Abstract PR-14: A synergy between the vaginal microbiome and HPV may have explanatory value for racial disparities in risk of pre-cervical cancer

Persistent infection with some types of mucosal human papillomavirus (HPV) is the etiological factor for the development of cervical cancer and its precursor lesions. Besides, several cofactors are known to play a role in cervical disease onset and progression either by favoring or by preventing HPV infection and persistence. The microbiome of a healthy female genital tract is characterized by the presence of 1 or few varieties of lactobacilli. However, high-throughput studies addressing the bacterial diversity and abundance in the female genital tract have shown that several factors, including hormonal levels, hygiene habits, and sexually transmitted diseases may disrupt the natural balance, favoring the outgrowth of some groups of bacteria, which in turn may favor some pathological states. Recently, the vaginal microbiome has emerged as a new variable that could greatly influence the natural history of HPV infections and their clinical impact. In this context, changes in the vaginal microbiome have been detected in women infected with HPV and women with HPV-associated lesions and cancer. However, the role of specific bacteria groups in the development/progression or prevention/regression of HPV-associated pathologies is not well understood. In this review we summarize the current knowledge concerning changes in vaginal microbiome and cervical disease. We discuss the potential functional interplay between specific bacterial groups and HPV infection outcomes.

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Association of changes in vaginal microbiome with oligoclonal T-cell expansion and early response to chemoradiation for cervical cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.5_suppl.8 ◽

2018 ◽

Vol 36 (5_suppl) ◽

pp. 8-8

Author(s):

Lauren Elizabeth Colbert ◽

Andrea Delgado Medrano ◽

Rebecca A. Previs ◽

Patricia J. Eifel ◽

Anuja Jhingran ◽

...

Keyword(s):

Cervical Cancer ◽

Radiation Therapy ◽

T Cell ◽

Clinical Studies ◽

Cell Expansion ◽

Bacterial Species ◽

Early Response ◽

Vaginal Microbiome ◽

T Cell Clonality ◽

Cell Clonality

8 Background: The composition of the vaginal microbiome has been shown to affect clearance of HPV virus and transformation to invasive cancer. Clinical studies correlating the vaginal microbiome with immune activation and response to cancer treatment are lacking. We profiled intratumoral T-cell clonality during radiation therapy and correlated it with the diversity of the vaginal flora. Methods: Thirty patients with newly diagnosed locally advanced cervical cancer were enrolled on a prospective study to characterize changes in the cervical microbiome during chemoradiation. Cervical samples were obtained before radiation therapy and during the 1st, 3rd, and 5th week of radiation therapy. The vaginal microbiome was characterized using 16 sRNA gene sequencing to produce operational taxonomic units (OTU’s) representing individual bacterial species. Disease response was categorized as early response (ER), late response (LR), or nonresponse (NR) on the basis of clinical examination at brachytherapy and 3-month PET/CT. Twenty patients had T-cell receptor β sequencing of DNA performed using the ImmunoSEQ platform. The maximum productive frequency of the top three clones (MP3) was used to assess T-cell clonality. Results: Early response was associated with clonal T-cell expansion with an increase of MP3 of 11.1% during treatment as compared to a decline of 6.1% in patients with LR/NR (p = 0.05). Early response was also associated with lower quantity of observed OTU’s of vaginal microbiota (25.0 [SD 12.68]) vs patients with LR/NR (41.15 [SD = 23.3]) (p = 0·03). Increased MP3 was associated with increased abundance of Corynebacteriales (R = 0.90; p < .0001) , Actinomycetales (R = 0.83; p < .0001) and Bifidobacteriales (R = 0.82; p < .0001) . Decreased MP3 was associated with increased abundance of lactobacillus (R = -0.61; p < .0001). Conclusions: Increased diversity of the vaginal microbiome is negatively associated with outcome, supporting previous clinical studies in non-cancer settings. Specific vaginal bacterial species are associated with increased or decreased T-cell clonality at completion of radiation.

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Racial disparities in cervical cancer: Worse than we thought

Cancer ◽

10.1002/cncr.30501 ◽

2017 ◽

Vol 123 (6) ◽

pp. 915-916 ◽

Cited By ~ 9

Author(s):

Heather J. Dalton ◽

John H. Farley

Keyword(s):

Cervical Cancer ◽

Racial Disparities

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Delays in Definitive Cervical Cancer Treatment: Longer Waits With Ethnic/Racial Disparities Nationwide

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2017.06.1588 ◽

2017 ◽

Vol 99 (2) ◽

pp. E412

Author(s):

S.J. Ramey ◽

D. Asher ◽

D. Kwon ◽

A.A. Ahmed ◽

A.H. Wolfson ◽

...

Keyword(s):

Cervical Cancer ◽

Cancer Treatment ◽

Racial Disparities

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Human papillomavirus infection and cervical intraepithelial neoplasia progression are associated with increased vaginal microbiome diversity in a Chinese cohort

10.21203/rs.3.rs-29830/v2 ◽

2020 ◽

Author(s):

Yulian Chen ◽

Xingdi Qiu ◽

Wenjing Wang ◽

Dong Li ◽

Anyue Wu ◽

...

Keyword(s):

Cervical Cancer ◽

Human Papillomavirus ◽

Intraepithelial Neoplasia ◽

Hpv Infection ◽

Vaginal Microbiome ◽

The Family ◽

Family Level ◽

Chinese Cohort ◽

Bacterial Richness ◽

Intraepithelial Lesions

Abstract Background: In this study, the association between human papillomavirus (HPV) infection and related cervical intraepithelial neoplasia (CIN) or cervical cancer and vaginal microbiome was evaluated in Chinese cohorts. Methods: The vaginal bacterial composition of five groups, HPV-infected women without CINs (HPV, n=78), women with low-grade squamous intraepithelial lesions (LSIL, n=51), women with high-grade squamous intraepithelial lesions (HSIL, n=23), women with invasive cervical cancer (Cancer, n=9) and healthy women without HPV infection (Normal, n=68), was characterized by deep sequencing of barcoded 16S rRNA gene fragments (V3-4) using Illumina MiSeq. Results: HPV infection increased vaginal bacterial richness and diversity regardless of the status of CINs. The vaginal bacterial richness and diversity were further augmented in women with cervical cancer. Lactobacillus was the most abundant genus in all groups. HPV infection had a negative influence on the abundances of Lactobacillus, Gardnerella and Atopobium. Accordingly, HPV infection increased the relative abundance of Prevotella, Bacillus, Anaerococcus, Sneathia, Megasphaera, Streptococcus and Anaerococcus. The increased proportions of Bacillus, Anaerococcus and the reduced abundance of Gradnerella vaginalis were probably related with the progression of CINs severity. HPV infection without CINs or cancerous lesions was strongly associated with Megasphaera. The most abundant bacterium in the LSIL group was Prevotella amnii. However, Prevotella timonensis, Shuttleworthia and Streptococcaceae at the family level were three taxa related to HSIL. Furthermore, more taxa were associated with the Cancer group including Bacillus, Sneathia, Acidovorax, Oceanobacillus profundus, Fusobacterium, Veillonellaceae at the family level, Anaerococcus and Porphyromonas uenonis. Samples in the Normal group were mostly assigned to CST III. HPV infection converted the vaginal bacterial community structure from CST III to CST IV. Furthermore, the proportions of CST IV were gradually augmented with the progression of the severity of CINs.Conclusions: This work interpreted the differential vaginal bacteria under HPV infection and various precancerous or cancerous lesions in a Chinese cohort. We distinguished the specific microbes and the vaginal bacterial structure that were related with the progression of CINs severity in Chinese women.

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The Mitigation of Racial Disparities in Cervical Cancer Screening Among U.S. Active Duty Service Women

Military Medicine ◽

10.1093/milmed/usaa427 ◽

2020 ◽

Cited By ~ 1

Author(s):

Jessica Pope ◽

Amanda Banaag ◽

Cathaleen Madsen ◽

Tranessia Hanson ◽

Munziba Khan ◽

...

Keyword(s):

Health Care ◽

Cervical Cancer ◽

Native American ◽

Cancer Screening ◽

Racial Disparities ◽

Cervical Cancer Screening ◽

Active Duty ◽

Cancer Screenings ◽

Women In The Navy ◽

The U.S

Abstract Introduction The U.S. Preventive Services Task Force recommends regular cervical cancer screening for women aged 21-65 years. Such screening is key to reducing mortality and morbidity. Despite improvement in the screening rate, cervical cancer still disproportionately affects women of minority groups because of access to quality health care. The Military Health System (MHS) mitigates this barrier through universal healthcare coverage for all active duty service members and their families. However, such racial/ethnic disparities, seen in civilian population, have not been studied in the MHS. Materials and Methods This is a retrospective cross-sectional study utilizing fiscal years 2011-2016 claims data obtained from the MHS Data Repository for 112,572 active duty service women aged 21-64 years. Study analyses included descriptive statistics on patient demographics, calculations of the proportion of patients who received cervical cancer screenings as well as the proportion of patients in compliance with USPSTF guidelines, and unadjusted odds ratios for the likelihood of compliance by race and military service. Results Of the study population, 50.0% of active duty women were screened for cervical cancer. When compared to White women, Black (1.05 OR, 1.03-1.08 CI), Native American/Alaskan Native (1.26 OR, 1.15-1.39 CI), and Other (1.12 OR, 1.06-1.18 CI) women were significantly more likely to receive cervical cancer screenings. The proportions of 3-year compliance were relatively equal within each race category (ranging from 43% to 45%), with no significant findings for the odds of compliance in any race when compared to White active duty women; however, proportions of 3-year compliance by service ranged from 11.7% in the Marines to 84.4% in the Navy, and active duty women in the Navy were six times more likely to be in compliance with guidelines than women in the Army. When looking at 5-year compliance in active duty women aged 30-64 years, women in the Navy were more likely than women in the Army to meet compliance guidelines (1.24 OR, 1.14-1.36 CI), while women in the Air Force were slightly less likely (0.90 OR, 0.82-0.98 CI). Conclusions The women in our population demonstrated similar or lower compliance than other studies conducted in the U.S. general population, and racial disparities for cervical cancer screening were partially mitigated in active duty service women. While our research demonstrates that universal insurance can help provide equal access and care, investigation into the factors that encourage greater usage among members of different military branches may help to understand and develop policies to improve health care systems.

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