IL-10, IL-15, IL-17, and GMCSF levels in cervical cancer tissue of Tanzanian women infected with HPV16/18 vs. non-HPV16/18 genotypes.

BACKGROUND: Despite comparable screening rates for precancerous lesions, higher incidence and mortality related to cervical cancer in minority women persists. Recent evidence suggests that minority women with precancerous cervical lesions harbor a wider range of human papillomavirus (HPV) genotypes, many of these distinct from HPV16/18, those most commonly found in Caucasian women. The goal of the analysis was to determine if inflammatory cytokines and chemokines varied by HPV 16/18 versus other genotypes in cervical cancer tissues from Tanzanian women. METHODS: HPV genotypes and concentrations of chemokines and cytokines were measured from homogenized fresh tumor tissue of thirty-one women with invasive cervical cancer (ICC). Risk factors for cervical cancer including age, parity, hormonal contraceptive use and cigarette smoking were obtained by questionnaire. Generalized linear models were used to evaluate differences between chemokines/cytokine levels in women infected with HPV16/18 and those infected with other HPV genotypes. RESULTS: After adjusting for age, parity and hormonal contraceptives, IL-17 was found significantly more frequently in invasive cervical cancer samples of women infected with HPV16/18 compared to women infected with other HPV genotypes (p = 0.033). In contrast, higher levels for granular macrophage colony-stimulating factor (p = 0.004), IL-10 (p = 0.037), and IL-15 (p = 0.041) were found in ICC tissues of women infected with genotypes other than HPV16/18 when compared to those of women infected with HPV16/18. CONCLUSIONS: While the small sample size limits inference, our data suggest that infection with different HPV genotypes is associated with distinct pro-inflammatory cytokine expression profiles; whether this explains some of the racial differences observed in cervical cancer is still unclear. Future studies are needed to confirm these findings

Landscape of <i>KRAS</i><SUP>G12C</SUP>, Associated Genomic Alterations, and Interrelation With Immuno-Oncology Biomarkers in <i>KRAS</i>-Mutated Cancers

PURPOSE: Promising single-agent activity from sotorasib and adagrasib in KRASG12C-mutant tumors has provided clinical evidence of effective KRAS signaling inhibition. However, comprehensive analysis of KRAS-variant prevalence, genomic alterations, and the relationship between KRAS and immuno-oncology biomarkers is lacking. MATERIALS AND METHODS: Retrospective analysis of deidentified records from 79,004 patients with various cancers who underwent next-generation sequencing was performed. Fisher's exact test evaluated the association between cancer subtypes and KRAS variants. Logistic regression assessed KRASG12C comutations with other oncogenes and the association between KRAS variants and immuno-oncology biomarkers. RESULTS: Of the 79,004 samples assessed, 13,758 (17.4%) harbored KRAS mutations, with 1,632 (11.9%) harboring KRASG12C and 12,126 (88.1%) harboring other KRAS variants (KRASnon-G12C). Compared with KRASnon-G12C across all tumor subtypes, KRASG12C was more prevalent in females (56% v 51%, false discovery rate-adjusted P value [FDR-P] = .0006), current or prior smokers (85% v 56%, FDR-P 60 years (73% v 63%, FDR-P ≤ .0001). The most frequent KRAS variants across all subtypes were G12D (29.5%), G12V (23.0%), G12C (11.9%), G13D (6.5%), and G12R (6.2%). KRASG12C was most prevalent in patients with non-small-cell lung cancer (9%), appendiceal (3.9%), colorectal (3.2%), tumor of unknown origin (1.6%), small bowel (1.43%), and pancreatic (1.3%) cancers. Compared with KRASnon-G12C-mutated, KRASG12C-mutated tumors were significantly associated with tumor mutational burden-high status (17.9% v 8.4%, odds ratio [OR] = 2.38; FDR-P < .0001). KRASG12C-mutated tumors exhibited a distinct comutation profile from KRASnon-G12C-mutated tumors, including higher comutations of STK11 (20.59% v 5.95%, OR = 4.10; FDR-P < .01) and KEAP1 (15.38% v 4.61%, OR = 3.76; FDR-P < .01). CONCLUSION: This study presents the first large-scale, pan-cancer genomic characterization of KRASG12C. The KRASG12C mutation was more prevalent in females and older patients and appeared to be associated with smoking status. KRASG12C tumors exhibited a distinct comutation profile and were associated with tumor mutational burden-high status