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Cervical cancer remains a leading cause of morbidity and mortality amongst females in Latin America (LATAM). Cervical cancer is a preventable disease and HPV vaccination is a main key strategy towards its elimination. This study analyzes HPV vaccine implementation current status and the main barriers to achieve adequate coverage in the region. Data from the nineteen sovereign states of LATAM (comprised of all Portuguese and Spanish-speaking nations located south of the United States) were collected, including year of HPV vaccine implementation, gender and age targets, the number of doses included in the public program and coverage by dose. Sixteen out of the 19 evaluated countries have already implemented HPV vaccination programs. However, despite its proven efficacy and safety, HPV vaccine uptake in LATAM has been lower than expected. There is an evident decline in adhesion, mainly regarding the second dose. Several reasons are probably involved, of note: limited knowledge of HPV and HPV vaccine, misguided safety concerns, high cost, cultural barriers, and the Covid19 pandemic. Proper strategies to overcome these barriers are needed to ensure successful uptake. Effective policies are: adopting the one dose schedule, delivering the vaccine on both health center and schools, and advising health professionals to recommend the vaccine. Further research regarding HPV vaccine hesitancy in Latin America is needed. [ABSTRACT FROM AUTHOR]

TP53 and ARID1A are frequently mutated across cancer but rarely in the same primary tumor. Endometrial cancer has the highest TP53-ARID1A mutual exclusivity rate. However, the functional relationship between TP53 and ARID1A mutations in the endometrium has not been elucidated. We used genetically engineered mice and in vivo genomic approaches to discern both unique and overlapping roles of TP53 and ARID1A in the endometrium. TP53 loss with oncogenic PIK3CAH1047R in the endometrial epithelium results in features of endometrial hyperplasia, adenocarcinoma, and intraepithelial carcinoma. Mutant endometrial epithelial cells were transcriptome profiled and compared to control cells and ARID1A/PIK3CA mutant endometrium. In the context of either TP53 or ARID1A loss, PIK3CA mutant endometrium exhibited inflammatory pathway activation, but other gene expression programs differed based on TP53 or ARID1A status, such as epithelial-to-mesenchymal transition. Gene expression patterns observed in the genetic mouse models are reflective of human tumors with each respective genetic alteration. Consistent with TP53-ARID1A mutual exclusivity, the p53 pathway is activated following ARID1A loss in the endometrial epithelium, where ARID1A normally directly represses p53 pathway genes in vivo, including the stress-inducible transcription factor, ATF3. However, co-existing TP53-ARID1A mutations led to invasive adenocarcinoma associated with mutant ARID1A-driven ATF3 induction, reduced apoptosis, TP63+ squamous differentiation and invasion. These data suggest TP53 and ARID1A mutations drive shared and distinct tumorigenic programs in the endometrium and promote invasive endometrial cancer when existing simultaneously. Hence, TP53 and ARID1A mutations may co-occur in a subset of aggressive or metastatic endometrial cancers, with ARID1A loss promoting squamous differentiation and the acquisition of invasive properties. Author summary: Endometrial cancer is the most commonly diagnosed gynecologic malignancy in the United States, with annual incidence continuing to rise. Although the majority of endometrial cancer patients have an excellent overall prognosis if the disease is confined to the endometrium, myometrial invasion and metastasis to other sites correlate with poor survival. Here, we used genetically engineered mice, in vivo genomics, and public cancer patient data to understand the relationship between TP53 and ARID1A, two of the most commonly mutated genes in endometrial cancer, in the context of mutant PIK3CA. Mutations in TP53 and ARID1A change different aspects of endometrial cell health but also share some similarities. ARID1A mutations specifically promote cancer cells to invade nearby tissue, a hallmark of metastasis, associated with squamous differentiation. Mice with co-existing TP53 and ARID1A mutations developed more invasive disease. Our studies suggest that co-existing TP53 and ARID1A tumor mutations may promote invasion and metastasis. [ABSTRACT FROM AUTHOR]