Association between the cervicovaginal microbiome, BRCA1 mutation status, and risk of ovarian cancer: a case-control study

Nené, Nuno R.; Reisel, Daniel; Leimbach, Andreas; Franchi, D.; Jones, Allison; Evans, Iona; Knapp, S.; Ryan, Andy; Ghazali, Shohreh; Timms, John F.; Paprotka, Tobias; Bjørge, Line; Zikán, Michal; Cibula, David; Colombo, Nicoletta; Widschwendter, Martin

doi:10.1016/s1470-2045(19)30340-7

Cited by 119 publications

(111 citation statements)

References 32 publications

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“…2), with an unexpected high incidence of HPV 90 (n = 12) which was reported in North America and Belgium but not in Hong Kong [20,21]. Another advantage offered by NGS is its potential utility for simultaneous characterization of cervicovaginal microbiome, with its possible role in dysplasia and carcinogenesis revealed by accumulating research evidence [22][23][24][25]. These merits may facilitate a multifaceted approach for evaluation of woman health in near feature.…”

Section: Discussionmentioning

confidence: 99%

An economical Nanopore sequencing assay for human papillomavirus (HPV) genotyping

Chan

et al. 2020

Diagn Pathol

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Background: Human papillomavirus (HPV) testing has been employed by several European countries to augment cytology-based cervical screening programs. A number of research groups have demonstrated potential utility of next-generation sequencing (NGS) for HPV genotyping, with comparable performance and broader detection spectrum than current gold standards. Nevertheless, most of these NGS platforms may not be the best choice for medium sample throughput and laboratories with less resources and space. In light of this, we developed a Nanopore sequencing assay for HPV genotyping and compared its performance with cobas HPV Test and Roche Linear Array HPV Genotyping Test (LA). Methods: Two hundred and one cervicovaginal swabs were routinely tested for Papanicolaou smear, cobas HPV Test and LA. Residual DNA was used for Nanopore protocol after routine testing. Briefly, HPV L1 region was amplified using PGMY and MGP primers, and PCR-positive specimens were sequenced on MinION flow cells (R9.4.1). Data generated in first 2 h were aligned with reference sequences from Papillomavirus Episteme database for genotyping. Results: Nanopore detected 96 HPV-positive (47.76%) and 95 HPV-negative (47.26%) specimens, with 10 lacking βglobin band and not further analyzed (4.98%). Substantial agreement was achieved with cobas HPV Test and LA (κ: 0.83-0.93). In particular, Nanopore appeared to be more sensitive than cobas HPV Test for HPV 52 (n = 7). For LA, Nanopore revealed higher concordance for high-risk (κ: 0.93) than non-high risk types (κ: 0.83), and with similar high-risk positivity in each cytology grading. Nanopore also provided better resolution for HPV 52 in 3 specimens co-infected with HPV 33 or 58, and for HPV 87 which was identified as HPV 84 by LA. Interestingly, Nanopore identified 5 additional HPV types, with an unexpected high incidence of HPV 90 (n = 12) which was reported in North America and Belgium but not in Hong Kong. Conclusions: We developed a Nanopore workflow for HPV genotyping which was economical (about USD 50.77 per patient specimen for 24-plex runs), and with comparable or better performance than 2 reference methods in the market. Future prospective study with larger sample size is warranted to further evaluate test performance and streamline the protocol.

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Section: Discussionmentioning

confidence: 99%

An economical Nanopore sequencing assay for human papillomavirus (HPV) genotyping

Chan

et al. 2020

Diagn Pathol

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“…Moreover, lipid and metabolite deregulation was reported in breasts of BRCA1/2 mutation carriers [26]. The proportion of women with a non-lactobacillus-dominated vaginal microbiome is significantly higher in women with extra-uterine Müllerian carcinomas and in yet unaffected BRCA1 mutation carriers than in unaffected non-carriers [30]. This attests to the potential complexity and multi-systemic involvement of cancer predisposition in these carriers.…”

Section: Introductionmentioning

confidence: 94%

Non-Surgical Cancer Risk Reduction in BRCA1 Mutation Carriers: Disabling the Remote Control

Widschwendter

Dubeau

2020

Cancers

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Women-specific cancers are a major health issue, particularly those associated with the BRCA1 germline mutation carrier state, which include triple-negative basal breast carcinomas and high-grade serous ovarian carcinomas (referred to as extra-uterine Müllerian carcinomas). Whereas many chronic diseases can currently be prevented (e.g., cardiovascular diseases), no recent tangible progress was made in cancer prevention of BRCA1 mutation carriers apart from surgical resections of at-risk organs. This lack of progress is largely due to (1) poor understanding of the initiating events triggered by known risk factors in the development of these cancers, (2) the fact that current preventive measures rely on evidence obtained from adjuvant breast cancer treatment that fail to protect against poor prognostic cancers, and (3) problems with using cancer incidence in high-risk women as an ethically justifiable endpoint in cancer prevention trials. Here, we propose that cancer predisposition in BRCA1 mutation carriers is driven, at least in part, by cell-nonautonomous mechanisms (i.e., driven by consequences of this carrier state on hormonal and other systemic factors controlled in organs other than those that are cancer-prone) and that biomarkers of epigenomic reprogramming, hypothesized to be a direct consequence of such cell-nonautonomous mechanisms, are attractive as intermediate surrogate endpoints to assess the efficacy of cancer risk-reducing strategies targeting these mechanisms.

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“…Dysbiotic vaginal microbiota deficient in lactobacilli with concomitant increase in pH is associated with persistent human papillomavirus (HPV) infection, cervical epithelial dysplasia and progression to invasive cervical carcinoma (48). Furthermore, vaginal microbiota dominated by Prevotella, Streptococcus, Atopobium, Ureaplasma, Mobiluncus; and deficient in lactobacilli was associated with increased predisposition to ovarian cancer or factors that influence its risk including age and BRCA1 germline mutations (49).…”

Section: Female Genital Tract Microbiotamentioning

confidence: 99%

Female Gut and Genital Tract Microbiota-Induced Crosstalk and Differential Effects of Short-Chain Fatty Acids on Immune Sequelae

2020

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The gut and genital tract microbiota of females represent very complex biological ecosystems that are in continuous communication with each other. The crosstalk between these two ecosystems impacts host physiological, immunological and metabolic homeostasis and vice versa. The vaginal microbiota evolved through a continuous translocation of species from the gut to the vagina or through a motherto-child transfer during delivery. Though the organisms retain their physio-biochemical characteristics while in the vagina, the immune responses elicited by their metabolic byproducts appear to be at variance with those in the gut. This has critical implications for the gynecological, reproductive as well as overall wellbeing of the host and by extension her offspring. The homeostatic and immunomodulatory effects of the bacterial fermentation products (short chain fatty acids, SCFAs) in the gut are better understood compared to the genital tract. While gut SCFAs prevent a leakage of bacteria and bacterial products from the gut in to circulation (leaky gut) and consequent systemic inflammation (anti-inflammatory/protective role); they have been shown to exhibit dysbiotic and proinflammatory effects in the genital tract that can lead to unfavorable gynecological and reproductive outcomes. Therefore, this review was conceived to critically examine the correlation between the female gut and genital tract microbiota. Secondly, we explored the metabolic patterns of the respective microbiota niches; and thirdly, we described the diverse effects of products of bacterial fermentation on immunological responses in the vaginal and rectal ecosystems.

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Association between the cervicovaginal microbiome, BRCA1 mutation status, and risk of ovarian cancer: a case-control study

Cited by 119 publications

References 32 publications

An economical Nanopore sequencing assay for human papillomavirus (HPV) genotyping

An economical Nanopore sequencing assay for human papillomavirus (HPV) genotyping

Non-Surgical Cancer Risk Reduction in BRCA1 Mutation Carriers: Disabling the Remote Control

Female Gut and Genital Tract Microbiota-Induced Crosstalk and Differential Effects of Short-Chain Fatty Acids on Immune Sequelae

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