HPV post-infection microenvironment and cervical cancer. Yuan Yi,Cai Xushan,Shen Fangrong,Ma Feng Cancer letters Human papillomavirus (HPV) is the most common sexually transmitted virus worldwide. More than 99% of cervical cancer cases are associated with certain types of HPVs, termed high-risk types. In addition to the well-known transformative properties, HPVs-infected cells actively instruct the local milieu and create a supportive post-infection microenvironment (PIM), which is becoming recognized as a key factor for the viral persistence, propagation, and malignant progression. The PIM is initiated and established via a complex interplay among virus-infected cells, immune cells, and host stroma, as well as their derived components including chemokines, cytokines, extracellular vesicles, and metabolites. In this review, we summarize the current understanding of these key components, characteristics, and effects of the PIM, and highlights the prospect of targeting the PIM as a potential strategy to improve therapeutic outcomes for cervical cancer. 10.1016/j.canlet.2020.10.034

High-Risk HPV Genotype Distribution According to Cervical Cytology and Age. Open forum infectious diseases Background:A retrospective study of a single laboratory's results from patients in the United States to investigate high-risk human papillomavirus (HPV) genotype distribution according to cervical cytology and age was performed. Methods:Anonymous results of 23 580 patients' cervical specimens sent to Medical Diagnostic Laboratories, LLC, for cervical cytology and HPV testing between August 2020 and August 2021 were analyzed. Results:Overall, any of the 14 high-risk HPV genotypes identified were detected in 2302 of the 23 580 patients (9.8%), with HPV 52 (1.4%), HPV 39 (1.3%), HPV 51 (1.3%), and HPV 16 (1.2%) being the most frequent in all patients. Multiple high-risk HPV infection was observed in 1.3% of all patients. HPV 16 was most likely to be a single high-risk genotype detected as compared with detection with other high-risk HPV genotypes, in contrast to HPV 33, which is least likely to be a single high-risk genotype detected as compared with detection with other high-risk HPV genotypes. High-risk HPV detection was greatest in patients under 25 years old (<21-year-olds, 24.6%, and 21-25-year-olds, 25.4%). In patients with low-grade squamous intraepithelial lesions, the most frequently detected high-risk HPV genotypes were HPV 51 (10.5%) and HPV 39 (9.1%), and in patients with high-grade squamous intraepithelial lesions, the most frequently detected high-risk HPV genotypes were HPV 16 (25.6%) and HPV 52 (17.1%). Conclusions:HPV genotyping and cervical cytology data analysis may contribute to and inform cervical cancer screening and HPV vaccination programs. 10.1093/ofid/ofac595

HPV and radiosensitivity of cervical cancer: a narrative review. Annals of translational medicine Background and Objective:Cervical cancer (CC), the most common gynecological malignancy, is divided into two categories: human papillomavirus-related [HPV positive (HPV+)] and non-HPV-related [HPV negative (HPV-)]. Compared with HPV- CC, HPV+ CC has better radiosensitivity and prognosis. We conducted a literature search and summarized relevant studies to explore the detailed mechanisms by which HPV+ improves the prognosis of CC compared to HPV-. Methods:PubMed was used to search the literature on human papillomavirus, cervical cancer, and radiotherapy up to June 2022. Key Content and Findings:Compared with HPV- CC, HPV+ CC has better radiotherapy outcomes and better prognosis. HPV improves the radiotherapy sensitivity of CC by inhibiting damaged DNA repair, increasing cell cycle arrest, reducing hypoxia, increasing cellular immune response, and other mechanisms. However, the effect of HPV on radiotherapy sensitivity of CC is not consistent and is affected by HPV type, viral load, and many other factors. Partial HPV+ CCs, due to hypoxia and other factors, are resistant to radiotherapy and have a poor prognosis. HPV- CC has poor radiotherapy sensitivity and poor prognosis. With the spread of the vaccine, HPV- CC will gradually increase, which is a cause for concern. Conclusions:The radiosensitivity was significantly increased in patients with HPV+ CC, compared to HPV- patients. HPV improves the radiotherapy sensitivity of cervical cancer through a number of pathways. Meanwhile, the relationship between HPV and radiotherapy sensitivity is influenced by a number of factors. Some HPV+ CCs showed radiotherapy resistance, and HPV- CCs deserve further attention. 10.21037/atm-22-5930

The vaginal metabolome and microbiota of cervical HPV-positive and HPV-negative women: a cross-sectional analysis. Borgogna J C,Shardell M D,Santori E K,Nelson T M,Rath J M,Glover E D,Ravel J,Gravitt P E,Yeoman C J,Brotman R M BJOG : an international journal of obstetrics and gynaecology OBJECTIVE:Characterise the vaginal metabolome of cervical HPV-infected and uninfected women. DESIGN:Cross-sectional. SETTING:The Center for Health Behavior Research at the University of Maryland School of Public Health. SAMPLE:Thirty-nine participants, 13 categorised as HPV-negative and 26 as HPV-positive (any genotype; HPV ), 14 of whom were positive with at least one high-risk HPV strain (hrHPV). METHOD:Self-collected mid-vaginal swabs were profiled for bacterial composition by 16S rRNA gene amplicon sequencing, metabolites by both gas and liquid chromatography mass spectrometry, and 37 types of HPV DNA. MAIN OUTCOME MEASURES:Metabolite abundances. RESULTS:Vaginal microbiota clustered into Community State Type (CST) I (Lactobacillus crispatus-dominated), CST III (Lactobacillus iners-dominated), and CST IV (low-Lactobacillus, 'molecular-BV'). HPV women had higher biogenic amine and phospholipid concentrations compared with HPV women after adjustment for CST and cigarette smoking. Metabolomic profiles of HPV and HPV women differed in strata of CST. In CST III, there were higher concentrations of biogenic amines and glycogen-related metabolites in HPV women than in HPV women. In CST IV, there were lower concentrations of glutathione, glycogen, and phospholipid-related metabolites in HPV participants than in HPV participants. Across all CSTs, women with hrHPV strains had lower concentrations of amino acids, lipids, and peptides compared with women who had only low-risk HPV (lrHPV). CONCLUSIONS:The vaginal metabolome of HPV women differed from HPV women in terms of several metabolites, including biogenic amines, glutathione, and lipid-related metabolites. If the temporal relation between increased levels of reduced glutathione and oxidised glutathione and HPV incidence/persistence is confirmed in future studies, anti-oxidant therapies may be considered as a non-surgical HPV control intervention. TWEETABLE ABSTRACT:Metabolomics study: Vaginal microenvironment of HPV women may be informative for non-surgical interventions. 10.1111/1471-0528.15981