Influence of sex, neutering, breed, age, and geographic origin on malignant tumor development in cats: a multicenter retrospective study

Influence of sex, neutering, breed, age, and geographic origin on malignant tumor development in cats: a multicenter retrospective study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Influence of sex, neutering, breed, age, and geographic origin on malignant tumor development in cats: a multicenter retrospective study Niccolò Fonti, Azzurra Carnio, Cristiano Cocumelli, Elena Sophie Dhein, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7981624/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 19 Jan, 2026 Read the published version in Scientific Reports → Version 1 posted 10 You are reading this latest preprint version Abstract Animal cancer registries (ACRs) are vital tools in veterinary oncology, offering insights into tumor epidemiology and supporting comparative research. Despite cancer being a major cause of feline mortality, data on feline tumor epidemiology remain limited. This study aimed to investigate temporal trends in histologically diagnosed feline tumors and assess how breed, sex, neuter status, age, and geographic origin affect malignancy and tumor distribution. A modified Vet-ICD-O-canine-1 coding system was applied to 5,289 tumors from two pathology-based ACRs in central Italy (2008–2023). Data were analyzed for time trends by the Cochrane-Armitage test, and logistic regression was used to assess the impact of the variables on tumor behavior ("malignant" vs. "benign") and the development of major cancer types. Of all tumors, 4,264 (80.6%) were malignant. Fibrosarcomas, adenocarcinomas, squamous cell carcinomas (SCCs), and lymphomas were the most common types of cancer. Malignancy risk increased by 8% per year of age. Females (OR = 1.39; 95%CI 1.19–1.62) and non-purebred cats (OR = 1.89; 95%CI 1.47–2.38) had higher odds of malignancy. Intact status was not associated with overall malignancy but increased adenocarcinoma risk. Temporal trends included rising SCCs and declining fibrosarcomas. These findings support previous findings and identify previously unknown risk factors, underscoring the value of multicenter ACR-based surveillance. Biological sciences/Cancer Health sciences/Diseases Health sciences/Oncology animal cancer registry malignancy cat veterinary oncology fibrosarcoma squamous cell carcinoma Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 1. Introduction Cancer represents a major health concern in both humans and animals, with millions of new cases diagnosed annually worldwide 1 , 2 . Among companion animals, cats are one of the most popular species worldwide, with an estimated 600 million individuals—including pets, strays, and feral cats—distributed across all continents except Antarctica 3 , 4 . These figures also rank the cat among the most common terrestrial mammals 5 . Their popularity as pets has steadily increased in recent decades 6 . In the United States alone, between 61 and 90 million cats are owned, underscoring their growing societal and clinical importance as companion animals 7 . Cats also bear a particularly high cancer burden: the proportion of malignant tumors is reported to be higher in felines than in other species, including dogs and humans 8 – 12 . Clinically, the species presents additional challenges, as cats often conceal illness and tend to exhibit non-specific clinical signs. As a result, neoplasms are frequently detected at an advanced stage, when therapeutic options are limited and prognosis is poor 13 , 14 . This combination of biological predisposition and clinical presentation highlights the need for a deeper epidemiological understanding of feline cancer. Animal cancer registries (ACRs) are essential to fill this gap, providing structured data that support the identification of risk factors and patterns in tumor occurrence. They also represent a cornerstone for comparative oncology, given the significant histopathological, genetic, and molecular similarities between tumors in cats, dogs, and humans 1 , 14 , 15 . The close cohabitation of cats and humans further strengthens the relevance of feline cancer studies. Sharing the same domestic environments, pets are exposed to similar allergens, dietary components, and environmental pollutants as their owners 16 . This parallel exposure makes them potential epidemiological sentinels for human cancer development 17 , 18 , particularly in a One Health context. Additional advantages of companion animals in cancer research include shorter latency periods following carcinogen exposure and shorter life expectancy, which result in faster disease progression and make them ideal subjects for prospective studies 17 , 19 . Moreover, pets are exposed to fewer lifestyle-related confounding factors—such as smoking, alcohol consumption, or occupational hazards—and their relatively stable environments enhance the reliability of epidemiological findings 20 , 21 . Despite these benefits, veterinary oncology still lacks the systematic data collection available in human medicine, where established registries guide the decision-making process 22 . Most registries in companion animals have been historically constrained, covering small populations or short timeframes 8 , 9 , 23 – 31 . Consequently, robust data on pet cancer distribution, biological behavior, and risk factors remain scarce. While canine oncology has received more attention, the epidemiology of feline tumors has been investigated less extensively. Available information is still fragmentary and often limited to studies with restricted sample sizes, geographical coverage, or temporal duration 10 , 31 . Recent international initiatives such as the Global Initiative for Veterinary Cancer Surveillance (GIVCS) have promoted harmonized classification systems and standardized coding to enhance comparability across studies and species 32 – 34 . These efforts are essential to integrate pet data into a broader epidemiological framework and to exploit their potential in a One Health perspective. Nonetheless, major gaps persist, and further efforts are needed to enhance the quantity and quality of ACR-based studies focused on cats, at both national and international levels. This study aimed to retrospectively describe a collection of histologically diagnosed feline tumors recorded by the UNIPI pathology-based ACR of the Department of Veterinary Sciences at the University of Pisa and the Animal Tumour Registry of the Lazio region, Rome. Data were obtained from routine diagnostic histological examinations performed between January 2008 and December 2023. The study analyzed temporal trends and assessed the influence of breed, sex, neutering status, age, and geographical origin on overall malignancy risk and on the development of the most common feline malignant tumor types: fibrosarcomas, adenocarcinomas, squamous cell carcinomas (SCCs), and lymphomas. 2. Results 2.1. Descriptive statistics 2.1.1. Sample size Over the course of the research period (2008 – 2023), a total of 5,538 tumor records (including metastases, recurrences, and tumors with uncertain biological behavior) were collected. After coding and cleaning, 3,518 records from the ACR of Pisa and 1,771 cases from the ACR of Lazio were included, totaling 5,289 primary tumor diagnoses in 5,154 cats. The number of primary tumors ranged from one to six per cat. The data set consisted mostly of tumor cases from the Tuscany (n = 2,513; 47.5%), Lazio (n = 1,785; 33.8%), and Liguria (n = 741; 14.0%) districts of origin (Fig. 1 ). 2.1.2. Tumor topographies and morphologies Figure 2 depicts the distribution of the most frequent tumor morphologies and the malignancy proportions by topography. The three most common tumor localizations were the skin [C44] (n = 1,543/5,289; 29.2%), the soft tissues [C49] (n = 1,387/5,289; 26.2%), and the mammary gland [C50] (n = 765/5,289; 14.5%) (Fig. 2 ). Fibromatous neoplasms [881–883] were the most diagnosed morphologies (n = 942/5,289; 17.8%), followed by adenomas and adenocarcinomas [814–838] (n = 856/5,289; 16.2%), squamous cell neoplasms [805–808] (n = 756/5,289; 14.3%), and lymphomas [959–972] (n = 507/5,289; 9.6%). The fibromatous neoplasms were mainly located in the soft tissue s (n = 848/942; 90.0%), and only few were diagnosed in the lip, oral cavity, pharynx [C00–14] (n = 58/942; 6.2%), and digestive organs [C15–26] (n = 9/942; 1.0%). The 72.7% (n = 622/856) of the adenomas and adenocarcinomas were in the mammary gland , comprising 81.3% (n = 622/765) of all mammary gland tumors, while the 12.0% (n = 103/856) were diagnosed in the digestive organs . The squamous cell neoplasms were mainly located in the skin (n = 465/756; 61.5%), in which they comprise the most common tumor type (n = 465/1,543; 30.1%), followed by basal cell neoplasms [809–811] (n = 312/1,543; 20.2%), adnexal and skin appendage neoplasms [839–842] (n = 270/1,543; 17.5%), and mast cell neoplasms (n = 269/1,543; 17.4%). The 28.2% of remaining squamous cell neoplasms were in the lip, oral cavity, pharynx site, comprising 52.3% of all tumors affecting this area (213/407 cases). Other oral neoplasms were the previously mentioned fibromatous neoplasms (58/407 cases; 14.3%), and odontogenic tumors [927–934] (32/407; 7.9%). For lymphomas , the most common localizations were the digestive organs (224/507; 44.2%), the lymph nodes (94/507; 18.5%), and the unknown [C80] —including the multiple sites [C80.91] code—localization (36/507; 7.1%) (Fig. 2 ). The absolute number of cases and the relative frequency of all tumor topographies and morphologies are reported in Supplementary Table 2. 2.1.3. Demographic features and age at tumor diagnosis Female cats were slightly more represented (n = 2,911; 55.0%) than males (n = 2,065; 39.0%), with the majority of collected cases involving neutered animals (n = 3,371; 63.7%). This higher proportion of neutered individuals was comparable across both registries and sexes (Table 1 ). The median age at tumor diagnosis was 11 years (range: <1–24), with males diagnosed at a younger age than females (median: 10.1 years for males and 11.0 years for females). Median ages of intact and neutered felines were similar. Moreover, malignant tumors were observed in cats with a higher median age (11.0 years) compared to those with benign tumors (10.0 years). Table 1 Absolute numbers, percentages, and median age at tumor diagnosis for 5,289 tumors from the Animal Cancer Registries (ACRs) of Pisa and Lazio and subdivided by sex and neuter status. The overall number and percentage of malignant tumors (Malignancy Proportion) are also provided. Sex Neuter status Pisa ACR Lazio ACR Total All tumors All tumors All tumors Malignant tumors n° % n° % n° % Age (range) 1 n° MP Male Intact 455 12.9% 153 8.6% 608 11.5% 9.7 468 77.0% Neutered 937 26.6% 520 29.4% 1457 27.5% 10.3 1120 76.9% Total 1392 39.6% 673 38.0% 2065 39.0% 10.1 1588 76.9% Female Intact 740 21.0% 257 14.5% 997 18.9% 10.7 829 83.1% Neutered 1114 31.7% 800 45.2% 1914 36.2% 11.0 1584 82.8% Total 1854 52.7% 1057 59.7% 2911 55.0% 10.9 2413 82.9% N.d. 272 7.7% 41 2.3% 313 5.9% 11.2 263 84.0% Total 3518 1771 5289 10.6 4264 80.6% 1 The median age and the range (in brackets) are reported in years; n° = absolute number of cases; MP = Malignancy Proportion; N.d.: not determined. Percentages are reported out of the total. 2.1.4. Breeds Most cases were from House Cat Shorthair/Longhair (HCS/HCL) (n = 4,562/5,289; 86.3%). Purebred cats comprised 7.2% of the total (n = 378/5,289), and the breed was unknown in 6.6% of the cases (n = 349/5,289). Overall, 21 different feline breeds were included (Supplementary Table 3). Among purebreds, the predominant breeds were the Persian (n = 164/5,289; 3.1%), the Siamese (n = 54/5,289; 1.0%), the Maine Coon (n = 35/5,289; 0.7%), and the Chartreux (n = 31/5,289; 0.6%). Figure 3 presents a summary of the tumor type distribution across these breeds. In HCS/HCL and Chartreux cats, fibromatous neoplasms were the prevalent diagnoses, while in Persian and Siamese cats, adenomas and adenocarcinomas were the most frequently observed tumor types. Conversely, basal cell neoplasms were overrepresented in the Maine Coon. 2.2. Malignancy Analysis Malignant tumors constituted 4,264 (80.6%) of the total. Predictor variables for the regression analysis were selected based on the results of the univariate analysis (Supplementary Table 4). Based on logistic regression analysis, Fig. 4 b illustrates the impact of age, sex, neuter status, breed, and district on the proportion of malignancies. The risk of malignancy increased by 8% per year (OR = 1.08; 95% CI 1.06–1.10). Females exhibited an increased risk in comparison to males (OR = 1.39; 95% CI 1.19–1.62), and neuter status was not associated with malignancy ( p = 0.537). In terms of districts, a marginally significant rise in malignancy was noted in the Liguria region (OR = 1.40; 95%CI 1.09–1.82), whereas the "breed" variable emerged as the predominant factor influencing malignancy risk, with a protective effect of being purebred compared to HCS/HCL (OR = 0.53; 95%CI 0.42–0.68). Unfortunately, an individual breed-based analysis had to be omitted due to the low number of purebred cats. The anatomical localizations with the highest (100.0%) malignancy proportion were the lymph nodes , the respiratory system , unknown topography , and intrathoracic organs (excl. lung) . The lowest malignancy proportions were observed in the male genital organs (20.0%), female genital organs (48.3%), nervous system (51.5%), and the skin (57.5%) (Fig. 2 ). Over the course of the years, there was no discernible upward or downward trend in the malignancy proportion (Fig. 4 a). The next part will delve more deeply into the most commonly diagnosed malignant tumor types within the datasets, evaluating the effects of the aforementioned factors as well as their frequency over time. 2.3. Risk by tumor types 2.3.1. Fibrosarcoma Out of 942 diagnosed fibromatous neoplasms , 98.3% (n = 926) were malignant, while benign tumors (mainly fibroma, NOS [8810/0] , and dermatofibroma [8832/0] ) accounted for just 1.6% (n = 15). The following investigations focused only on fibrosarcoma, including both fibrosarcoma, NOS [88100/3] and FISSs [8800.2/3] . Age analyses indicated that fibrosarcoma was more prevalent in middle-aged and older felines, with a 5% risk increase for each year of age (OR = 1.05; 95% CI 1.03–1.07). The risk of a female cat receiving a fibrosarcoma diagnosis was significantly lower than that of a male cat (OR = 0.59; 95% CI 0.50–0.69) (Fig. 5 b). Neutered and intact cats had no differential risk of fibrosarcoma diagnosis. Purebred cats had a markedly reduced risk of fibrosarcoma in comparison to HCS/HCL (OR = 0.67; 95% CI 0.48–0.92). Cases from the Liguria district showed a higher risk compared to Tuscany (OR = 1.37; 95% CI 1.08–1.73). The relative frequency of fibrosarcoma diagnoses has significantly decreased (p < 0.001) since the beginning of the study period (Fig. 5 a). 2.3.2. Adenocarcinoma Out of 856 diagnosed adenoma and adenocarcinomas , 95.1% (n = 814) were malignant (i.e. adenocarcinomas). Benign tumors accounted for 4.9% (n = 42). This lower proportion of adenomas was strongly marked in mammary tumors (2.4%; n = 15/622), in tumors from the respiratory system (0%; n = 0/35) and nose, ear, sinuses, larynx (0%; n = 0/21). Conversely, in the endocrine glands (42.9%; n = 9/21) and eye and adnexa (57.1%; n = 4/7), the proportions of adenomas were much higher. The following assessments focused only on adenocarcinomas (Fig. 5 d). Older cats were more commonly affected, with a 4% risk increase for each year of age (OR = 1.04; 95% CI 1.02–1.07). Female cats had a markedly increased risk of adenocarcinoma compared to males (OR = 6.85; 95% CI 5.39–8.83). Neutered cats showed a reduced risk (OR = 0.79; 95% CI 0.66–0.94). Purebred cats had a significantly increased risk of developing adenocarcinoma in comparison to HCS/HCL (OR = 0.67; 95% CI 0.48–0.92). The relative frequency of adenocarcinoma diagnoses has significantly decreased (p < .001) since the beginning of the study period (Fig. 5 c). 2.3.3. Squamous cell carcinoma Out of 756 diagnosed squamous cell neoplasms , 97.6% (n = 738) were malignant (i.e. squamous cell carcinoma (SCC)), while papilloma, NOS [8050/0] accounted for 2.4% only (n = 18). SCCs were the most diagnosed tumor type in both the skin and oral cavity (Fig. 2 ). Considering the skin, 82.0% (n = 370/451) of SCCs affected the head, with the majority of them at the external ear [C44.2] (37.0%; n = 167/451), skin of other and unspecified parts of head [C44.3] (24.8%; n = 112/451), eyelid, NOS [C44.1] (10.4%; n = 47/451), and skin of occiput, nape and neck [C44.4] (8.7%; n = 39/451). The risk of developing SCC increased with age (OR = 1.05; 95% CI 1.02–1.07), while all the other variables didn’t seem to significantly affect the SCC-risk (Fig. 5 f). The relative frequency of SCC diagnoses has constantly increased during the study period (p = 0.001), starting from 10.3% in 2008 and reaching up to 15.9% in 2023 (Fig. 5 e). 2.3.4. Lymphoma Compared to other tumor diagnoses, older cats showed a reduced risk for lymphoma (OR = 0.90; 95% CI 0.88–0.93) (Fig. 5 h). The risk of a female cat being diagnosed with lymphoma compared with that of a male was significantly lower (OR = 0.64; 95% CI 0.52–0.79), while neuter status didn’t show any significant contribution. In addition, there were no significant differences between the risk for purebred cats and HCS/HCL. Cases from Liguria (OR = 1.37; 95% CI 1.00–1.87) and other districts (OR = 1.61; 95% CI 1.02–2.45) showed a higher risk compared to Tuscany (Fig. 5 h). During the research period, the relative frequency of lymphoma diagnoses remained stable (p = 0.671), without significant increasing or decreasing trends (Fig. 5 g). The output of all the logistic regressions, including confidence intervals and statistical significance for each tumor type and overall malignancy risk, is detailed in Supplementary Table 5. 3. Discussion This study provides one of the most comprehensive assessments of risk factors for feline tumor malignancy, based on 5,289 samples collected over 15 years 10 , 35 , 36 . With an overall malignancy proportion of 80.6%, the findings align with previous reports 8 – 11 , 35 , 37 – 42 , though notable exceptions—such as a recent 54.1% rate reported in South Korea—highlight potential geographic variability 36 . The high incidence of malignancy in cats may be linked to evolutionary and dietary traits common to obligate carnivores 43 . Age emerged as a significant risk factor, with the risk of malignancy increasing by approximately 8% per year, supporting the cumulative nature of oncogenic mutations over time 35 , 36 . Females showed higher odds of malignant tumors, likely reflecting the high prevalence of mammary neoplasms in cats 9 , 11 , 35 , 36 , 41 . Neutering didn’t affect overall malignancy risk but was associated with variations in specific tumor types. However, limitations concerning the exact timing of neutering prevent definitive conclusions, and further prospective studies focused on the influence of neutering on feline cancer development are warranted. Geographic origin had a modest yet statistically significant influence on malignancy risk, echoing findings in canine studies 44 , 45 . While this may reflect differences in diagnostic practices rather than environmental exposures, it underscores the need for more granular, region-focused research. Unfortunately, the limited number of purebred cats prevented statistical analysis at the individual breed level, although differences in tumor distribution were noted among the five most common breeds. Nevertheless, purebred status showed a strong contribution to malignancy risk, with an almost 50% reduction compared to HCS/HCL cats. This protective role was previously highlighted by Graf et al. 10 . No differences in the proportion of malignancy by breed were found in other studies, albeit with smaller sample sizes 35 , 36 . Unlike dogs, several feline breeds still maintain moderate genetic diversity and show lower levels of inbreeding, potentially explaining this paradoxical finding 46 , 47 . As a result, exogenous factors such as viral agents and environmental exposures may play a more prominent role in shaping malignancy risk in cats. The four most common feline malignant tumor types were specifically addressed for risk factor identification and temporal trends. Fibrosarcomas, adenocarcinomas, SCCs, and lymphomas are frequently reported as the most common malignancies in cats, albeit in varying proportions 11 , 41 , 42 , 48 – 50 . Our study identified fibrosarcoma as the most commonly diagnosed neoplasm from 2008 to 2023, accounting for 17.5% of the total cases. These data overlap with those of Graf et al. 48 . An increased risk in older, male, and HCS/HCL cats was found. Prior studies have shown no breed or sex predisposition; however, a higher risk in females 48 and neutered cats 50 has been recently reported, and certain breeds were significantly less likely to develop fibrosarcoma than non-purebred cats 48 , 51 , 52 , a result consistent with our findings. The relative frequency of fibrosarcoma has decreased by nearly 50% since 2008. A significant proportion of fibrosarcomas in our study were FISS, and the etiopathogenesis of these tumors remains a subject of controversy. Numerous studies demonstrate the impact of the vaccine adjuvant alum, which is incorporated to stimulate the immune response when utilizing an inactivated aetiological agent, mainly rabies or FeLV vaccination 53 – 55 . There are limited registers that monitor the temporal trends of tumors for comparative analysis. However, our data confirm the observations made by the Swiss Feline Cancer Registries, which have noted a similar decreasing trend since 2009, correlating it with the introduction of a non-adjuvanted FeLV vaccine 51 . The current situation in Italy mirrors that of Switzerland, where rabies vaccination is not mandatory. Recent introductions of non-adjuvanted and recombinant vaccines support an increased risk of fibrosarcoma development in cats following the administration of adjuvanted vaccines, particularly those containing alum. Feline adenocarcinomas predominantly originated from the mammary gland, which exhibited a high proportion of malignant tumors (95.2%). This finding elucidates the marked predisposition of female and intact animals to this tumor type, and corroborates the more aggressive biological behavior of these tumors in cats compared to dogs 35 , 36 , 40 , 41 , 48 , 56 – 59 . Purebred cats showed a significantly increased risk of developing adenocarcinoma in comparison to HCS/HCL. The logit result is consistent with the tumor distribution findings, as adenocarcinoma was the most common tumor type in Persians and Siamese 14 , 48 , 58 , 60 , 61 . In our study, no sex or breed predispositions were observed for SCC 48 , 62 . Notably, the temporal trend analysis revealed a consistent and significant increase in SCC diagnoses. While the role of papillomavirus remains debated, chronic sunlight exposure is regarded as the primary factor implicated in the development of cutaneous SCC 37 , 63 , 64 . Research indicates that countries offering a complete or semi-outdoor lifestyle for cats exhibit a higher incidence of SCC 11 , 37 , 49 , 65 , 66 compared to those with restricted UV light exposure and predominantly indoor cat populations 36 , 48 , 52 . Southern latitudes may lead to increased exposure to ultraviolet (UV) light, which could account for the discrepancies observed in various studies 11 , 36 , 49 and the higher occurrence reported here. In a One Health approach, the observed increase in feline SCC occurrence supports concerns regarding climate change and the global increase in UV irradiation, specifically in the Mediterranean area 11 , 67 . While an improvement in the diagnosis of feline UV-induced lesions in recent years should not be ruled out, this temporal trend is noteworthy and closely aligns with the ones observed in human skin cancers 68 – 70 . The current findings on lymphoma confirmed that this neoplasm primarily occurs in the digestive tract 11 , 41 , 48 , 71 , with an an enhanced risk in males 8 , 48 , 72 , 73 and relatively young individuals compared to other tumor types 48 , 73 , 74 . This study benefits from a multi-center design, a representative sample of feline tumors, and alignment with previous pathology- and population-based registries 9 – 11 , 39 , 41 , 48 , 50 . Nevertheless, some limitations must be acknowledged. The retrospective nature of the analysis and reliance on histopathologic diagnoses, while ensuring diagnostic accuracy, may introduce selection bias, as cytologically diagnosed neoplasms were not included. Submission for histology in clinical practice is influenced by multiple factors and may affect tumor representation 44 , 75 . Conversely, the adoption of Vet-ICD-O represents a valuable asset for standardizing data collection, inclusion criteria, and data sharing 34 . In the absence of feline-specific codes, the use of Vet-ICD-O-canine-1codes for tumors with similar biological and prognostic features, the creation of de novo codes for feline-specific entities, and the provided criteria for defining biological behavior (detailed in Supplementary Table 1) may support broader application of this system to feline oncology and promote more consistent epidemiological research. While logistic regression offers adjusted estimates and facilitates between-group comparisons, odds ratios should not be interpreted as direct measures of incidence 76 . The lack of reliable population denominators further limits external validation. In Italy, the expansion of national pet registries offers a promising avenue for improving denominator estimates. A centralized system—the Sistema Informativo Nazionale degli Animali da Compagnia (SINAC)—is currently being implemented within the Ministry of Health’s national digital database (BDN), in accordance with D. Lgs. 134/2022 and EU Regulation 2016/429. In this scenario, multicentric initiatives such as the Italian Network of Laboratories for Veterinary Oncology (NILOV), to which both research centers involved in this study are affiliated, represent an important step toward more structured and harmonized pet cancer surveillance systems in Italy and may support future population-based studies in the feline species 45 , 50 . 4. Conclusion We analyzed malignancy patterns and risk factors, confirming an age-related increase in malignancy and a higher risk in females. Unlike in dogs, purebred cats showed a lower malignancy risk than mixed breeds. While the overall proportion of malignant tumors remained stable over time, fibrosarcoma and adenocarcinoma decreased, whereas squamous cell carcinoma diagnoses increased. These findings highlight the importance of standardized, collaborative data collection and support future investigations into endogenous and environmental cancer risk factors, with implications for translational research in a One Health framework. 5. Material and methods 5.1. Data collection and processing The owners' informed consent and the use of anonymized data in research activities was collected by clinicians and provided along with clinical information including the species, breed, age, sex, neutering status, date of diagnosis, postal code area, individual ID, symptoms, anamnestic information, tumor staging. The data collected by the two ACRs were extracted from their respective laboratory information management systems and processed using Microsoft Excel version 16.84 (Microsoft 2024, www.microsoft.com ) and R Language and Environment for Statistical Computing studio R version 4.4.0 77 , with the dplyr package 78 . Only confirmed primary tumor diagnoses were retained, whilst metastases or recurrences were omitted. Multiple tumors (i.e., distinct tumors with different histotypes in the same feline subject) were maintained separately and managed in accordance with the WHO ICD-O-3.1 criteria 79 , 80 . Since a tumor classification and coding system specifically developed for the feline species has not yet been published, the tumor's histological type (morphology) and anatomical localization (topography) were coded using Vet-ICD-O-canine-1 34 . Topographic sites were grouped according to Dhein et al. 80 . For tumor morphologies, minor modifications were made to adapt the coding system to the feline species. Peripheral odontogenic fibroma was considered a tumor 81 and was therefore included in the group of odontogenic tumors [927–934] , using the term and ICD-O-3.2 code peripheral odontogenic fibroma [9322/0] 80 . Diagnoses of actinic keratosis were included in the dataset with the de-novo code [8070.1/2] in the group of squamous cell neoplasms [805–808]. Feline injection-site sarcomas (FISSs) were coded with the de-novo code [8800.2/3] in analogy to the sarcoma associated with Spirocerca lupi [8800.1/3] from the Vet-ICD-O-Canine1 34 , but were added to the group of fibromatous neoplasms [881–883] according to the Swiss Feline Cancer Registry 48 , 51 . Mammary carcinomas with ‘ in situ ’ tumor behavior were excluded as previously stated 82 , 83 . The binary variable “malignancy” (benign "B" vs. malignant "M") was assigned to each case based on the Vet-ICD-O behaviour code 35 , 44 , 83 . Tumors bearing the labels [/0] and [/3] were grouped as benign and malignant, respectively. Neoplasms uncertain whether benign or malignant [/1] and in situ [/2] were classified according to the scheme provided in Supplementary Table 1. Feline breeds were classified according to the Fédération Internationale Féline 84 . To avoid any confusion with the FIFe-recognized “European” (EUR) breed, the cats defined as “tabby” or “Common European” or “Domestic Shorthair/Domestic Longhair” have been classified as “House Cat Shorthair/Longhair” (HCS/HCL) (i.e., “mixed-breed”, as having undocumented or unknown parentage). 5.2. Statistical analysis Categorical data were summarized as absolute counts and percentages. Continuous data (i.e. age) were described by median and range. Pearson’s Chi-square test and a subsequent multiple logistic regression model were used to assess the influence of the independent variables “age”, “sex” (male/female), “neuter status” (intact/neutered), “district of origin” (Tuscany, Lazio, Liguria, and other districts) and “breed” (mixed-breed/purebred) on the dichotomous “malignancy” outcome, as detailed in Fonti et al. for the canine species 44 . The logit model was applied to the four most diagnosed malignant tumors (fibrosarcomas, adenocarcinomas, SCCs, and lymphomas), too. In these models, two distinct groups were compared: those cases with the specific category of tumor, and those that were not diagnosed with the tumor of interest, with a case-control study design 44 . Adjusted Odds Ratios (ORs) were therefore obtained. To ensure clarity, the words "risk" and "OR" were used interchangeably throughout the paper. To determine if the overall malignancy proportions and the relative frequencies for the 4 most common malignant tumor types increased or decreased during the 16-year research period, the Cochran-Armitage trend test was applied. The minimum conditions for significant differences were a 95% confidence interval (95% CI) that did not overlap 1 and a p value < 0.05. All statistical analyses were performed using R Language and Environment for Statistical Computing studio R version 4.4.0 77 . Data were plotted using the pheatmap and ggplot2 packages 85 , 86 . Declarations 7. Funding This research is supported by the Ministry of University and Research (MUR) as part of the PON 2014–2020 “Research and Innovation" resources – Green/Innovation Action – DM MUR 1061/2022. 8. Declaration of competing interest The authors of this research paper have no financial or personal interests that could have influenced this paper. 9. Data availability statement Data and code implemented for this study are available on request. 10. Credit authorship contribution statement N. Fonti: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Visualization, Writing – original draft. A. Carnio: Data curation, Investigation, Writing – review & editing. C. Cocumelli: Investigation, Writing – review & editing. E.S. Dhein: Data curation, Formal analysis, Methodology, Writing – review & editing. C. Eleni: Investigation, Resources, Writing – review & editing. V. Galietta: Investigation, Writing – review & editing. F. Guscetti: Conceptualization, Supervision, Writing – review & editing. A. Lachi: Formal analysis, Methodology, Validation. F. Parisi: Investigation, Writing – review & editing. A. Poli: Funding acquisition, Investigation, Supervision. P. Scaramozzino: Resources, Validation, Writing – review & editing. F. Millanta: Conceptualization, Funding acquisition, Investigation, Project administration, Resources, Supervision, Writing – review & editing. Author Contribution N. Fonti: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Visualization, Writing – original draft. A. Carnio: Data curation, Investigation, Writing – review & editing. C. Cocumelli: Investigation, Writing – review & editing. E.S. Dhein: Data curation, Formal analysis, Methodology, Writing – review & editing. C. Eleni: Investigation, Resources, Writing – review & editing. V. Galietta: Investigation, Writing – review & editing. F. Guscetti: Conceptualization, Supervision, Writing – review & editing. A. Lachi: Formal analysis, Methodology, Validation. F. Parisi: Investigation, Writing – review & editing. A. Poli: Funding acquisition, Investigation, Supervision. P. Scaramozzino: Resources, Validation, Writing – review & editing. F. Millanta: Conceptualization, Funding acquisition, Investigation, Project administration, Resources, Supervision, Writing – review & editing. Acknowledgement We gratefully acknowledge all the veterinary practitioners and dog owners who have provided samples and valuable medical history data. Data Availability Data and code implemented for this study are available on request. References Schiffman, J. D. & Breen, M. Comparative oncology: what dogs and other species can teach us about humans with cancer. Philos. Trans. R Soc. B Biol. Sci. 370 , 20140231 (2015). Bray, F. et al. 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07:27:52","extension":"jpeg","order_by":9,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":483992,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7981624/v1/0c4b562fff2b78546526820d.jpeg"},{"id":96250069,"identity":"095dd47a-1abe-4f18-89a5-c39ccbc94cc6","added_by":"auto","created_at":"2025-11-19 07:37:21","extension":"jpeg","order_by":10,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":2177924,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage5.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7981624/v1/290c0b20c2263ba432417126.jpeg"},{"id":96088660,"identity":"6e042294-f12d-436a-bcd4-ffe6323ec50e","added_by":"auto","created_at":"2025-11-17 12:58:32","extension":"png","order_by":11,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":28822,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7981624/v1/0baeb1c61d0aa88a004356aa.png"},{"id":96088651,"identity":"8ca60719-2aae-453c-939c-620d4a47e177","added_by":"auto","created_at":"2025-11-17 12:58:32","extension":"png","order_by":12,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":49086,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7981624/v1/64c511bb071749cbafeefa14.png"},{"id":96248479,"identity":"c6687557-cd08-4a3d-993a-28bd8f715cef","added_by":"auto","created_at":"2025-11-19 07:28:29","extension":"png","order_by":13,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":55287,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-7981624/v1/6a6b805bd0b25da64a0936f6.png"},{"id":96088654,"identity":"5885429e-28d9-47f6-988f-473570cba6f4","added_by":"auto","created_at":"2025-11-17 12:58:32","extension":"png","order_by":14,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":200146,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-7981624/v1/eb40f87d9dce7bae5303f6d8.png"},{"id":96088649,"identity":"6a34e964-de9a-4ac1-90a8-44905d813f67","added_by":"auto","created_at":"2025-11-17 12:58:32","extension":"png","order_by":15,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":774817,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-7981624/v1/ae4efb43f16c899eda50e18b.png"},{"id":96088658,"identity":"f91bb050-c363-407b-8f68-a7fe49216871","added_by":"auto","created_at":"2025-11-17 12:58:32","extension":"xml","order_by":16,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":164602,"visible":true,"origin":"","legend":"","description":"","filename":"f006d67fc35c48ebb74bdd0a976c75771structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7981624/v1/35499b8feeafe4bce8628bbe.xml"},{"id":96088662,"identity":"af13ddef-6ed0-49a6-892f-929d690b0fd8","added_by":"auto","created_at":"2025-11-17 12:58:32","extension":"html","order_by":17,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":179375,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7981624/v1/2de92837b80f4ae87f4a3d55.html"},{"id":96088639,"identity":"2e1a7766-74f4-47cc-a023-4ad62389eed3","added_by":"auto","created_at":"2025-11-17 12:58:32","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":2756618,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eChoropleth map depicting the Italian districts of provenance for the 5,289 feline tumor cases included in the study. The color gradient is proportional to case numerosity. The geographical location of both registries is also shown: A = ACR of Pisa; B = ACR of Lazio.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-7981624/v1/1c24cc335c345dc3140692eb.png"},{"id":96088642,"identity":"116e09ba-bc67-4b26-9b16-27d31bccfe7c","added_by":"auto","created_at":"2025-11-17 12:58:32","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":3983454,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eAbsolute number of the top ten most common tumor types and malignancy proportions (%) per topographical site in the 5,289 tumor cases included in the study.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-7981624/v1/8cb4d34fcbc7b9bb419337bf.png"},{"id":96249073,"identity":"671b31cf-f7a6-42fd-8528-8e89ad0db31a","added_by":"auto","created_at":"2025-11-19 07:30:13","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":3019311,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eHeath map showing the proportional morbidity (% out of the total tumors) for the 4,846 tumor cases detected in the 5 most common feline breeds. Each row sums up to 100%. The breeds are clustered according to their similarities in the tumor distribution patterns. The total number of cases is reported in round brackets.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-7981624/v1/9c643d4e99e9e7dbb777c8b5.png"},{"id":96248656,"identity":"d3f266a1-1d22-48a0-8fdc-5b0aa6bca411","added_by":"auto","created_at":"2025-11-19 07:28:55","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":3218440,"visible":true,"origin":"","legend":"\u003cp\u003eTemporal trend and logistic regression results (forest plot) for malignant tumor risk.\u003cem\u003e (a) Relative frequency (%) of malignant tumors on the total number of tumors diagnosed by year over the study period. p = 0.083. (b) Odds ratios (ORs) and 95% confidence intervals (95% CI) for receiving a malignant tumor diagnosis. CI = Confidence Interval; \u0026lt;1 year, male, intact, Tuscany district, and mixed-breed (i.e. House Cat Shorthair/Longhair) were taken as reference (black square); * (p \u0026lt; .05), ** (p \u0026lt; .01), *** (p \u0026lt; .001).\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-7981624/v1/64b51d06146a02fb45e42c07.png"},{"id":96249995,"identity":"5a799ec3-17f1-4c83-8017-c6e84f90223d","added_by":"auto","created_at":"2025-11-19 07:37:01","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":12928594,"visible":true,"origin":"","legend":"\u003cp\u003eTemporal trend and logistic regression results (forest plot) for the four most common feline cancer types. (a-b) fibrosarcoma, (c-d) adenocarcinoma, (e-f) squamous cell carcinoma, (g-h) lymphoma. \u003cem\u003e(a,c,e,g) Relative frequency (%) of the cancer type diagnoses on the total number of tumors diagnosed by year over the study period. ns = not significant. (b,d,f,h) Odds ratios (ORs) and 95% confidence intervals (95% CI) for each cancer type. CI = Confidence Interval; \u0026lt;1 year, male, intact, Tuscany district, and mixed-breed (i.e. House Cat Shorthair/Longhair) were taken as reference (black square); * (p \u0026lt; 0.05), ** (p \u0026lt; 0.01), *** (p \u0026lt; 0.001).\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Figure5.png","url":"https://assets-eu.researchsquare.com/files/rs-7981624/v1/f5d990edb6909ff05478fabd.png"},{"id":101151641,"identity":"e8be26dd-6ae6-4f3b-b2d2-fd260a18864a","added_by":"auto","created_at":"2026-01-26 16:00:05","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":24066223,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7981624/v1/cc0b29f1-06f2-4662-a072-58b57a658221.pdf"},{"id":96248625,"identity":"205dc1cc-bb1e-4a13-984e-6360a2ad9a4e","added_by":"auto","created_at":"2025-11-19 07:28:49","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":265112,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryInformation.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7981624/v1/a7653055ac04c0e3ffe3d1a9.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Influence of sex, neutering, breed, age, and geographic origin on malignant tumor development in cats: a multicenter retrospective study","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eCancer represents a major health concern in both humans and animals, with millions of new cases diagnosed annually worldwide\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. Among companion animals, cats are one of the most popular species worldwide, with an estimated 600\u0026nbsp;million individuals\u0026mdash;including pets, strays, and feral cats\u0026mdash;distributed across all continents except Antarctica\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. These figures also rank the cat among the most common terrestrial mammals\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. Their popularity as pets has steadily increased in recent decades\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. In the United States alone, between 61 and 90\u0026nbsp;million cats are owned, underscoring their growing societal and clinical importance as companion animals\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eCats also bear a particularly high cancer burden: the proportion of malignant tumors is reported to be higher in felines than in other species, including dogs and humans\u003csup\u003e\u003cspan additionalcitationids=\"CR9 CR10 CR11\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. Clinically, the species presents additional challenges, as cats often conceal illness and tend to exhibit non-specific clinical signs. As a result, neoplasms are frequently detected at an advanced stage, when therapeutic options are limited and prognosis is poor\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. This combination of biological predisposition and clinical presentation highlights the need for a deeper epidemiological understanding of feline cancer.\u003c/p\u003e\u003cp\u003eAnimal cancer registries (ACRs) are essential to fill this gap, providing structured data that support the identification of risk factors and patterns in tumor occurrence. They also represent a cornerstone for comparative oncology, given the significant histopathological, genetic, and molecular similarities between tumors in cats, dogs, and humans\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e,\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThe close cohabitation of cats and humans further strengthens the relevance of feline cancer studies. Sharing the same domestic environments, pets are exposed to similar allergens, dietary components, and environmental pollutants as their owners\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. This parallel exposure makes them potential epidemiological sentinels for human cancer development\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e,\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e, particularly in a \u003cem\u003eOne Health\u003c/em\u003e context.\u003c/p\u003e\u003cp\u003eAdditional advantages of companion animals in cancer research include shorter latency periods following carcinogen exposure and shorter life expectancy, which result in faster disease progression and make them ideal subjects for prospective studies\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e,\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. Moreover, pets are exposed to fewer lifestyle-related confounding factors\u0026mdash;such as smoking, alcohol consumption, or occupational hazards\u0026mdash;and their relatively stable environments enhance the reliability of epidemiological findings\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e,\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eDespite these benefits, veterinary oncology still lacks the systematic data collection available in human medicine, where established registries guide the decision-making process\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e. Most registries in companion animals have been historically constrained, covering small populations or short timeframes\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan additionalcitationids=\"CR24 CR25 CR26 CR27 CR28 CR29 CR30\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e. Consequently, robust data on pet cancer distribution, biological behavior, and risk factors remain scarce.\u003c/p\u003e\u003cp\u003eWhile canine oncology has received more attention, the epidemiology of feline tumors has been investigated less extensively. Available information is still fragmentary and often limited to studies with restricted sample sizes, geographical coverage, or temporal duration\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e. Recent international initiatives such as the Global Initiative for Veterinary Cancer Surveillance (GIVCS) have promoted harmonized classification systems and standardized coding to enhance comparability across studies and species\u003csup\u003e\u003cspan additionalcitationids=\"CR33\" citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e. These efforts are essential to integrate pet data into a broader epidemiological framework and to exploit their potential in a One Health perspective. Nonetheless, major gaps persist, and further efforts are needed to enhance the quantity and quality of ACR-based studies focused on cats, at both national and international levels.\u003c/p\u003e\u003cp\u003eThis study aimed to retrospectively describe a collection of histologically diagnosed feline tumors recorded by the UNIPI pathology-based ACR of the Department of Veterinary Sciences at the University of Pisa and the Animal Tumour Registry of the Lazio region, Rome. Data were obtained from routine diagnostic histological examinations performed between January 2008 and December 2023. The study analyzed temporal trends and assessed the influence of breed, sex, neutering status, age, and geographical origin on overall malignancy risk and on the development of the most common feline malignant tumor types: fibrosarcomas, adenocarcinomas, squamous cell carcinomas (SCCs), and lymphomas.\u003c/p\u003e"},{"header":"2. Results","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e2.1. Descriptive statistics\u003c/h2\u003e\u003cdiv id=\"Sec4\" class=\"Section3\"\u003e\u003ch2\u003e2.1.1. Sample size\u003c/h2\u003e\u003cp\u003eOver the course of the research period (2008\u003cem\u003e\u0026ndash;\u003c/em\u003e2023), a total of 5,538 tumor records (including metastases, recurrences, and tumors with uncertain biological behavior) were collected. After coding and cleaning, 3,518 records from the ACR of Pisa and 1,771 cases from the ACR of Lazio were included, totaling 5,289 primary tumor diagnoses in 5,154 cats. The number of primary tumors ranged from one to six per cat. The data set consisted mostly of tumor cases from the Tuscany (n\u0026thinsp;=\u0026thinsp;2,513; 47.5%), Lazio (n\u0026thinsp;=\u0026thinsp;1,785; 33.8%), and Liguria (n\u0026thinsp;=\u0026thinsp;741; 14.0%) districts of origin (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section3\"\u003e\u003ch2\u003e2.1.2. Tumor topographies and morphologies\u003c/h2\u003e\u003cp\u003eFigure \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e depicts the distribution of the most frequent tumor morphologies and the malignancy proportions by topography. The three most common tumor localizations were the \u003cem\u003eskin [C44]\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;1,543/5,289; 29.2%), the \u003cem\u003esoft tissues [C49]\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;1,387/5,289; 26.2%), and the \u003cem\u003emammary gland [C50]\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;765/5,289; 14.5%) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003eFibromatous neoplasms [881\u0026ndash;883]\u003c/em\u003e were the most diagnosed morphologies (n\u0026thinsp;=\u0026thinsp;942/5,289; 17.8%), followed by \u003cem\u003eadenomas and adenocarcinomas [814\u0026ndash;838]\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;856/5,289; 16.2%), \u003cem\u003esquamous cell neoplasms [805\u0026ndash;808]\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;756/5,289; 14.3%), and \u003cem\u003elymphomas [959\u0026ndash;972]\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;507/5,289; 9.6%).\u003c/p\u003e\u003cp\u003eThe \u003cem\u003efibromatous neoplasms\u003c/em\u003e were mainly located in the \u003cem\u003esoft tissue\u003c/em\u003es (n\u0026thinsp;=\u0026thinsp;848/942; 90.0%), and only few were diagnosed in the \u003cem\u003elip, oral cavity, pharynx [C00\u0026ndash;14]\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;58/942; 6.2%), and \u003cem\u003edigestive organs [C15\u0026ndash;26]\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;9/942; 1.0%). The 72.7% (n\u0026thinsp;=\u0026thinsp;622/856) of the \u003cem\u003eadenomas and adenocarcinomas\u003c/em\u003e were in the \u003cem\u003emammary gland\u003c/em\u003e, comprising 81.3% (n\u0026thinsp;=\u0026thinsp;622/765) of all mammary gland tumors, while the 12.0% (n\u0026thinsp;=\u0026thinsp;103/856) were diagnosed in the \u003cem\u003edigestive organs\u003c/em\u003e. The \u003cem\u003esquamous cell neoplasms\u003c/em\u003e were mainly located in the \u003cem\u003eskin\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;465/756; 61.5%), in which they comprise the most common tumor type (n\u0026thinsp;=\u0026thinsp;465/1,543; 30.1%), followed by \u003cem\u003ebasal cell neoplasms [809\u0026ndash;811]\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;312/1,543; 20.2%), \u003cem\u003eadnexal and skin appendage neoplasms [839\u0026ndash;842]\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;270/1,543; 17.5%), and mast cell neoplasms (n\u0026thinsp;=\u0026thinsp;269/1,543; 17.4%). The 28.2% of remaining \u003cem\u003esquamous cell neoplasms\u003c/em\u003e were in the \u003cem\u003elip, oral cavity, pharynx\u003c/em\u003e site, comprising 52.3% of all tumors affecting this area (213/407 cases). Other oral neoplasms were the previously mentioned \u003cem\u003efibromatous neoplasms\u003c/em\u003e (58/407 cases; 14.3%), and \u003cem\u003eodontogenic tumors [927\u0026ndash;934]\u003c/em\u003e (32/407; 7.9%). For \u003cem\u003elymphomas\u003c/em\u003e, the most common localizations were the \u003cem\u003edigestive organs\u003c/em\u003e (224/507; 44.2%), the \u003cem\u003elymph nodes\u003c/em\u003e (94/507; 18.5%), and the \u003cem\u003eunknown [C80]\u003c/em\u003e\u0026mdash;including the \u003cem\u003emultiple sites [C80.91]\u003c/em\u003e code\u0026mdash;localization (36/507; 7.1%) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The absolute number of cases and the relative frequency of all tumor topographies and morphologies are reported in Supplementary Table\u0026nbsp;2.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec6\" class=\"Section3\"\u003e\u003ch2\u003e2.1.3. Demographic features and age at tumor diagnosis\u003c/h2\u003e\u003cp\u003eFemale cats were slightly more represented (n\u0026thinsp;=\u0026thinsp;2,911; 55.0%) than males (n\u0026thinsp;=\u0026thinsp;2,065; 39.0%), with the majority of collected cases involving neutered animals (n\u0026thinsp;=\u0026thinsp;3,371; 63.7%). This higher proportion of neutered individuals was comparable across both registries and sexes (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The median age at tumor diagnosis was 11 years (range: \u0026lt;1\u0026ndash;24), with males diagnosed at a younger age than females (median: 10.1 years for males and 11.0 years for females). Median ages of intact and neutered felines were similar. Moreover, malignant tumors were observed in cats with a higher median age (11.0 years) compared to those with benign tumors (10.0 years).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eAbsolute numbers, percentages, and median age at tumor diagnosis for 5,289 tumors from the Animal Cancer Registries (ACRs) of Pisa and Lazio and subdivided by sex and neuter status. The overall number and percentage of malignant tumors (Malignancy Proportion) are also provided.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"11\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eSex\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eNeuter status\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003ePisa ACR\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003eLazio ACR\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"5\" nameend=\"c11\" namest=\"c7\"\u003e\u003cp\u003eTotal\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003eAll tumors\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003eAll tumors\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c9\" namest=\"c7\"\u003e\u003cp\u003eAll tumors\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e\u003cp\u003eMalignant tumors\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003en\u0026deg;\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e%\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003en\u0026deg;\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003e%\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003en\u0026deg;\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003e%\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003eAge (range)\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c10\"\u003e\u003cp\u003en\u0026deg;\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c11\"\u003e\u003cp\u003eMP\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eIntact\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e455\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e12.9%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e153\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e8.6%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e608\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e11.5%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e9.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e468\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e\u003cp\u003e77.0%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNeutered\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e937\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e26.6%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e520\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e29.4%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e1457\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e27.5%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e10.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e1120\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e\u003cp\u003e76.9%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTotal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1392\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e39.6%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e673\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e38.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e2065\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e39.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e10.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e1588\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e\u003cp\u003e76.9%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eIntact\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e740\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e21.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e257\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e14.5%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e997\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e18.9%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e10.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e829\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e\u003cp\u003e83.1%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNeutered\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1114\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e31.7%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e800\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e45.2%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e1914\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e36.2%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e11.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e1584\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e\u003cp\u003e82.8%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTotal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1854\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e52.7%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1057\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e59.7%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e2911\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e55.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e10.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e2413\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e\u003cp\u003e82.9%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eN.d.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e272\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e7.7%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e41\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e2.3%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e313\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e5.9%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e11.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e263\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e\u003cp\u003e84.0%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3518\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1771\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e5289\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e10.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e4264\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e\u003cp\u003e80.6%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003csup\u003e1\u003c/sup\u003e The median age and the range (in brackets) are reported in years; n\u0026deg; = absolute number of cases; MP\u0026thinsp;=\u0026thinsp;Malignancy Proportion; N.d.: not determined. Percentages are reported out of the total.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec7\" class=\"Section3\"\u003e\u003ch2\u003e2.1.4. Breeds\u003c/h2\u003e\u003cp\u003eMost cases were from House Cat Shorthair/Longhair (HCS/HCL) (n\u0026thinsp;=\u0026thinsp;4,562/5,289; 86.3%). Purebred cats comprised 7.2% of the total (n\u0026thinsp;=\u0026thinsp;378/5,289), and the breed was unknown in 6.6% of the cases (n\u0026thinsp;=\u0026thinsp;349/5,289). Overall, 21 different feline breeds were included (Supplementary Table\u0026nbsp;3). Among purebreds, the predominant breeds were the Persian (n\u0026thinsp;=\u0026thinsp;164/5,289; 3.1%), the Siamese (n\u0026thinsp;=\u0026thinsp;54/5,289; 1.0%), the Maine Coon (n\u0026thinsp;=\u0026thinsp;35/5,289; 0.7%), and the Chartreux (n\u0026thinsp;=\u0026thinsp;31/5,289; 0.6%). Figure\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e presents a summary of the tumor type distribution across these breeds. In HCS/HCL and Chartreux cats, \u003cem\u003efibromatous neoplasms\u003c/em\u003e were the prevalent diagnoses, while in Persian and Siamese cats, \u003cem\u003eadenomas and adenocarcinomas\u003c/em\u003e were the most frequently observed tumor types. Conversely, \u003cem\u003ebasal cell neoplasms\u003c/em\u003e were overrepresented in the Maine Coon.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003e2.2. Malignancy Analysis\u003c/h2\u003e\u003cp\u003eMalignant tumors constituted 4,264 (80.6%) of the total. Predictor variables for the regression analysis were selected based on the results of the univariate analysis (Supplementary Table\u0026nbsp;4). Based on logistic regression analysis, Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eb illustrates the impact of age, sex, neuter status, breed, and district on the proportion of malignancies. The risk of malignancy increased by 8% per year (OR\u0026thinsp;=\u0026thinsp;1.08; 95% CI 1.06\u0026ndash;1.10). Females exhibited an increased risk in comparison to males (OR\u0026thinsp;=\u0026thinsp;1.39; 95% CI 1.19\u0026ndash;1.62), and neuter status was not associated with malignancy (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.537). In terms of districts, a marginally significant rise in malignancy was noted in the Liguria region (OR\u0026thinsp;=\u0026thinsp;1.40; 95%CI 1.09\u0026ndash;1.82), whereas the \"breed\" variable emerged as the predominant factor influencing malignancy risk, with a protective effect of being purebred compared to HCS/HCL (OR\u0026thinsp;=\u0026thinsp;0.53; 95%CI 0.42\u0026ndash;0.68). Unfortunately, an individual breed-based analysis had to be omitted due to the low number of purebred cats.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe anatomical localizations with the highest (100.0%) malignancy proportion were the \u003cem\u003elymph nodes\u003c/em\u003e, the \u003cem\u003erespiratory system\u003c/em\u003e, \u003cem\u003eunknown topography\u003c/em\u003e, and \u003cem\u003eintrathoracic organs (excl. lung)\u003c/em\u003e. The lowest malignancy proportions were observed in the \u003cem\u003emale genital organs\u003c/em\u003e (20.0%), \u003cem\u003efemale genital organs\u003c/em\u003e (48.3%), \u003cem\u003enervous system\u003c/em\u003e (51.5%), and the \u003cem\u003eskin\u003c/em\u003e (57.5%) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eOver the course of the years, there was no discernible upward or downward trend in the malignancy proportion (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ea).\u003c/p\u003e\u003cp\u003eThe next part will delve more deeply into the most commonly diagnosed malignant tumor types within the datasets, evaluating the effects of the aforementioned factors as well as their frequency over time.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\u003ch2\u003e2.3. Risk by tumor types\u003c/h2\u003e\u003cdiv id=\"Sec10\" class=\"Section3\"\u003e\u003ch2\u003e2.3.1. Fibrosarcoma\u003c/h2\u003e\u003cp\u003eOut of 942 diagnosed \u003cem\u003efibromatous neoplasms\u003c/em\u003e, 98.3% (n\u0026thinsp;=\u0026thinsp;926) were malignant, while benign tumors (mainly \u003cem\u003efibroma, NOS [8810/0]\u003c/em\u003e, and \u003cem\u003edermatofibroma [8832/0]\u003c/em\u003e) accounted for just 1.6% (n\u0026thinsp;=\u0026thinsp;15). The following investigations focused only on fibrosarcoma, including both \u003cem\u003efibrosarcoma, NOS [88100/3]\u003c/em\u003e and FISSs \u003cem\u003e[8800.2/3]\u003c/em\u003e. Age analyses indicated that fibrosarcoma was more prevalent in middle-aged and older felines, with a 5% risk increase for each year of age (OR\u0026thinsp;=\u0026thinsp;1.05; 95% CI 1.03\u0026ndash;1.07). The risk of a female cat receiving a fibrosarcoma diagnosis was significantly lower than that of a male cat (OR\u0026thinsp;=\u0026thinsp;0.59; 95% CI 0.50\u0026ndash;0.69) (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eb).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eNeutered and intact cats had no differential risk of fibrosarcoma diagnosis. Purebred cats had a markedly reduced risk of fibrosarcoma in comparison to HCS/HCL (OR\u0026thinsp;=\u0026thinsp;0.67; 95% CI 0.48\u0026ndash;0.92). Cases from the Liguria district showed a higher risk compared to Tuscany (OR\u0026thinsp;=\u0026thinsp;1.37; 95% CI 1.08\u0026ndash;1.73). The relative frequency of fibrosarcoma diagnoses has significantly decreased (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) since the beginning of the study period (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ea).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec11\" class=\"Section3\"\u003e\u003ch2\u003e2.3.2. Adenocarcinoma\u003c/h2\u003e\u003cp\u003eOut of 856 diagnosed \u003cem\u003eadenoma and adenocarcinomas\u003c/em\u003e, 95.1% (n\u0026thinsp;=\u0026thinsp;814) were malignant (i.e. adenocarcinomas). Benign tumors accounted for 4.9% (n\u0026thinsp;=\u0026thinsp;42). This lower proportion of adenomas was strongly marked in mammary tumors (2.4%; n\u0026thinsp;=\u0026thinsp;15/622), in tumors from the \u003cem\u003erespiratory system\u003c/em\u003e (0%; n\u0026thinsp;=\u0026thinsp;0/35) and \u003cem\u003enose, ear, sinuses, larynx\u003c/em\u003e (0%; n\u0026thinsp;=\u0026thinsp;0/21). Conversely, in the \u003cem\u003eendocrine glands\u003c/em\u003e (42.9%; n\u0026thinsp;=\u0026thinsp;9/21) and \u003cem\u003eeye and adnexa\u003c/em\u003e (57.1%; n\u0026thinsp;=\u0026thinsp;4/7), the proportions of adenomas were much higher. The following assessments focused only on adenocarcinomas (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ed). Older cats were more commonly affected, with a 4% risk increase for each year of age (OR\u0026thinsp;=\u0026thinsp;1.04; 95% CI 1.02\u0026ndash;1.07). Female cats had a markedly increased risk of adenocarcinoma compared to males (OR\u0026thinsp;=\u0026thinsp;6.85; 95% CI 5.39\u0026ndash;8.83). Neutered cats showed a reduced risk (OR\u0026thinsp;=\u0026thinsp;0.79; 95% CI 0.66\u0026ndash;0.94). Purebred cats had a significantly increased risk of developing adenocarcinoma in comparison to HCS/HCL (OR\u0026thinsp;=\u0026thinsp;0.67; 95% CI 0.48\u0026ndash;0.92). The relative frequency of adenocarcinoma diagnoses has significantly decreased (p\u0026thinsp;\u0026lt;\u0026thinsp;.001) since the beginning of the study period (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ec).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section3\"\u003e\u003ch2\u003e2.3.3. Squamous cell carcinoma\u003c/h2\u003e\u003cp\u003eOut of 756 diagnosed \u003cem\u003esquamous cell neoplasms\u003c/em\u003e, 97.6% (n\u0026thinsp;=\u0026thinsp;738) were malignant (i.e. squamous cell carcinoma (SCC)), while \u003cem\u003epapilloma, NOS [8050/0]\u003c/em\u003e accounted for 2.4% only (n\u0026thinsp;=\u0026thinsp;18). SCCs were the most diagnosed tumor type in both the skin and oral cavity (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Considering the skin, 82.0% (n\u0026thinsp;=\u0026thinsp;370/451) of SCCs affected the head, with the majority of them at the \u003cem\u003eexternal ear [C44.2]\u003c/em\u003e (37.0%; n\u0026thinsp;=\u0026thinsp;167/451), \u003cem\u003eskin of other and unspecified parts of head [C44.3]\u003c/em\u003e (24.8%; n\u0026thinsp;=\u0026thinsp;112/451), \u003cem\u003eeyelid, NOS [C44.1]\u003c/em\u003e (10.4%; n\u0026thinsp;=\u0026thinsp;47/451), and \u003cem\u003eskin of occiput, nape and neck [C44.4]\u003c/em\u003e (8.7%; n\u0026thinsp;=\u0026thinsp;39/451).\u003c/p\u003e\u003cp\u003eThe risk of developing SCC increased with age (OR\u0026thinsp;=\u0026thinsp;1.05; 95% CI 1.02\u0026ndash;1.07), while all the other variables didn\u0026rsquo;t seem to significantly affect the SCC-risk (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ef). The relative frequency of SCC diagnoses has constantly increased during the study period (p\u0026thinsp;=\u0026thinsp;0.001), starting from 10.3% in 2008 and reaching up to 15.9% in 2023 (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ee).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section3\"\u003e\u003ch2\u003e2.3.4. Lymphoma\u003c/h2\u003e\u003cp\u003eCompared to other tumor diagnoses, older cats showed a reduced risk for lymphoma (OR\u0026thinsp;=\u0026thinsp;0.90; 95% CI 0.88\u0026ndash;0.93) (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eh). The risk of a female cat being diagnosed with lymphoma compared with that of a male was significantly lower (OR\u0026thinsp;=\u0026thinsp;0.64; 95% CI 0.52\u0026ndash;0.79), while neuter status didn\u0026rsquo;t show any significant contribution. In addition, there were no significant differences between the risk for purebred cats and HCS/HCL. Cases from Liguria (OR\u0026thinsp;=\u0026thinsp;1.37; 95% CI 1.00\u0026ndash;1.87) and other districts (OR\u0026thinsp;=\u0026thinsp;1.61; 95% CI 1.02\u0026ndash;2.45) showed a higher risk compared to Tuscany (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eh). During the research period, the relative frequency of lymphoma diagnoses remained stable (p\u0026thinsp;=\u0026thinsp;0.671), without significant increasing or decreasing trends (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eg).\u003c/p\u003e\u003cp\u003eThe output of all the logistic regressions, including confidence intervals and statistical significance for each tumor type and overall malignancy risk, is detailed in Supplementary Table\u0026nbsp;5.\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"3. Discussion","content":"\u003cp\u003eThis study provides one of the most comprehensive assessments of risk factors for feline tumor malignancy, based on 5,289 samples collected over 15 years\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e,\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eWith an overall malignancy proportion of 80.6%, the findings align with previous reports\u003csup\u003e\u003cspan additionalcitationids=\"CR9 CR10\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e,\u003cspan additionalcitationids=\"CR38 CR39 CR40 CR41\" citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u003c/sup\u003e, though notable exceptions\u0026mdash;such as a recent 54.1% rate reported in South Korea\u0026mdash;highlight potential geographic variability\u003csup\u003e\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e. The high incidence of malignancy in cats may be linked to evolutionary and dietary traits common to obligate carnivores\u003csup\u003e\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u003c/sup\u003e. Age emerged as a significant risk factor, with the risk of malignancy increasing by approximately 8% per year, supporting the cumulative nature of oncogenic mutations over time\u003csup\u003e\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e,\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eFemales showed higher odds of malignant tumors, likely reflecting the high prevalence of mammary neoplasms in cats\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e,\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e,\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u003c/sup\u003e. Neutering didn\u0026rsquo;t affect overall malignancy risk but was associated with variations in specific tumor types. However, limitations concerning the exact timing of neutering prevent definitive conclusions, and further prospective studies focused on the influence of neutering on feline cancer development are warranted.\u003c/p\u003e\u003cp\u003eGeographic origin had a modest yet statistically significant influence on malignancy risk, echoing findings in canine studies\u003csup\u003e\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e,\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e\u003c/sup\u003e. While this may reflect differences in diagnostic practices rather than environmental exposures, it underscores the need for more granular, region-focused research.\u003c/p\u003e\u003cp\u003eUnfortunately, the limited number of purebred cats prevented statistical analysis at the individual breed level, although differences in tumor distribution were noted among the five most common breeds. Nevertheless, purebred status showed a strong contribution to malignancy risk, with an almost 50% reduction compared to HCS/HCL cats. This protective role was previously highlighted by Graf et al.\u003csup\u003e10\u003c/sup\u003e. No differences in the proportion of malignancy by breed were found in other studies, albeit with smaller sample sizes\u003csup\u003e\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e,\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e. Unlike dogs, several feline breeds still maintain moderate genetic diversity and show lower levels of inbreeding, potentially explaining this paradoxical finding\u003csup\u003e\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e,\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e\u003c/sup\u003e. As a result, exogenous factors such as viral agents and environmental exposures may play a more prominent role in shaping malignancy risk in cats.\u003c/p\u003e\u003cp\u003eThe four most common feline malignant tumor types were specifically addressed for risk factor identification and temporal trends. Fibrosarcomas, adenocarcinomas, SCCs, and lymphomas are frequently reported as the most common malignancies in cats, albeit in varying proportions\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e,\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e,\u003cspan additionalcitationids=\"CR49\" citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eOur study identified fibrosarcoma as the most commonly diagnosed neoplasm from 2008 to 2023, accounting for 17.5% of the total cases. These data overlap with those of Graf et al.\u003csup\u003e48\u003c/sup\u003e. An increased risk in older, male, and HCS/HCL cats was found. Prior studies have shown no breed or sex predisposition; however, a higher risk in females\u003csup\u003e\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e\u003c/sup\u003e and neutered cats\u003csup\u003e\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e\u003c/sup\u003e has been recently reported, and certain breeds were significantly less likely to develop fibrosarcoma than non-purebred cats\u003csup\u003e\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e,\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e,\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e\u003c/sup\u003e, a result consistent with our findings. The relative frequency of fibrosarcoma has decreased by nearly 50% since 2008. A significant proportion of fibrosarcomas in our study were FISS, and the etiopathogenesis of these tumors remains a subject of controversy. Numerous studies demonstrate the impact of the vaccine adjuvant alum, which is incorporated to stimulate the immune response when utilizing an inactivated aetiological agent, mainly rabies or FeLV vaccination\u003csup\u003e\u003cspan additionalcitationids=\"CR54\" citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e\u003c/sup\u003e. There are limited registers that monitor the temporal trends of tumors for comparative analysis. However, our data confirm the observations made by the Swiss Feline Cancer Registries, which have noted a similar decreasing trend since 2009, correlating it with the introduction of a non-adjuvanted FeLV vaccine\u003csup\u003e\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e\u003c/sup\u003e. The current situation in Italy mirrors that of Switzerland, where rabies vaccination is not mandatory. Recent introductions of non-adjuvanted and recombinant vaccines support an increased risk of fibrosarcoma development in cats following the administration of adjuvanted vaccines, particularly those containing alum.\u003c/p\u003e\u003cp\u003eFeline adenocarcinomas predominantly originated from the mammary gland, which exhibited a high proportion of malignant tumors (95.2%). This finding elucidates the marked predisposition of female and intact animals to this tumor type, and corroborates the more aggressive biological behavior of these tumors in cats compared to dogs\u003csup\u003e\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e,\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e,\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e,\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e,\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e,\u003cspan additionalcitationids=\"CR57 CR58\" citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e\u003c/sup\u003e. Purebred cats showed a significantly increased risk of developing adenocarcinoma in comparison to HCS/HCL. The logit result is consistent with the tumor distribution findings, as adenocarcinoma was the most common tumor type in Persians and Siamese\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e,\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e,\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e,\u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e,\u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eIn our study, no sex or breed predispositions were observed for SCC\u003csup\u003e\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e,\u003cspan citationid=\"CR62\" class=\"CitationRef\"\u003e62\u003c/span\u003e\u003c/sup\u003e. Notably, the temporal trend analysis revealed a consistent and significant increase in SCC diagnoses. While the role of papillomavirus remains debated, chronic sunlight exposure is regarded as the primary factor implicated in the development of cutaneous SCC\u003csup\u003e\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e,\u003cspan citationid=\"CR63\" class=\"CitationRef\"\u003e63\u003c/span\u003e,\u003cspan citationid=\"CR64\" class=\"CitationRef\"\u003e64\u003c/span\u003e\u003c/sup\u003e. Research indicates that countries offering a complete or semi-outdoor lifestyle for cats exhibit a higher incidence of SCC\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e,\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e,\u003cspan citationid=\"CR65\" class=\"CitationRef\"\u003e65\u003c/span\u003e,\u003cspan citationid=\"CR66\" class=\"CitationRef\"\u003e66\u003c/span\u003e\u003c/sup\u003e compared to those with restricted UV light exposure and predominantly indoor cat populations\u003csup\u003e\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e,\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e,\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e\u003c/sup\u003e. Southern latitudes may lead to increased exposure to ultraviolet (UV) light, which could account for the discrepancies observed in various studies\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e,\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e\u003c/sup\u003e and the higher occurrence reported here. In a One Health approach, the observed increase in feline SCC occurrence supports concerns regarding climate change and the global increase in UV irradiation, specifically in the Mediterranean area\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR67\" class=\"CitationRef\"\u003e67\u003c/span\u003e\u003c/sup\u003e. While an improvement in the diagnosis of feline UV-induced lesions in recent years should not be ruled out, this temporal trend is noteworthy and closely aligns with the ones observed in human skin cancers\u003csup\u003e\u003cspan additionalcitationids=\"CR69\" citationid=\"CR68\" class=\"CitationRef\"\u003e68\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR70\" class=\"CitationRef\"\u003e70\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThe current findings on lymphoma confirmed that this neoplasm primarily occurs in the digestive tract\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e,\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e,\u003cspan citationid=\"CR71\" class=\"CitationRef\"\u003e71\u003c/span\u003e\u003c/sup\u003e, with an an enhanced risk in males\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e,\u003cspan citationid=\"CR72\" class=\"CitationRef\"\u003e72\u003c/span\u003e,\u003cspan citationid=\"CR73\" class=\"CitationRef\"\u003e73\u003c/span\u003e\u003c/sup\u003e and relatively young individuals compared to other tumor types\u003csup\u003e\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e,\u003cspan citationid=\"CR73\" class=\"CitationRef\"\u003e73\u003c/span\u003e,\u003cspan citationid=\"CR74\" class=\"CitationRef\"\u003e74\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThis study benefits from a multi-center design, a representative sample of feline tumors, and alignment with previous pathology- and population-based registries\u003csup\u003e\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e,\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e,\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e,\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e\u003c/sup\u003e. Nevertheless, some limitations must be acknowledged. The retrospective nature of the analysis and reliance on histopathologic diagnoses, while ensuring diagnostic accuracy, may introduce selection bias, as cytologically diagnosed neoplasms were not included. Submission for histology in clinical practice is influenced by multiple factors and may affect tumor representation\u003csup\u003e\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e,\u003cspan citationid=\"CR75\" class=\"CitationRef\"\u003e75\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eConversely, the adoption of Vet-ICD-O represents a valuable asset for standardizing data collection, inclusion criteria, and data sharing\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e. In the absence of feline-specific codes, the use of Vet-ICD-O-canine-1codes for tumors with similar biological and prognostic features, the creation of \u003cem\u003ede novo\u003c/em\u003e codes for feline-specific entities, and the provided criteria for defining biological behavior (detailed in Supplementary Table\u0026nbsp;1) may support broader application of this system to feline oncology and promote more consistent epidemiological research.\u003c/p\u003e\u003cp\u003eWhile logistic regression offers adjusted estimates and facilitates between-group comparisons, odds ratios should not be interpreted as direct measures of incidence \u003csup\u003e\u003cspan citationid=\"CR76\" class=\"CitationRef\"\u003e76\u003c/span\u003e\u003c/sup\u003e. The lack of reliable population denominators further limits external validation. In Italy, the expansion of national pet registries offers a promising avenue for improving denominator estimates. A centralized system\u0026mdash;the Sistema Informativo Nazionale degli Animali da Compagnia (SINAC)\u0026mdash;is currently being implemented within the Ministry of Health\u0026rsquo;s national digital database (BDN), in accordance with D. Lgs. 134/2022 and EU Regulation 2016/429. In this scenario, multicentric initiatives such as the Italian Network of Laboratories for Veterinary Oncology (NILOV), to which both research centers involved in this study are affiliated, represent an important step toward more structured and harmonized pet cancer surveillance systems in Italy and may support future population-based studies in the feline species\u003csup\u003e\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e,\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e"},{"header":"4. Conclusion","content":"\u003cp\u003eWe analyzed malignancy patterns and risk factors, confirming an age-related increase in malignancy and a higher risk in females. Unlike in dogs, purebred cats showed a lower malignancy risk than mixed breeds. While the overall proportion of malignant tumors remained stable over time, fibrosarcoma and adenocarcinoma decreased, whereas squamous cell carcinoma diagnoses increased. These findings highlight the importance of standardized, collaborative data collection and support future investigations into endogenous and environmental cancer risk factors, with implications for translational research in a One Health framework.\u003c/p\u003e"},{"header":"5. Material and methods","content":"\u003cdiv id=\"Sec17\" class=\"Section2\"\u003e\u003ch2\u003e5.1. Data collection and processing\u003c/h2\u003e\u003cp\u003eThe owners' informed consent and the use of anonymized data in research activities was collected by clinicians and provided along with clinical information including the species, breed, age, sex, neutering status, date of diagnosis, postal code area, individual ID, symptoms, anamnestic information, tumor staging.\u003c/p\u003e\u003cp\u003eThe data collected by the two ACRs were extracted from their respective laboratory information management systems and processed using Microsoft Excel version 16.84 (Microsoft 2024, \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e\u003ca href=\"http://www.microsoft.com\" target=\"_blank\"\u003ewww.microsoft.com\u003c/a\u003e\u003c/span\u003e\u003cspan address=\"http://www.microsoft.com\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) and R Language and Environment for Statistical Computing studio R version 4.4.0\u003csup\u003e77\u003c/sup\u003e, with the \u003cem\u003edplyr\u003c/em\u003e package\u003csup\u003e\u003cspan citationid=\"CR78\" class=\"CitationRef\"\u003e78\u003c/span\u003e\u003c/sup\u003e. Only confirmed primary tumor diagnoses were retained, whilst metastases or recurrences were omitted. Multiple tumors (i.e., distinct tumors with different histotypes in the same feline subject) were maintained separately and managed in accordance with the WHO ICD-O-3.1 criteria\u003csup\u003e\u003cspan citationid=\"CR79\" class=\"CitationRef\"\u003e79\u003c/span\u003e,\u003cspan citationid=\"CR80\" class=\"CitationRef\"\u003e80\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eSince a tumor classification and coding system specifically developed for the feline species has not yet been published, the tumor's histological type (morphology) and anatomical localization (topography) were coded using Vet-ICD-O-canine-1\u003csup\u003e34\u003c/sup\u003e. Topographic sites were grouped according to Dhein et al.\u003csup\u003e80\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eFor tumor morphologies, minor modifications were made to adapt the coding system to the feline species. Peripheral odontogenic fibroma was considered a tumor\u003csup\u003e\u003cspan citationid=\"CR81\" class=\"CitationRef\"\u003e81\u003c/span\u003e\u003c/sup\u003e and was therefore included in the group of \u003cem\u003eodontogenic tumors [927\u0026ndash;934]\u003c/em\u003e, using the term and ICD-O-3.2 code \u003cem\u003eperipheral odontogenic fibroma [9322/0]\u003c/em\u003e\u003csup\u003e80\u003c/sup\u003e. Diagnoses of \u003cem\u003eactinic keratosis\u003c/em\u003e were included in the dataset with the \u003cem\u003ede-novo\u003c/em\u003e code \u003cem\u003e[8070.1/2]\u003c/em\u003e in the group of \u003cem\u003esquamous cell neoplasms [805\u0026ndash;808]. Feline injection-site sarcomas\u003c/em\u003e (FISSs) were coded with the \u003cem\u003ede-novo\u003c/em\u003e code \u003cem\u003e[8800.2/3]\u003c/em\u003e in analogy to the \u003cem\u003esarcoma associated with Spirocerca lupi [8800.1/3]\u003c/em\u003e from the Vet-ICD-O-Canine1\u003csup\u003e34\u003c/sup\u003e, but were added to the group of \u003cem\u003efibromatous neoplasms [881\u0026ndash;883]\u003c/em\u003e according to the Swiss Feline Cancer Registry\u003csup\u003e\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e,\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e\u003c/sup\u003e. Mammary carcinomas with \u0026lsquo;\u003cem\u003ein situ\u003c/em\u003e\u0026rsquo; tumor behavior were excluded as previously stated\u003csup\u003e\u003cspan citationid=\"CR82\" class=\"CitationRef\"\u003e82\u003c/span\u003e,\u003cspan citationid=\"CR83\" class=\"CitationRef\"\u003e83\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThe binary variable \u0026ldquo;malignancy\u0026rdquo; (benign \"B\" vs. malignant \"M\") was assigned to each case based on the Vet-ICD-O behaviour code\u003csup\u003e\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e,\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e,\u003cspan citationid=\"CR83\" class=\"CitationRef\"\u003e83\u003c/span\u003e\u003c/sup\u003e. Tumors bearing the labels [/0] and [/3] were grouped as benign and malignant, respectively. Neoplasms \u003cem\u003euncertain whether benign or malignant [/1]\u003c/em\u003e and \u003cem\u003ein situ [/2]\u003c/em\u003e were classified according to the scheme provided in Supplementary Table\u0026nbsp;1.\u003c/p\u003e\u003cp\u003eFeline breeds were classified according to the F\u0026eacute;d\u0026eacute;ration Internationale F\u0026eacute;line\u003csup\u003e\u003cspan citationid=\"CR84\" class=\"CitationRef\"\u003e84\u003c/span\u003e\u003c/sup\u003e. To avoid any confusion with the FIFe-recognized \u0026ldquo;European\u0026rdquo; (EUR) breed, the cats defined as \u0026ldquo;tabby\u0026rdquo; or \u0026ldquo;Common European\u0026rdquo; or \u0026ldquo;Domestic Shorthair/Domestic Longhair\u0026rdquo; have been classified as \u0026ldquo;House Cat Shorthair/Longhair\u0026rdquo; (HCS/HCL) (i.e., \u0026ldquo;mixed-breed\u0026rdquo;, as having undocumented or unknown parentage).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec18\" class=\"Section2\"\u003e\u003ch2\u003e5.2. Statistical analysis\u003c/h2\u003e\u003cp\u003eCategorical data were summarized as absolute counts and percentages. Continuous data (i.e. age) were described by median and range. Pearson\u0026rsquo;s Chi-square test and a subsequent multiple logistic regression model were used to assess the influence of the independent variables \u0026ldquo;age\u0026rdquo;, \u0026ldquo;sex\u0026rdquo; (male/female), \u0026ldquo;neuter status\u0026rdquo; (intact/neutered), \u0026ldquo;district of origin\u0026rdquo; (Tuscany, Lazio, Liguria, and other districts) and \u0026ldquo;breed\u0026rdquo; (mixed-breed/purebred) on the dichotomous \u0026ldquo;malignancy\u0026rdquo; outcome, as detailed in Fonti et al. for the canine species\u003csup\u003e\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThe logit model was applied to the four most diagnosed malignant tumors (fibrosarcomas, adenocarcinomas, SCCs, and lymphomas), too. In these models, two distinct groups were compared: those cases with the specific category of tumor, and those that were not diagnosed with the tumor of interest, with a case-control study design\u003csup\u003e\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e\u003c/sup\u003e. Adjusted Odds Ratios (ORs) were therefore obtained. To ensure clarity, the words \"risk\" and \"OR\" were used interchangeably throughout the paper.\u003c/p\u003e\u003cp\u003eTo determine if the overall malignancy proportions and the relative frequencies for the 4 most common malignant tumor types increased or decreased during the 16-year research period,\u003c/p\u003e\u003cp\u003ethe Cochran-Armitage trend test was applied. The minimum conditions for significant differences were a 95% confidence interval (95% CI) that did not overlap 1 and a p value\u0026thinsp;\u0026lt;\u0026thinsp;0.05. All statistical analyses were performed using R Language and Environment for Statistical Computing studio R version 4.4.0\u003csup\u003e77\u003c/sup\u003e. Data were plotted using the \u003cem\u003epheatmap\u003c/em\u003e and \u003cem\u003eggplot2\u003c/em\u003e packages\u003csup\u003e\u003cspan citationid=\"CR85\" class=\"CitationRef\"\u003e85\u003c/span\u003e,\u003cspan citationid=\"CR86\" class=\"CitationRef\"\u003e86\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003ch2\u003e7. Funding\u003c/h2\u003e\u003cp\u003eThis research is supported by the Ministry of University and Research (MUR) as part of the PON 2014\u0026ndash;2020 \u0026ldquo;Research and Innovation\" resources \u0026ndash; Green/Innovation Action \u0026ndash; DM MUR 1061/2022.\u003c/p\u003e\u003cp\u003e8. Declaration of competing interest\u003c/p\u003e\u003cp\u003eThe authors of this research paper have no financial or personal interests that could have influenced this paper.\u003c/p\u003e\u003cp\u003e9. Data availability statement\u003c/p\u003e\u003cp\u003eData and code implemented for this study are available on request.\u003c/p\u003e\u003cp\u003e10. Credit authorship contribution statement\u003c/p\u003e\u003cp\u003eN. Fonti: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Visualization, Writing \u0026ndash; original draft. A. Carnio: Data curation, Investigation, Writing \u0026ndash; review \u0026amp; editing. C. Cocumelli: Investigation, Writing \u0026ndash; review \u0026amp; editing. E.S. Dhein: Data curation, Formal analysis, Methodology, Writing \u0026ndash; review \u0026amp; editing. C. Eleni: Investigation, Resources, Writing \u0026ndash; review \u0026amp; editing. V. Galietta: Investigation, Writing \u0026ndash; review \u0026amp; editing. F. Guscetti: Conceptualization, Supervision, Writing \u0026ndash; review \u0026amp; editing. A. Lachi: Formal analysis, Methodology, Validation. F. Parisi: Investigation, Writing \u0026ndash; review \u0026amp; editing. A. Poli: Funding acquisition, Investigation, Supervision. P. Scaramozzino: Resources, Validation, Writing \u0026ndash; review \u0026amp; editing. F. Millanta: Conceptualization, Funding acquisition, Investigation, Project administration, Resources, Supervision, Writing \u0026ndash; review \u0026amp; editing.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eN. Fonti: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Visualization, Writing \u0026ndash; original draft. A. Carnio: Data curation, Investigation, Writing \u0026ndash; review \u0026amp; editing. C. Cocumelli: Investigation, Writing \u0026ndash; review \u0026amp; editing. E.S. Dhein: Data curation, Formal analysis, Methodology, Writing \u0026ndash; review \u0026amp; editing. C. Eleni: Investigation, Resources, Writing \u0026ndash; review \u0026amp; editing. V. Galietta: Investigation, Writing \u0026ndash; review \u0026amp; editing. F. Guscetti: Conceptualization, Supervision, Writing \u0026ndash; review \u0026amp; editing. A. Lachi: Formal analysis, Methodology, Validation. F. Parisi: Investigation, Writing \u0026ndash; review \u0026amp; editing. A. Poli: Funding acquisition, Investigation, Supervision. P. Scaramozzino: Resources, Validation, Writing \u0026ndash; review \u0026amp; editing. F. Millanta: Conceptualization, Funding acquisition, Investigation, Project administration, Resources, Supervision, Writing \u0026ndash; review \u0026amp; editing.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eWe gratefully acknowledge all the veterinary practitioners and dog owners who have provided samples and valuable medical history data.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eData and code implemented for this study are available on request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSchiffman, J. D. \u0026amp; Breen, M. Comparative oncology: what dogs and other species can teach us about humans with cancer. \u003cem\u003ePhilos. Trans. R Soc. B Biol. Sci.\u003c/em\u003e \u003cb\u003e370\u003c/b\u003e, 20140231 (2015).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBray, F. et al. 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Version 1.0, 8.\u003c/em\u003e (2019).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"animal cancer registry, malignancy, cat, veterinary oncology, fibrosarcoma, squamous cell carcinoma","lastPublishedDoi":"10.21203/rs.3.rs-7981624/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7981624/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eAnimal cancer registries (ACRs) are vital tools in veterinary oncology, offering insights into tumor epidemiology and supporting comparative research. Despite cancer being a major cause of feline mortality, data on feline tumor epidemiology remain limited. This study aimed to investigate temporal trends in histologically diagnosed feline tumors and assess how breed, sex, neuter status, age, and geographic origin affect malignancy and tumor distribution. A modified Vet-ICD-O-canine-1 coding system was applied to 5,289 tumors from two pathology-based ACRs in central Italy (2008\u0026ndash;2023). Data were analyzed for time trends by the Cochrane-Armitage test, and logistic regression was used to assess the impact of the variables on tumor behavior (\"malignant\" vs. \"benign\") and the development of major cancer types. Of all tumors, 4,264 (80.6%) were malignant. Fibrosarcomas, adenocarcinomas, squamous cell carcinomas (SCCs), and lymphomas were the most common types of cancer. Malignancy risk increased by 8% per year of age. Females (OR\u0026thinsp;=\u0026thinsp;1.39; 95%CI 1.19\u0026ndash;1.62) and non-purebred cats (OR\u0026thinsp;=\u0026thinsp;1.89; 95%CI 1.47\u0026ndash;2.38) had higher odds of malignancy. Intact status was not associated with overall malignancy but increased adenocarcinoma risk. Temporal trends included rising SCCs and declining fibrosarcomas. These findings support previous findings and identify previously unknown risk factors, underscoring the value of multicenter ACR-based surveillance.\u003c/p\u003e","manuscriptTitle":"Influence of sex, neutering, breed, age, and geographic origin on malignant tumor development in cats: a multicenter retrospective study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-17 12:58:27","doi":"10.21203/rs.3.rs-7981624/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-11-21T19:58:17+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-21T02:00:51+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-20T20:08:54+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"307737015156890931562122470508573121992","date":"2025-11-06T01:22:29+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"59664958808543033347688944589788710083","date":"2025-11-05T23:50:54+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"183950643127298570055917959480912010240","date":"2025-11-05T17:03:22+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-11-05T16:04:22+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-10-30T06:17:25+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-10-30T06:17:15+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2025-10-29T15:31:08+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e74b1e38-2a65-4fd8-96b5-fceda722544c","owner":[],"postedDate":"November 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":57532637,"name":"Biological sciences/Cancer"},{"id":57532638,"name":"Health sciences/Diseases"},{"id":57532639,"name":"Health sciences/Oncology"}],"tags":[],"updatedAt":"2026-01-26T15:59:28+00:00","versionOfRecord":{"articleIdentity":"rs-7981624","link":"https://doi.org/10.1038/s41598-026-35379-8","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2026-01-19 15:56:51","publishedOnDateReadable":"January 19th, 2026"},"versionCreatedAt":"2025-11-17 12:58:27","video":"","vorDoi":"10.1038/s41598-026-35379-8","vorDoiUrl":"https://doi.org/10.1038/s41598-026-35379-8","workflowStages":[]},"version":"v1","identity":"rs-7981624","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7981624","identity":"rs-7981624","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}