High-risk human papillomavirus (HPV) is etiologically related to cervical cancer, other anogenital cancers and oropharyngeal carcinomas. Low-risk HPV, especially HPV6 and HPV11, cause genital warts and laryngeal papillomas. However, the accumulating data suggests that HPV6 and HPV11 may cause malignant lesions at non-cervical anatomic sites. This review aims to estimate the proportions of single and dual HPV6/11 infections in multiple cancers reported in the last 10 years in the Cochrane, Embasa and PubMed databases. Secondly, the genomes of HPV6/11 were compared with the most common high-risk genotype, HPV16, to determine the similarities and differences. A total of 11 articles were selected, including between one and 334 HPV+ cancer patients. The frequencies of single or dual HPV6/11 infections ranged between 0–5.5% for penile and 0–87.5% for laryngeal cancers and were null for vulvar, vaginal and oral cancers. The genomic similarities between HPV6/11 and HPV16 mainly involved the E7 gene, indicating a limited ability to block cell differentiation. The presence of single or dual HPV6/11 infections in variable proportions of penile and laryngeal cancers support the vaccination strategies that cover these genotypes, not only for preventing genital warts but also for cancer prevention. Other risk factors and co-carcinogens are likely to participate in epithelial carcinogenesis associated with low-risk HPV.

Klotho proteins, αKlotho, βKlotho, and γKlotho, exert tumor-suppressive activities via the fibroblast growth factor receptors and multiple cell-signaling pathways. There is a growing interest in Klotho proteins as potential diagnostic and prognostic biomarkers for multiple diseases. However, recent advances regarding their roles and potential applications in cancer remain disperse and require an integrated analysis. The present review analyzed research articles published between 2012 and 2022 in the Cochrane and Scopus scientific databases to study the role of Klotho in cancer and their potential as tools for diagnosing specific cancer types, predicting tumor aggressiveness and prognosis. Twenty-six articles were selected, dealing with acute myeloid leukemia and with bladder, breast, colorectal, esophageal, gastric, hepatocellular, ovarian, pancreatic, prostatic, pulmonary, renal, and thyroid cancers. αKlotho was consistently associated with improved prognosis and may be useful in estimating patient survival. A single study reported the use of soluble αKlotho levels in blood serum as a tool to aid the diagnosis of esophageal cancer. γKlotho was associated with increased aggressiveness of bladder, breast, and prostate cancer, and βKlotho showed mixed results. Further clinical development of Klotho-based assays will require careful identification of specific tumor subtypes where Klotho proteins may be most valuable as diagnostic or prognostic tools.

Cancer-associated cachexia (CAC), also known as wasting syndrome, is a systemic condition that affects multiple tissues and organs via a variety of metabolic pathways. Systemic inflammation, progressive weight loss, depletion of adipose tissue, and skeletal muscle impairment are some of the hallmark features of cachexia. Despite various studies on the clinical features of CAC, the complexity of the syndrome continues to pose significant challenges in clinical practice, leading to late diagnoses and the absence of a standardised treatment. Men and women respond differently to CAC, which may be prompted by the pre-existing physiologic sex differences. This review presents the sexual dimorphism associated with the hallmark pathways involved in CAC. A comprehensive understanding of sexual dimorphism in these pathways could drive research on cachexia to prioritise the inclusion of more females in related studies in order to achieve personalised sex-based therapeutic approaches and, consequently, enhance treatment efficacy and better patient outcomes.

Penile cancer is an uncommon malignancy that occurs most frequently in developing countries. Two pathways for penile carcinogenesis are currently recognized: one driven by human papillomavirus (HPV) infection and another HPV-independent route, associated with chronic inflammation. Progress on the clinical management of this disease has been slow, partly due to the lack of preclinical models for translational research. However, exciting recent developments are changing this landscape, with new in vitro and in vivo models becoming available. These include mouse models for HPV⁺ and HPV⁻ penile cancer and multiple cell lines representing HPV⁻ lesions. The present review addresses these new advances, summarizing available models, comparing their characteristics and potential uses and discussing areas that require further improvement. Recent breakthroughs achieved using these models are also discussed, particularly those developments pertaining to HPV-driven cancer. Two key aspects that still require improvement are the establishment of cell lines that can represent HPV⁺ penile carcinomas and the development of mouse models to study metastatic disease. Overall, the growing array of in vitro and in vivo models for penile cancer provides new and useful tools for researchers in the field and is expected to accelerate pre-clinical research on this disease.

Histopathological analysis is an essential exam for detecting various types of cancer. The process is traditionally time-consuming and laborious. Taking advantage of deep learning models, assisting the pathologist in the diagnosis process is possible. In this work, a study was carried out based on the DenseNet neural network. It consisted of changing its architecture through combinations of Transformer and MBConv blocks to investigate its impact on classifying histopathological images of penile cancer. Due to the limited number of samples in this dataset, pre-training is performed on another larger lung and colon cancer histopathological image dataset. Various combinations of these architectural components were systematically evaluated to compare their performance. The results indicate significant improvements in feature representation, demonstrating the effectiveness of these combined elements resulting in an F1-Score of up to 95.78%. Its diagnostic performance confirms the importance of deep learning techniques in men’s health.

High-risk human papillomavirus (HPV) is the etiologic agent of several types of cancer. Mast cells’ role as either a driving or opposing force for cancer progression remains controversial. MicroRNAs are dysregulated in several HPV-induced cancers, and can influence mast cell biology. The aim of this study was to evaluate mast cell infiltration and to identify microRNAs potentially regulating this process. Transgenic male mice (K14-HPV16; HPV⁺) and matched wild-type mice (HPV⁻) received 7,12-Dimethylbenz[a]anthracene (DMBA) (or vehicle) over 17 weeks. Following euthanasia, chest skin and ear tissue samples were collected. Mast cell infiltration was evaluated by immunohistochemistry. MicroRNAs associated with mast cell infiltration were identified using bioinformatic tools. MicroRNA and mRNA relative expression was evaluated by RT-qPCR. Immunohistochemistry showed increased mast cell infiltration in HPV⁺ mice (p < 0.001). DMBA did not have any statistically significant influence on this distribution. Ear tissue of HPV⁺ mice showed increased mast cell infiltration (p < 0.01) when compared with chest skin samples. Additionally, reduced relative expression of miR-125b-5p (p = 0.008, 2^−ΔΔCt = 2.09) and miR-223-3p (p = 0.013, 2^−ΔΔCt = 4.42) seems to be associated with mast cell infiltration and increased expression of target gene Cxcl10. These results indicate that HPV16 may increase mast cell infiltration by down-regulating miR-223-3p and miR-125b-5p.