasibility of parenchymal-sparing surgery, offering a cautious assessment of HCA lesions.

Precursor Lesions, Overdiagnosis, and Oral Cancer: A Critical Review.

Despite the profession placing great emphasis on oral potentially malignant disorders (OPMDs) as a gateway for early recognition and consequently better outcomes for oral cancer, the death rates for lip and oral cavity cancer have remained stagnant for three decades. Evidence shows that only a small fraction of oral cancers are in fact preceded by OPMDs, and that most OPMDs have an annual transformation rate of less than 1%. As OPMDs encompass a very heterogeneous group of oral conditions, it could be argued that only patients with oral mucosal diseases bearing a substantial risk of malignant transformation warrant close surveillance and treatment, these include proliferative leukoplakia, erythroplakia, non-homogeneous leukoplakia, as well as diseases presenting with severe dysplasia at biopsy. In this narrative review, I discuss the intricate epidemiology of the malignancies that we colloquially refer to as oral cancer, explore the limitations of focusing on OPMDs to reduce the incidence and mortality of oral cavity cancer, and argue that a may-be cancer label represents overdiagnosis for most OPMDs.

Endometriosis in Menopausal Women-A New Age Is Coming? Literature Review.

Endometriosis is a chronic inflammatory disease, characterized by the presence of ectopic endometrial tissue, that leads to dysmenorrhea, painful intercourse and infertility. The shift in paradigm from the previous belief that endometriosis exclusively impacts women of reproductive age has brought attention to the condition in both premenarchal and postmenopausal women. Currently, 2-4% of postmenopausal women have endometriosis. Many women experience menopausal symptoms during the peri- and postmenopausal periods and require extensive investigations and monitoring in order to avoid the recurrence of endometriosis symptoms or the risk of malignant transformation when treatment with menopausal hormones is elected. Our goal was to compile and present a clear and concise overview of the existing literature on postmenopausal endometriosis, offering an up-to-date and precise summary of the available information.

Leukoplakia with Diverse Grades of Epithelial Dysplasia – A Case Series and Review of Literature with Updated Management Protocol

Oral leukoplakia is considered the most potentially malignant disorder of the oral cavity, with a high risk of malignant transformation. Based on the clinical manifestation, it has been classified as a homogeneous and non-homogeneous variant. It has been considered predominantly a white lesion of the oral cavity that cannot be classified under any other definable lesions. Leukoplakia is a term used to describe the lesion clinically. There are various components responsible for the threatening change of oral leukoplakia. The clinical diagnosis of leukoplakia is confirmed by histopathology, which commonly indicates intense epithelial dysplasia. This manuscript describes a series of cases diagnosed clinically as leukoplakia and their grades of epithelial dysplasia, a Review of literature about etiology and the key pathogenesis behind it, risk determinants for malignant transformation, chair side investigation for epithelial dysplasia, and updated management protocol.

Knowledge About the Importance of Early Diagnosis and Treatment of Oral Potentially Malignant Disorders Among the South Indian Population: An Institutional Retrospective Study.

The significant malignant transformation rates of oral potentially malignant disorders (OPMDs) demand early diagnosis and proper management of OPMDs not only to reduce symptoms but also to prevent their aggressive outcomes. This retrospective study aimed to quantify the need for patient-related awareness in identifying OPMDs by quantitatively evaluating the association between the type of referral in OPMD cases. This study also aims to analyze the association between gender and types of referral in OPMDs. The sample size of n=1577 (500-leukoplakia, 500-oral submucous fibrosis (OSMF), 500-lichen planus, 77-lichenoid reaction) was considered in the present retrospective study. Data regarding the sample cases were extracted from the common patient database of the Saveetha Dental College and Hospitals from June 2019 to February 2024. Random sampling method was used, and the OPMDs were categorized into two groups based on the chief complaint as self-referred and specialist-referred cases. The segregated data were tabulated in Microsoft Excel (Microsoft® Corp., Redmond, WA) and then exported to IBMSPSSStatistics for Windows, Version 23 (Released 2015; IBM Corp., Armonk, New York, United States) for statistical analysis. Pearson's chi-square test was conducted to analyze the association of referral type, OPMDs, and gender. Out of 1577 OPMD cases, 929 (58.9%) were specialist-referral cases and 648 (41.1%) were self-referral cases. Among OPMDs, lichen planus was the most self-referred 310 (62%) and leukoplakia was the most specialist-referred 470 (78.6%) category. This study found a statistically significant correlation between the type of referrals and the type of OPMDs (p=0.000). Self-referral was more commonly observed in females (23.3%) than males (17.8%) in general and among all categories of OPMDs except lichenoid reactions. This observation was also statistically significant (p=0.000). Conclusion: Among OPMDs selected in the present study, lichen planus and OSMF were more self-referred and leukoplakia cases were mostly specialist-referred. This study highlights the need of detecting less symptomatic lesions, such as leukoplakia, which has a high risk of malignant transformation. The lack of awareness about the identification of OPMDs among patients can result in delayed diagnosis and treatment, which may further result in progression to aggressive outcomes.

Abstract 3674: Blood-based differentiation of malignant and benign pancreatic lesions using analysis of fragmentation patterns in cell-free DNA

Abstract Pancreatic ductal adenocarcinoma (PDAC) remains lethal, with a five-year survival rate of less than 10%. For patients with pancreatic cystic lesions (PCL), analysis of DNA from cyst fluid has shown promise in determining the risk of malignant transformation. However, obtaining cyst fluid requires an invasive procedure. We recently developed an approach for blood-based cancer detection by analyzing fragmentation characteristics in plasma cell-free DNA (cfDNA). In this study, we evaluate the performance of this method in differentiating between patients with malignant and benign pancreatic lesions. We collected plasma samples from 81 patients at the time of endoscopic evaluation or surgical resection of a PCL. We simultaneously obtained plasma samples from 209 PDAC patients and 56 healthy individuals. Using plasma cfDNA whole genome sequencing data from patients with PDAC and healthy individuals, we trained and cross-validated an ensemble machine learning model based on 10 genomic features capturing plasma cfDNA fragmentation patterns. This model was applied to sequencing data from patients with PCL for independent evaluation of diagnostic performance. In training and cross-validation, the model demonstrated an area under the receiver operating characteristic curve (AUROC) of 0.90 for differentiating PDAC samples from healthy individuals. Of the 81 PCL patients, ten patients (12.3%) were found to have a malignant PCL, with either high-grade dysplasia or invasive carcinoma. The trained model showed an AUROC of 0.78 for differentiating malignant from benign lesions, achieving 50% sensitivity and 62.5% positive predictive value at 95% specificity. Our results are a novel demonstration that a peripheral blood test based on plasma cfDNA analysis can enable differentiation between malignant and benign pancreatic lesions. This approach may improve risk-stratification and clinical decision-making regarding the necessity for surgical resection. Larger studies and clinical trials to validate these results and evaluate their impact on outcomes are warranted. Citation Format: Clayton T. Marcinak, Michelle D. Stephens, Bradon R. McDonald, Nabeel Merali, Stephanie M. McGregor, Sharon M. Weber, Adam E. Frampton, Shivan Sivakumar, Rebecca M. Minter, Muhammed Murtaza. Blood-based differentiation of malignant and benign pancreatic lesions using analysis of fragmentation patterns in cell-free DNA [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3674.

Integration of ζ-deficient CARs into the CD3ζ gene conveys potent cytotoxicity in T and NK cells

AbstractChimeric antigen receptor (CAR)-redirected immune cells hold significant therapeutic potential for oncology, autoimmune diseases, transplant medicine, and infections. All approved CAR-T therapies rely on personalized manufacturing using undirected viral gene transfer, which results in nonphysiological regulation of CAR-signaling and limits their accessibility due to logistical challenges, high costs and biosafety requirements. Random gene transfer modalities pose a risk of malignant transformation by insertional mutagenesis. Here, we propose a novel approach utilizing CRISPR-Cas gene editing to redirect T cells and natural killer (NK) cells with CARs. By transferring shorter, truncated CAR-transgenes lacking a main activation domain into the human CD3ζ (CD247) gene, functional CAR fusion-genes are generated that exploit the endogenous CD3ζ gene as the CAR’s activation domain. Repurposing this T/NK-cell lineage gene facilitated physiological regulation of CAR expression and redirection of various immune cell types, including conventional T cells, TCRγ/δ T cells, regulatory T cells, and NK cells. In T cells, CD3ζ in-frame fusion eliminated TCR surface expression, reducing the risk of graft-versus-host disease in allogeneic off-the-shelf settings. CD3ζ-CD19-CAR-T cells exhibited comparable leukemia control to TCRα chain constant (TRAC)-replaced and lentivirus-transduced CAR-T cells in vivo. Tuning of CD3ζ-CAR-expression levels significantly improved the in vivo efficacy. Notably, CD3ζ gene editing enabled redirection of NK cells without impairing their canonical functions. Thus, CD3ζ gene editing is a promising platform for the development of allogeneic off-the-shelf cell therapies using redirected killer lymphocytes.

An Incidental Discovery of the Intrathoracic Accessory Liver Lobe in a 72-Year-Old Man: Case Report and Literature Review

Accessory liver lobe is a rare finding, with the most common cases being accessory liver tissue on the gallbladder wall separate from the orthotopic liver. As the incidence of the ectopic liver is low there are only several case reports in published literature that describe similar presentations. We report a case of intrathoracic liver lobe that was connected to the main liver by a thick pedicle. Due to benign presentation, the patient was discharged without any surgical intervention. This case highlights the importance of understanding anatomical variability of internal organs, understanding the risks of torsion and malignant transformation of the accessory liver tissue. The literature review provides an excellent overview of published case series and reports, and outlines current recommendations on imaging, diagnosis, and management.

Potential Immunohistochemical Biomarkers for Grading Oral Dysplasia: A Literature Review.

Oral cancer is a prevalent global health issue, with significant morbidity and mortality rates. Despite available preventive measures, it remains one of the most common cancers, emphasising the need for improved diagnostic and prognostic tools. This review focuses on oral potentially malignant disorders (OPMDs), precursors to oral cancer, specifically emphasising oral epithelial dysplasia (OED). The World Health Organisation (WHO) provides a three-tier grading system for OED, and recent updates have expanded the criteria to enhance diagnostic precision. In the prognostic evaluation of OED, histological grading is presently regarded as the gold standard; however, its subjectivity and unreliability in anticipating malignant transformation or recurrence pose notable limitations. The primary objective is to investigate whether specific immunohistochemical biomarkers can enhance OED grading assessment according to the WHO classification. Biomarkers exhibit significant potential for comprehensive cancer risk evaluation, early detection, diagnosis, prognosis, and treatment optimisation. Technological advancements, including sequencing and nanotechnology, have expanded detection capabilities. Some analysed biomarkers are most frequently chosen, such as p53, Ki-67, cadherins/catenins, and other proteins used to differentiate OED grades. However, further research is needed to confirm these findings and discover new potential biomarkers for precise dysplasia grading and minimally invasive assessment of the risk of malignant transformation.

Leveraging artificial intelligence for perioperative cancer risk assessment of oral potentially malignant disorders.

Oral potentially malignant disorders (OPMDs) are mucosal conditions with an inherent disposition to develop oral squamous cell carcinoma. Surgical management is the most preferred strategy to prevent malignant transformation in OPMDs, and surgical approaches to treatment include conventional scalpel excision, laser surgery, cryotherapy, and photodynamic therapy. However, in reality, since all patients with OPMDs will not develop oral squamous cell carcinoma in their lifetime, there is a need to stratify patients according to their risk of malignant transformation to streamline surgical intervention for patients with the highest risks. Artificial intelligence (AI) has the potential to integrate disparate factors influencing malignant transformation for robust, precise, and personalized cancer risk stratification of OPMD patients than current methods to determine the need for surgical resection, excision, or re-excision. Therefore, this article overviews existing AI models and tools, presents a clinical implementation pathway, and discusses necessary refinements to aid the clinical application of AI-based platforms for cancer risk stratification of OPMDs in surgical practice.

Oral Potentially Malignant Disorders and Oral Cancer in Saudi Arabia: An Epidemiological Review of the Literature.

Background: Oral potentially malignant disorders (OPMDs) are a group of chronic oral mucosal diseases associated with an increased risk of malignant transformation. Multiple studies have investigated the prevalence of these conditions in multiple regions; however, there are limited data about the prevalence of OPMDs in the Kingdom of Saudi Arabia (KSA). This paper aims to review the prevalence of OPMDs in the KSA, to ensure better understanding of the population risk and propose a more standardised approach to the diagnosis and management of this group across the KSA. In addition, this review will discuss the prevalence of oral cancer in the KSA, considering independent risk factors for oral cancer development. Methods: Electronic databases including PubMed, Medline, Medscape, ScienceDirect, StatPearls, BMC Oral Health and the Cochrane Library were searched with the keywords "Oral Potentially Malignant Disorders"; "Saudi Arabia"; and "Oral Cancer". Identified articles were reviewed independently by 2 reviewers against defined inclusion and exclusion criteria. Results: 16 studies were included in this review. The prevalence of OPMDs in KSA varies significantly depending on age, gender, social habits, background disease and dental status. Conclusions: This review highlights the need for up-to-date data on the prevalence, distribution, and characteristics of OPMDs in KSA. The diverse prevalence rates and distinct characteristics of various OPMDs emphasise the necessity for targeted preventive measures. As the data on OPMDs in KSA remains limited, future research efforts should prioritise the establishment of comprehensive epidemiological studies to inform effective public health interventions in this region.

State of the Art in the Diagnosis and Assessment of Oral Malignant and Potentially Malignant Disorders: Present Insights and Future Outlook-An Overview.

Oral Potentially Malignant Disorder (OPMD) is a significant concern for clinicians due to the risk of malignant transformation. Oral Squamous Cell Carcinoma (OSCC) is a common type of cancer with a low survival rate, causing over 200,000 new cases globally each year. Despite advancements in diagnosis and treatment, the five-year survival rate for OSCC patients remains under 50%. Early diagnosis can greatly improve the chances of survival. Therefore, understanding the development and transformation of OSCC and developing new diagnostic methods is crucial. The field of oral medicine has been advanced by technological and molecular innovations, leading to the integration of new medical technologies into dental practice. This study aims to outline the potential role of non-invasive imaging techniques and molecular signatures for the early detection of Oral Malignant and Potentially Malignant Disorders.

Proliferative verrucous leukoplakia: a general dental practitioner-focused clinical review

Proliferative verrucous leukoplakia (PVL) is a distinct type of oral leukoplakia which has the potential to enlarge or develop into new areas of leukoplakia coupled with areas of a warty surface texture. PVL is usually diagnosed from the fifth decade onwards and is more common in female patients. The most frequent sites involved tend to be gingivae, followed by buccal mucosa and lateral border of tongue. It is one of the oral potentially malignant conditions with a high risk of malignant transformation. It is important for general dental practitioners (GDPs) to identify such lesions to facilitate referral for further investigation and diagnosis. Management is challenging with long-term monitoring and surgical excision when appropriate; however, PVL tends to recur following surgical excision. This article provides an up-to-date review tailored for GDPs on the present knowledge of PVL and illustrates the management challenges with clinical cases.

New insights into the role of the oral leukoplakia microenvironment in malignant transformation.

Oral leukoplakia is the most frequent and potentially malignant lesion of the oral cavity. Although dysplasia grading remains the main factor for risk assessment, challenges persist in determining the exact risk of transformation, and the literature has focused on studying alternative biomarkers. The interaction between dysplastic epithelial cells and the microenvironment starts early, and the communication is mainly mediated by lymphocytes, inflammatory factors, fibroblasts, and the extracellular matrix, leading to dysplastic progression. Leukoplakia-infiltrating leukocytes (LILs) and leukoplakia-associated fibroblasts (LAFs) play crucial roles in the dysplastic microenvironment. The immune response is related to intraepithelial T lymphocyte infiltration, mechanisms of immunosuppression coordinated by regulatory T cells, M2 macrophage polarization, and increased numbers of Langerhans cells; in contrast, fibroblastic and extracellular matrix factors are associated with increased numbers of pro-tumorigenic myofibroblasts, increased expression of metalloproteinases vs. decreased expression of TIMPs, and increased expression of chemokines and other inflammatory mediators. The microenvironment offers insights into the progression of leukoplakia to carcinoma, and understanding the complexity of the oral microenvironment in potentially malignant diseases aids in determining the risk of malignant transformation and proposing new therapeutic alternatives.

What can we learn from treatments of oral lichen planus?

Oral lichen planus (OLP), a T-lymphocyte-mediated disease of the oral mucosa, has a complex pathogenesis that involves a number of factors. The disease is characterized by recurrent episodes and requires continuous follow up, and there is no curative treatment available. Erosive lichen planus, among others, has a risk of malignant transformation and requires standardized treatment to control its progression. Different clinical subtypes of oral lichen planus require appropriate treatment. Pharmacological treatments are the most widely available and have the greatest variety of options and a number of novel pharmacological treatments are presented as highlights, including JAK enzyme inhibitors. The second is photodynamic therapy, which is the leading physiological treatment. In addition, periodontal treatment and psychological treatment should not be neglected. In this review, we briefly discuss the most recent developments in therapies for oral lichen planus after summarizing the most widely used clinical treatments, aiming to provide different proposals for future clinical treatment.

Field Cancerization Therapies for the Management of Actinic Keratosis: An Updated Review.

Field cancerization theory highlights that the skin surrounding actinic keratoses (AK) is also at increased risk for possible malignant transformation; thus, field-directed treatments may both reduce the risk of AK recurrence and potentially reduce the risk of development of cutaneous squamous cell carcinoma (cSCC). Photodynamic therapy (PDT) with either aminolevulinic acid (ALA) or methylaminolevulinate (MAL), as well as topical treatments such as 5-fluorouracil (5-FU), diclofenac gel, piroxicam, imiquimod, and ingenol mebutate, have all shown higher efficacy than vehicle treatments. PDT is widely recognized for its high efficacy; however, concerns for associated pain have driven new studies to begin using alternative illumination and pretreatment techniques, including lasers. Among topical treatments, a combination of 5-FU and salicylic acid (5-FU-SA) has shown to be the most effective but also causes the most adverse reactions. Tirbanibulin, a new topical agent approved for use in 2020, boasts a favorable safety profile in comparison with imiquimod, 5-FU, and diclofenac. Meanwhile, ingenol mebutate is no longer recommended for the treatment of AKs due to concerns for increased risk of cSCC development. Moving forward, an increasing number of studies push for standardization of outcome measures to better predict risk of future cSCC and use of more effective measures of cost to better guide patients. Here, we present an updated and comprehensive narrative review both confirming the efficacy of previously mentioned therapies as well as highlighting new approaches to PDT and discussing the use of lasers and novel topical treatments for treatment of AK.