Shujun Gao

Human Papillomavirus (HPV) Type Distribution in Cervical Carcinoma, Low‐Grade, and High‐Grade Squamous Intraepithelial Lesions in Women Under 25 Years Old From the Largest Women Hospital in China

ABSTRACT This study aimed to profile high‐risk HPV genotypes across the spectrum of cervical lesions (low‐grade squamous intraepithelial lesion [LSIL], HSIL, carcinoma) in young patients under 25. Patients under 25 with histologically confirmed LSIL ( n  = 200), HSIL ( n  = 200), or cervical cancer (CC) ( n  = 32) between January 2018 and December 2021 underwent real‐time PCR‐based HPV genotyping (21 types) to assess type‐specific prevalence. The overall HPV detection rates were 91% in LSIL and 100% in both HSIL and CC. HR‐HPV and LR‐HPV was observed in 90.5%/14.5% of LSIL cases, 87.5%/5.5% of HSIL cases, and 93.8%/12.5% of CC cases. HPV16 was the most prevalent genotype (25.5%), followed by HPV52 and HPV58 in LSIL. The most frequent HR‐HPV genotype in HSIL were HPV16 (63.0%), followed by HPV33, HPV52, HPV58, and HPV18. HPV16 (43.8%) and HPV18 (34.4%) were the most common genotypes in CC tissues, followed by HPV68, HPV53, HPV6, HPV31, HPV52, and HPV59. In squamous cell carcinoma, HPV16 was predominant (70.0%), followed by HPV6, HPV59, and HPV68. HPV18 prevalence was significantly higher in adenocarcinoma, adenosquamous carcinoma, and neuroendocrine carcinoma (100.0%, 71.4%, and 100.0%, respectively) than in squamous cell carcinoma. Theoretically, the protective rates of 2‐valent, 4‐valent, and 9‐valent HPV vaccine were 75.0%, 84.4%, and 87.5%, respectively for CC in Chinese women under 25 years old. The results of this study provide baseline information on the HPV genotypes distribution in women under 25 years of age, which may contribute to promoting the implementation of CC prevention and control programs for this demographic.

Altered vaginal eukaryotic virome is associated with different cervical disease status

Viruses are important components of the human body. Growing evidence suggests that they are engaged in the physiology and disease status of the host. Even though the vaginal microbiome is involved in human papillomavirus (HPV) infection and cervical cancer (CC) progression, little is known about the role of the vaginal virome. In this pilot exploratory study, using unbiased viral metagenomics, we aim to investigate the vaginal eukaryotic virome in women with different levels of cervical lesions, and examine their associations with different cervical disease status. An altered eukaryotic virome was observed in women with different levels of lesions and Lactobacillus profiles. Anelloviruses and papillomaviruses are the most commonly detected eukaryotic viruses of the vaginal virome. Higher abundance and richness of anelloviruses and papillomaviruses were associated with low-grade squamous intraepithelial lesion (LSIL) and CC. Besides, higher anellovirus abundance was also associated with lactobacillus-depleted microbiome profiles and bacterial community state (CST) type IV. Furthermore, increased correlations between Anelloviridae and Papillomaviridae occurred in the women with increased cervical disease severity level from LSIL to CC. These data suggest underlying interactions between different microbes as well as the host physiology. Higher abundance and diversity of both anelloviruses and papillomaviruses shared by LSIL and CC suggest that anellovirus may be used as a potential adjunct biomarker to predict the risk of HPV persistent infection and/or CC. Future studies need to focus on the clinical relevance of anellovirus abundance with cervical disease status, and the evaluation of their potential as a new adjunct biomarker for the prediction and prognoses of CC.

Lactobacillus crispatus -derived nCEV vesicles promote cutaneous wound healing and inhibit HPV16 infection

ABSTRACT Cervical cancer (CC) is a common gynecological malignancy, primarily associated with persistent infection by high-risk human papillomavirus (HPV). The vaginal microbiota, dominated by Lactobacillus species, plays a critical role in maintaining a healthy vaginocervical microenvironment. However, the influence of Lactobacillus on the pathogenesis and treatment of CC remains underexplored. Here, we report that the optimized 60–80 nm size dominant of extracellular vesicles from various Lactobacillus species (nLEVs) significantly affects cutaneous wound healing and HPV infection. Specifically, nCEVs from Lactobacillus crispatus demonstrate superior efficacy compared to nIEVs from Lactobacillus iners in promoting cell migration, angiogenesis, and wound healing via macrophage M2 polarization and blocking intravaginal HPV16 infection. Moreover, metabolic profiling revealed that D-lactate may be key to the functions of nCEVs. Altogether, our findings uncover a novel nCEV/D-lactate-mediated mechanism that promotes homeostasis and offers potential new approaches for the prevention and treatment of CC. IMPORTANCE This study identifies Lactobacillus crispatus -derived vesicles (nCEVs) as crucial for cervicovaginal homeostasis, functioning through promoting wound healing via macrophage polarization and blocking HPV infection, and delivering D-lactate—a key bioactive component. These insights advance microbiome-based female healthcare interventions.