RESUMO
Cervical cancer is driven by persistent infection of human papillomavirus (HPV), which is influenced by HPV type and intratypic variants, yet the impact of HPV type and intratypic variants on patient outcomes is far less understood. Here, we examined the association of cervical cancer stage and survival with HPV type, clade, lineage, and intratypic variants within the HPV E6 locus. Of 1,028 HPV-positive cases recruited through the CerGE study, 301 were in-situ and 727 were invasive cervical cancer (ICC), with an average post-diagnosis follow-up of 4.8 years. HPV sequencing was performed using tumor-isolated DNA to assign HPV type, HPV 16 lineage, clade, and intratypic variants within the HPV 16 E6 locus, of which nonsynonomous variants were functionally annotated by molecular modeling. HPV 18-related types were more prevalent in ICC compared to in-situ disease and associated with significantly worse recurrence-free survival (RFS) compared to HPV 16-related types. The HPV 16 Asian American lineage D3 and Asian lineage A4 associated more frequently with ICC than with in situ disease and women with an intratypic HPV 16 lineage B exhibited a trend toward worse RFS than those with A, C, or D lineages. Participants with intratypic E6 variants predicted to stabilize the E6-E6AP-p53 complex had worse RFS. Variants within the highly immunogenic HPV 16 E6 region (E14-I34) were enriched in ICC compared to in-situ lesions but were not associated with survival. Collectively, our results suggest that cervical cancer outcome is associated with HPV variants that affect virus-host interactions.
Assuntos
Proteínas de Ligação a DNA/genética , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Proteínas Oncogênicas Virais/genética , Proteínas Repressoras/genética , Neoplasias do Colo do Útero/virologia , Adulto , Sequência de Bases , DNA Viral/genética , Proteínas de Ligação a DNA/metabolismo , Feminino , Variação Genética/genética , Humanos , Proteínas Oncogênicas Virais/metabolismo , Infecções por Papillomavirus/virologia , Ligação Proteica/genética , Proteínas Repressoras/metabolismo , Análise de Sequência de DNARESUMO
BACKGROUND: Outpatient surgeries account for 60-70% of all procedures. Increased surgical duration has been demonstrated to be an independent risk factor for the development of venous thromboembolism (VTEs) after inpatient surgeries. In contrast, it is currently unknown if surgical duration increases the risk of VTEs for outpatient surgeries. MATERIALS AND METHODS: The 2005 through 2016 NSQIP Participant Use Data Files were queried to extract all patients scheduled for outpatient surgery. A z-score for surgical duration was calculated for each procedure to allow for standardization across surgeries of expected shorter or longer duration. The primary outcome measured was incidence of VTEs within 30 days of surgery. RESULTS: A total of 3474 patients out of 1,863,523 (0.19%) had a VTE. After adjusting for confounding factors, the first and fifth quintiles compared to the middle quintile had odds ratios (ORs) of 0.75 (95% CI 0.68, 0.80) and 1.43 (95% CI, 1.35%-1.52%), respectively, P < 0.001. Patients who developed VTEs were more likely to be readmitted to the hospital, OR (95%CI) of 51.9 (48.0-56.2), C statistic = 0.67. CONCLUSION: Surgical duration is associated with the development of VTEs after outpatient surgery. While the overall incidence of VTE is low and does not require generalized prophylaxis, clinical practitioners should consider prophylaxis for patients undergoing outpatient surgery performed with excessive time compared to the average surgical procedure duration.