{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T13:23:57Z","timestamp":1790429037350,"version":"4.1.0"},"reference-count":134,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2019,7,13]],"date-time":"2019-07-13T00:00:00Z","timestamp":1562976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Every year nearly half a million new cases of cervix cancer are diagnosed worldwide, making this malignancy the fourth commonest cancer in women. In 2018, more than 270,000 women died of cervix cancer globally with 85% of them being from developing countries. The majority of these cancers are caused by the infection with carcinogenic strains of human papillomavirus (HPV), which is also causally implicated in the development of other malignancies, including cancer of the anus, penis cancer and head and neck cancer. HPV is by far the most common sexually transmitted infection worldwide, however, most infected people do not develop cancer and do not even have a persistent infection. The development of highly effective HPV vaccines against most common high-risk HPV strains is a great medical achievement of the 21st century that could prevent up to 90% of cervix cancers. In this article, we review the current understanding of the balanced virus-host interaction that can lead to either virus elimination or the establishment of persistent infection and ultimately malignant transformation. We also highlight the influence of certain factors inherent to the host, including the immune status, genetic variants and the coexistence of other microbe infections and microbiome composition in the dynamic of HPV infection induced carcinogenesis.<\/jats:p>","DOI":"10.3390\/microorganisms7070199","type":"journal-article","created":{"date-parts":[[2019,7,15]],"date-time":"2019-07-15T04:55:27Z","timestamp":1563166527000},"page":"199","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["The Host-Microbe Interplay in Human Papillomavirus-Induced Carcinogenesis"],"prefix":"10.3390","volume":"7","author":[{"given":"Rei","family":"Wakabayashi","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Kindai University, Osaka-Sayama, Osaka 589-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Nakahama","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Kindai University, Osaka-Sayama, Osaka 589-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viet","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Faculty of Medical technology, Hanoi Medical University, Ton That Tung 1, DongDa, Hanoi 100-000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1794-6666","authenticated-orcid":false,"given":"J. Luis","family":"Espinoza","sequence":"additional","affiliation":[{"name":"Department of Hematology and Rheumatology, Faculty of Medicine, Kindai University, Osaka-Sayama, Osaka 589-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,7,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Gravitt, P.E., and Winer, R.L. (2017). Natural history of hpv infection across the lifespan: Role of viral latency. Viruses, 9.","DOI":"10.3390\/v9100267"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.humimm.2009.10.009","article-title":"Activating killer cell immunoglobulin-like receptors 3ds1 and 2ds1 protect against developing the severe form of recurrent respiratory papillomatosis","volume":"71","author":"Bonagura","year":"2010","journal-title":"Hum. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"372","DOI":"10.2119\/molmed.2014.00098","article-title":"Decreased langerhans cell responses to il-36\u03b3: Altered innate immunity in patients with recurrent respiratory papillomatosis","volume":"20","author":"DeVoti","year":"2014","journal-title":"Mol. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1590\/0100-3984.2014.0002","article-title":"Ultrasound scan as a potential source of nosocomial and crossinfection: A literature review","volume":"48","author":"Miyague","year":"2015","journal-title":"Radiol. Bras."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2896","DOI":"10.3389\/fmicb.2018.02896","article-title":"Involvement of human papillomaviruses in cervical cancer","volume":"9","author":"Wang","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1136\/sextrans-2018-053606","article-title":"Systematic review and evidence synthesis of non-cervical human papillomavirus-related disease health system costs and quality of life estimates","volume":"95","author":"Ong","year":"2019","journal-title":"Sex. Transm. Infect."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Kobayashi, K., Hisamatsu, K., Suzui, N., Hara, A., Tomita, H., and Miyazaki, T. (2018). A review of hpv-related head and neck cancer. J. Clin. Med., 7.","DOI":"10.3390\/jcm7090241"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"14667","DOI":"10.1038\/srep14667","article-title":"Worldwide prevalence of human papillomavirus and relative risk of prostate cancer: A meta-analysis","volume":"5","author":"Yang","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.lungcan.2013.10.002","article-title":"Human papilloma virus in non-small cell lung cancer in never smokers: A systematic review of the literature","volume":"83","author":"Hasegawa","year":"2014","journal-title":"Lung Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e2015052","DOI":"10.4178\/epih\/e2015052","article-title":"Human papillomavirus infection and risk of lung cancer in never-smokers and women: An \u2018adaptive\u2019 meta-analysis","volume":"37","author":"Bae","year":"2015","journal-title":"Epidemiol. Health"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1158\/1055-9965.EPI-13-0666","article-title":"Characterizing the temporal dynamics of human papillomavirus DNA detectability using short-interval sampling","volume":"23","author":"Liu","year":"2014","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"198","DOI":"10.2174\/1874357901206010198","article-title":"Evidence and impact of human papillomavirus latency","volume":"6","author":"Gravitt","year":"2012","journal-title":"Open Virol. J."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Amb\u00fchl, L.M.M., Villadsen, A.B., Baandrup, U., Dybk\u00e6r, K., and S\u00f8rensen, S. (2017). Hpv16 e6 and e7 upregulate interferon-induced antiviral response genes isg15 and ifit1 in human trophoblast cells. Pathogens, 6.","DOI":"10.3390\/pathogens6030040"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Shanmugasundaram, S., and You, J. (2017). Targeting persistent human papillomavirus infection. Viruses, 9.","DOI":"10.3390\/v9080229"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2624","DOI":"10.3390\/v5112624","article-title":"Role of innate immunity against human papillomavirus (hpv) infections and effect of adjuvants in promoting specific immune response","volume":"5","author":"Lamoyi","year":"2013","journal-title":"Viruses"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Xi, J., Chen, J., Xu, M., Yang, H., Luo, J., Pan, Y., Wang, X., Qiu, L., Yang, J., and Sun, Q. (2017). Genetic variability and functional implication of the long control region in hpv-16 variants in southwest china. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0182388"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Campos, S.K. (2017). Subcellular trafficking of the papillomavirus genome during initial infection: The remarkable abilities of minor capsid protein l2. Viruses, 9.","DOI":"10.20944\/preprints201711.0007.v1"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"7199","DOI":"10.1128\/JVI.78.13.7199-7207.2004","article-title":"E1 empty set e4 protein of human papillomavirus type 16 associates with mitochondria","volume":"78","author":"Raj","year":"2004","journal-title":"J. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e486s","DOI":"10.6061\/clinics\/2018\/e486s","article-title":"Regulation of hpv transcription","volume":"73","author":"Ribeiro","year":"2018","journal-title":"Clinics (Sao Paulo)"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s13046-017-0541-1","article-title":"Hrhpv e5 oncoprotein: Immune evasion and related immunotherapies","volume":"36","author":"Barros","year":"2017","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Morgan, I.M., DiNardo, L.J., and Windle, B. (2017). Integration of human papillomavirus genomes in head and neck cancer: Is it time to consider a paradigm shift?. Viruses, 9.","DOI":"10.3390\/v9080208"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Alizon, S., Murall, C.L., and Bravo, I.G. (2017). Why human papillomavirus acute infections matter. Viruses, 9.","DOI":"10.1101\/144576"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Bordignon, V., Di Domenico, E.G., Trento, E., D\u2019Agosto, G., Cavallo, I., Pontone, M., Pimpinelli, F., Mariani, L., and Ensoli, F. (2017). How human papillomavirus replication and immune evasion strategies take advantage of the host DNA damage repair machinery. Viruses, 9.","DOI":"10.3390\/v9120390"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"S16","DOI":"10.1016\/j.vaccine.2005.09.002","article-title":"Immune responses to human papillomavirus","volume":"24","author":"Stanley","year":"2006","journal-title":"Vaccine"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.virusres.2016.11.014","article-title":"Host cell restriction factors that limit transcription and replication of human papillomavirus","volume":"231","author":"Porter","year":"2017","journal-title":"Virus Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"12922","DOI":"10.1038\/srep12922","article-title":"The human papillomavirus (hpv) e7 protein antagonises an imiquimod-induced inflammatory pathway in primary human keratinocytes","volume":"5","author":"Richards","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.blre.2016.10.001","article-title":"Nf-\u03bab signaling pathway and its potential as a target for therapy in lymphoid neoplasms","volume":"31","author":"Yu","year":"2017","journal-title":"Blood Rev."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Karim, R., Meyers, C., Backendorf, C., Ludigs, K., Offringa, R., van Ommen, G.J., Melief, C.J., van der Burg, S.H., and Boer, J.M. (2011). Human papillomavirus deregulates the response of a cellular network comprising of chemotactic and proinflammatory genes. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0017848"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"11372","DOI":"10.1128\/JVI.05279-11","article-title":"High-risk human papillomaviruses repress constitutive kappa interferon transcription via e6 to prevent pathogen recognition receptor and antiviral-gene expression","volume":"85","author":"Reiser","year":"2011","journal-title":"J. Virol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4588","DOI":"10.1038\/onc.2010.203","article-title":"Tlr9 triggering in burkitt\u2019s lymphoma cell lines suppresses the ebv bzlf1 transcription via histone modification","volume":"29","author":"Zauner","year":"2010","journal-title":"Oncogene"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3186","DOI":"10.4049\/jimmunol.178.5.3186","article-title":"Tlr9 expression and function is abolished by the cervical cancer-associated human papillomavirus type 16","volume":"178","author":"Hasan","year":"2007","journal-title":"J. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1084\/jem.20122394","article-title":"The human papillomavirus type 16 e7 oncoprotein induces a transcriptional repressor complex on the toll-like receptor 9 promoter","volume":"210","author":"Hasan","year":"2013","journal-title":"J. Exp. Med."},{"key":"ref_33","first-page":"672","article-title":"Antigen presentation by mhc-dressed cells","volume":"5","author":"Nakayama","year":"2014","journal-title":"Front. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1038\/ni.1724","article-title":"Cross-presentation of viral and self antigens by skin-derived cd103+ dendritic cells","volume":"10","author":"Bedoui","year":"2009","journal-title":"Nat. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.pvr.2017.08.002","article-title":"Modulation of antigen presenting cell functions during chronic hpv infection","volume":"4","author":"Bashaw","year":"2017","journal-title":"Papillomavirus Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.virusres.2016.11.004","article-title":"Manipulation of the innate immune response by human papillomaviruses","volume":"231","author":"Hong","year":"2017","journal-title":"Virus Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"6537","DOI":"10.1038\/ncomms7537","article-title":"The interferon-related developmental regulator 1 is used by human papillomavirus to suppress nf\u03bab activation","volume":"6","author":"Tummers","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e27257","DOI":"10.4161\/onci.27257","article-title":"Human papillomavirus (hpv) deregulation of toll-like receptor 9","volume":"3","author":"Hasan","year":"2014","journal-title":"Oncoimmunology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.immuni.2006.01.005","article-title":"Dendritic cells rapidly recruited into epithelial tissues via ccr6\/ccl20 are responsible for cd8+ t cell crosspriming in vivo","volume":"24","author":"Etchart","year":"2006","journal-title":"Immunity"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1002\/eji.201242654","article-title":"E-cadherin interactions are required for langerhans cell differentiation","volume":"43","author":"Mayumi","year":"2013","journal-title":"Eur. J. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Sperling, T., O\u0142dak, M., Walch-R\u00fcckheim, B., Wickenhauser, C., Doorbar, J., Pfister, H., Malejczyk, M., Majewski, S., Keates, A.C., and Smola, S. (2012). Human papillomavirus type 8 interferes with a novel c\/ebp\u03b2-mediated mechanism of keratinocyte ccl20 chemokine expression and langerhans cell migration. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1002833"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"14852","DOI":"10.1128\/JVI.79.23.14852-14862.2005","article-title":"Decreased migration of langerhans precursor-like cells in response to human keratinocytes expressing human papillomavirus type 16 e6\/e7 is related to reduced macrophage inflammatory protein-3alpha production","volume":"79","author":"Guess","year":"2005","journal-title":"J. Virol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1128\/JVI.79.1.116-123.2005","article-title":"Macrophages kill human papillomavirus type 16 e6-expressing tumor cells by tumor necrosis factor alpha- and nitric oxide-dependent mechanisms","volume":"79","author":"Routes","year":"2005","journal-title":"J. Virol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1159\/000374115","article-title":"Interleukin-17a promotes arginase-1 production and 2,4-dinitrochlorobenzene-induced acute hyperinflammation in human papillomavirus e7 oncoprotein-expressing skin","volume":"7","author":"Tran","year":"2015","journal-title":"J. Innate Immun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/1476-4598-9-82","article-title":"Regulation of mcp-1 chemokine transcription by p53","volume":"9","author":"Hacke","year":"2010","journal-title":"Mol. Cancer"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4391","DOI":"10.1158\/1078-0432.CCR-09-0489","article-title":"Hpv16 tumor associated macrophages suppress antitumor t cell responses","volume":"15","author":"Lepique","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Jimenez-Perez, M.I., Jave-Suarez, L.F., Ortiz-Lazareno, P.C., Bravo-Cuellar, A., Gonzalez-Ramella, O., Aguilar-Lemarroy, A., Hernandez-Flores, G., Pereira-Suarez, A.L., Daneri-Navarro, A., and del Toro-Arreola, S. (2012). Cervical cancer cell lines expressing nkg2d-ligands are able to down-modulate the nkg2d receptor on nkl cells with functional implications. BMC Immunol., 13.","DOI":"10.1186\/1471-2172-13-7"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"39231","DOI":"10.1038\/srep39231","article-title":"A functional polymorphism in the nkg2d gene modulates nk-cell cytotoxicity and is associated with susceptibility to human papilloma virus-related cancers","volume":"6","author":"Espinoza","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Cho, H., Chung, J.Y., Kim, S., Braunschweig, T., Kang, T.H., Kim, J., Chung, E.J., Hewitt, S.M., and Kim, J.H. (2014). Mica\/b and ulbp1 nkg2d ligands are independent predictors of good prognosis in cervical cancer. BMC Cancer, 14.","DOI":"10.1186\/1471-2407-14-957"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"4930","DOI":"10.1038\/sj.onc.1203860","article-title":"Transcriptional regulation of the major histocompatibility complex (mhc) class i heavy chain, tap1 and lmp2 genes by the human papillomavirus (hpv) type 6b, 16 and 18 e7 oncoproteins","volume":"19","author":"Georgopoulos","year":"2000","journal-title":"Oncogene"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1002\/ijc.20558","article-title":"E5 protein of human papillomavirus type 16 selectively downregulates surface hla class i","volume":"113","author":"Ashrafi","year":"2005","journal-title":"Int. J. Cancer"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"52","DOI":"10.3389\/fimmu.2018.00052","article-title":"Sensing bacterial-induced DNA damaging effects","volume":"9","author":"Espinoza","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Arreygue-Garcia, N.A., Daneri-Navarro, A., del Toro-Arreola, A., Cid-Arregui, A., Gonzalez-Ramella, O., Jave-Suarez, L.F., Aguilar-Lemarroy, A., Troyo-Sanroman, R., Bravo-Cuellar, A., and Delgado-Rizo, V. (2008). Augmented serum level of major histocompatibility complex class i-related chain a (mica) protein and reduced nkg2d expression on nk and t cells in patients with cervical cancer and precursor lesions. BMC Cancer, 8.","DOI":"10.1186\/1471-2407-8-16"},{"key":"ref_54","first-page":"673","article-title":"Cancer immunotherapy by targeting ido1\/tdo and their downstream effectors","volume":"5","author":"Platten","year":"2014","journal-title":"Front. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2686","DOI":"10.1038\/jid.2013.222","article-title":"Indoleamine 2,3-dioxygenase activity contributes to local immune suppression in the skin expressing human papillomavirus oncoprotein e7","volume":"133","author":"Mittal","year":"2013","journal-title":"J. Investig. Dermatol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e00270-16","DOI":"10.1128\/mBio.00270-16","article-title":"Suppression of antitumor immune responses by human papillomavirus through epigenetic downregulation of cxcl14","volume":"7","author":"Cicchini","year":"2016","journal-title":"mBio"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12950-015-0109-9","article-title":"Cxcl14 as an emerging immune and inflammatory modulator","volume":"13","author":"Lu","year":"2016","journal-title":"J. Inflamm. (Lond.)"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.cyto.2008.08.009","article-title":"Constitutive expression of cxcl14 in healthy human and murine epithelial tissues","volume":"44","author":"Meuter","year":"2008","journal-title":"Cytokine"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.immuni.2005.08.012","article-title":"Cutaneous cxcl14 targets blood precursors to epidermal niches for langerhans cell differentiation","volume":"23","author":"Schaerli","year":"2005","journal-title":"Immunity"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1084\/jem.194.6.855","article-title":"Monocyte selectivity and tissue localization suggests a role for breast and kidney-expressed chemokine (brak) in macrophage development","volume":"194","author":"Kurth","year":"2001","journal-title":"J. Exp. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1089\/vim.2006.19.468","article-title":"E6 and e7 oncoproteins from human papillomavirus type 16 induce activation of human transforming growth factor beta1 promoter throughout sp1 recognition sequence","volume":"19","year":"2006","journal-title":"Viral Immunol."},{"key":"ref_62","first-page":"113","article-title":"Tgf-beta signalling pathway factors in hpv-induced cervical lesions","volume":"69","author":"Iancu","year":"2010","journal-title":"Roum. Arch. Microbiol. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1158\/0008-5472.CAN-06-3388","article-title":"High number of intraepithelial cd8+ tumor-infiltrating lymphocytes is associated with the absence of lymph node metastases in patients with large early-stage cervical cancer","volume":"67","author":"Piersma","year":"2007","journal-title":"Cancer Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1038\/bjc.2015.277","article-title":"Stromal infiltration of cd8 t cells is associated with improved clinical outcome in hpv-positive oropharyngeal squamous carcinoma","volume":"113","author":"Oguejiofor","year":"2015","journal-title":"Br. J. Cancer"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.molimm.2018.02.005","article-title":"Immunological network analysis in hpv associated head and neck squamous cancer and implications for disease prognosis","volume":"96","author":"Chen","year":"2018","journal-title":"Mol. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"4132","DOI":"10.1200\/JCO.2016.68.2955","article-title":"Human papillomavirus drives tumor development throughout the head and neck: Improved prognosis is associated with an immune response largely restricted to the oropharynx","volume":"34","author":"Chakravarthy","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1002\/ijc.31027","article-title":"Immune evasion mechanisms of human papillomavirus: An update","volume":"142","author":"Steinbach","year":"2018","journal-title":"Int. J. Cancer"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1111\/imm.12101","article-title":"Increased expression of programmed death (pd)-1 and its ligand pd-l1 correlates with impaired cell-mediated immunity in high-risk human papillomavirus-related cervical intraepithelial neoplasia","volume":"139","author":"Yang","year":"2013","journal-title":"Immunology"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e27","DOI":"10.3802\/jgo.2018.29.e27","article-title":"Programmed death-1 (pd-1) expression in cervical intraepithelial neoplasia and its relationship with recurrence after conization","volume":"29","author":"Chang","year":"2018","journal-title":"J. Gynecol. Oncol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2938","DOI":"10.7150\/jca.22532","article-title":"Pd-l1 expression correlates with tumor infiltrating lymphocytes and response to neoadjuvant chemotherapy in cervical cancer","volume":"9","author":"Meng","year":"2018","journal-title":"J. Cancer"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2373","DOI":"10.1038\/s41598-018-20779-2","article-title":"Microparticles produced by human papillomavirus type 16 e7-expressing cells impair antigen presenting cell function and the cytotoxic t cell response","volume":"8","author":"Zhang","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.ijid.2019.03.022","article-title":"Mucosal and cutaneous human papillomavirus seroprevalence among adults in the prevaccine era in germany\u2014results from a nationwide population-based survey","volume":"83","author":"Loenenbach","year":"2019","journal-title":"Int. J. Infect. Dis."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/1750-9378-5-19","article-title":"Hpv\u2014immune response to infection and vaccination","volume":"5","author":"Stanley","year":"2010","journal-title":"Infect. Agents Cancer"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.ygyno.2017.04.004","article-title":"Hpv vaccines\u2014A review of the first decade","volume":"146","author":"Harper","year":"2017","journal-title":"Gynecol. Oncol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1093\/infdis\/jis489","article-title":"Humoral, mucosal, and cell-mediated immunity against vaccine and nonvaccine genotypes after administration of quadrivalent human papillomavirus vaccine to hiv-infected children","volume":"206","author":"Weinberg","year":"2012","journal-title":"J. Infect. Dis."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2708","DOI":"10.1200\/JCO.2012.47.2738","article-title":"Evaluation of human papillomavirus antibodies and risk of subsequent head and neck cancer","volume":"31","author":"Kreimer","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1200\/JCO.2014.57.8435","article-title":"Human papillomavirus antibodies and future risk of anogenital cancer: A nested case-control study in the european prospective investigation into cancer and nutrition study","volume":"33","author":"Kreimer","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1002\/ijc.24117","article-title":"Diminished ifn-gamma and il-10 and elevated foxp3 mrna expression in the cervix are associated with cin 2 or 3","volume":"124","author":"Scott","year":"2009","journal-title":"Int. J. Cancer"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1038\/bjc.2017.329","article-title":"A positive-feedback loop between tumour infiltrating activated treg cells and type 2-skewed macrophages is essential for progression of laryngeal squamous cell carcinoma","volume":"117","author":"Sun","year":"2017","journal-title":"Br. J. Cancer"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1111\/j.1349-7006.2009.01153.x","article-title":"Regulatory (foxp3+) t cells as target for immune therapy of cervical intraepithelial neoplasia and cervical cancer","volume":"100","author":"Loddenkemper","year":"2009","journal-title":"Cancer Sci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1097\/GCO.0b013e32831a9890","article-title":"Host immune responses to cervical cancer","volume":"21","author":"Patel","year":"2009","journal-title":"Curr. Opin. Obstet. Gynecol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/1756-9966-33-35","article-title":"Cd45ra-foxp3high but not cd45ra+foxp3low suppressive t regulatory cells increased in the peripheral circulation of patients with head and neck squamous cell carcinoma and correlated with tumor progression","volume":"33","author":"Sun","year":"2014","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s40425-019-0497-0","article-title":"Tbet-positive regulatory t cells accumulate in oropharyngeal cancers with ongoing tumor-specific type 1\u2009t cell responses","volume":"7","author":"Santegoets","year":"2019","journal-title":"J. Immunother. Cancer"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"D\u2019Costa, Z.J., Jolly, C., Androphy, E.J., Mercer, A., Matthews, C.M., and Hibma, M.H. (2012). Transcriptional repression of e-cadherin by human papillomavirus type 16 e6. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0048954"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.virol.2013.06.020","article-title":"High-risk human papillomavirus e6 inhibits monocyte differentiation to langerhans cells","volume":"444","author":"Iijima","year":"2013","journal-title":"Virology"},{"key":"ref_86","first-page":"369","article-title":"Il-10 expression is regulated by hpv e2 protein in cervical cancer cells","volume":"4","author":"Moreno","year":"2011","journal-title":"Mol. Med. Rep."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cytogfr.2017.03.002","article-title":"The role of interleukin 10 in human papilloma virus infection and progression to cervical carcinoma","volume":"34","author":"Berti","year":"2017","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.ygyno.2005.11.039","article-title":"Immunohistochemical analysis of cd4+ and cd8+ t-cell subsets in high risk human papillomavirus-associated pre-malignant and malignant lesions of the uterine cervix","volume":"102","author":"Mauny","year":"2006","journal-title":"Gynecol. Oncol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/S0042-6822(03)00103-X","article-title":"The e5 protein of human papillomavirus type 16 perturbs mhc class ii antigen maturation in human foreskin keratinocytes treated with interferon-gamma","volume":"310","author":"Zhang","year":"2003","journal-title":"Virology"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1038\/sj.onc.1210725","article-title":"Hpv-16 e5 oncoprotein upregulates lipid raft components caveolin-1 and ganglioside gm1 at the plasma membrane of cervical cells","volume":"27","author":"Suprynowicz","year":"2008","journal-title":"Oncogene"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1054\/bjoc.1999.1103","article-title":"Association between high-risk hpv types, hla drb1* and dqb1* alleles and cervical cancer in british women","volume":"82","author":"Cuzick","year":"2000","journal-title":"Br. J. Cancer"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1097\/01.AOG.0000139834.84628.61","article-title":"Regression of low-grade cervical intraepithelial neoplasia in patients with hla-drb1*13 genotype","volume":"104","author":"Cartier","year":"2004","journal-title":"Obstet. Gynecol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1111\/cas.12760","article-title":"Human leukocyte antigen class ii drb1*1302 allele protects against cervical cancer: At which step of multistage carcinogenesis?","volume":"106","author":"Matsumoto","year":"2015","journal-title":"Cancer Sci."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"238","DOI":"10.7150\/jca.27103","article-title":"Association of smug1 snps in intron region and linkage disequilibrium with occurrence of cervical carcinoma and hpv infection in chinese population","volume":"10","author":"Ye","year":"2019","journal-title":"J. Cancer"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"4120","DOI":"10.1073\/pnas.0730640100","article-title":"Transforming growth factor beta 1 inhibits expression of nkp30 and nkg2d receptors: Consequences for the nk-mediated killing of dendritic cells","volume":"100","author":"Castriconi","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"7075","DOI":"10.1007\/s13277-016-5028-8","article-title":"Transforming growth factor-\u03b21 in carcinogenesis, progression, and therapy in cervical cancer","volume":"37","author":"Zhu","year":"2016","journal-title":"Tumour Biol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1158\/1078-0432.CCR-09-2877","article-title":"Association of tgf-beta1 genetic variants with hpv16-positive oropharyngeal cancer","volume":"16","author":"Guan","year":"2010","journal-title":"Clin. Cancer Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2225","DOI":"10.1158\/1078-0432.CCR-17-1904","article-title":"Genetic variants predict clinical outcomes of hpv-positive oropharyngeal cancer patients after definitive radiotherapy","volume":"24","author":"Tao","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.3324\/haematol.2009.008318","article-title":"Nkg2d gene polymorphism has a significant impact on transplant outcomes after hla-fully-matched unrelated bone marrow transplantation for standard risk hematologic malignancies","volume":"94","author":"Espinoza","year":"2009","journal-title":"Haematologica"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1158\/0008-5472.CAN-05-2776","article-title":"Identification of the nkg2d haplotypes associated with natural cytotoxic activity of peripheral blood lymphocytes and cancer immunosurveillance","volume":"66","author":"Hayashi","year":"2006","journal-title":"Cancer Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1002\/ijc.23456","article-title":"Opposite impact of nkg2d genotype by lifestyle exposure to risk of aerodigestive tract cancer among japanese","volume":"123","author":"Furue","year":"2008","journal-title":"Int. J. Cancer"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.3324\/haematol.2011.058529","article-title":"Human microrna-1245 downregulates the nkg2d receptor in nk cells and impairs nkg2d-mediated functions","volume":"97","author":"Espinoza","year":"2012","journal-title":"Haematologica"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1111\/imm.13039","article-title":"Conserved and variable natural killer cell receptors: Diverse approaches to viral infections","volume":"156","author":"Khakoo","year":"2019","journal-title":"Immunology"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"981","DOI":"10.2147\/DDDT.S163304","article-title":"The combination of anti-kir monoclonal antibodies with anti-pd-1\/pd-l1 monoclonal antibodies could be a critical breakthrough in overcoming tumor immune escape in nsclc","volume":"12","author":"He","year":"2018","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_105","first-page":"2071","article-title":"Meta-analysis of polymorphic variants conferring genetic risk to cervical cancer in indian women supports cyp1a1 as an important associated locus","volume":"19","author":"Sengupta","year":"2018","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1097\/01.cco.0000239885.13537.36","article-title":"Human papillomavirus-related tumors in hiv","volume":"18","author":"Palefsky","year":"2006","journal-title":"Curr. Opin. Oncol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1001\/jama.2012.5664","article-title":"Risk of cervical precancer and cancer among hiv-infected women with normal cervical cytology and no evidence of oncogenic hpv infection","volume":"308","author":"Keller","year":"2012","journal-title":"JAMA"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1093\/cid\/civ569","article-title":"Cervical precancer risk in hiv-infected women who test positive for oncogenic human papillomavirus despite a normal pap test","volume":"61","author":"Keller","year":"2015","journal-title":"Clin. Infect. Dis."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Lee, J.E., Lee, S., Lee, H., Song, Y.M., Lee, K., Han, M.J., Sung, J., and Ko, G. (2013). Association of the vaginal microbiota with human papillomavirus infection in a korean twin cohort. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0063514"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"e02785-18","DOI":"10.1128\/mBio.02785-18","article-title":"Relationship between the cervical microbiome, hiv status, and precancerous lesions","volume":"10","author":"Klein","year":"2019","journal-title":"mBio"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.ajog.2018.12.011","article-title":"Vaginal dysbiosis and the risk of human papillomavirus and cervical cancer: Systematic review and meta-analysis","volume":"221","author":"Brusselaers","year":"2018","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1093\/infdis\/jiu004","article-title":"Bacteria in the vaginal microbiome alter the innate immune response and barrier properties of the human vaginal epithelia in a species-specific manner","volume":"209","author":"Doerflinger","year":"2014","journal-title":"J. Infect. Dis."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Audirac-Chalifour, A., Torres-Poveda, K., Bahena-Rom\u00e1n, M., T\u00e9llez-Sosa, J., Mart\u00ednez-Barnetche, J., Cortina-Ceballos, B., L\u00f3pez-Estrada, G., Delgado-Romero, K., Burguete-Garc\u00eda, A.I., and Cant\u00fa, D. (2016). Cervical microbiome and cytokine profile at various stages of cervical cancer: A pilot study. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0153274"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.fertnstert.2018.06.036","article-title":"Cervicovaginal microbiota, women\u2019s health, and reproductive outcomes","volume":"110","author":"Kroon","year":"2018","journal-title":"Fertil. Steril."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1038\/ismej.2014.26","article-title":"Lactobacillus-dominated cervicovaginal microbiota associated with reduced hiv\/sti prevalence and genital hiv viral load in african women","volume":"8","author":"Borgdorff","year":"2014","journal-title":"ISME J."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"e00055-18","DOI":"10.1128\/mSphere.00055-18","article-title":"Anti-hiv-1 activity of lactic acid in human cervicovaginal fluid","volume":"3","author":"Tyssen","year":"2018","journal-title":"mSphere"},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Torcia, M.G. (2019). Interplay among vaginal microbiome, immune response and sexually transmitted viral infections. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20020266"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"4036","DOI":"10.1038\/s41598-017-03466-6","article-title":"Microbial signatures associated with oropharyngeal and oral squamous cell carcinomas","volume":"7","author":"Banerjee","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.canlet.2017.11.009","article-title":"Gastric microbiota: An emerging player in helicobacter pylori-induced gastric malignancies","volume":"414","author":"Espinoza","year":"2018","journal-title":"Cancer Lett."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"288","DOI":"10.12659\/MSM.911478","article-title":"Proteomic screening for serum biomarkers for cervical cancer and their clinical significance","volume":"25","author":"Chen","year":"2019","journal-title":"Med. Sci. Monit."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"3322","DOI":"10.1038\/s41598-017-02672-6","article-title":"Isolation, detection, and quantification of cancer biomarkers in hpv-associated malignancies","volume":"7","author":"Inan","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Espinoza, J.L. (2018). Machine learning for tackling microbiota data and infection complications in immunocompromised patients with cancer. J. Intern. Med.","DOI":"10.1111\/joim.12746"},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Owais, M., Arsalan, M., Choi, J., and Park, K.R. (2019). Effective diagnosis and treatment through content-based medical image retrieval (cbmir) by using artificial intelligence. J. Clin. Med., 8.","DOI":"10.3390\/jcm8040462"},{"key":"ref_124","first-page":"CD009069","article-title":"Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors","volume":"5","author":"Arbyn","year":"2018","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1016\/j.rpor.2018.05.001","article-title":"The current status of immunotherapy for cervical cancer","volume":"23","author":"Orbegoso","year":"2018","journal-title":"Rep. Pract. Oncol. Radiother."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1177\/1758834017708742","article-title":"Pembrolizumab in cervical cancer: Latest evidence and clinical usefulness","volume":"9","author":"Borcoman","year":"2017","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1186\/1479-5876-11-88","article-title":"Hpv16 synthetic long peptide (hpv16-slp) vaccination therapy of patients with advanced or recurrent hpv16-induced gynecological carcinoma, a phase ii trial","volume":"11","author":"Welters","year":"2013","journal-title":"J. Transl. Med."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1001\/jamaoncol.2018.4051","article-title":"Combining immune checkpoint blockade and tumor-specific vaccine for patients with incurable human papillomavirus 16-related cancer: A phase 2 clinical trial","volume":"5","author":"Massarelli","year":"2019","journal-title":"JAMA Oncol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1128\/CVI.00043-12","article-title":"Human papillomavirus immunization is associated with increased expression of different innate immune regulatory receptors","volume":"19","author":"Colmenares","year":"2012","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"2480","DOI":"10.1099\/vir.0.055137-0","article-title":"Analysis of the genetic diversity and phylogenetic relationships of putative human papillomavirus types","volume":"94","author":"Chouhy","year":"2013","journal-title":"J. Gen. Virol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s12985-019-1132-x","article-title":"Alpha, beta, gamma human papillomaviruses (hpv) detection with a different sets of primers in oropharyngeal swabs, anal and cervical samples","volume":"16","author":"Sias","year":"2019","journal-title":"Virol. J."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1002\/ijc.28176","article-title":"Cutaneous alpha, beta and gamma human papillomaviruses in relation to squamous cell carcinoma of the skin: A population-based study","volume":"133","author":"Farzan","year":"2013","journal-title":"Int. J. Cancer"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.virusres.2016.11.013","article-title":"The biology of beta human papillomaviruses","volume":"231","author":"Tommasino","year":"2017","journal-title":"Virus Res."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Viarisio, D., M\u00fcller-Decker, K., Accardi, R., Robitaille, A., D\u00fcrst, M., Beer, K., Jansen, L., Flechtenmacher, C., Bozza, M., and Harbottle, R. (2018). Beta hpv38 oncoproteins act with a hit-and-run mechanism in ultraviolet radiation-induced skin carcinogenesis in mice. PLoS Pathog., 14.","DOI":"10.1371\/journal.ppat.1006783"}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/7\/7\/199\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:05:18Z","timestamp":1760187918000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/7\/7\/199"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,13]]},"references-count":134,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2019,7]]}},"alternative-id":["microorganisms7070199"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms7070199","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,13]]}}}