Melanoma is the most aggressive type of skin cancer. Despite the available therapies, the minimum residual disease is still refractory. Reactive oxygen and nitrogen species (ROS and RNS) play a dual role in melanoma, where redox imbalance is involved from initiation to metastasis and resistance. Redox proteins modulate the disease by controlling ROS/RNS levels in immune response, proliferation, invasion, and relapse. Chemotherapeutics such as BRAF and MEK inhibitors promote oxidative stress, but high ROS/RNS amounts with a robust antioxidant system allow cells to be adaptive and cooperate to non-toxic levels. These proteins could act as biomarkers and possible targets. By understanding the complex mechanisms involved in adaptation and searching for new targets to make cells more susceptible to treatment, the disease might be overcome. Therefore, exploring the role of redox-sensitive proteins and the modulation of redox homeostasis may provide clues to new therapies. This study analyzes information obtained from a public cohort of melanoma patients about the expression of redox-generating and detoxifying proteins in melanoma during the disease stages, genetic alterations, and overall patient survival status. According to our analysis, 66% of the isoforms presented differential expression on melanoma progression: NOS2, SOD1, NOX4, PRX3, PXDN and GPX1 are increased during melanoma progression, while CAT, GPX3, TXNIP, and PRX2 are decreased. Besides, the stage of the disease could influence the result as well. The levels of PRX1, PRX5 and PRX6 can be increased or decreased depending on the stage. We showed that all analyzed isoforms presented some genetic alteration on the gene, most of them (78%) for increased mRNA expression. Interestingly, 34% of all melanoma patients showed genetic alterations on TRX1, most for decreased mRNA expression. Additionally, 15% of the isoforms showed a significant reduction in overall patient survival status for an altered group (PRX3, PRX5, TR2, and GR) and the unaltered group (NOX4). Although no such specific antioxidant therapy is approved for melanoma yet, inhibitors or mimetics of these redox-sensitive proteins have achieved very promising results. We foresee that forthcoming investigations on the modulation of these proteins will bring significant advances for cancer therapy.

Human papillomavirus (HPV) is a major public health concern, responsible for multiple types of cancer. This study aimed to provide an overview of the burden and temporal trends of HPV-associated cancers in Mexico using national hospital discharge and mortality databases from 2011–2019, including cervical, vulvar, vaginal, penile, anal, oropharyngeal, oral cavity, and laryngeal cancers. Hospitalization and mortality rates per 100,000 population were estimated; HPV-attributable fractions applied, and age-standardized temporal trends evaluated using joinpoint regression. Cervical cancer was the leading contributor, accounting for 88.5% of hospitalizations and 90.9% of HPV-attributable deaths. Hospitalization rates for cervical cancer increased between 2011–2014 (APC = 7.5%, 95% CI: 2.3, 18.0), then declined (APC = −3.0%, 95% CI: −7.8, −0.9). Other HPV-associated cancers had lower hospitalization rates, generally below 1 per 100,000, except for penile and head and neck cancers in males. Significant increases in hospitalization rates were observed in males for anal cancer from 2011–2019 (APC = 7.1%, 95% CI: 0.8, 15.1) and oropharyngeal cancer from 2017–2019 (APC = 18.0%, 95% CI: 4.0, 31.6), while in females, for vaginal cancer from 2017–2019 (APC = 30.7%, 95% CI: 10.6, 45.3) and oral cavity cancer from 2011–2019 (APC = 8.4%, 95% CI: 2.4, 29.1). Mortality for most cancers showed decreasing or stable trends over the study period, except for vulvar cancer in females (AAPC = 1.9%, 95% CI: 0.4, 4.1) and oropharyngeal cancer in both sexes (AAPC = 4.0%, 95% CI: 0.7, 8.0). Across most cancers, males were hospitalized at older ages but died younger than females, except for anal cancer. Overall, the burden of HPV-associated cancers is substantial. While cervical cancer remains prevalent and requires continued elimination efforts, the rising burden of anal and oropharyngeal cancers among males, highlights the need to strengthen public health strategies and raise awareness of HPV’s broader impact across both sexes.

Human papillomavirus (HPV)-associated cancers represent a substantial public health burden. This study analyzed the national burden of hospitalization and mortality from HPV-associated cancers in Brazil between 2011 and 2019. Outcomes included average annual numbers, crude and age-standardized rates per 100,000 population, and trends estimated via joinpoint regression for cervical, vulvar, vaginal, penile, anal, and head and neck cancers (oropharynx, larynx, and oral cavity). Between 2011 and 2019, HPV-attributable cancers accounted for an average of 29,155 hospitalizations (14.3 per 100,000) and 7526 deaths (3.7 per 100,000) annually across both sexes. Among females, there were an average of 24,921 hospitalizations (24.0 per 100,000) and 6430 deaths annually, largely driven by cervical cancer. Among males, there were an estimated 4234 HPV-attributable hospitalizations and 1096 deaths per year (4.1 and 1.1 per 100,000, respectively), with penile, anal, and oropharyngeal cancers being the largest contributors. Cervical cancer accounted for 74.3% of HPV-attributable hospitalizations, followed by anal (10.4%), head and neck (9.2%), and penile cancers (3.4%). Most HPV-associated cancers showed stable hospitalization and mortality trends over time. For cervical cancer, hospitalizations rose by 3.9% annually between 2016 and 2019, while mortality rose by 0.7% annually over the entire period. Anal cancer showed significant increases in both hospitalizations (AAPC = 3.1%) and mortality (AAPC = 10.9%). These findings underscore the need for continued efforts to prevent and reduce the burden of HPV-associated cancers in Brazil, including expanded cohort vaccination, consideration of higher-valency vaccines, and improved access to early detection and timely treatment for both sexes.