Insulin receptor substrates 1 and 2 (IRS-1 and IRS-2) are signaling adaptor proteins that participate in canonical pathways, where insulin cascade activation occurs, as well as in non-canonical pathways, in which phosphorylation of substrates is carried out by a diverse array of receptors including integrins, cytokines, steroid hormones, and others. IRS proteins are subject to a spectrum of post-translational modifications essential for their activation, encompassing phosphorylation events in distinct tyrosine, serine, and threonine residues. Tyrosine residue phosphorylation is intricately linked to the activation of the insulin receptor cascade and its interaction with SH2 domains within a spectrum of proteins, including PI3K. Conversely, serine residue phosphorylation assumes a different function, serving to attenuate the effects of insulin. In this review, we have identified over 50 serine residues within IRS-1 that have been reported to undergo phosphorylation orchestrated by a spectrum of kinases, thereby engendering the activation or inhibition of different signaling pathways. Furthermore, we delineate the phosphorylation of over 10 distinct tyrosine residues at IRS-1 or IRS-2 in response to insulin, a process essential for signal transduction and the subsequent activation of PI3K.

Human papillomavirus (HPV) infection is associated with precancerous lesions and cancer of the genital tract both in women and men. The high incidence of cervical cancer worldwide focused the research on this infection mainly in women and to a lesser extent in men. In this review, we summarized epidemiological, immunological, and diagnostic data associated with HPV and cancer in men. We presented an overview of the main characteristics of HPV and infection in men that are associated with different types of cancer but also associated with male infertility. Men are considered important vectors of HPV transmission to women; therefore, identifying the sexual and social behavioral risk factors associated with HPV infection in men is critical to understand the etiology of the disease. It is also essential to describe how the immune response develops in men during HPV infection or when vaccinated, since this knowledge could help to control the viral transmission to women, decreasing the incidence of cervical cancer, but also could reduce other HPV-associated cancers among men who have sex with men (MSM). Finally, we summarized the methods used over time to detect and genotype HPV genomes, as well as some diagnostic tests that use cellular and viral biomarkers that were identified in HPV-related cancers.

Antibodies against the Human Papillomavirus (HPV) L1 protein are associated with past infections and related to the evolution of the disease, whereas antibodies against L1 Virus-Like Particles (VLPs) are used to follow the neutralizing antibody response in vaccinated women. In this study, serum antibodies against conformational (VLPs) and linear epitopes of HPV16/18 L1 protein were assessed to distinguish HPV-vaccinated women from those naturally infected or those with uterine cervical lesions. The VLPs-16/18 were generated in baculovirus, and L1 proteins were obtained from denatured VLPs. Serum antibodies against VLPs and L1 proteins were evaluated by ELISA. The ELISA-VLPs and ELISA-L1 16/18 assays were validated with a vaccinated women group by ROC analysis and the regression analysis to distinguish the different populations of female patients. The anti-VLPs-16/18 and anti-L1-16/18 antibodies effectively detect vaccinated women (AUC = 1.0/0.79, and 0.94/0.84, respectively). The regression analysis showed that anti-VLPs-16/18 and anti-L1-16/18 antibodies were associated with the vaccinated group (OR = 2.11 × 10⁸/16.50 and 536.0/49.2, respectively). However, only the anti-L1-16 antibodies were associated with the high-grade lesions and cervical cancer (CIN3/CC) group (OR = 12.18). In conclusion, our results suggest that anti-VLPs-16/18 antibodies are effective and type-specific to detect HPV-vaccinated women, but anti-L1-16 antibodies better differentiate the CIN3/CC group. However, a larger population study is needed to validate these results.