Oxidative damage and antioxidants in cervical cancer.

The pathogenesis of cervical cancer is related to oxidative damage caused by persistent infection by one of the oncogenic types of human papillomavirus (HPV). This damage comes from oxidative stress, which is the imbalance caused by the increase in reactive oxygen and nitrogen species and impaired antioxidant mechanisms, promoting tumor progression through metabolic processes. The incorporation of HPV into the cellular genome leads to the expression of oncoproteins, which are associated with chronic inflammation and increased production of reactive oxygen species, oxidizing proteins, lipids and DNA. The increase in these parameters is related, in general, to the reduction of circulating levels of enzymatic antioxidants-superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase; and non-enzymatic antioxidants-reduced glutathione, coenzyme Q10 and vitamins A, C and E, according to tumor staging. In contrast, some enzymatic antioxidants suffer upregulation in the tumor tissue as a way of adapting to the oxidative environment generated by themselves, such as glutathione-S-transferase, reduced glutathione, glutathione peroxidase, superoxide dismutase 2, induced nitric oxide synthase, peroxiredoxins 1, 3 and 6, and thioredoxin reductase 2. The decrease in the expression and activity of certain circulatory antioxidants and increasing the redox status of the tumor cells are thus key to cervical carcinoma prognosis. In addition, vitamin deficit is considered a possible modifiable risk factor by supplementation, since the cellular functions can have a protective effect on the development of cervical cancer. In this review, we will discuss the impact of oxidative damage on cervical cancer progression, as well as the main oxidative markers and therapeutic potentialities of antioxidants.

A serum lipidomic strategy revealed potential lipid biomarkers for early-stage cervical cancer.

AIMS: Cervical cancer (CC) is a common tumor of women worldwide. Here, we conducted a non-targeted lipidomic study to discover novel lipid biomarkers for early-stage CC. MAIN METHODS: The lipidomic analysis of 71 samples in discovery set and 72 samples in validation set were performed by coupling ultra-high-pressure liquid chromatography (UHPLC) with quadrupole time-of-flight tandem mass spectrometry (Q-TOF-MS). Lipids with variable importance (VIP) values greater than 1, adj. p < 0.05 (the adjusted p value obtained from false discovery rate correction) and fold change (FC) higher than 1.5 were reserved as potential biomarkers. Subsequently, receiver operating characteristic (ROC) curve and binary logistic regression were implemented to assess the diagnostic potential of these biomarkers and to acquire the best biomarker combination. KEY FINDINGS: A lipid biomarker panel, including phosphatidylcholine (PC, PC 14:0/18:2) and phosphatidylethanolamine (PE, PE 15:1e/22:6 and PE 16:1e/18:2), was established. This panel was effective in distinguishing between CC and non-CC (squamous intraepithelial lesions [SIL] and healthy controls) within the area under the ROC curve (AUC), sensitivity, and specificity reaching 0.966, 0.952, and 0.860 for discovery set and 0.961, 0.920, and 0.915 for external validation set. Furthermore, this panel was also capable of discriminating early-stage CC from SIL with AUC, sensitivity, and specificity reaching 0.946, 0.952, and 0.800 for discovery set and 0.956, 0.960, and 0.815 for external validation set. SIGNIFICANCE: The combination of PC 14:0/18:2, PE 15:1e/22:6, and PE 16:1e/18:2 could serve as a promising serum biomarker for discriminating early-stage CC from SIL and healthy subjects.

Virological and Serological Predictors of Anal High-grade Squamous Intraepithelial Lesions Among Human Immunodeficiency Virus-positive Men Who Have Sex With Men.

BACKGROUND: Our objective was to identify virological and serological predictors of anal high-grade squamous intraepithelial lesions (HSIL) in human immunodeficiency virus (HIV)-positive men who have sex with men (MSM). METHODS: HIV-positive MSM were recruited from a longitudinal study during which anal self-swabs and serum were collected at up to 5 bi-annual visits. Swabs were human papillomavirus (HPV) genotyped, and the type-specific HPV viral load in the anal swabs was determined. Serum antibodies to the E6, E7, E1, E2, and L1 proteins of 7 high-risk HPV (hrHPV) types and HPV6 and 11 were analyzed. The participants who had a high-resolution anoscopy after the last study visit were included in the current analysis. Anal HSIL was diagnosed by histopathological examinations of anal biopsies. The causative HPV type of anal HSIL was determined in whole tissue sections (WTS) and by laser capture micro-dissection if more than one HPV-type was found in WTS. Multivariable logistic regression was used to study whether persistent anal HPV infections, HPV viral loads, and seropositivity for HPV were predictors of anal HSIL, either in general or caused by the concordant HPV type. RESULTS: Of 193 HIV-positive MSM, 50 (26%) were diagnosed with anal HSIL. HrHPV persistence in anal swabs was common, varying by hrHPV type between 3-21%. Anal HPV persistence was the only determinant independently associated with anal HSIL, both in general and by concordant, causative HPV type. CONCLUSIONS: Persistent HPV infections were strongly associated with anal HSIL, in general as well as for the concordant HPV type.