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. 2022 Jan 18;12:794546. doi: 10.3389/fmicb.2021.794546

TABLE 3.

LitSuggest positively classified articles (n = 15) involving HPV and the oral microbiome in HNC patients.

Yeara Authorb Purpose of studyc Findingsd PMIDe
2021 Gougousis et al., 2021 (review) Review the significance of biomarkers based on epigenetics and microbiome profile in the diagnosis of HPV-related OSCC. Streptococcus salivarius (+), Streptococcus gordonii (+), Gemella haemolysans, Gemella morbillorum (+), Johnsonella ignava (+), and Streptococcus parasanguinis (+) highly associated with tumor site. Gemella adiacens (+) association with non-tumor site. HPV+ correlation between the genera Haemophilus and Gemella in oral cavity cancer. Actinomyces (+), Parvimonas (+), Selenomonas (+), and Prevotella (+) in OCC compared to OPC. Corynebacterium (+) and Kingella (+) are associated with decreased risk of oral cancer. 33521000
2021 De Keukeleire et al., 2021 (review) Knowledge and biomarkers in HNC-SCC. HPV is a biomarker of HNC-SCC; Lactobacilli (+); Haemophilus (–); Neisseria (–); Gemellaceae (–); Aggregatibacter (–); Streptococci (–); Fusobacteria (+); Fusobacterium nucleatum (+) associated with lower tumor stage 33916646
2021 De Martin et al., 2021 Characterize microbiome of human palatine tonsil crypts in patients with high-risk HPV-associated tonsil cancer compared to sleep apnea controls. Firmicutes (+); Actinobacteria (+); Veillonella (+); Streptococcus (+); Prevotella (+); Filifactor alocis and Prevotella melaninogenica were distinct features of tonsil cancer 34367729
2021 Oliva et al., 2021 Characterize oral and gut microbiome of HPV+ OSCC patients before and after CRT. F. nucleatum (+), G. morbillorum (+), G. haemolysans (+), Leptotrichia hofstadii (+), Selenomonas sputigena (+), and Selenomonas infelix (+) in stage III OSCC 33750907
2021 Rajasekaran et al., 2021 Characterize microbiome in patients with HPV-associated early tonsil SCC compared to benign tonsil specimens. Burkholderia pseudomallei was unique to cancer specimens. Fusobacteria was identified in HPV-associated OSCC patients in tonsil and lymph node specimens. Negative nodes showed signatures for Anaplasma phagocytophilum, Bacillus subtilis, Chlamydia trachomatis, Chlamydophila psittaci, Lactococcus lactis, and Proteus mirabilis 33905914
2021 Shigeishi et al., 2021a Characterize HPV16 DNA prevalence and PD inflammation in older Japanese women. Prevotella intermedia (+), Porphyromonas (+), Veillonella (–), and Prevotella (–) in HPV+ periodontal inflammation 33456534
2021 Shigeishi et al., 2021b (review) Review recent findings of oral HPV infection in relation to periodontitis. HPV localizes to inflammatory periodontal tissue, and periodontal pockets may act as a reservoir for HPV. Smoking is associated with HPV and periodontitis. Carcinogenic HPV and periodontitis may lead to OCC, but HPV E6/E7 has not been fully investigated in patients with periodontitis. Oral HPV prevalence may be associated with periodontitis. 33728046
2021 Zakrzewski et al., 2021 Compare microbial composition, diversity, and specific bacterial phytotypes between HPV+ and HPV– oropharyngeal tumors using saliva, normal tissue, and tumor tissue. Treponema (+) and Spirochaetes (+) were associated with normal tissues of HPV+ patients; Neisseria, Veillonella, Fusobacterium, P. melaninogenica, and Porphyromonas were associated with HPV status (not significant). Fusobacteria (–) in saliva samples (not significant); Leptotrichia (–) in HPV-; Rothia (–) in HPV+ tumor tissues; Atopobium (–) in normal tissue HPV+ patients. 34278648
2020 Bahig et al., 2020 Characterize tumor microenvironment of HPV-associated OSCC with RT +/– cisplatin-based chemotherapy using surface swab of tonsil, base of tongue, and buccal mucosa. Decreased α-diversity over course of treatment. Veillonella (+) and Leptotrichia (+) at tumor site. Actinomyces (–) and Leptotrichia (–) over the course of radiation. Gemella (–) and Streptococcus (–) between baseline and 1 week and returned to baseline at week 5. Veillonella (+) and Topobium (+) at week 5. 33367119
2019 Chowdhry et al., 2019 Explore deep-seated infected granulation tissue removed during periodontal flap surgery procedures for residential bacterial species between HPV+ and HPV– chronic periodontitis patients. Deep-seated granulation tissues showed Firmicutes (+), Proteobacteria (+), and Bacteroidetes (+). Veillonella arula (+), Selenomonas noxia (+), Neisseria oralis (+), P. intermedia (+), Prevotella nigrescens (+), Capnocytophaga ochracea (+) in HPV+ samples. Prevotella (+), Macellibacteroides fermentans (+), Porphyromonas endodontalis (+), Campylobacter rectus (+), Treponema phagedenis (+) in HPV– samples. Pseudoxanthomas kaohsiungensis (+) in females and Desulfobulbus rhabdoformis (+) in males. 31111067
2018 Lim et al., 2018 Characterize the oral microbiome fluctuation associated with OCC and OSCC compared to healthy controls using oral wash samples. Rothia (–), Haemophilus (–), Corynebacterium (–), Paludibacter (–), Porphyromonas (–), Capnocytophaga (–) in OCC and OSCC. Oribacterium (+) in OCC and OSCC. Actinomyces (+), Parvimonas (+), Selenomonas (+), and Prevotella (+) in OCC compared to OSCC. Haemophilus (+), Gemella (+) with HPV+. Actinomyces (+), Actinobacillus (+), Lautropia (+), Fusobacterium (+), Aggregatibacter (+) in high-risk individuals. Panel of bacterial species Rothia, Haemophilus, Corynebacterium, Paludibacter, Porphyromonas, Oribacterium, and Capynocytophaga showed an area under curve of 0.98, sensitivity of 100%, and specificity of 90% 30123780
2018 Tuominen et al., 2018 Investigate the association between HPV infection and microbiome composition in the placenta, uterine cervix, and mouth in women Selenomonas (+), TM7 (+), Megasphaera (+) with HPV+ in oral samples. Haemophilus (+) with HPV– oral samples. Higher richness in HPV+ than HPV– samples. 29955075
2017 Guerrero-Preston et al., 2017 Characterize microbial species in the saliva microbiome and tumor characteristics in HNC-SCC patients. Veillonella dispar (+) in all samples. S. salivarius (+), Streptococcus vestibularis (+) in HNC-SCC samples. Lactobacillus spp. (+), Parvimonas micra (+), Streptococcus mutans (+), and F. nucleatum (+) in salivary HNC-SCC samples. Fusobacterium periodonticum (–), Leptotrichia trevisanii (–), L. hofstadii (–), and Leptotrichia (–) in HNC-SCC compared to controls. Lower diversity in HNC-SCC than controls regardless of HPV status. No significant differences when comparing HPV+ to HPV– saliva HNC-SCC samples with control. F. periodonticum (+) in saliva from HNC-SCC patients. Lactobacillus rhamnosus (+), Lactobacillus salivarius (+), Lactobacillus vaginalis (+), Lactobacillus reuteri (+), Lactobacillus fermentum (+), Lactobacillus johnsonii (+), Lactobacillus gasseri (+) in subset of HNC-SCC samples from Johns Hopkins University. Lactobacillus was 710 time higher, and L. vaginalis was 52 times higher in HNC-SCC samples compared to controls. 29340028
2017 Wolf et al., 2017 Compare oral salivary microbiome samples of patients with OCC and OSCC vs. healthy controls. Shannon index found higher diversity in tumor patients but was not significant. Highest LEfSe LDA was from Proteobacteria. Prevotella (+), Haemophilus (+), Neisseria (+), Streptococcus (+), and Veillonella (+) in healthy controls. Actinomyces (+), Schwartzia (+), Treponema (+), and Selenomonas (+) in HNC-SCC patients. HPV+ patients demonstrated normal microbiome compared to healthy controls. 28725009
2016 Guerrero-Preston et al., 2016 Compare saliva microbiome from HPV+ and HPV–, OCC, OSCC, and normal cavity epithelium. Firmicutes (+), Proteobacteria (+), Bacteroidetes (+), Actinobacteria (–), and Fusobacteria (–) prior to surgery. At lower levels Streptococcus (+), Prevotella (+), Haemophilus (+), Lactobacillus (+), Veillonella (+), Citrobacter (–), Kingella (–) prior to surgery. HNC-SCC patients exhibited lower richness and diversity compared to controls. Streptococcus, Dialister, and Veillonella were able to discriminate tumor from control samples. Neisseria (–), Aggregatibacter (–), Haemophilus (–), and Leptotrichia (–) in tumor samples. Enterobacteriaceae and Oribacterium discriminate OCC from OSCC and normal samples. Gemellaceae (+) and Leuconostoc (+) only observed in HPV+ samples. α-diversity was reduced post-surgery. 27259999

Using Pythonv3.6.2 program, 203 PubMed articles were retrieved for classification from the model that matched the search terms “HPV” and “microbiome.” LitSuggest program determined 36 articles to be positively associated with “HPV” and “oral microbiome.” Manual validation of the 36 positively classified articles resulted in 21 articles being discarded. The remaining 15 articles were manually validated as positively classified articles that relate to HNC, HPV, and the oral microbiome.

aYear of publication.

bFirst listed author.

cPurpose or outcomes explored during the study.

dFindings/results of the study.

ePubMed ID. HPV, human papillomavirus; HNC, head and neck cancer; OSCC, oral squamous cell carcinoma; OCC, oral cavity cancer; OPC, oropharyngeal cancer; SCC, squamous cell carcinoma; CRT, chemoradiotherapy; PD, Parkinson’s disease; LDA, linear discriminant analysis; RT, radiotherapy.

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