Cânceres orofaríngeos em mulheres: carcinogênese, risco relativo, incidência e tendência de mortalidade (1996-2023)

Abstract

This dissertation is composed of four chapters, which respectively aimed to: (1) summarize the evidence on the implications of the HPV16 oncoproteins E6 and E7 in cervical and oropharyngeal carcinogenesis, as well as their potential use in the development of diagnostic tests and therapeutic vaccines; (2) assess the relative risk of oropharyngeal malignancies in women treated for high-grade squamous intraepithelial lesions of the uterine cervix (HSIL [CIN 2/3]); (3) analyze temporal trends and the spatial distribution of oropharyngeal cancer diagnoses among the Brazilian female population between 2013 and 2023; and (4) analyze spatiotemporal trends in mortality from oropharyngeal cancers among women in Brazil from 1996 to 2023.In Chapter 1, a scoping review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). The study protocol was registered on the Open Science Framework (OSF). The findings indicate that the E6/E7 oncoproteins are associated with clinically relevant implications, including their use as biomarkers for screening and prognosis of cervical and oropharyngeal cancers. Their modulation has also been explored as a therapeutic target, with potential impact on early diagnosis and vaccine development.In Chapter 2, a systematic review was carried out following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered in the International Prospective Register of Systematic Reviews (PROSPERO). A total of 1,337 studies were retrieved, of which only five met the inclusion criteria. The results suggest that women treated for HSIL have an increased risk of developing oropharyngeal neoplasms compared with those without such lesions.Chapters 3 and 4 comprised ecological epidemiological studies. Incidence and mortality data were obtained from the Oncologia Brasil Panel, and population data from the Brazilian Institute of Geography and Statistics (IBGE). Trend analyses were performed using the Joinpoint Regression Program, and spatial distribution analyses using TerraView. In Chapter 3, 4,250 cases of oropharyngeal cancers in women were identified between 2013 and 2023. The highest number of diagnoses occurred among women aged 50–69 years (n = 2,454; 57.74%). An increasing trend was observed in the North, Northeast, Southeast, and South regions, with p-values ranging from <0.001 to 0.017, and a significant average annual percent change (AAPC) (p = 0.002). Most tumors were diagnosed at advanced stages (TNM stages III and IV; n = 2,330; 82.56%). Spatial autocorrelation analysis was statistically significant (p = 0.015).In Chapter 4, a total of 6,629 deaths from oropharyngeal cancers in women were recorded between 1996 and 2023. The most affected age group was 50–69 years (n = 5,781; 87.23%). Most women were White (n = 3,254; 49.74%), widowed (n = 2,132; 32.14%), and had no formal education (n = 1,531; 23.12%). Temporal trend analysis indicated an annual increase of 3.32% (95% CI: 2.76–3.89; p < 0.001). In the macroregional analysis, the Northeast showed a marked increase between 1996 and 2008 (APC = 9.15%; 95% CI: 6.90–15.19), followed by a deceleration between 2008 and 2023 (APC = 3.59%; 95% CI: −0.53–5.13). Spatial autocorrelation analysis showed variable statistical significance (p-values ranging from 0.001 to 0.008).Overall, the HPV E6 and E7 oncoproteins play a role in the dysregulation of cellular pathways, constituting viable biomarkers for early diagnosis and strategic targets for vaccine development. The finding that women previously treated for HSIL have an increased risk of developing oropharyngeal neoplasms reinforces the hypothesis of viral persistence or reactivation as an etiopathogenic link between these malignancies. From an epidemiological perspective, the upward trends in both incidence and mortality from oropharyngeal cancers among women highlight the need for integrated screening strategies and early intervention.