Queratosis actínicas en pacientes trasplantados de órgano sólido: revisión de la literatura / Actinic Keratosis in Solid Organ Transplant Recipients: A Medical Literature Review

La inmunosupresión farmacológica de los pacientes trasplantados de órgano solido constituye un importante factor de riesgo tanto para la aparición de queratosis actínicas (QA) como para su progresión a carcinomas escamosos (CE). El tratamiento tanto de las lesiones clínicas como preclínicas en este grupo de pacientes es obligatorio debido a la elevada posibilidad de evolución a CE. Por otra parte, la prevención presenta también un papel importante que debemos tener en cuenta. Existen un gran número de estudios realizados en pacientes inmunocompetentes sobre el tratamiento y la prevención de QA, pero no en pacientes inmunosuprimidos. Esta revisión pretende resumir el conocimiento actual sobre los tratamientos y medidas de prevención de la QA en loas pacientes trasplantados de órgano sólido.(AU)

Pharmacological immunosuppression in solid organ transplant recipients is a significant risk factor in the occurrence of actinic keratosis (AK) and later progression into squamous cell carcinomas (SCC). Treating clinical and preclinical lesions is mandatory in this group of patients due to the high changes of progression into SCC. On the other hand, prevention of AK should be considered because it plays a crucial role.Several studies have been published on immunocompetent patients, as well as on the management and prevention of AK, but not on immunosuppressed patients.This review aims to summarize the current knowledge on the management and prevention measures of AK in solid organ transplant recipients.(AU)

[Translated article] Actinic Keratosis in Solid Organ Transplant Recipients: A Medical Literature Review / Queratosis actínicas en pacientes trasplantados de órgano sólido: revisión de la literatura

La inmunosupresión farmacológica de los pacientes trasplantados de órgano solido constituye un importante factor de riesgo tanto para la aparición de queratosis actínicas (QA) como para su progresión a carcinomas escamosos (CE). El tratamiento tanto de las lesiones clínicas como preclínicas en este grupo de pacientes es obligatorio debido a la elevada posibilidad de evolución a CE. Por otra parte, la prevención presenta también un papel importante que debemos tener en cuenta. Existen un gran número de estudios realizados en pacientes inmunocompetentes sobre el tratamiento y la prevención de QA, pero no en pacientes inmunosuprimidos. Esta revisión pretende resumir el conocimiento actual sobre los tratamientos y medidas de prevención de la QA en loas pacientes trasplantados de órgano sólido.(AU)

Pharmacological immunosuppression in solid organ transplant recipients is a significant risk factor in the occurrence of actinic keratosis (AK) and later progression into squamous cell carcinomas (SCC). Treating clinical and preclinical lesions is mandatory in this group of patients due to the high changes of progression into SCC. On the other hand, prevention of AK should be considered because it plays a crucial role.Several studies have been published on immunocompetent patients, as well as on the management and prevention of AK, but not on immunosuppressed patients.This review aims to summarize the current knowledge on the management and prevention measures of AK in solid organ transplant recipients.(AU)

Actinic keratoses and squamous cell carcinoma limited to photo-exposed skin in vitiligo vulgaris in pigmented skin type.

Vitiligo skin has a lesser number of photoprotective melanocytes-theoretically, there is a higher risk of development of non-melanoma skin cancers in such patients. But most studies in Caucasian patients have shown decreased incidence of non-melanoma skin cancers in patients with vitiligo. In Indian patients, there is a paucity of literature on such adverse events. We report a case of actinic keratoses, cutaneous horn with dysplasia and squamous cell carcinoma developing exclusively over photo-exposed vitiligo lesions in an Indian woman in her 60s (housewife, Fitzpatrick skin type V and average daily photo-exposure time 2-4 hours) of long-standing vitiligo vulgaris without any history of phototherapy. The photoprotected lesional skin was completely normal with no clinically appreciable enlarged regional lymph nodes. Shave and elliptical excision of the suspicious lesions were done, and histopathology showed various degrees of malignant transformation in various lesions. The patient was started on topical imiquimod for the lesions of actinic keratoses and was referred for staging and wide excision of squamous cell carcinoma lesion. We report this case for its rarity and to emphasise the fact that there is a need for counselling for lifestyle modification in patients with vitiligo as the use of sunscreens is often not practised by Indian patients due to financial constraints and physical measures such as using full sleeves, high-collared dresses and scarves should be encouraged.

The causal effects of atopic dermatitis on the risk of skin cancers: A two-sample Mendelian randomization study.

BACKGROUND: Observational and epidemiological studies show conflicting results on the relationship between atopic dermatitis and skin cancer. Additionally, observational studies are susceptible to the reverse causation and confounders, thus, may not interpret true causal relationships. The causal effects of atopic dermatitis on the risk of skin cancers remains unclear. OBJECTIVES: To investigate the causal relationship between atopic dermatitis and skin cancer including cutaneous malignant melanoma, cutaneous squamous cell carcinoma, basal cell carcinoma and actinic keratosis. METHODS: We performed a two-sample Mendelian randomization analysis based on summary datasets of public genome-wide association studies of European ancestry. The inverse variance-weighted approach was applied as the main analysis. MR-Egger and weighted median methods were used to complement the inverse variance-weighted results. A series of sensitivity analyses were used to ensure the robustness of the causality estimates. RESULTS: Inverse variance-weighted method showed that genetically predicted dermatitis patients were significantly associated with an increased incidence of basal cell carcinoma (OR, 1.20; 95% CI, 1.10-1.31; p = 4.07E-05) and cutaneous squamous cell carcinoma (OR, 1.14; 95% CI, 1.10-1.19; p = 1.05E-11). However, we did not find a significant causality for atopic dermatitis on melanoma neither did we find actinic keratosis. Subsequent sensitive analyses supported these results. CONCLUSIONS: Our study identified the causality between atopic dermatitis basal cell carcinoma and squamous cell carcinoma. Accordingly, regular skin cancer screening is recommended for patients with atopic dermatitis.

Needs and challenges among general practitioners in the management of actinic keratosis: a qualitative study.

BACKGROUND: Because of the increasing incidence of actinic keratosis (AK), optimal use of limited healthcare resources is essential. Although most patients can be managed in primary care, dermatology referrals are common. More profound knowledge of general practitioners' (GPs) considerations might assist in enhancing AK care. METHODS: The aim of the current study was to gain insight into AK management in primary care by exploring the needs and challenges among GPs in the Netherlands. A qualitative study was conducted based on semi-structured in-depth interviews with 15 conveniently sampled Dutch GPs, focusing on the needs and challenges in AK management. A literature-informed, predefined topic list guided the interviews, which were recorded, transcribed ad verbatim, and thematically analysed using the Framework Method. RESULTS: All GPs reported AK to be a clinical diagnosis and most GPs indicated that most AK patients could be managed in primary care. Cryotherapy was preferred and experience with 5-FU therapy was limited. Most GPs applied cryotherapy without discussing other treatment options with patients. Reasons for dermatology referrals included an incomplete treatment response, extensive lesions, difficult-to-treat areas, and serious doubts about the diagnosis. GPs reported a need for more education, especially on 5-FU therapy. Their main challenges were dealing with diagnostic uncertainty, treating extensive lesions, managing treatment-related skin reactions, and reconciling patient misconceptions. CONCLUSIONS: This study shows various AK management approaches among Dutch GPs with suboptimal guideline compliance due to diverse underlying barriers. It suggests that more education might contribute to a more standardised and uniform AK management and supports further transition of AK care from hospital to primary care.

Epidemiology and risk factors for multiple squamous cell carcinomas in a cohort of organ transplant recipients from northern Italy: a single center study.

BACKGROUND: Keratinocyte cancers account for the most frequent oncological complication in organ transplant recipients. To date, many different risk factors have been reported, unless variability among the studies exist. We aimed to determine the incidence and risk factors for keratinocyte neoplasms in a cohort of kidney transplant and liver transplant recipients. METHODS: A cohort of 338 patients were included in this retrospective study and followed-up from transplantation until the end of December 2021, with a 2-year minimum transplant time. Each skin cancer was collected in a specific database, together with all the demographic data and dermatological history and feature of patients. RESULTS: In our cohort, liver transplant patients presented a higher keratinocyte cancer incidence compared to kidney transplant recipients. Regarding the risk factors for skin cancer in the entire group of patients, we observed a significant association with the detection of actinic keratosis and solar lentigo, and such relation was stronger when considering patients developing multiple skin cancers, in which fair skin types and occupational sun exposure were also associated. Furthermore, while actinic keratosis and a history of previous dialysis were significantly associated with the development of a least one squamous cell carcinoma, the presence of keratotic lesions and azathioprine intake resulted connected with the appearance of multiple squamous neoplasms. CONCLUSIONS: We report here that, in our cohort, factors potentially leading to immune dysfunction were found to play a causative role in the development of the more aggressive histotype of keratinocyte tumors, and such association seemed more convincing in case of multiple squamous cell carcinomas.

Systemic Photoprotection in Melanoma and Non-Melanoma Skin Cancer.

Non-melanoma skin cancers (NMSCs), which include basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and actinic keratosis (AK), are the most common cancer diseases in the Caucasian race. If diagnosed late and improperly treated, BCC and SCC can become locally advanced and metastasize. Malignant melanoma (MM) is less frequent but more lethal than NMSC. Given the individual and social burdens of skin cancers, performing an adequate prevention is needed. Ultraviolet (UV) ray exposure is one of the main risk factors for skin cancer. Thus, the first-choice prevention strategy is represented by photoprotection that can be both topical and systemic. The latter consists of the oral administration of molecules which protect human skin against the damaging effects of UV rays, acting through antioxidant, anti-inflammatory, or immunomodulator mechanisms. Although several compounds are commonly used for photoprotection, only a few molecules have demonstrated their effectiveness in clinical trials and have been included in international guidelines for NMSC prevention (i.e., nicotinamide and retinoids). Moreover, none of them have been demonstrated as able to prevent MM. Clinical and preclinical data regarding the most common compounds used for systemic photoprotection are reported in this review, with a focus on the main mechanisms involved in their photoprotective properties.

Single-cell RNA-seq reveals actinic keratosis-specific keratinocyte subgroups and their crosstalk with secretory-papillary fibroblasts.

BACKGROUND AND AIM: Actinic keratosis (AK) represents an intraepidermal malignant neoplasm with the proliferation of atypical keratinocytes. AK lesions are regarded as early in situ squamous cell carcinomas (SCCs) having the potential to progress into invasive SCC (iSCC) and metastasize, causing death. This study aimed to investigate the heterogeneity of keratinocytes and how this heterogeneity promoted AK development and progression. METHODS: We employed single-cell RNA sequencing (scRNA-seq) to examine the heterogeneity of keratinocytes and dermal fibroblast clusters in AKs and adjacent normal skins. Cell clustering, pseudotime trajectory construction, gene ontology enrichment analysis, transcription factor network analysis, and cell-cell communication were used to investigate the heterogeneity of keratinocytes in AK. The cellular identity and function were verified by immunohistochemical and immunofluorescence staining. RESULTS: Using scRNA-seq, we revealed 13 keratinocyte subgroups (clusters 0-12) in AK tissues and characterized 2 AK-specific clusters. Cluster 9 displayed high levels of IL1R2 and WFDC2, and cluster 11 showed high levels of FADS2 and FASN. The percentages of cells in these two clusters significantly increased in AK compared with normal tissues. The existence and spatial localization of AK-specific IL1R2+WFDC2+ cluster were verified by immunohistochemical and immunofluorescence staining. Functional studies indicated that the genes identified in the IL1R2+WFDC2+ cluster were crucial for epithelial cell proliferation, migration, and angiogenesis. Further immunofluorescent staining revealed the interactions between AK-specific keratinocytes and secretory-papillary fibroblasts mainly through ANGPTL4-ITGA5 signalling pathway rarely seen in normal tissues. CONCLUSION: The findings of this study might help better understand AK pathogenesis.

Regular use of vitamin D supplement is associated with fewer melanoma cases compared to non-use: a cross-sectional study in 498 adult subjects at risk of skin cancers.

There are conflicting results on the role of vitamin D system in cutaneous carcinogenesis. Therefore, it was investigated whether the use of oral vitamin D supplements associates with photoaging, actinic keratoses, pigment cell nevi, and skin cancers. In this cross-sectional study, 498 adults (aged 21-79 years, 253 males, 245 females, 96 with immunosuppression) subjects at risk of any type of skin cancer were examined, and possible confounding factors were evaluated. The subjects were divided into three groups based on their self-reported use of oral vitamin D supplements: non-use, occasional use, or regular use. The serum level of 25-hydroxyvitamin-D3 was analyzed in 260 subjects. In 402 immunocompetent subjects, vitamin D use did not associate with photoaging, actinic keratoses, nevi, basal, and squamous cell carcinoma. In contrast, there were lower percentages of subjects with a history of past or present melanoma (32/177, 18.1% versus 32/99, 32.3%, P = 0.021) or any type of skin cancer (110/177, 62.1% versus 74/99, 74.7%, P = 0.027) among regular users compared to non-users. In the logistic regression analysis, the odds ratio for melanoma was 0.447 ( P = 0.016, 95% confidence interval, 0.231-0.862) among regular users. Furthermore, the investigator-estimated risk class of skin cancers was significantly lower among regular users. Serum 25-hydroxyvitamin-D3 did not show marked associations with skin-related parameters. The results on 96 immunosuppressed subjects were somewhat similar, although the number of subjects was low. In conclusion, regular use of vitamin D associates with fewer melanoma cases, when compared to non-use, but the causality between them is obscure.

The role of HPV in keratinocyte skin cancer development: A systematic review.

Keratinocyte skin cancers are the most frequent malignancy, accounting for approximately 30% of all cancers. Although beta genus HPV are the main etiologic agents for squamous cell carcinoma development in patients with epidermodysplasia verruciformis and organ transplant recipients, their role in non-melanoma skin cancer (NMSC) progression in the general population remains controversial. The aim of our review is to summarize current scientific data and to systematically analyse evidence regarding the role of HPV in keratinocyte skin cancers. A total of 2284 patients were included, of which 724 with actinic keratoses, 290 with Bowen's disease, 949 with cutaneous squamous cell carcinomas and 321 with keratoacanthomas. In the case of actinic keratoses, the majority were positive for beta (n = 372, 58.49%) and gamma HPV (n = 256, 40.25%) and only a few (n = 6, 0.94%) were positive for alpha subtypes. Similarly, most of the cutaneous squamous cell carcinomas were positive for beta (n = 248, 55.98%) and gamma HPV (n = 172, 33.82%) and 23 cases (2.42%) were positive for alpha subtypes. Bowen's disease lesions were mostly positive for beta (n = 43, 55.84%) and alpha HPV (n = 30, 38.96%), in contrast to the gamma genus (n = 4, 5.19%). Keratoacanthomas showed a high distribution among beta genus (n = 79, 50.31%) and an equal proportion between alpha (n = 39, 24.84%) and gamma (n = 39, 24.84%) genera. Studies published so far identifying HPV in keratinocyte skin cancers reflect the difference in detection methods rather than a type-specific tendency towards either actinic keratoses, Bowen's disease, squamous cell carcinoma or keratoacanthoma. On the other hand, recent evidence regarding the role of HPV vaccination in patients with non-melanoma skin cancer brings into perspective the idea of a beta-HPV vaccine or a combined alpha and beta-HPV vaccine that could be used as an adjuvant treatment measure in patients with recalcitrant non-melanoma skin cancer.

De Novo Skin Neoplasms in Liver-Transplanted Patients: Single-Center Prospective Evaluation of 105 Cases.

Background and Objectives: Solid-organ transplant recipients (SOTRs) are notably considered at risk for developing cutaneous malignancies. However, most of the existing literature is focused on kidney transplant-related non-melanoma skin cancers (NMSCs). Conflicting data have been published so far on NMSC incidence among liver transplant recipients (LTRs), and whether LTRs really should be considered at lower risk remains controversial. The aim of the present study was to prospectively collect data on the incidence of cutaneous neoplasms in an LTR cohort. Materials and Methods: All LTRs transplanted at the Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit of Modena University Hospital from October 2015 to June 2021 underwent a post-transplant periodic skin check at the Dermatology Unit according to our institutional integrated care pathway. Data on the presence of cutaneous malignant and premalignant lesions were collected at every timepoint. Results: A total of 105 patients were enrolled in the present study. Nearly 15% of the patients developed cutaneous cancerous and/or precancerous lesions during the follow-up period. Almost half of the skin cancerous lesions were basal cell carcinomas. Actinic keratoses (AKs) were observed in six patients. Four patients developed in situ squamous cell carcinomas, and one patient was diagnosed with stage I malignant melanoma. Otherwise, well-established risk factors for the occurrence of skin tumors, such as skin phototype, cumulative sun exposure, and familial history of cutaneous neoplasms, seemed to have no direct impact on skin cancer occurrence in our cohort, as well as an immunosuppressive regimen and the occurrence of non-cutaneous neoplasms. Conclusions: Close dermatological follow-up is crucial for LTRs, and shared protocols of regular skin checks in this particular subset of patients are needed in transplant centers.

Correlation of skin cancer and actinic keratosis-related knowledge and sun protection behaviors and sunscreen use among a sample of Jordanian population.

BACKGROUND: The incidence of skin cancer and actinic keratosis has increased worldwide. Measuring the public awareness, attitude, and knowledge about these diseases and the skin protection behaviors are highly important to undertake preventive measures. METHODS: To investigate skin cancer and actinic keratosis-related knowledge, sun protection behaviors, and sunscreen usage among Jordanians, a questionnaire was developed. The questionnaire was provided as a google form to individuals via social media and the data were analyzed using SPSS® 23. RESULTS: A total of 1277 individuals, aged 18-65 years filled the questionnaire. The median melanoma and actinic keratosis knowledge score were 7 (4-9) and 4 (0-9), respectively. The melanoma knowledge was higher among females, those with a medical background, a high level of education, and in the central region, whereas the AK knowledge was higher among those with a medical background. Overall, 75.9% of the participants used sunscreen at least often to prevent sunburn, uneven skin tone, or tanning, 72% were using sunscreen with an SPF of 30 at least. However, 45.3% and 49.2% of sunscreen users did not comply with application, and reapplication times, respectively. Moreover, 58.4% of participants applied less than the recommended amount of sunscreen. CONCLUSION: Our study revealed that public awareness of actinic keratosis is low among Jordanians. Although it was found that a high proportion of Jordanians use sunscreens there are deficits in sunscreen practice indicating an urgent need to design effective interventions to increase awareness of actinic keratosis and correct use of sunscreen via health campaigns or healthcare professions.

Actinic keratoses contiguous with squamous cell carcinomas are mostly non-hyperkeratotic and with severe dysplasia.

AIMS: Actinic keratosis (AK) is a precursor of cutaneous squamous cell carcinoma (SCC). No validated parameters can predict which AKs will progress into SCCs, but especially thick AKs are under suspicion. The clinical and histopathological thickness of AKs is strongly correlated. This study aimed to investigate the thicknesses and degree of dysplasia of AKs contiguous with SCCs assuming these AKs represent the AKs that have undergone malignant transformation. METHODS: Files of the Pathology Department, Hospital of Southern Jutland, Denmark, were reviewed. 111 cases met the inclusion criteria: a skin biopsy containing an invasive SCC. All SCCs merged with an AK at the edge. Degree of dysplasia, epidermal thickness and stratum corneum thicknesses of AKs were measured. RESULTS: All AKs showed severe dysplasia. Most AKs had a stratum corneum thickness under 0.1 mm and an epidermal thickness under 0.5 mm, corresponding to clinically thin and non-hyperkeratotic AKs. CONCLUSIONS: Our result suggests malignant progression potential of AKs regardless of thickness.

Pulse rate and blood pressure changes during low-irradiance PDT compared with conventional PDT in the treatment of facial actinic keratoses: A retrospective study.

BACKGROUND: Conventional photodynamic therapy (c-PDT) is a highly effective treatment for actinic keratoses. Besides pain as the main side effect, blood pressure (BP) increases and hypertensive crises may occur during treatment. Reducing the irradiation intensity while keeping the total dose constant (low-irradiance PDT) can achieve a clinically relevant reduction in pain. This study aimed to evaluate the influence of li-PDT on the BP and pulse (PR) during therapy and the incidence of post-interventional hypertension compared with c-PDT. METHODS: We retrospectively analyzed the treatment data of 79 patients (39 c-PDT and 40 li-PDT). BP and PR measurements were performed in all patients before PDT, at mid-exposure, and immediately after PDT. In addition, the pain was assessed by using the visual analog scale. RESULTS: Patients treated with li-PDT reported significantly lower pain than those receiving c-PDT (p < .0005). Additionally, they showed less systolic (SBP) and diastolic (DBP) BP increase (∆SBP: p < .0005, ∆DBP: p = .015) and overall lower absolute BP values (SBP: p < .0005, DBP: p = .008) compared with c-PDT. They were also significantly less likely to develop post-interventional hypertension (p = .037) or higher stages of arterial hypertension. Regarding PR, there was no difference in absolute values between both groups, but the increase from onset to half irradiation duration was significantly higher in c-PDT (p = .013). CONCLUSIONS: Li-PDT is an excellent option to reduce the elevation of arterial BP and decrease the incidence of post-interventional hypertension and hypertensive crisis. This finding has considerable relevance, especially with the risk profile of many PDT patients in mind (advanced age and cardiovascular history).

Positive association between actinic keratosis and internal malignancies: a nationwide population-based cohort study.

Little is known about the comorbidities in actinic keratosis patients. To evaluate the association of actinic keratosis with certain malignancies. All patients with actinic keratosis (n = 61,438) and age- and sex-matched control subjects (n = 307,190) at a 5:1 ratio were enrolled using data from the Korean National Health Insurance Service between the years 2007 and 2014. In subjects with actinic keratosis, overall cancer incidence was higher than that for controls after income level, habitat, diabetes, hypertension, and dyslipidemia were adjusted (Hazard Ratio [HR] = 1.43 [95% confidence interval 1.38-1.47]). The positive association of specific cancers were observed in the following order: skin cancer (HR = 3.43 [2.47-4.75]), oral cavity and pharyngeal cancer (HR = 1.99 [1.57-2.52]), lymphoma (HR = 1.59 [1.28-1.96]), leukemia (HR = 1.35 [1.03-1.77]), prostate cancer (HR = 1.35 [1.21-1.51]), renal cancer (HR = 1.29 [1.02-1.63]), liver cancer (HR = 1.21 [1.09-1.35]), thyroid cancer (HR = 1.20 [1.05-1.38]), and gastric cancer (HR = 1.13 [1.03-1.23]). Although further research on pathologic mechanism is needed, the implications of a positive correlation between actinic keratosis and internal organ malignancies has great significance.

Safety of topical interventions for the treatment of actinic keratosis.

Introduction: Actinic keratosis (AK) are proliferations of atypical keratinocytes that may eventually progress to cutaneous squamous cell carcinoma. Therefore, AK requires consequent and early treatment. Areas covered: A variety of effective approaches is currently available for the clearance of AK. These interventions may be applied either in a lesion-directed or field-directed mode as AK can occur as single or multiple lesions. Field-directed approaches typically comprise topical drug-mediated interventions which aim at eliminating all visible lesions and also at clearing subclinical changes of the actinically damaged field. However, most treatment options are associated with local adverse events such as erythema, scaling, pain, and rarely with systemic symptoms. This expert review provides a comprehensive and up-to-date overview of the safety considerations of the commonly prescribed topical treatment agents cyclooxygenase inhibitors, 5-fluorouracil, imiquimod, ingenol mebutate, and photodynamic therapy. All these therapies have been proven efficient, yet they differ considerably regarding their safety profile. Expert opinion: In the future, safety concerns will relate to long-term and irreversible adverse drug events instead of application site reactions. In particular, the rate of treatment-associated non-melanoma skin cancers will increasingly come into focus and warrant investigation in postmarketing surveillance trials with a long-term follow-up.

Ten-Year Follow-up of Persons With Sun-Damaged Skin Associated With Subsequent Development of Cutaneous Squamous Cell Carcinoma.

Importance: Risk of cutaneous squamous cell carcinoma (cSCC) after the diagnosis of actinic keratosis (AK) has not been studied during long follow-up periods. Objective: To estimate the risk up to 10 years and identify risk factors for cSCC development. Design, Setting, and Participants: This longitudinal cohort study, performed from January 1, 2009, to February 29, 2020, examined Kaiser Permanente Northern California patients with AK and control patients matched 1:1 on age, sex, race/ethnicity, medical center, and date of the initial diagnosis plus 30 days in the patients with AK. Exposures: Patients with AK and control participants were followed up for up to 10 years for incidence of cSCC. Main Outcomes and Measures: Incident cSCC was obtained from pathologic data, and subdistribution hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards regression analysis, accounting for competing risks, calendar year, demographic factors, and number of AKs. Results: The study included 220 236 patients with AK and 220 236 matched control patients (mean [SD] age, 64.1 [12.2] years; 231 248 [52.5%] female). After losses to follow-up were accounted for, risk of cSCC increased with each year of follow-up by 1.92% (95% CI, 1.89%-1.95%) in patients with AK and 0.83% (95% CI, 0.81%-0.85%) in matched control patients (subdistribution HR, 1.90; 95% CI, 1.85-1.95). However, among patients 49 years or younger, those diagnosed with AK were nearly 7 times more likely to be diagnosed with cSCC than those without AK (HR, 6.77; 95% CI, 5.50-8.32). At 10 years, the cumulative incidence of cSCC reached 17.1% (95% CI, 16.9%-17.4%) in patients with AK and 5.7% (95% CI, 5.5%-5.9%) in control patients. Increased numbers of AKs were modestly associated with increased cSCC risk (≥15 AKs vs 1 AK: subdistribution HR, 1.89; 95% CI, 1.75-2.04). Older patients had much higher risk of cSCC than younger patients (compared with those ≤49 years of age at AK diagnosis; ≥80 years of age: subdistribution HR, 8.18; 95% CI, 7.62-8.78). Other than AK, risk factors for cSCC included older age, White race (a proxy for skin type), history of basal cell carcinoma, and male sex. Risk decreased between 2009 and 2019 (2018-2019 vs 2009-2010: subdistribution HR, 0.67; 95% CI, 0.63-0.72). Conclusions and Relevance: The results of this longitudinal cohort study can be used to develop recommendations to increase early detection of cSCC. Additional research is needed to understand the effect of AK treatment on cSCC risk and outcomes of cSCC.

Group clinic for chemoprevention of squamous cell carcinoma: a pilot study.

Topical 5-fluorouracil (5-FU) is a valuable treatment of actinic keratosis (AK), but its use is limited by bothersome side effects. To evaluate patient satisfaction with a regimen of 5-FU for AK in group clinics, we offered participation in shared medical appointments (SMAs) to dermatology clinic patients diagnosed with AK at the Providence VA Medical Center in Rhode Island. Approximately 3 to 4 patients attended each pair of sessions spaced 2 weeks apart. At each visit, photographs and feedback were obtained; at the second visit, clinicians graded the patients' reactions to 5-FU according to a validated numeric scale. Of the 14 study patients who attended the second SMA, 10 stated that they completed 2 weeks of 5-FU therapy, and the other 4 stated that they completed at least 11 days. The validated scale used during the second visit to grade the patients' 5-FU reactions confirmed that all 14 patients demonstrated at least 1 expected adverse skin reaction. Feedback about the group setting was uniformly positive, with specific appreciation for the educational aspects, normalization of the treatment process, and opportunities to ask questions. The group clinic setting for 5-FU was well received and is a promising model for delivering this important treatment.