Salivary Microbiome Profiling of HPV+ and HPV− Oropharyngeal Head and Neck Cancer Patients Undergoing Durvalumab Immunotherapy Suggests Prevotella melaninogenica and Veillonella atypica as Key Players: A Pilot Study
Simple Summary
Abstract
1. Introduction
2. Methods
2.1. Patient Recruitment and Treatment
2.2. Saliva Sample Collection
2.3. Bacterial DNA Isolation and 16S Bacterial Taxa Identification
2.4. Statistical Analyses
2.4.1. α-Diversity
2.4.2. β-Diversity
2.4.3. Linear Decomposition Model (LDM) Analysis
2.4.4. Receiver Operating Characteristic Curves
3. Results
3.1. α- and β-Diversity
3.2. LDM Analysis
3.3. Mann–Whitney U-Tests
3.4. MaAsLin2 and ROC Analysis
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Timepoint Comparisons | Samples | Taxa | Samples | Taxa |
---|---|---|---|---|
A | BCD | |||
A vs. BCD | 17 | 373 | 47 | 391 |
AB | CD | |||
AB vs. CD | 34 | 400 | 30 | 370 |
A | B | |||
A vs. B | 17 | 373 | 17 | 361 |
A | C | |||
A vs. C | 17 | 373 | 17 | 347 |
A | D | |||
A vs. D | 13 | 373 | 13 | 336 |
HPV comparisons | HPV+ samples | Taxa | HPV− samples | Taxa |
HPV+ vs. HPV− all timepoints | 18 | 299 | 46 | 376 |
HPV+ vs. HPV− A only | 5 | 281 | 12 | 326 |
HPV+ vs. HPV− B only | 5 | 234 | 12 | 335 |
HPV+ vs. HPV− C only | 5 | 247 | 12 | 317 |
HPV+ vs. HPV− D only | 3 | 217 | 10 | 314 |
Taxa a | Raw p-Value b | Adjusted p-Value c | Population Level Mean RA d | Direction e |
---|---|---|---|---|
Actinomyces massiliensis | 8.33 × 10−5 | 0.00251 | 0.000105 | - |
Actinomyces sp4769 | 8.33 × 10−5 | 0.00251 | 0.000363 | - |
Corynebacterium durum | 8.33 × 10−5 | 0.00251 | 0.000305 | - |
Gemella sanguinis | 8.33 × 10−5 | 0.00251 | 0.0059 | - |
NA sp31630 | 8.33 × 10−5 | 0.00251 | 0.000742 | - |
Oribacterium sinus | 8.33 × 10−5 | 0.00251 | 0.00664 | - |
NA sp37035 | 8.33 × 10−5 | 0.00251 | 0.00196 | - |
Veillonella atypica | 8.33 × 10−5 | 0.00251 | 0.0252 | - |
Leptotrichia trevisanii | 8.33 × 10−5 | 0.00251 | 0.000311 | - |
Actinomyces naeslundii | 0.000167 | 0.00377 | 0.000376 | - |
Prevotella melaninogenica | 0.000167 | 0.00377 | 0.0475 | - |
Streptococus dentisani mitis | 0.000167 | 0.00377 | 0.00205 | - |
Selenomonas noxia | 0.000333 | 0.00696 | 0.00114 | - |
Streptococcus australis | 0.000417 | 0.00754 | 0.000792 | - |
Streptococcus constellatus intermedius | 0.000417 | 0.00754 | 0.000797 | - |
Selenomons p37072 | 0.000583 | 0.00989 | 0.000208 | - |
Gardnerella vaginalis | 0.000917 | 0.0131 | 0.000172 | - |
Howardella sp32242 | 0.000917 | 0.0131 | 0.000299 | + |
NA sp35322 | 0.000917 | 0.0131 | 0.00116 | - |
Corynebacterium matruchotii | 0.0015 | 0.0194 | 0.000799 | - |
Rothia aeria | 0.0015 | 0.0194 | 0.000266 | - |
Streptococcus infantis parasanguinis | 0.00175 | 0.0216 | 0.000434 | - |
Atopobium parvulum | 0.00208 | 0.0246 | 0.00835 | - |
Alloprevotella sp13512 sp13518 | 0.0025 | 0.0258 | 0.000126 | - |
NA sp31584 | 0.0025 | 0.0258 | 1.42 × 10−5 | - |
Leptotrichia hofstadii | 0.0025 | 0.0258 | 7.64 × 10−5 | - |
NA sp4820 | 0.00258 | 0.0258 | 0.000131 | - |
Prevotella scopos | 0.00267 | 0.0258 | 0.000237 | - |
NA sp35348 | 0.00283 | 0.0261 | 0.000904 | - |
Alloprevotella sp13517 | 0.00308 | 0.0261 | 0.000138 | - |
Lactobacillus iners | 0.00308 | 0.0261 | 3.94 × 10−5 | - |
Streptococcus infantis sanguinis | 0.00308 | 0.0261 | 0.000365 | - |
Peptoclostridium sp34351 | 0.00342 | 0.0281 | 1.12 × 10−5 | - |
Prevotella nanceiensis | 0.00383 | 0.0297 | 0.000806 | - |
Neisseria sp49954 | 0.00383 | 0.0297 | 0.000181 | - |
Streptococcus cristatus | 0.00425 | 0.032 | 0.00611 | - |
Leptotrichia buccalis hofstadii | 0.0045 | 0.0322 | 2.98 × 10−5 | - |
Porphyromonas gingivalis | 0.00458 | 0.0322 | 0.000156 | - |
NA sp31682 | 0.00475 | 0.0322 | 0.000332 | - |
NA sp37532 | 0.00475 | 0.0322 | 0.000675 | - |
Streptococcus lactarius parasanguinis | 0.005 | 0.0331 | 0.000369 | - |
Porphyromonas endodontalis | 0.00525 | 0.0339 | 0.000799 | - |
Lachnoanaerobaculum orale | 0.00567 | 0.0349 | 0.0031 | - |
Leptotrichia sp37519 | 0.00567 | 0.0349 | 0.00654 | - |
Bacteroides sp12340 | 0.006 | 0.0354 | 0.000204 | - |
NA sp66013 | 0.006 | 0.0354 | 0.00328 | - |
Streptococcus sp30088 | 0.00617 | 0.0355 | 0.000304 | - |
Lactobacillus fermentum | 0.00642 | 0.0355 | 0.0132 | + |
NA sp19816 | 0.0065 | 0.0355 | 6.1 × 10−5 | - |
Stomatobaculum longum | 0.00658 | 0.0355 | 0.00447 | - |
NA sp32067 | 0.00667 | 0.0355 | 8.71 × 10−5 | - |
Selenomonas sp37074 | 0.0075 | 0.0391 | 0.000275 | - |
Mogibacterium vescum | 0.00825 | 0.0422 | 0.00321 | - |
Streptococcus intermedius | 0.00875 | 0.044 | 0.00114 | - |
Actinomyces johnsonii | 0.00925 | 0.0449 | 0.000187 | - |
Actinomyces gerencseriae | 0.00927 | 0.0449 | 0.000272 | - |
Neisseria sicca | 0.00973 | 0.0463 | 2.06 × 10−5 | - |
Fusobacterium periodonticum | 0.0111 | 0.0516 | 0.00707 | - |
Scardovia wiggsiae | 0.0112 | 0.0516 | 0.000256 | - |
Moryella sp33027 | 0.0118 | 0.0533 | 8.17 × 10−6 | - |
Desulfovibrio sp52730 | 0.0136 | 0.0606 | 7.93 × 10−6 | - |
Streptococcus infantis oralis sanguinis | 0.0144 | 0.0629 | 0.000125 | - |
Lactobacillus gasseri | 0.0153 | 0.0654 | 0.0286 | + |
Streptococcus sobrinus | 0.0154 | 0.0654 | 3.92 × 10−5 | - |
Actinomyces oris | 0.0168 | 0.0703 | 0.00258 | - |
Campylobacter concisus | 0.0174 | 0.0712 | 0.00288 | - |
Kocuria kristinae | 0.0177 | 0.0712 | 2.71 × 10−5 | - |
Porphyromonas sp13376 | 0.0178 | 0.0712 | 0.00434 | - |
Neisseria flavescens mucosa | 0.0185 | 0.0717 | 0.000108 | - |
NA sp66034 | 0.0185 | 0.0717 | 5.73 × 10−5 | - |
Streptococcus infantis oralis parasanguinis | 0.0188 | 0.072 | 2.62 × 10−5 | - |
Actinomyces sp4767 | 0.0204 | 0.0766 | 7.17 × 10−5 | - |
Lachnoanaerobaculum umeaense | 0.0206 | 0.0766 | 0.000172 | - |
NA sp13878 | 0.0214 | 0.0785 | 0.000492 | - |
Prevotella dentalis | 0.022 | 0.0796 | 0.000268 | - |
Mogibacterium neglectum vescum | 0.0236 | 0.0843 | 5.2 × 10−5 | - |
Actinomyces dentalis orihominis | 0.025 | 0.0861 | 0.000735 | - |
Lacobacillus crispatus | 0.025 | 0.0861 | 4.82 × 10−5 | - |
Prevotella jejuni melaninogenica | 0.0254 | 0.0861 | 1.94 × 10−6 | - |
NA sp32913 | 0.0254 | 0.0861 | 2.09 × 10−6 | - |
Selenomonas artemidis | 0.026 | 0.0871 | 0.000533 | - |
Alloscardovia omnicolens | 0.0265 | 0.0877 | 0.00125 | - |
Lactobacillus rhamnosus | 0.0275 | 0.0896 | 0.00137 | + |
NA sp31126 | 0.0278 | 0.0896 | 8.06 × 10−5 | - |
Prevotella pleuritidis | 0.0285 | 0.091 | 0.000359 | + |
Musa textilis | 0.031 | 0.0975 | 3.09 × 10−6 | - |
Actionmyces dentalis orihominis sp4753 | 0.0312 | 0.0975 | 0.000164 | - |
Feature a | Effect Size b | Standard Error c | p-Value d |
---|---|---|---|
Actinomyces sp4769 | 3.650674 | 0.313348 | 6.19 × 10−17 |
Corynebacterium durum | 2.671046 | 0.37376 | 1.53 × 10−9 |
NA sp37035 | 4.475144 | 0.618709 | 1.09 × 10−9 |
Leptotrichia trevisanii | 2.324937 | 0.366879 | 3.54 × 10−8 |
Actinomyces massiliensis | 1.709514 | 0.299844 | 4.03 × 10−7 |
Oribacterium sinus | 2.070299 | 0.369039 | 5.68 × 10−7 |
Gemella sanguinis | 4.292765 | 0.820719 | 2.34 × 10−6 |
Actinomyces naeslundii | 2.28903 | 0.46307 | 6.70 × 10−6 |
NA sp31630 | 2.821748 | 0.570336 | 6.59 × 10−6 |
Streptococcus australis | 2.233489 | 0.512714 | 5.36 × 10−5 |
Selenomonas noxia | 2.720517 | 0.627544 | 5.76 × 10−5 |
Gardnerella vaginalis | 1.471213 | 0.351596 | 9.64 × 10−5 |
Porphyromonas endodontalis | 2.49114 | 0.59271 | 9.05 × 10−5 |
Streptococcus dentisani mitis | 3.326154 | 0.78488 | 8.04 × 10−5 |
Howardella sp32242 | −2.15071 | 0.510985 | 8.87 × 10−5 |
NA sp35348 | 2.716136 | 0.682613 | 0.000192 |
Leptotrichia sp37519 | 3.237624 | 0.818936 | 0.000209 |
Rothia aeria | 1.271655 | 0.325619 | 0.000245 |
Streptococcus constellatus intermedius | 2.421821 | 0.630378 | 0.000301 |
Selenomonas sp37072 | 1.689886 | 0.44746 | 0.000372 |
Leptotrichia wadei | 3.302522 | 0.876053 | 0.00038 |
Streptococcus cristatus | 2.164533 | 0.578395 | 0.000415 |
Veillonella atypica | 3.225777 | 0.864835 | 0.000432 |
Streptococcus infantis sanguinis | 1.654843 | 0.445433 | 0.000453 |
Lactobacillus fermentum | −3.49841 | 0.968022 | 0.000625 |
Actinomyces gerencseriae | 1.78548 | 0.509526 | 0.000881 |
Actinomyces oris | 2.590536 | 0.737814 | 0.000862 |
Corynebacterium matruchotii | 1.831948 | 0.545537 | 0.001379 |
Actinomyces johnsonii | 1.35515 | 0.408988 | 0.001578 |
Scardovia wiggsiae | 1.531826 | 0.464295 | 0.001647 |
Haemophilus parainfluenzae | 2.849527 | 0.877864 | 0.001931 |
Stomatobaculum longum | 1.97897 | 0.625083 | 0.002446 |
Actinomyces dentalis orihominis | 1.923268 | 0.613446 | 0.002677 |
Streptococcus infantis | 2.39051 | 0.763754 | 0.002718 |
NA sp4820 | 1.060871 | 0.342166 | 0.002961 |
NA sp31682 | 1.59527 | 0.515906 | 0.003033 |
Leptotrichia hofstadii | 0.882742 | 0.284776 | 0.002967 |
Lachnoanaerobaculum orale | 1.992016 | 0.649435 | 0.003259 |
Streptococcus intermedius | 1.966111 | 0.646455 | 0.003511 |
NA sp37033 | 1.753744 | 0.576544 | 0.003506 |
Streptococcus sp30088 | 0.995509 | 0.329461 | 0.003714 |
NA sp35322 | 2.10789 | 0.697398 | 0.003705 |
Alloscardovia omnicolens | 2.002643 | 0.667595 | 0.003953 |
Atopobium parvulum | 1.44814 | 0.491433 | 0.004592 |
bacterium enrichment | 1.77799 | 0.602781 | 0.004555 |
Streptococcus lactarius parasanguinis | 1.392599 | 0.472742 | 0.004605 |
Prevotella denticola | 1.967924 | 0.674051 | 0.004957 |
Campylobacter concisus | 1.702208 | 0.58613 | 0.005175 |
Rothia dentocariosa | 1.973771 | 0.681746 | 0.005306 |
Lactobacillus gasseri | −3.21474 | 1.141644 | 0.006604 |
Streptococcus gordonii | 2.114021 | 0.765832 | 0.00768 |
Prevotella buccae | −0.8825 | 0.321439 | 0.007996 |
NA sp19816 | 0.830921 | 0.308142 | 0.009117 |
Prevotella dentalis | 1.337058 | 0.513677 | 0.011672 |
Pseudoramibacter alactolyticus | −1.22081 | 0.470152 | 0.011866 |
Fusobacterium periodonticum | 2.455544 | 0.9578 | 0.012923 |
Veillonella sp37198 | −0.96167 | 0.376411 | 0.013224 |
Species with AUC > 0.800 (n = 10) a | p-Value b | AUC c | Threshold d | SE e | SP f | A g | BCDavg h | FC i | BCD Increase or Decrease j | HPV− k | HPV+ l | FC m | HPV+ Higher or Lower n |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Actinomyces sp4769 | <0.0001 | 0.932 | 0.000327 | 0.833 | 1 | 0.0044 | 0.0063 | 0.4201 | Increase | 0.0009 | 0.0223 | 23.8868 | Higher |
NA sp37035 | <0.0001 | 0.908 | 0.001 | 1 | 0.826 | 0.0490 | 0.0254 | −0.4828 | Decrease | 0.0363 | 0.0888 | 1.4429 | Higher |
Gemella sanguinis | <0.0001 | 0.903 | 0.003522 | 1 | 0.696 | 0.0940 | 0.0812 | −0.1361 | Decrease | 0.1458 | 0.2300 | 0.5776 | Higher |
Oribacterium sinus | <0.0001 | 0.89 | 0.007 | 0.778 | 0.87 | 0.1442 | 0.0931 | −0.3549 | Decrease | 0.1791 | 0.2444 | 0.3645 | Higher |
Leptotrichia trevisanii | <0.0001 | 0.837 | 0 | 0.778 | 0.87 | 0.0048 | 0.0050 | 0.0492 | Increase | 0.0019 | 0.0179 | 8.2892 | Higher |
Actinomyces naeslundii | <0.0001 | 0.831 | 0.00017 | 0.889 | 0.761 | 0.0043 | 0.0066 | 0.5226 | Increase | 0.0118 | 0.0121 | 0.0247 | Higher |
Veillonella atypica | <0.0001 | 0.831 | 0.02 | 1 | 0.652 | 0.3840 | 0.4079 | 0.0622 | Increase | 0.8490 | 0.7587 | −0.1063 | Lower |
NA sp31630 | <0.0001 | 0.818 | 0.00019 | 0.889 | 0.696 | 0.0128 | 0.0115 | −0.0979 | Decrease | 0.0157 | 0.0316 | 1.0059 | Higher |
Corynebacterium durum | <0.0001 | 0.813 | 0.000196 | 0.667 | 0.957 | 0.0037 | 0.0053 | 0.4249 | Increase | 0.0017 | 0.0178 | 9.3332 | Higher |
Actinomyces massiliensis | <0.0001 | 0.812 | 0 | 0.722 | 0.891 | 0.0015 | 0.0017 | 0.1555 | Increase | 0.0017 | 0.0050 | 1.9731 | Higher |
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Mougeot, J.-L.; Beckman, M.; Kooshki, M.; Neuberger, J.; Shukla, K.; Furdui, C.; Bahrani Mougeot, F.; Porosnicu, M. Salivary Microbiome Profiling of HPV+ and HPV− Oropharyngeal Head and Neck Cancer Patients Undergoing Durvalumab Immunotherapy Suggests Prevotella melaninogenica and Veillonella atypica as Key Players: A Pilot Study. Cancers 2025, 17, 452. https://doi.org/10.3390/cancers17030452
Mougeot J-L, Beckman M, Kooshki M, Neuberger J, Shukla K, Furdui C, Bahrani Mougeot F, Porosnicu M. Salivary Microbiome Profiling of HPV+ and HPV− Oropharyngeal Head and Neck Cancer Patients Undergoing Durvalumab Immunotherapy Suggests Prevotella melaninogenica and Veillonella atypica as Key Players: A Pilot Study. Cancers. 2025; 17(3):452. https://doi.org/10.3390/cancers17030452
Chicago/Turabian StyleMougeot, Jean-Luc, Micaela Beckman, Mitra Kooshki, Justin Neuberger, Kirtikar Shukla, Cristina Furdui, Farah Bahrani Mougeot, and Mercedes Porosnicu. 2025. "Salivary Microbiome Profiling of HPV+ and HPV− Oropharyngeal Head and Neck Cancer Patients Undergoing Durvalumab Immunotherapy Suggests Prevotella melaninogenica and Veillonella atypica as Key Players: A Pilot Study" Cancers 17, no. 3: 452. https://doi.org/10.3390/cancers17030452
APA StyleMougeot, J.-L., Beckman, M., Kooshki, M., Neuberger, J., Shukla, K., Furdui, C., Bahrani Mougeot, F., & Porosnicu, M. (2025). Salivary Microbiome Profiling of HPV+ and HPV− Oropharyngeal Head and Neck Cancer Patients Undergoing Durvalumab Immunotherapy Suggests Prevotella melaninogenica and Veillonella atypica as Key Players: A Pilot Study. Cancers, 17(3), 452. https://doi.org/10.3390/cancers17030452