Immunology of HPV-mediated cervical cancer: current understanding

References

• 2018. Global Health Observatory-International Agency for Research on Cancer. World Health Organization, Geneva. who.int/gho/database/en/. Accessed June 11, 2020.
   Google Scholar
• Walboomers JM, Jacobs MV, Manos MM, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999;189(1):12–19. doi:10.1002/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F.
   PubMed Web of Science ®Google Scholar
• Muñoz N, Bosch FX, de Sanjosé S, et al. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med. 2003;348(6):518–527. doi:10.1056/NEJMoa021641.
   PubMed Web of Science ®Google Scholar
• de Sanjose S, Quint WG, Alemany L, Retrospective International Survey and HPV Time Trends Study Group, et al. Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. Lancet Oncol. 2010;11(11):1048–1056. doi:10.1016/S1470-2045(10)70230-8.
   PubMed Web of Science ®Google Scholar
• World Health Organization Human papillomavirus (HPV) vaccines: WHO position paper. Wkly Epidemiol Rec. 2017;19:241–268. May 2017.
   Google Scholar
• Zur Hausen H. Papillomaviruses in the causation of human cancers - a brief historical account. Virology. 2009;384(2):260–265. doi:10.1016/j.virol.2008.11.046.
   PubMed Web of Science ®Google Scholar
• Zur Hausen H. Condylomata acuminata and human genital cancer. Cancer Res. 1976;36(2 pt 2):794.
   PubMed Web of Science ®Google Scholar
• Zur Hausen H, de Villiers EM, Gissmann L. Papillomavirus infections and human genital cancer. Gynecol Oncol. 1981;12(2 Pt 2):S124–S128. doi:10.1016/0090-8258(81)90067-6.
   PubMed Web of Science ®Google Scholar
• Boshart M, Gissmann L, Ikenberg H, et al. A new type of papillomavirus DNA, its presence in genital cancer biopsies and in cell lines derived from cervical cancer. EMBO J. 1984;3(5):1151–1157.
   PubMed Web of Science ®Google Scholar
• Gertig DM, Brotherton JM, Budd AC, et al. Impact of a population-based HPV vaccination program on cervical abnormalities: a data linkage study. BMC Med. 2013;11:227. doi:10.1186/1741-7015-11-227.
   PubMed Web of Science ®Google Scholar
• Powell SE, Hariri S, Steinau M, et al. Impact of human papillomavirus (HPV) vaccination on HPV 16/18-related prevalence in precancerous cervical lesions. Vaccine. 2012;31(1):109–113. doi:10.1016/j.vaccine.2012.10.092.
   PubMed Web of Science ®Google Scholar
• Cuschieri K, Kavanagh K, Cameron R, et al. 2017. The massive decline of clinically relevant Human Papillomavirus (HPV) 16 and 18 infection in Scotland. Presented at Microbiology Society Annual Conference 2017. Edinburgh, UK, April 03-06, 2017.
   Google Scholar
• Tabrizi SN, Brotherton JM, Kaldor JM, et al. Assessment of herd immunity and cross-protection after a human papillomavirus vaccination programme in Australia: a repeat cross-sectional study. Lancet Infect Dis. 2014;14(10):958–966. doi:10.1016/S1473-3099(14)70841-2.
   PubMed Web of Science ®Google Scholar
• Favre M. Structural polypeptides of rabbit, bovine, and human papillomaviruses. J Virol. 1975;15(5):1239–1247. doi:10.1128/JVI.15.5.1239-1247.1975.
   PubMed Web of Science ®Google Scholar
• Baker TS, Newcomb WW, Olson NH, et al. Structures of bovine and human papillomaviruses. Analysis by cryoelectron microscopy and three-dimensional image reconstruction. Biophys J. 1991;60(6):1445–1456. doi:10.1016/S0006-3495(91)82181-6.
   PubMed Web of Science ®Google Scholar
• Burd EM. Human papillomavirus and cervical cancer. Clin Microbiol Rev. 2003;16(1):1–17. doi:10.1128/cmr.16.1.1-17.2003.
   PubMed Web of Science ®Google Scholar
• International Human Papillomavirus Reference Center. Human papillomavirus reference clones. http://www.nordicehealth.se/hpvcenter/reference_clones/., accessed June 11, 2020.
   Google Scholar
• Day PM, Schelhaas M. Concepts of papillomavirus entry into host cells. Curr Opin Virol. 2014;4:24–31. doi:10.1016/j.coviro.2013.11.002.
   PubMed Web of Science ®Google Scholar
• Evander M, Frazer IH, Payne E, et al. Identification of the alpha6 integrin as a candidate receptor for papillomaviruses. J Virol. 1997;71(3):2449–2456. doi:10.1128/JVI.71.3.2449-2456.1997.
   PubMed Web of Science ®Google Scholar
• Giroglou T, Florin L, Schäfer F, et al. Human papillomavirus infection requires cell surface heparan sulfate. J Virol. 2001;75(3):1565–1570. doi:10.1128/JVI.75.3.1565-1570.2001.
   PubMed Web of Science ®Google Scholar
• Gilbert DM, Cohen SN. Bovine papilloma virus plasmids replicate randomly in mouse fibroblasts throughout S phase of the cell cycle. Cell. 1987;50(1):59–68. doi:10.1016/0092-8674(87)90662-3.
   PubMed Web of Science ®Google Scholar
• Flores ER, Lambert PF. Evidence for a switch in the mode of human papillomavirus type 16 DNA replication during the viral life cycle. J Virol. 1997;71(10):7167–7179. doi:10.1128/JVI.71.10.7167-7179.1997.
   PubMed Web of Science ®Google Scholar
• Flores ER, Allen-Hoffmann BL, Lee D, et al. Establishment of the human papillomavirus type 16 (HPV-16) life cycle in an immortalized human foreskin keratinocyte cell line. Virology. 1999;262(2):344–354. doi:10.1006/viro.1999.9868.
   PubMed Web of Science ®Google Scholar
• Porter SS, Stepp WH, Stamos JD, et al. Host cell restriction factors that limit transcription and replication of human papillomavirus. Virus Res. 2017;231:10–20. doi:10.1016/j.virusres.2016.11.014.
   PubMed Web of Science ®Google Scholar
• Spriggs CC, Laimins LA. Human Papillomavirus and the DNA damage response: exploiting host repair pathways for viral replication. Viruses. 2017;9(8):232. doi:10.3390/v9080232.
   PubMed Web of Science ®Google Scholar
• Mohr IJ, Clark R, Sun S, et al. Targeting the E1 replication protein to the papillomavirus origin of replication by complex formation with the E2 transactivator. Science. 1990;250(4988):1694–1699. doi:10.1126/science.2176744.
   PubMed Web of Science ®Google Scholar
• Frattini MG, Laimins LA. Binding of the human papillomavirus E1 origin-recognition protein is regulated through complex formation with the E2 enhancer-binding protein. Proc Natl Acad Sci USA. 1994;91(26):12398–12402. doi:10.1073/pnas.91.26.12398.
   PubMed Web of Science ®Google Scholar
• Sedman J, Stenlund A. Co-operative interaction between the initiator E1 and the transcriptional activator E2 is required for replicator specific DNA replication of bovine papillomavirus in vivo and in vitro. EMBO J. 1995;14(24):6218–6228. doi:10.1002/j.1460-2075.1995.tb00312.x.
   PubMed Web of Science ®Google Scholar
• Thomas JT, Hubert WG, Ruesch MN, et al. Human papillomavirus type 31 oncoproteins E6 and E7 are required for the maintenance of episomes during the viral life cycle in normal human keratinocytes. Proc Natl Acad Sci USA. 1999;96(15):8449–8454. doi:10.1073/pnas.96.15.8449.
   PubMed Web of Science ®Google Scholar
• Yim EK, Park JS. The role of HPV E6 and E7 oncoproteins in HPV-associated cervical carcinogenesis. Cancer Res Treat. 2005;37(6):319–324. doi:10.4143/crt.2005.37.6.319.
   PubMedGoogle Scholar
• Thomas M, Pim D, Banks L. The role of the E6-p53 interaction in the molecular pathogenesis of HPV. Oncogene. 1999;18(53):7690–7700. doi:10.1038/sj.onc.1202953.
   PubMed Web of Science ®Google Scholar
• Syrjänen SM, Syrjänen KJ. New concepts on the role of human papillomavirus in cell cycle regulation. Ann Med. 1999;31(3):175–187. doi:10.3109/07853899909115976.
   PubMed Web of Science ®Google Scholar
• Jeon S, Allen-Hoffmann BL, Lambert PF. Integration of human papillomavirus type 16 into the human genome correlates with a selective growth advantage of cells. J Virol. 1995;69(5):2989–2997. doi:10.1128/JVI.69.5.2989-2997.1995.
   PubMed Web of Science ®Google Scholar
• Moody CA, Laimins LA. Human papillomavirus oncoproteins: pathways to transformation. Nat Rev Cancer. 2010;10(8):550–560. doi:10.1038/nrc2886.
   PubMed Web of Science ®Google Scholar
• Schwarz E, Freese UK, Gissmann L, et al. Structure and transcription of human papillomavirus sequences in cervical carcinoma cells. Nature. 1985;314(6006):111–114. doi:10.1038/314111a0.
   PubMed Web of Science ®Google Scholar
• Baker CC, Phelps WC, Lindgren V, et al. Structural and transcriptional analysis of human papillomavirus type 16 sequences in cervical carcinoma cell lines. J Virol. 1987;61(4):962–971. doi:10.1128/JVI.61.4.962-971.1987.
   PubMed Web of Science ®Google Scholar
• Zur Hausen H. Papillomaviruses-to vaccination and beyond. Biochemistry Mosc. 2008;73(5):498–503. doi:10.1134/s0006297908050027.
   PubMed Web of Science ®Google Scholar
• Zhou Q, Zhu K, Cheng H. Toll-like receptors in human papillomavirus infection. Arch Immunol Ther Exp (Warsz).). 2013;61(3):203–215. doi:10.1007/s00005-013-0220-7.
   PubMed Web of Science ®Google Scholar
• Hornung V, Ablasser A, Charrel-Dennis M, et al. AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC. Nature. 2009;458(7237):514–518. doi:10.1038/nature07725.
   PubMed Web of Science ®Google Scholar
• Kerur N, Veettil MV, Sharma-Walia N, et al. IFI16 acts as a nuclear pathogen sensor to induce the inflammasome in response to Kaposi Sarcoma-associated herpesvirus infection. Cell Host Microbe. 2011;9(5):363–375. doi:10.1016/j.chom.2011.04.008.
   PubMed Web of Science ®Google Scholar
• Westrich JA, Warren CJ, Pyeon D. Evasion of host immune defenses by human papillomavirus. Virus Res. 2017;231:21–33. doi:10.1016/j.virusres.2016.11.023.
   PubMed Web of Science ®Google Scholar
• Takeuchi O, Akira S. Pattern Recognition Receptors and Inflammation. Cell. 2010;140(6):805–820. doi:10.1016/j.cell.2010.01.022.
   PubMed Web of Science ®Google Scholar
• Doorbar J. The papillomavirus life cycle. J Clin Virol. 2005;32:7–S15. doi:10.1016/j.jcv.2004.12.006.
   PubMed Web of Science ®Google Scholar
• Chow LT, Broker TR, Steinberg BM. The natural history of human papillomavirus infections of the mucosal epithelia. Apmis. 2010;118(6-7):422–449. doi:10.1111/j.1600-0463.2010.02625.x.
   PubMed Web of Science ®Google Scholar
• Stanley MA, Pett M. Papillomaviruses. In: Mahy BWJ, ter Meulen V, eds. Wilson’s Microbiology & Microbial Infections. Topley & Virology. Vol. 2. 10th ed. Wiley-Blackwell. Hoboken, NJ; 2007: 448–472.
   Google Scholar
• Ablasser A, Bauernfeind F, Hartmann G, et al. RIG-I-dependent sensing of poly(dA:dT) through the induction of an RNA polymerase III-transcribed RNA intermediate. Nat Immunol. 2009;10(10):1065–1072. doi:10.1038/ni.1779.
   PubMed Web of Science ®Google Scholar
• Chiu YH, Macmillan JB, Chen ZJ. RNA polymerase III detects cytosolic DNA and induces type I interferons through the RIG-I pathway. Cell. 2009;138(3):576–591. doi:10.1016/j.cell.2009.06.015.
   PubMed Web of Science ®Google Scholar
• Woodworth CD, Notario V, DiPaolo JA. Transforming growth factors beta 1 and 2 transcriptionally regulate human papillomavirus (HPV) type 16 early gene expression in HPV-immortalized human genital epithelial cells. J Virol. 1990;64(10):4767–4775. doi:10.1128/JVI.64.10.4767-4775.1990.
   PubMed Web of Science ®Google Scholar
• Braun L, Durst M, Mikumo R, Gruppuso P. Differential response of nontumorigenic and tumorigenic human papillomavirus type 16-positive epithelial cells to transforming growth factor β1. Cancer Res. 1990;50:7324–7332.
   PubMed Web of Science ®Google Scholar
• Kyo S, Inoue M, Hayasaka N, Inoue T, et al. Regulation of early gene expression of human papillomavirus type 16 by inflammatory cytokines. Virology. 1994;200(1):130–139. doi:10.1006/viro.1994.1171.
   PubMed Web of Science ®Google Scholar
• Scott M, Stites DP, Moscicki AB. Th1 cytokine patterns in cervical human papillomavirus infection. Clin Diagn Lab Immunol. 1999;6(5):751–755.
   PubMedGoogle Scholar
• Scott M, Nakagawa M, Moscicki AB. Cell-mediated immune response to human papillomavirus infection. Clin Diagn Lab Immunol. 2001;8(2):209–220. doi:10.1128/CDLI.8.2.209-220.2001.
   PubMedGoogle Scholar
• LaFleur DW, Nardelli B, Tsareva T, et al. Interferon-kappa, a novel type I interferon expressed in human keratinocytes. J Biol Chem. 2001;276(43):39765–39771. doi:10.1074/jbc.M102502200.
   PubMed Web of Science ®Google Scholar
• Lembo D, Donalisio M, De Andrea M, et al. A cell-based high-throughput assay for screening inhibitors of human papillomavirus-16 long control region activity. Faseb J. 2006;20(1):148–150. doi:10.1096/fj.05-3904fje.
   PubMedGoogle Scholar
• Song SH, Lee JK, Lee NW, et al. Interferon-gamma (IFN-gamma): a possible prognostic marker for clearance of high-risk human papillomavirus (HPV)). Gynecol Oncol. 2008;108(3):543–548. doi:10.1016/j.ygyno.2007.11.006.
   PubMed Web of Science ®Google Scholar
• Rincon-Orozco B, Halec G, Rosenberger S, et al. Epigenetic silencing of interferon-kappa in human papillomavirus type 16-positive cells. Cancer Res. 2009;69(22):8718–8725. doi:10.1158/0008-5472.CAN-09-0550.
   PubMed Web of Science ®Google Scholar
• Andersen JM, Al-Khairy D, Ingalls RR. Innate immunity at the mucosal surface: role of Toll-like receptor 3 and Toll-like receptor 9 in cervical epithelial cell responses to microbial pathogens. Biol Reprod. 2006;74(5):824–831. doi:10.1095/biolreprod.105.048629.
   PubMed Web of Science ®Google Scholar
• Lebre MC, van der Aar AM, van Baarsen L, et al. Human keratinocytes express functional Toll-like receptor 3, 4, 5, and 9. J Invest Dermatol. 2007;127(2):331–341. doi:10.1038/sj.jid.5700530.
   PubMed Web of Science ®Google Scholar
• Karim R, Meyers C, Backendorf C, et al. Human papillomavirus deregulates the response of a cellular network comprising of chemotactic and proinflammatory genes. PLoS One. 2011;6(3):e17848 doi:10.1371/journal.pone.0017848.
   PubMed Web of Science ®Google Scholar
• Karim R, Tummers B, Meyers C, et al. Human papillomavirus (HPV) upregulates the cellular deubiquitinase UCHL1 to suppress the keratinocyte's innate immune response. PLoS Pathog. 2013;9(5):e1003384 doi:10.1371/journal.ppat.1003384.
   PubMed Web of Science ®Google Scholar
• Nees M, Geoghegan JM, Hyman T, Frank S, Miller L, et al. Papillomavirus type 16 oncogenes downregulate expression of interferon-responsive genes and upregulate proliferation-associated and NF-kappaB-responsive genes in cervical keratinocytes. J Virol. 2001;75(9):4283–4296. doi:10.1128/JVI.75.9.4283-4296.2001.
   PubMed Web of Science ®Google Scholar
• Hong S, Mehta KP, Laimins LA. Suppression of STAT-1 expression by human papillomaviruses is necessary for differentiation-dependent genome amplification and plasmid maintenance. J Virol. 2011;85(18):9486–9494. doi:10.1128/JVI.05007-11.
   PubMed Web of Science ®Google Scholar
• Park JS, Kim EJ, Kwon HJ, et al. Inactivation of interferon regulatory factor-1 tumor suppressor protein by HPV E7 oncoprotein. Implication for the E7-mediated immune evasion mechanism in cervical carcinogenesis. J Biol Chem. 2000;275(10):6764–6769. doi:10.1074/jbc.275.10.6764.
   PubMed Web of Science ®Google Scholar
• Um SJ, Rhyu JW, Kim EJ, et al. Abrogation of IRF-1 response by high-risk HPV E7 protein in vivo. Cancer Lett. 2002;179(2):205–212. doi:10.1016/s0304-3835(01)00871-0.
   PubMed Web of Science ®Google Scholar
• Antonsson A, Payne E, Hengst K, et al. The human papillomavirus type 16 E7 protein binds human interferon regulatory factor-9 via a novel PEST domain required for transformation. J Interferon Cytokine Res. 2006;26(7):455–461. doi:10.1089/jir.2006.26.455.
   PubMed Web of Science ®Google Scholar
• Sunthamala N, Thierry F, Teissier S, et al. E2 proteins of high risk human papillomaviruses down-modulate STING and IFN-κ transcription in keratinocytes. PLoS One. 2014;9(3):e91473 doi:10.1371/journal.pone.0091473.
   PubMed Web of Science ®Google Scholar
• DeCarlo CA, Severini A, Edler L, et al. IFN-κ, a novel type I IFN, is undetectable in HPV-positive human cervical keratinocytes. Lab Invest. 2010;90(10):1482–1491. doi:10.1038/labinvest.2010.95.
   PubMed Web of Science ®Google Scholar
• Chang YE, Laimins LA. Microarray analysis identifies interferon-inducible genes and Stat-1 as major transcriptional targets of human papillomavirus type 31. J Virol. 2000;74(9):4174–4182. doi:10.1128/jvi.74.9.4174-4182.2000.
   PubMed Web of Science ®Google Scholar
• Zhou F, Chen J, Zhao KN. Human papillomavirus 16-encoded E7 protein inhibits IFN-γ-mediated MHC class I antigen presentation and CTL-induced lysis by blocking IRF-1 expression in mouse keratinocytes. J Gen Virol. 2013;94(Pt 11):2504–2514. doi:10.1099/vir.0.054486-0.
   PubMedGoogle Scholar
• Mota F, Rayment N, Kanan J, et al. Differential regulation of HLA-DQ expression by keratinocytes and Langerhans cells in normal and premalignant cervical epithelium. Tissue Antigens. 1998;52(3):286–293. doi:10.1111/j.1399-0039.1998.tb03046.x.
   PubMedGoogle Scholar
• Mota F, Rayment N, Chong S, et al. The antigen-presenting environment in normal and human papillomavirus (HPV)-related premalignant cervical epithelium. Clin Exp Immunol. 1999;116(1):33–40. doi:10.1046/j.1365-2249.1999.00826.x.
   PubMed Web of Science ®Google Scholar
• Cromme FV, Meijer CJ, Snijders PJ, et al. Analysis of MHC class I and II expression in relation to presence of HPV genotypes in premalignant and malignant cervical lesions. Br J Cancer. 1993;67(6):1372–1380. doi:10.1038/bjc.1993.254.
   PubMed Web of Science ®Google Scholar
• Cromme FV, Snijders PJ, van den Brule AJ, et al. MHC class I expression in HPV 16 positive cervical carcinomas is post-transcriptionally controlled and independent from c-myc overexpression. Oncogene. 1993;8(11):2969–2975.
   PubMed Web of Science ®Google Scholar
• Vivier E, Tomasello E, Baratin M, et al. Functions of natural killer cells. Nat Immunol. 2008;9(5):503–510. doi:10.1038/ni1582.
   PubMed Web of Science ®Google Scholar
• Cerwenka A, Lanier LL. Natural killer cells, viruses and cancer. Nat Rev Immunol. 2001;1(1):41–49. doi:10.1038/35095564.
   PubMed Web of Science ®Google Scholar
• Vitale M, Cantoni C, Pietra G, et al. Effect of tumor cells and tumor microenvironment on NK-cell function. Eur J Immunol. 2014;44(6):1582–1592. doi:10.1002/eji.201344272.
   PubMed Web of Science ®Google Scholar
• Garcia-Iglesias T, Del Toro-Arreola A, Albarran-Somoza B, et al. Low NKp30, NKp46 and NKG2D expression and reduced cytotoxic activity on NK cells in cervical cancer and precursor lesions. BMC Cancer. 2009;9:186. doi:10.1186/1471-2407-9-186.
   PubMed Web of Science ®Google Scholar
• Arreygue-Garcia NA, Daneri-Navarro A, Del Toro-Arreola A, et al. 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. 2008;8:16doi:10.1186/1471-2407-8-16.
   PubMed Web of Science ®Google Scholar
• Kobayashi A, Greenblatt RM, Anastos K, et al. Functional attributes of mucosal immunity in cervical intraepithelial neoplasia and effects of HIV infection. Cancer Res. 2004;64(18):6766–6774. doi:10.1158/0008-5472.CAN-04-1091.
   PubMed Web of Science ®Google Scholar
• Ferns DM, Heeren AM, Samuels S, et al. Classical and non-classical HLA class I aberrations in primary cervical squamous- and adenocarcinomas and paired lymph node metastases. J Immunother Cancer. 2016;4:78. doi:10.1186/s40425-016-0184-3.
   PubMed Web of Science ®Google Scholar
• Spaans VM, Peters AA, Fleuren GJ, Jordanova ES. HLA-E expression in cervical adenocarcinomas: association with improved long-term survival. J Transl Med. 2012;10:184doi:10.1186/1479-5876-10-184.
   PubMed Web of Science ®Google Scholar
• Gimenes F, Teixeira JJ, de Abreu AL, et al. Human leukocyte antigen (HLA)-G and cervical cancer immunoediting: a candidate molecule for therapeutic intervention and prognostic biomarker? Biochim Biophys Acta. 2014;1846(2):576–589. doi:10.1016/j.bbcan.2014.10.004.
   PubMed Web of Science ®Google Scholar
• Textor S, Dürst M, Jansen L, et al. Activating NK cell receptor ligands are differentially expressed during progression to cervical cancer. Int J Cancer. 2008;123(10):2343–2353. doi:10.1002/ijc.23733.
   PubMed Web of Science ®Google Scholar
• Cho H, Chung JY, Kim S, et al. MICA/B and ULBP1 NKG2D ligands are independent predictors of good prognosis in cervical cancer. BMC Cancer. 2014;14(1):957. doi:10.1186/1471-2407-14-957.
   PubMedGoogle Scholar
• Sato N, Saga Y, Mizukami H, et al. Downregulation of indoleamine-2,3-dioxygenase in cervical cancer cells suppresses tumor growth by promoting natural killer cell killer cell accumulation. Oncol Rep. 2012;28(5):1574–1578. doi:10.3892/or.2012.1984.
   PubMed Web of Science ®Google Scholar
• Garzetti GG, Ciavattini A, Goteri G, et al. HPV DNA positivity and natural killer cell activity in the clinical outcome of mild cervical dysplasia: integration between virus and immune system. Gynecol Obstet Invest. 1995;39(2):130–135. doi:10.1159/000292394.
   PubMed Web of Science ®Google Scholar
• Georgopoulos NT, Proffitt JL, Blair GE. 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. Oncogene. 2000;19(42):4930–4935. doi:10.1038/sj.onc.1203860.
   PubMed Web of Science ®Google Scholar
• Li H, Ou X, Xiong J, Wang T. HPV16E7 mediates HADC chromatin repression and downregulation of MHC class I genes in HPV16 tumorigenic cells through interaction with an MHC class I promoter. Biochem Biophys Res Commun. 2006;349(4):1315–1321. doi:10.1016/j.bbrc.2006.08.182.
   PubMed Web of Science ®Google Scholar
• Ashrafi GH, Haghshenas MR, Marchetti B, et al. E5 protein of human papillomavirus type 16 selectively downregulates surface HLA class I. Int J Cancer. 2005;113(2):276–283. doi:10.1002/ijc.20558.
   PubMed Web of Science ®Google Scholar
• Bottley G, Watherston OG, Hiew YL, et al. High-risk human papillomavirus E7 expression reduces cell-surface MHC class I molecules and increases susceptibility to natural killer cells. Oncogene. 2008;27(12):1794–1799. doi:10.1038/sj.onc.1210798.
   PubMed Web of Science ®Google Scholar
• Embgenbroich M, Burgdorf S. Current concepts of antigen cross-presentation. Front Immunol. 2018;9:1643doi:10.3389/fimmu.2018.01643.
   PubMed Web of Science ®Google Scholar
• Collin M, Bigley V. Human dendritic cell subsets: an update. Immunology. 2018;154(1):3–20. doi:10.1111/imm.12888.
   PubMed Web of Science ®Google Scholar
• Heath WR, Carbone FR. The skin-resident and migratory immune system in steady state and memory: innate lymphocytes, dendritic cells and T cells. Nat Immunol. 2013;14(10):978–985. doi:10.1038/ni.2680.
   PubMed Web of Science ®Google Scholar
• Bashaw AA, Leggatt GR, Chandra J, et al. Modulation of antigen presenting cell functions during chronic HPV infection. Papillomavirus Res. 2017;4:58–65. doi:10.1016/j.pvr.2017.08.002.
   PubMed Web of Science ®Google Scholar
• Jimenez-Flores R, Mendez-Cruz R, Ojeda-Ortiz J, et al. High-risk human papilloma virus infection decreases the frequency of dendritic Langerhans' cells in the human female genital tract. Immunology. 2006;117(2):220–228. doi:10.1111/j.1365-2567.2005.02282.x.
   PubMed Web of Science ®Google Scholar
• Yang W, Song Y, Lu YL, et al. 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. Immunology. 2013;139(4):513–522. doi:10.1111/imm.12101.
   PubMed Web of Science ®Google Scholar
• Song MY, Park SH, Nam HJ, et al. Enhancement of vaccine-induced primary and memory CD8(+) T-cell responses by soluble PD-1. J Immunother. 2011;34(3):297–306. doi:10.1097/CJI.0b013e318210ed0e.
   PubMed Web of Science ®Google Scholar
• Almand B, Clark JI, Nikitina E, et al. Increased production of immature myeloid cells in cancer patients: a mechanism of immunosuppression in cancer. J Immunol. 2001;166(1):678–689. doi:10.4049/jimmunol.166.1.678.
   PubMed Web of Science ®Google Scholar
• Almand B, Resser JR, Lindman B, et al. Clinical significance of defective dendritic cell differentiation in cancer. Clin Cancer Res. 2000;6(5):1755–1766.
   PubMed Web of Science ®Google Scholar
• Tang A, Amagai M, Granger LG, et al. Adhesion of epidermal Langerhans cells to keratinocytes mediated by E-cadherin. Nature. 1993;361(6407):82–85. doi:10.1038/361082a0.]
   PubMed Web of Science ®Google Scholar
• Blauvelt A, Katz SI, Udey MC. Human Langerhans cells express E-cadherin. J Invest Dermatol. 1995;104(2):293–296. doi:10.1111/1523-1747.ep12612830.
   PubMed Web of Science ®Google Scholar
• Jakob T, Udey MC. Regulation of E-cadherin-mediated adhesion in Langerhans cell-like dendritic cells by inflammatory mediators that mobilize Langerhans cells in vivo. J Immunol. 1998;160(8):4067–4073.
   PubMed Web of Science ®Google Scholar
• Schwarzenberger K, Udey MC. Contact allergens and epidermal proinflammatory cytokines modulate Langerhans cell E-cadherin expression in situ. J Invest Dermatol. 1996;106(3):553–558. doi:10.1111/1523-1747.ep12344019.
   PubMed Web of Science ®Google Scholar
• Leong CM, Doorbar J, Nindl I, et al. Loss of epidermal Langerhans cells occurs in human papillomavirus alpha, gamma, and mu but not beta genus infections. J Invest Dermatol. 2010;130(2):472–480. doi:10.1038/jid.2009.266.
   PubMed Web of Science ®Google Scholar
• Shannon B, Yi TJ, Perusini S, et al. Association of HPV infection and clearance with cervicovaginal immunology and the vaginal microbiota. Mucosal Immunol. 2017;10(5):1310–1319. doi:10.1038/mi.2016.129.
   PubMed Web of Science ®Google Scholar
• Jiang B, Xue M. Correlation of E6 and E7 levels in high-risk HPV16 type cervical lesions with CCL20 and Langerhans cells. Genet Mol Res. 2015;14(3):10473–10481. doi:10.4238/2015.September.8.8.
   PubMed Web of Science ®Google Scholar
• Medzhitov R, Janeway CA. Jr. Decoding the patterns of self and nonself by the innate immune system. Science. 2002;296(5566):298–300. doi:10.1126/science.1068883.
   PubMed Web of Science ®Google Scholar
• Yang X, Cheng Y, Li C. The role of TLRs in cervical cancer with HPV infection: a review. Signal Transduct Target Ther. 2017;2:17055doi:10.1038/sigtrans.2017.55.
   PubMed Web of Science ®Google Scholar
• Medzhitov R. Toll-like receptors and innate immunity. Nat Rev Immunol. 2001;1(2):135–145. doi:10.1038/35100529.
   PubMed Web of Science ®Google Scholar
• El-Omar EM, Ng MT, Hold GL. Polymorphisms in Toll-like receptor genes and risk of cancer. Oncogene. 2008;27(2):244–252. doi:10.1038/sj.onc.1210912.
   PubMed Web of Science ®Google Scholar
• Kawai T, Akira S. Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity. 2011;34(5):637–650. doi:10.1016/j.immuni.2011.05.006.
   PubMed Web of Science ®Google Scholar
• Hasan UA, Bates E, Takeshita F, et al. TLR9 expression and function is abolished by the cervical cancer-associated human papillomavirus type 16. J Immunol. 2007;178(5):3186–3197. doi:10.4049/jimmunol.178.5.3186.
   PubMed Web of Science ®Google Scholar
• Kalali BN, Köllisch G, Mages J, et al. Double-stranded RNA induces an antiviral defense status in epidermal keratinocytes through TLR3-, PKR-, and MDA5/RIG-I-mediated differential signaling. J Immunol. 2008;181(4):2694–2704. doi:10.4049/jimmunol.181.4.2694.
   PubMed Web of Science ®Google Scholar
• Daud II, Scott ME, Ma Y, et al. Association between toll-like receptor expression and human papillomavirus type 16 persistence. Int J Cancer. 2011;128(4):879–886. doi:10.1002/ijc.25400.
   PubMed Web of Science ®Google Scholar
• Kelly MG, Alvero AB, Chen R, et al. TLR-4 signaling promotes tumor growth and paclitaxel chemoresistance in ovarian cancer. Cancer Res. 2006;66(7):3859–3868. doi:10.1158/0008-5472.CAN-05-3948.
   PubMed Web of Science ®Google Scholar
• de Matos LG, Candido EB, Vidigal PV, et al. Association between Toll-like receptor and tumor necrosis factor immunological pathways in uterine cervical neoplasms. Tumori. 2017;103(1):81–86. doi:10.5301/tj.5000576.
   PubMed Web of Science ®Google Scholar
• Hasimu A, Ge L, Li QZ, et al. Expressions of Toll-like receptors 3, 4, 7, and 9 in cervical lesions and their correlation with HPV16 infection in Uighur women. Chin J Cancer. 2011;30(5):344–350. doi:10.5732/cjc.010.10456.
   PubMedGoogle Scholar
• Rahkola P, Mikkola TS, Ylikorkala O, et al. Association between high risk papillomavirus DNA and nitric oxide release in the human uterine cervix. Gynecol Oncol. 2009;114(2):323–326. doi:10.1016/j.ygyno.2009.05.003.
   PubMed Web of Science ®Google Scholar
• Dong J, Cheng M, Sun H. Function of inducible nitric oxide synthase in the regulation of cervical cancer cell proliferation and the expression of vascular endothelial growth factor. Mol Med Rep. 2014;9(2):583–589. doi:10.3892/mmr.2013.1838.
   PubMed Web of Science ®Google Scholar
• Ludlow LE, Johnstone RW, Clarke CJ. The HIN-200 family: more than interferon-inducible genes?. Exp Cell Res. 2005;308(1):1–17. doi:10.1016/j.yexcr.2005.03.032.
   PubMed Web of Science ®Google Scholar
• Reinholz M, Kawakami Y, Salzer S, et al. HPV16 activates the AIM2 inflammasome in keratinocytes. Arch Dermatol Res. 2013;305(8):723–732. doi:10.1007/s00403-013-1375-0.
   PubMed Web of Science ®Google Scholar
• Unterholzner L, Keating SE, Baran M, et al. IFI16 is an innate immune sensor for intracellular DNA. Nat Immunol. 2010;11(11):997–1004. doi:10.1038/ni.1932.
   PubMed Web of Science ®Google Scholar
• Jakobsen MR, Bak RO, Andersen A, et al. IFI16 senses DNA forms of the lentiviral replication cycle and controls HIV-1 replication. Proc Natl Acad Sci Usa. 2013;110(48):E4571–4580. doi:10.1073/pnas.1311669110.
   PubMed Web of Science ®Google Scholar
• Lo Cigno I, De Andrea M, Borgogna C, et al. The nuclear DNA sensor IFI16 acts as a restriction factor for human papillomavirus replication through epigenetic modifications of the viral promoters. J Virol. 2015;89(15):7506–7520. doi:10.1128/JVI.00013-15.
   PubMed Web of Science ®Google Scholar
• Fitzgerald KA, McWhirter SM, Faia KL, et al. IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway. Nat Immunol. 2003;4(5):491–496. doi:10.1038/ni921.
   PubMed Web of Science ®Google Scholar
• Tanaka Y, Chen ZJ. STING specifies IRF3 phosphorylation by TBK1 in the cytosolic DNA signaling pathway. Sci Signal. 2012;5(214):ra20doi:10.1126/scisignal.2002521.
   PubMed Web of Science ®Google Scholar
• Ablasser A, Goldeck M, Cavlar T, et al. cGAS produces a 2'-5'-linked cyclic dinucleotide second messenger that activates STING. Nature. 2013;498(7454):380–384. doi:10.1038/nature12306.
   PubMed Web of Science ®Google Scholar
• Stetson DB, Medzhitov R. Type I interferons in host defense. Immunity. 2006;25(3):373–381. doi:10.1016/j.immuni.2006.08.007.
   PubMed Web of Science ®Google Scholar
• Fensterl V, Sen GC. Interferons and viral infections. Biofactors. 2009;35(1):14–20. doi:10.1002/biof.6.
   PubMed Web of Science ®Google Scholar
• Stadnyk AW. Cytokine production by epithelial cells. FASEB J. 1994;8(13):1041–1047. doi:10.1096/fasebj.8.13.7926369.
   PubMed Web of Science ®Google Scholar
• Woodworth CD, Simpson S. Comparative lymphokine secretion by cultured normal human cervical keratinocytes, papillomavirus-immortalized, and carcinoma cell lines. Am J Pathol. 1993;142(5):1544–1555.
   PubMed Web of Science ®Google Scholar
• Scott ME, Ma Y, Kuzmich L, Moscicki AB. Diminished IFN-gamma and IL-10 and elevated Foxp3 mRNA expression in the cervix are associated with CIN 2 or 3. Int J Cancer. 2009;124(6):1379–1383. doi:10.1002/ijc.24117.
   PubMed Web of Science ®Google Scholar
• Reiser J, Hurst J, Voges M, et al. High-risk human papillomaviruses repress constitutive kappa interferon transcription via E6 to prevent pathogen recognition receptor and antiviral-gene expression. J Virol. 2011;85(21):11372–11380. doi:10.1128/JVI.05279-11.
   PubMed Web of Science ®Google Scholar
• Meraz MA, White JM, Sheehan KC, et al. Targeted disruption of the Stat1 gene in mice reveals unexpected physiologic specificity in the JAK-STAT signaling pathway. Cell. 1996;84(3):431–442. doi:10.1016/s0092-8674(00)81288-x.
   PubMed Web of Science ®Google Scholar
• Ronco LV, Karpova AY, Vidal M, Howley PM. Human papillomavirus 16 E6 oncoprotein binds to interferon regulatory factor-3 and inhibits its transcriptional activity. Genes Dev. 1998;12(13):2061–2072. doi:10.1101/gad.12.13.2061.
   PubMed Web of Science ®Google Scholar
• Li S, Labrecque S, Gauzzi MC, et al. The human papilloma virus (HPV)-18 E6 oncoprotein physically associates with Tyk2 and impairs Jak-STAT activation by interferon-alpha. Oncogene. 1999;18(42):5727–5737. doi:10.1038/sj.onc.1202960.
   PubMed Web of Science ®Google Scholar
• Arany I, Goel A, Tyring SK. Interferon response depends on viral transcription in human papillomavirus-containing lesions. Anticancer Res. 1995;15(6B):2865–2869.
   PubMed Web of Science ®Google Scholar
• Markiewski MM, Lambris JD. The role of complement in inflammatory diseases from behind the scenes into the spotlight. Am J Pathol. 2007;171(3):715–727. doi:10.2353/ajpath.2007.070166.
   PubMed Web of Science ®Google Scholar
• Ricklin D, Hajishengallis G, Yang K, et al. Complement: a key system for immune surveillance and homeostasis. Nat Immunol. 2010;11(9):785–797. doi:10.1038/ni.1923.
   PubMed Web of Science ®Google Scholar
• Markiewski MM, DeAngelis RA, Benencia F, et al. Modulation of the antitumor immune response by complement. Nat Immunol. 2008;9(11):1225–1235. doi:10.1038/ni.1655.
   PubMed Web of Science ®Google Scholar
• Canales NA, Marina VM, Castro JS, et al. A1BG and C3 are overexpressed in patients with cervical intraepithelial neoplasia III. Oncol Lett. 2014;8(2):939–947. doi:10.3892/ol.2014.2195.
   PubMed Web of Science ®Google Scholar
• Verhaegen H, De Cock W, De Cree J, Verbruggen F. Increase of serum complement levels in cancer patients with progressing tumors. Cancer. 1976;38(4):1608–1613. doi:10.1002/1097-0142(197610)38:4<1608::AID-CNCR2820380427>3.0.CO;2-6.
   PubMed Web of Science ®Google Scholar
• Corrales L, Ajona D, Rafail S, et al. Anaphylatoxin C5a creates a favorable microenvironment for lung cancer progression. J Immunol. 2012;189(9):4674–4683. doi:10.4049/jimmunol.1201654.
   PubMed Web of Science ®Google Scholar
• de Visser KE, Korets LV, Coussens LM. Early neoplastic progression is complement independent. Neoplasia. 2004;6(6):768–776. doi:10.1593/neo.04250.
   PubMed Web of Science ®Google Scholar
• Stanley M. Immune responses to human papillomavirus. Vaccine. 2006;24:S16–S22. doi:10.1016/j.vaccine.2005.09.002.
   PubMed Web of Science ®Google Scholar
• Moerman-Herzog A, Nakagawa M. Early defensive mechanisms against human papillomavirus infection. Clin Vaccine Immunol. 2015;22(8):850–857. doi:10.1128/CVI.00223-15.
   PubMedGoogle Scholar
• Azar KK, Tani M, Yasuda H, et al. Increased secretion patterns of interleukin-10 and tumor necrosis factor-alpha in cervical squamous intraepithelial lesions. Hum Pathol. 2004;35(11):1376–1384. doi:10.1016/j.humpath.2004.08.012.
   PubMed Web of Science ®Google Scholar
• Alves JJP, De Medeiros Fernandes TAA, De Araújo JMG, et al. Th17 response in patients with cervical cancer. Oncol Lett. 2018;16(5):6215–6227. doi:10.3892/ol.2018.9481.
   PubMed Web of Science ®Google Scholar
• Tanaka A, Sakaguchi S. Regulatory T cells in cancer immunotherapy. Cell Res. 2017;27(1):109–118. doi:10.1038/cr.2016.151.
   PubMed Web of Science ®Google Scholar
• van der Burg SH, Piersma SJ, de Jong A, et al. Association of cervical cancer with the presence of CD4+ regulatory T cells specific for human papillomavirus antigens. Proc Natl Acad Sci USA. 2007;104(29):12087–12092. doi:10.1073/pnas.0704672104.
   PubMed Web of Science ®Google Scholar
• Loddenkemper C, Hoffmann C, Stanke J, et al. Regulatory (FOXP3+) T cells as target for immune therapy of cervical intraepithelial neoplasia and cervical l cancer. Cancer Sci. 2009;100(6):1112–1117. doi:10.1111/j.1349-7006.2009.01153.x.
   PubMed Web of Science ®Google Scholar
• Stone SC, Rossetti RA, Lima AM, Lepique AP. HPV associated tumor cells control tumor microenvironment and leukocytosis in experimental models. Immun Inflamm Dis. 2014;2(2):63–75. doi:10.1002/iid3.21.
   PubMedGoogle Scholar
• Prata TT, Bonin CM, Ferreira AM, et al. Local immunosuppression induced by high viral load of human papillomavirus: characterization of cellular phenotypes producing interleukin-10 in cervical neoplastic lesions. Immunology. 2015;146(1):113–121. doi:10.1111/imm.12487.
   PubMed Web of Science ®Google Scholar
• Bhairavabhotla RK, Verm V, Tongaonkar H, et al. Role of IL-10 in immune suppression in cervical cancer. Indian J Biochem Biophys. 2007;44(5):350–356.
   PubMed Web of Science ®Google Scholar
• Moir S, Fauci AS. B cells in HIV infection and disease. Nat Rev Immunol. 2009;9(4):235–245. doi:10.1038/nri2524.
   PubMed Web of Science ®Google Scholar
• Dörner T, Jacobi AM, Lipsky PE. B cells in autoimmunity. Arthritis Res Ther. 2009;11(5):247doi:10.1186/ar2780.
   PubMed Web of Science ®Google Scholar
• Sarvaria A, Madrigal JA, Saudemont A. B cell regulation in cancer and anti-tumor immunity. Cell Mol Immunol. 2017;14(8):662–674. doi:10.1038/cmi.2017.35.
   PubMed Web of Science ®Google Scholar
• Tang A, Dadaglio G, Oberkampf M, et al. B cells promote tumor progression in a mouse model of HPV-mediated cervical cancer. Int J Cancer. 2016;139(6):1358–1371. doi:10.1002/ijc.30169.
   PubMed Web of Science ®Google Scholar
• Kim SS, Shen S, Miyauchi S, et al. B cells improve overall survival in HPV-associated squamous cell carcinomas and are activated by radiation and PD-1 blockade. Clin Cancer Res. 2020;26(13):3345–3359. doi:10.1158/1078-0432.CCR-19-3211.
   PubMed Web of Science ®Google Scholar
• Chen Z, Zhu Y, Du R, et al. Role of regulatory B cells in the progression of cervical cancer. Mediators Inflamm. 2019;2019:1–8. doi:10.1155/2019/6519427.
   Web of Science ®Google Scholar
• Rodriguez AC, Schiffman M, Herrero R, et al. Low risk of type-specific carcinogenic HPV re-appearance with subsequent cervical intraepithelial neoplasia grade 2/3. Int J Cancer. 2012;131(8):1874–1881. doi:10.1002/ijc.27418.
   PubMed Web of Science ®Google Scholar
• Beachler DC, Jenkins G, Safaeian M, et al. Natural acquired immunity against subsequent genital human papillomavirus infection: a systematic review and meta-analysis. J Infect Dis. 2016;213(9):1444–1454. doi:10.1093/infdis/jiv753.
   PubMed Web of Science ®Google Scholar
• Coseo SE, Porras C, Dodd LE, et al. Evaluation of the polyclonal ELISA HPV serology assay as a biomarker for human papillomavirus exposure. Sex Transm Dis. 2011;38:976–982.
   PubMed Web of Science ®Google Scholar
• Combes JD, Pawlita M, Waterboer T, et al. Antibodies against high-risk human papillomavirus proteins as markers for invasive cervical cancer. Int J Cancer. 2014;135(10):2453–2461. doi:10.1002/ijc.28888.
   PubMed Web of Science ®Google Scholar
• Kirnbauer R, Taub J, Greenstone H, et al. Efficient self-assembly of human papillomavirus type 16 L1 and L1-L2 into virus-like particles. J Virol. 1993;67(12):6929–6936. doi:10.1128/JVI.67.12.6929-6936.1993.
   PubMed Web of Science ®Google Scholar
• Rocha-Zavaleta L, Ambrosio JP, Mora-Garcia ML, et al. Detection of antibodies against a human papillomavirus (HPV) type 16 peptide that differentiate high-risk from low-risk HPV-associated low-grade squamous intraepithelial lesions. J Gen Virol. 2004;85(9):2643–2650. doi:10.1099/vir.0.80077-0.
   PubMedGoogle Scholar
• Heino P, Skyldberg B, Lehtinen M, et al. Human papillomavirus type 16 capsids expose multiple type-restricted and type-common antigenic epitopes. J Gen Virol. 1995;76(5):1141–1153. doi:10.1099/0022-1317-76-5-1141.
   PubMedGoogle Scholar
• Le Cann P, Chabaud M, Leboulleux D, et al. Detection of antibodies to L1, L2, and E4 proteins of human papillomavirus types 6, 11, and 16 by ELISA using synthetic peptides. J Med Virol. 1995;45(4):410–414. doi:10.1002/jmv.1890450410.
   PubMed Web of Science ®Google Scholar
• Zumbach K, Kisseljov F, Sacharova O, et al. Antibodies against oncoproteins E6 and E7 of human papillomavirus types 16 and 18 in cervical-carcinoma patients from Russia. Int J Cancer. 2000;85(3):313–318. doi:10.1002/(SICI)1097-0215(20000201)85:3<313::AID-IJC3>3.0.CO;2-W.
   PubMed Web of Science ®Google Scholar
• Meschede W, Zumbach K, Braspenning J, et al. Antibodies against early proteins of human papillomaviruses as diagnostic markers for invasive cervical cancer. J Clin Microbiol. 1998;36(2):475–480. doi:10.1128/JCM.36.2.475-480.1998.
   PubMed Web of Science ®Google Scholar
• Nindl I, Zumbach K, Pawlita M, et al. Absence of antibody against human papillomavirus type 16 E6 and E7 in patients with cervical cancer is independent of sequence variations. J Infect Dis. 2000;181(5):1764–1767. doi:10.1086/315451.
   PubMed Web of Science ®Google Scholar
• Ramezani A, Aghakhani A, Soleymani S, et al. Significance of serum antibodies against HPV E7, Hsp27, Hsp20 and Hp91 in Iranian HPV-exposed women. BMC Infect Dis. 2019;19(1):142. doi:10.1186/s12879-019-3780-2.
   PubMedGoogle Scholar
• Maciag PC, Villa LL. Genetic susceptibility to HPV infection and cervical cancer. Braz J Med Biol Res. 1999;32(7):915–922. doi:10.1590/s0100-879x1999000700017.
   PubMed Web of Science ®Google Scholar
• Hildesheim A, Wang SS. Host and viral genetics and risk of cervical cancer: a review. Virus Res. 2002;89(2):229–240. doi:10.1016/s0168-1702(02)00191-0.
   PubMed Web of Science ®Google Scholar
• The MHC sequencing consortium Complete sequence and gene map of a human major histocompatibility complex. Nature. 1999;401:921–923.
   PubMed Web of Science ®Google Scholar
• Gameiro SF, Zhang A, Ghasemi F, et al. Analysis of class I major histocompatibility complex gene transcription in human tumors caused by human papillomavirus infection. Viruses. 2017;9(9):252. doi:10.3390/v9090252.
   PubMed Web of Science ®Google Scholar
• Cicchini L, Blumhagen RZ, Westrich JA, et al. High-risk human papillomavirus E7 alters host DNA methylome and represses HLA-E expression in human keratinocytes. Sci Rep. 2017;7(1):3633doi:10.1038/s41598-017-03295-7.
   PubMedGoogle Scholar
• Isaacson Wechsler E, Wang Q, Roberts I, et al. Reconstruction of human papillomavirus type 16-mediated early-stage neoplasia implicates E6/E7 deregulation and the loss of contact inhibition in neoplastic progression. J Virol. 2012;86(11):6358–6364. doi:10.1128/JVI.07069-11.
   PubMed Web of Science ®Google Scholar
• McBride AA, Warburton A. The role of integration in oncogenic progression of HPV-associated cancers. PLoS Pathog. 2017;13(4):e1006211doi:10.1371/journal.ppat.1006211.
   PubMed Web of Science ®Google Scholar
• Burgers WA, Blanchon L, Pradhan S, et al. Viral oncoproteins target the DNA methyltransferases. Oncogene. 2007;26(11):1650–1655. doi:10.1038/sj.onc.1209950.
   PubMed Web of Science ®Google Scholar
• Laurson J, Khan S, Chung R, et al. Epigenetic repression of E-cadherin by human papillomavirus 16 E7 protein. Carcinogenesis. 2010;31(5):918–926. doi:10.1093/carcin/bgq027.
   PubMed Web of Science ®Google Scholar
• Hasan UA, Zannetti C, Parroche P, et al. The human papillomavirus type 16 E7 oncoprotein induces a transcriptional repressor complex on the Toll-like receptor 9 promoter. J Exp Med. 2013;210(7):1369–1387. doi:10.1084/jem.20122394.
   PubMed Web of Science ®Google Scholar
• Pacini L, Savini C, Ghittoni R, et al. Downregulation of toll-like receptor 9 expression by beta human papillomavirus 38 and implications for cell cycle control. J Virol. 2015;89(22):11396–11405. doi:10.1128/JVI.02151-15.
   PubMed Web of Science ®Google Scholar
• Cicchini L, Westrich JA, Xu T, et al. Suppression of antitumor immune responses by human papillomavirus through epigenetic downregulation of CXCL14. mBio. 2016;7(3): e00270–16. doi:10.1128/mBio.00270-16.
   PubMed Web of Science ®Google Scholar
• Senba M, Buziba N, Mori N, et al. Human papillomavirus infection induces NF-κB activation in cervical cancer: A comparison with penile cancer. Oncol Lett. 2011;2(1):65–68. doi:10.3892/ol.2010.207.
   PubMed Web of Science ®Google Scholar
• Leone P, Shin EC, Perosa F, et al. MHC class I antigen processing and presenting machinery: organization, function, and defects in tumor cells. J Natl Cancer Inst. 2013;105(16):1172–1187. doi:10.1093/jnci/djt184.
   PubMedGoogle Scholar
• Evans M, Borysiewicz LK, Evans AS, et al. Antigen processing defects in cervical carcinomas limit the presentation of a CTL epitope from human papillomavirus 16 E6. J Immunol. 2001;167(9):5420–5428. doi:10.4049/jimmunol.167.9.5420.
   PubMed Web of Science ®Google Scholar
• Hasim A, Abudula M, Aimiduo R, et al. Post-transcriptional and epigenetic regulation of antigen processing machinery (APM) components and HLA-I in cervical cancers from Uighur women. PLoS One. 2012;7(9):e44952 doi:10.1371/journal.pone.0044952.
   PubMed Web of Science ®Google Scholar
• Mehta AM, Jordanova ES, Kenter GG, et al. Association of antigen processing machinery and HLA class I defects with clinicopathological outcome in cervical carcinoma. Cancer Immunol Immunother. 2007;57(2):197–206. doi:10.1007/s00262-007-0362-8.
   PubMed Web of Science ®Google Scholar
• Mehta AM, Jordanova ES, Corver WE, et al. Single nucleotide polymorphisms in antigen processing machinery component ERAP1 significantly associate with clinical outcome in cervical carcinoma. Genes Chromosomes Cancer. 2009;48(5):410–418. doi:10.1002/gcc.20648.
   PubMed Web of Science ®Google Scholar
• Steinbach A, Winter J, Reuschenbach M, et al. ERAP1 overexpression in HPV-induced malignancies: a possible novel immune evasion mechanism. Oncoimmunology. 2017;6(7):e1336594. doi:10.1080/2162402X.2017.1336594.
   PubMed Web of Science ®Google Scholar
• Gruener M, Bravo IG, Momburg F, et al. The E5 protein of the human papillomavirus type 16 down-regulates HLA-I surface expression in calnexin-expressing but not in calnexin-deficient cells. Virol J. 2007;4:116. doi:10.1186/1743-422X-4-116.
   PubMed Web of Science ®Google Scholar
• de Boer MA, Jordanova ES, van Poelgeest MI, et al. Circulating human papillomavirus type 16 specific T-cells are associated with HLA Class I expression on tumor cells, but not related to the amount of viral oncogene transcripts. Int J Cancer. 2007;121(12):2711–2715. doi:10.1002/ijc.23035.
   PubMed Web of Science ®Google Scholar
• World Health Organization. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Human Papillomaviruses. Vol. 90. Lyon, International Agency for Research on Cancer, 2007. Available at https://monographs.iarc.fr/wp-content/uploads/2018/06/mono90.pdf. Accessed June 14, 2020.
   Google Scholar
• Naud PS, Roteli-Martins CM, De Carvalho NS, et al. Sustained efficacy, immunogenicity, and safety of the HPV-16/18 AS04-adjuvanted vaccine: final analysis of a long-term follow-up study up to 9.4 years post-vaccination. Hum Vaccin Immunother. 2014;10(8):2147–2162. doi:10.4161/hv.29532.
   PubMed Web of Science ®Google Scholar
• Schwarz TF, Huang LM, Valencia A, et al. A ten-year study of immunogenicity and safety of the AS04-HPV-16/18 vaccine in adolescent girls aged 10-14 years. Hum Vaccin Immunother. 2019;15(7-8):1970–1979. ‐doi:10.1080/21645515.2019.1625644.
   PubMed Web of Science ®Google Scholar
• World Health Organization. HPV Vaccine Background Document. 2020. Available at https://www.who.int/immunization/sage/meetings/2016/october/1_HPV_vaccine_background_document_27Sept2016.pdf?ua=1. Accessed June 14, 2020.
   Google Scholar
• Nygård M, Saah A, Munk C, et al. Evaluation of the long-term anti-human papillomavirus 6 (HPV6), 11, 16, and 18 immune responses generated by the quadrivalent HPV vaccine. Clin Vaccine Immunol. 2015;22(8):943–948. doi:10.1128/CVI.00133-15.
   PubMed Web of Science ®Google Scholar
• Guevara A, Cabello R, Woelber L, et al. Antibody persistence and evidence of immune memory at 5years following administration of the 9-valent HPV vaccine. Vaccine. 2017;35(37):5050–5057. ‐doi:10.1016/j.vaccine.2017.07.017.
   PubMed Web of Science ®Google Scholar
• Pattyn J, Van Keer S, Tjalma W, et al. Infection and vaccine-induced HPV-specific antibodies in cervicovaginal secretions. A review of the literature. Papillomavirus Res. 2019;8:100185doi:10.1016/j.pvr.2019.100185.
   PubMed Web of Science ®Google Scholar
• Noronha AS, Markowitz LE, Dunne EF. Systematic review of human papillomavirus vaccine coadministration. Vaccine. 2014;32(23):2670–2674. doi:10.1016/j.vaccine.2013.12.037.
   PubMed Web of Science ®Google Scholar
• Dauner JG, Pan Y, Hildesheim A, et al. Characterization of the HPV-specific memory B cell and systemic antibody responses in women receiving an unadjuvanted HPV16 L1 VLP vaccine. Vaccine. 2010;28(33):5407–5413. doi:10.1016/j.vaccine.2010.06.018.
   PubMed Web of Science ®Google Scholar
• Nicoli F, Mantelli B, Gallerani E, et al. HPV-specific systemic antibody responses and memory B cells are independently maintained up to 6 years and in a vaccine-specific manner following immunization with Cervarix and Gardasil in adolescent and young adult women in vaccination programs in Italy. Vaccines (Basel). 2020;8(1):26. doi:10.3390/vaccines8010026.
   Web of Science ®Google Scholar
• Giannini SL, Hanon E, Moris P, et al. Enhanced humoral and memory B cellular immunity using HPV16/18 L1 VLP vaccine formulated with the MPL/aluminium salt combination (AS04) compared to aluminium salt only. Vaccine. 2006;24(33-34):5937–5949. doi:10.1016/j.vaccine.2006.06.005.
   PubMed Web of Science ®Google Scholar