Longitudinal characterization of the tumoral microbiome during radiotherapy in HPV-associated oropharynx cancer

Bahig, Houda; Fuller, Clifton D.; Mitra, Analava; Yoshida-Court, Kyoko; Solley, Travis; Ng, Sweet Ping; Abu-Gheida, Ibrahim; Elgohari, Baher; Delgado, Andrea; Rosenthal, D.I.; Garden, Adam S.; Frank, Steven J.; Reddy, Jay P.; Colbert, Lauren E.; Klopp, Ann H.

doi:10.1016/j.ctro.2020.11.007

Cited by 10 publications

(6 citation statements)

References 40 publications

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“…[14][15][16][17][18][19][20][21] Tonsil cancer occurs only in adults and the few available datasets on the adult microbiome in tonsil cancer have not considered the inclusion of control cohorts. 22,23 Here, we have analyzed the tonsillar crypt microbiome from two different patient cohorts. We have enrolled patients with HR-HPV-positive squamous cell carcinoma of the tonsil and have established a control cohort of adult patients with obstructive sleep apnea (OSA).…”

Section: Introductionmentioning

confidence: 99%

Distinct microbial communities colonize tonsillar squamous cell carcinoma

et al. 2021

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Squamous cell carcinoma of the tonsil is one of the most frequent cancers of the oropharynx. The escalating rate of tonsil cancer during the last decades is associated with the increase of high riskhuman papilloma virus (HR-HPV) infections. While the microbiome in oropharyngeal malignant diseases has been characterized to some extent, the microbial colonization of HR-HPV-associated tonsil cancer remains largely unknown. Using 16S rRNA gene amplicon sequencing, we have characterized the microbiome of human palatine tonsil crypts in patients suffering from HR-HPV-associated tonsil cancer in comparison to a control cohort of adult sleep apnea patients. We found an increased abundance of the phyla Firmicutes and Actinobacteria in tumor patients, whereas the abundance of Spirochetes and Synergistetes was significantly higher in the control cohort. Furthermore, the accumulation of several genera such as Veillonella, Streptococcus and Prevotella_7 in tonsillar crypts was associated with tonsil cancer. In contrast, Fusobacterium, Prevotella and Treponema_2 were enriched in sleep apnea patients. Machine learning-based bacterial species analysis indicated that a particular bacterial composition in tonsillar crypts is tumor-predictive. Species-specific PCR-based validation in extended patient cohorts confirmed that differential abundance of Filifactor alocis and Prevotella melaninogenica is a distinct trait of tonsil cancer. This study shows that tonsil cancer patients harbor a characteristic microbiome in the crypt environment that differs from the microbiome of sleep apnea patients on all phylogenetic levels. Moreover, our analysis indicates that profiling of microbial communities in distinct tonsillar niches provides microbiome-based avenues for the diagnosis of tonsil cancer.

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Section: Introductionmentioning

confidence: 99%

Distinct microbial communities colonize tonsillar squamous cell carcinoma

et al. 2021

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“…This disruptive impact can vary based on the duration and dosages of the therapy. A progressively reducing alpha diversity of tumor microbiome over the course of radiotherapy in HPV-associated oropharynx cancer was infact recently reported [ 28 ]. A general shift in microbial composition attributed to the perioperative procedures like antibiotic administration, mechanical bowel preparation and dietary restrictions can also add to the confounders needing accommodation in modelling the tumor associated ecosystem [ 127 ].…”

Section: Limitations and Considerationsmentioning

confidence: 86%

“…A recent report highlighting high tumor-bacterial diversity in advanced stage papillary thyroid carcinoma (PTC) lesions, as compared to mild lesions adds to the corroboration [ 22 ]. Evidence in support of a significantly perturbed microbial community in cancer associated tissue across various tumor types, as compared to matched and unmatched healthy samples, are rather well reported [ 10 , 22 , 28 , 122 ].…”

Section: Limitations and Considerationsmentioning

confidence: 99%

Environmental insults and compensative responses: when microbiome meets cancer

Nagpal

Mande

2023

Discov Onc

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Tumor microenvironment has recently been ascribed a new hallmark—the polymorphic microbiome. Accumulating evidence regarding the tissue specific territories of tumor-microbiome have opened new and interesting avenues. A pertinent question is regarding the functional consequence of the interface between host-microbiome and cancer. Given microbial communities have predominantly been explored through an ecological perspective, it is important that the foundational aspects of ecological stress and the fight to ‘survive and thrive’ are accounted for tumor-micro(b)environment as well. Building on existing evidence and classical microbial ecology, here we attempt to characterize the ecological stresses and the compensative responses of the microorganisms inside the tumor microenvironment. What insults would microbes experience inside the cancer jungle? How would they respond to these insults? How the interplay of stress and microbial quest for survival would influence the fate of tumor? This work asks these questions and tries to describe this underdiscussed ecological interface of the tumor and its microbiota. It is hoped that a larger scientific thought on the importance of microbial competition sensing vis-à-vis tumor-microenvironment would be stimulated.

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“…A previous study by Bahig et al (2020) investigating the tumor microenvironment of HPV-associated SCC patients, determined an increased abundance of Leptotrichia genus in oral samples at baseline which declined over the course of radiation. This study was positively classified in our LitSuggest analysis ( Table 3 ).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, few studies investigated multiple primary tumor sites in SCC patients. Most identified studies in our analysis focused on investigating oropharyngeal SCC ( Guerrero-Preston et al, 2016 ; Wolf et al, 2017 ; Lim et al, 2018 ; Bahig et al, 2020 ; Gougousis et al, 2021 ; Oliva et al, 2021 ; Zakrzewski et al, 2021 ). Only two positively classified articles were found to characterize the microbiome in the tonsil of SCC patients ( Table 3 ; De Martin et al, 2021 ; Rajasekaran et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Haemophilus pittmaniae and Leptotrichia spp. Constitute a Multi-Marker Signature in a Cohort of Human Papillomavirus-Positive Head and Neck Cancer Patients

et al. 2022

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ObjectivesHuman papillomavirus (HPV) is a known etiological factor of oropharyngeal head and neck cancer (HNC). HPV positivity and periodontal disease have been associated with higher HNC risk, suggesting a role for oral bacterial species. Our objective was to determine oral microbiome profiles in HNC patients (HPV-positive and HPV-negative) and in healthy controls (HC).MethodsSaliva samples and swabs of buccal mucosa, supragingival plaque, and tongue were collected from HNC patients (N = 23 patients, n = 92 samples) before cancer therapy. Next-generation sequencing (16S-rRNA gene V3–V4 region) was used to determine bacterial taxa relative abundance (RA). β-Diversities of HNC HPV+ (N = 16 patients, n = 64 samples) and HNC HPV– (N = 7 patients, n = 28 samples) groups were compared using PERMANOVA (pMonte Carlo < 0.05). LEfSe discriminant analysis was performed to identify differentiating taxa (Log LDA > 2.0). RA differences were analyzed by Mann–Whitney U-test (α = 0.05). CombiROC program was used to determine multi-marker bacterial signatures. The Microbial Interaction Network Database (MIND) and LitSuggest online tools were used for complementary analyses.ResultsHNC vs. HC and HNC HPV+ vs. HNC HPV– β-diversities differed significantly (pMonte Carlo < 0.05). Streptococcus was the most abundant genus for HNC and HC groups, while Rothia mucilaginosa and Haemophilus parainfluenzae were the most abundant species in HNC and HC patients, respectively, regardless of antibiotics treatment. LEfSe analysis identified 43 and 44 distinctive species for HNC HPV+ and HNC HPV– groups, respectively. In HNC HPV+ group, 26 periodontal disease-associated species identified by LefSe had a higher average RA compared to HNC HPV– group. The significant species included Alloprevotella tannerae, Fusobacterium periodonticum, Haemophilus pittmaniae, Lachnoanaerobaulum orale, and Leptotrichia spp. (Mann–Whitney U-test, p < 0.05). Of 43 LEfSe-identified species in HPV+ group, 31 had a higher RA compared to HPV– group (Mann–Whitney U-test, p < 0.05). MIND analysis confirmed interactions between Haemophilus and Leptotrichia spp., representing a multi-marker signature per CombiROC analysis [area under the curve (AUC) > 0.9]. LitSuggest correctly classified 15 articles relevant to oral microbiome and HPV status.ConclusionOral microbiome profiles of HNC HPV+ and HNC HPV– patients differed significantly regarding periodontal-associated species. Our results suggest that oral bacterial species (e.g., Leptotrichia spp.), possessing unique niches and invasive properties, coexist with HPV within HPV-induced oral lesions in HNC patients. Further investigation into host–microbe interactions in HPV-positive HNC patients may shed light into cancer development.

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Longitudinal characterization of the tumoral microbiome during radiotherapy in HPV-associated oropharynx cancer

Cited by 10 publications

References 40 publications

Distinct microbial communities colonize tonsillar squamous cell carcinoma

Distinct microbial communities colonize tonsillar squamous cell carcinoma

Environmental insults and compensative responses: when microbiome meets cancer

Haemophilus pittmaniae and Leptotrichia spp. Constitute a Multi-Marker Signature in a Cohort of Human Papillomavirus-Positive Head and Neck Cancer Patients

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