Abstract
The prevalent human papillomaviruses (HPVs) infect either cutaneous or mucosal epithelium. Active Infections lead to epithelial hyperprolifeation and are usually cleared in healthy individuals within a year. Persistent infections in the anogenital tracts by certain high-risk genotypes such as HPV-16, HPV-18 and closely related types, can progress to high grade dysplasias and carcinomas in women and men, including cervical, vulva, penile and anal cancers. A significant fraction of the head and neck cancers are also caused by HPV-16. The viral oncogenes responsible for neoplastic conversion are E6 and E7 that disrupt the pathways controlled by the two major tumor suppressor genes, p53 and members of pRB family. Because HPV cannot be propagated in conventional submerged monolayer cell cultures, organotypic epithelial raft cultures that generate a stratified and differentiated epithelium have been used to study the viral life cycle. This article describes several systems to examine aspects of the viral productive phase, along with the advantages and limitations. Animal model systems of HPV carcinogenesis are also briefly described.
Keywords: human papillomaviruses (HPVs), productive program, HPV-associated cancers, model systems
Footnotes
ORCID: 0000-0001-7586-9569
References
- Adams JC, Watt FM. Fibronectin inhibits the terminal differentiation of human keratinocytes. Nature. 1989;340:307–309. doi: 10.1038/340307a0. [DOI] [PubMed] [Google Scholar]
- Allen-Hoffmann BL, Schlosser SJ, Ivarie CA, Sattler CA, Meisner LF, O’Connor SL. Normal growth and differentiation in a spontaneously immortalized near-diploid human keratinocyte cell line, NIKS. J Invest Dermatol. 2000;114:444–455. doi: 10.1046/j.1523-1747.2000.00869.x. [DOI] [PubMed] [Google Scholar]
- Asselineau D, Prunieras M. Reconstruction of “simplified’ skin: control of fabrication. Br J Dermatol. 1984;111(Suppl27):219–222. doi: 10.1111/j.1365-2133.1984.tb15608.x. [DOI] [PubMed] [Google Scholar]
- Banerjee NS, Wang HK, Broker TR, Chow LT. Human papillomavirus (HPV) E7 induces prolonged G2 following S phase reentry in differentiated human keratinocytes. J Biol Chem. 2011;286:15473–115482. doi: 10.1074/jbc.M110.197574. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bedell MA, Hudson JB, Golub TR, Turek ME, Hosken M, Wilbanks GD, Laimins LA. Amplification of human papillomavirus genomes in vitro is dependent on epithelial differentiation. J Virol. 1991;65:2254–2260. doi: 10.1128/jvi.65.5.2254-2260.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Blanton RA, Perez-Reyes N, Merrick DT, McDougall JK. Epithelial cells immortalized by human papillomaviruses have premalignant characteristics in organotypic culture. Am J Pathol. 1991;138:673–685. [PMC free article] [PubMed] [Google Scholar]
- Bonnez W. The HPV xenograft severe combined immunodeficiency mouse model. Methods Mol Med. 2005;119:203–216. doi: 10.1385/1-59259-982-6:203. [DOI] [PubMed] [Google Scholar]
- Borgogna C, Zavattaro E, De Andrea M, Griffin HM, Dell’Oste V, Azzimonti B, Landini MM, Peh WL, Pfister H, Doorbar J, Landolfo S, Gariglio M. Characterization of beta papillomavirus E4 expression in tumours from Epidermodysplasia Verruciformis patients and in experimental models. Virology. 2012;423:195–204. doi: 10.1016/j.virol.2011.11.029. [DOI] [PubMed] [Google Scholar]
- Boyce ST, Ham RG. Calcium-regulated differentiation of normal human epidermal keratinocytes in chemically defined clonal culture and serum-free serial culture. J Invest Dermatol. 1983;81:33s–40s. doi: 10.1111/1523-1747.ep12540422. [DOI] [PubMed] [Google Scholar]
- Bravo IG, Félez-Sánchez M. Papillomaviruses: Viral evolution, cancer and evolutionary medicine. Evol Med Public Health. 2015;1:32–51. doi: 10.1093/emph/eov003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bulut G, Üren A. Generation of k14-e7/Δn87βcat double transgenic mice as a model of cervical cancer. Methods Mol Biol. 2015;1249:393–406. doi: 10.1007/978-1-4939-2013-6_29. [DOI] [PubMed] [Google Scholar]
- Buonomo T, Carraresi L, Rossini M, Martinelli R. Involvement of aryl hydrocarbon receptor signaling in the development of small cell lung cancer induced by HPV E6/E7 oncoproteins. J Transl Med. 2011;9:2. doi: 10.1186/1479-5876-9-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bzhalava D, Eklund C, Dillner J. International standardization and classification of human papillomavirus types. Virology. 2015;476:341–344. doi: 10.1016/j.virol.2014.12.028. [DOI] [PubMed] [Google Scholar]
- Cancer Genome Atlas Network. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature. 2015;517:576–582. doi: 10.1038/nature14129. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chen Y, Pirisi L, Creek KE. Ski protein levels increase during in vitro progression of HPV16-immortalized human keratinocytes and in cervical cancer. Virology. 2013;444:100–108. doi: 10.1016/j.virol.2013.05.039. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cheng S, Schmidt-Grimminger DC, Murant T, Broker TR, Chow LT. Differentiation-dependent up-regulation of the human papillomavirus E7 gene reactivates cellular DNA replication in suprabasal differentiated keratinocytes. Genes Dev. 1995;9:2335–2349. doi: 10.1101/gad.9.19.2335. [DOI] [PubMed] [Google Scholar]
- Chow LT, Broker TR. Human papillomavirus infections: warts or cancer? Cold Spring Harb Perspect Biol. 2013;5:a012997. doi: 10.1101/cshperspect.a012997. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chung SH, Lambert PF. Prevention and treatment of cervical cancer in mice using estrogen receptor antagonists. Proc Natl Acad Sci U S A. 2009;106:19467–19472. doi: 10.1073/pnas.0911436106. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chung TK, Van Hummelen P, Chan PK, Cheung TH, Yim SF, Yu MY, et al. Int J Cancer. 2015. Genomic aberrations in cervical adenocarcinomas in Hong Kong Chinese women. [DOI] [PubMed] [Google Scholar]
- Creek KE, Geslani G, Batova A, Pirisi L. Progressive loss of sensitivity to growth control by retinoic acid and transforming growth factor-beta at late stages of human papillomavirus type 16-initiated transformation of human keratinocytes. Adv Exp Med Biol. 1995;375:117–135. doi: 10.1007/978-1-4899-0949-7_11. [DOI] [PubMed] [Google Scholar]
- Dollard SC, Wilson JL, Demeter LM, Bonnez W, Reichman RC, Broker TR, Chow LT. Production of human papillomavirus and modulation of the infectious program in epithelial raft cultures. Genes Dev. 1992;6:1131–1142. doi: 10.1101/gad.6.7.1131. [DOI] [PubMed] [Google Scholar]
- Donaldson MM, Mackintosh LJ, Bodily JM, Dornan ES, Laimins LA, Morgan IM. An interaction between human papillomavirus 16 E2 and TopBP1 is required for optimum viral DNA replication and episomal genome establishment. J Virol. 2013;86:12806–12815. doi: 10.1128/JVI.01002-12. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gosmann C, Frazer IH, Mattarollo SR, Blumenthal A. IL-18, but not IL-12, induces production of IFN-γ in the immune-suppressive environment of HPV16 E7 transgenic hyperplastic skin. J Invest Dermatol. 2014;134:2562–2569. doi: 10.1038/jid.2014.201. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gosmann C, Mattarollo SR, Bridge JA, Frazer IH, Blumenthal A. IL-17 suppresses immune effector functions in human papillomavirus-associated epithelial hyperplasia. J Immunol. 2014;193:2248–2257. doi: 10.4049/jimmunol.1400216. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Geimanen J, Isok-Paas H, Pipitch R, Salk K, Laos T, Orav M, Reinson T, Ustav M, Jr, Ustav M, Ustav E. Development of a cellular assay system to study the genome replication of highand low-risk mucosal and cutaneous human papillomaviruses. J Virol. 2011;85:3315–3329. doi: 10.1128/JVI.01985-10. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Genovese NJ, Banerjee NS, Broker TR, Chow LT. Casein kinase II motif-dependent phosphorylation of HPV E7 protein promotes p130 degradation and S-phase induction in differentiated human keratinocytes. J Virol. 2008;82:4862–4873. doi: 10.1128/JVI.01202-07. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Genovese NJ, Broker TR, Chow LT. Nonconserved lysine residues attenuate the biological function of the low-risk human papillomavirus E7 protein. J Virol. 2011;85:5546–5554. doi: 10.1128/JVI.02166-10. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gomez LM, Ma Y, Ho C, McGrath CM, Nelson DB, Parry S. Placental infection with human papillomavirus is associated with spontaneous preterm delivery. Hum Reprod. 2008;23:709–715. doi: 10.1093/humrep/dem404. [DOI] [PubMed] [Google Scholar]
- Gunasekharan V, Laimins LA. Human papillomaviruses modulate microRNA 145 expression to directly control genome amplification. J Virol. 2013;87:6037–6043. doi: 10.1128/JVI.00153-13. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Halbert CL, Demers GW, Galloway DA. The E6 and E7 genes of human papillomavirus type 6 have weak immortalizing activity in human epithelial cells. J Virol. 1992;66:2125–2134. doi: 10.1128/jvi.66.4.2125-2134.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Henken FE, Banerjee NS, Snijders PJ, Meijer CJ, De-Castro Arce J, Rösl F, Broker TR, Chow LT, Steenbergen RD. PIK3CA-mediated PI3-kinase signaling is essential for HPV-induced transformation in vitro. Mol Cancer. 2011;10:71. doi: 10.1186/1476-4598-10-71. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hiroshima Y, Zhang Y, Zhang N, Maawy A, Mii S, Yamamoto M, Uehara F, Miwa S, Yano S, Murakami T, Momiyama M, Chishima T, Tanaka K, Ichikawa Y, Bouvet M, Murata T, Endo I, Hoffman RM. Establishment of a patient-derived orthotopic Xenograft (PDOX) model of HER-2-positive cervical cancer expressing the clinical metastatic pattern. PLoS One. 2015;10:e0117417. doi: 10.1371/journal.pone.0117417. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Honegger A, Schilling D, Bastian S, Sponagel J, Kuryshev V, Sültmann H, Scheffner M, Hoppe-Seyler K, Hoppe-Seyler F. Dependence of Intracellular and Exosomal microRNAs on Viral E6/E7 Oncogene Expression in HPV-positive Tumor Cells. PLoS Pathog. 2015;11:e1004712. doi: 10.1371/journal.ppat.1004712. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hong S, Dutta A, Laimins LA. The acetyltransferase tip60 is a critical regulator of the differentiation-dependent amplification of human papillomaviruses. J Virol. 2015;89:4668–4675. doi: 10.1128/JVI.03455-14. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hong S, Laimins LA. The JAK-STAT transcriptional regulator, STAT-5, activates the ATM DNA damage pathway to induce HPV 31 genome amplification upon epithelial differentiation. PLoS Pathog. 2013;9:e1003295. doi: 10.1371/journal.ppat.1003295. [DOI] [PMC free article] [PubMed] [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;85:9486–9494. doi: 10.1128/JVI.05007-11. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hoskins EE, Morreale RJ, Werner SP, Higginbotham JM, Laimins LA, Lambert PF, Brown DR, Gillison ML, Nuovo GJ, Witte DP, Kim MO, Davies SM, Mehta PA, Butsch Kovacic M, Wikenheiser-Brokamp KA, Wells SI. The fanconi anemia pathway limits human papillomavirus replication. J Virol. 2012;86:8131–8138. doi: 10.1128/JVI.00408-12. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Howley PM, Pfister HJ. Virology. 2015. Beta genus papillomaviruses and skin cancer. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Howie HL, Katzenellenbogen RA, Galloway DA. Papillomavirus E6 proteins. Virology. 2009;384:324–334. doi: 10.1016/j.virol.2008.11.017. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hufbauer M, Lazić D, Reinartz M, Akgül B, Pfister H, Weissenborn SJ. Skin tumor formation in human papillomavirus 8 transgenic mice is associated with a deregulation of oncogenic miRNAs and their tumor suppressive targets. J Dermatol Sci. 2011;64:7–15. doi: 10.1016/j.jdermsci.2011.06.008. [DOI] [PubMed] [Google Scholar]
- Hurlin PJ, Kaur P, Smith PP, Perez-Reyes N, Blanton RA, McDougall JK. Progression of human papillomavirus type 18-immortalized human keratinocytes to a malignant phenotype. Proc Natl Acad Sci U S A. 1991;88:570–574. doi: 10.1073/pnas.88.2.570. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jabbar S, Strati K, Shin MK, Pitot HC, Lambert PF. Human papillomavirus type 16 E6 and E7 oncoproteins act synergistically to cause head and neck cancer in mice. Virology. 2010;407:60–67. doi: 10.1016/j.virol.2010.08.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jagu SJ, Kwak K, Schiller JT, Lowy DR, Kleanthous H, Kalnin K, Wang HK, Chow LT, Huh WK, Jaganathan K, Chivukula S, Roden RB. Phylogenetic considerations in designing a broadly protective multimeric L2 vaccine. J Virol. 2013;87:6127–6136. doi: 10.1128/JVI.03218-12. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jian Y, Schmidt-Grimminger DC, Chien WM, Wu X, Broker TR, Chow LT. Post-transcriptional induction of p21cip1 protein by human papillomavirus E7 inhibits unscheduled DNA synthesis reactivated in differentiated keratinocytes. Oncogene. 1988;17:2027–2038. doi: 10.1038/sj.onc.1202142. [DOI] [PubMed] [Google Scholar]
- Jung ID, Shin SJ, Lee MG, Kang TH, Han HD, Lee SJ, Kim WS, Kim HM, Park WS, Kim HW, Yun CH, Lee EK, Wu TC, Park YM. Enhancement of tumor-specific T cell-mediated immunity in dendritic cell-based vaccines by mycobacterium tuberculosis heat shock protein X. J Immunol. 2014;193:1233–1245. doi: 10.4049/jimmunol.1400656. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kho EY, Wang HK, Banerjee NS, Broker TR, Chow LT. HPV-18 E6 mutants reveal p53 modulation of viral DNA amplification in organotypic cultures. Proc Natl Acad Sci USA. 2013;110:7542–7549. doi: 10.1073/pnas.1304855110. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lambert PF, Ozbun MA, Collins A, Holmgren S, Lee D, Nakahara T. Using an immortalized cell line to study the HPV life cycle in organotypic “raft” cultures. Methods Mol Med. 2005;119:141–155. doi: 10.1385/1-59259-982-6:141. [DOI] [PubMed] [Google Scholar]
- Lazarczyk M, Cassonnet P, Pons C, Jacob Y, Favre M. The EVER proteins as a natural barrier against papillomaviruses: a new insight into the pathogenesis of human papillomavirus infections. Microbiol Mol Biol Rev. 2009;73:348–370. doi: 10.1128/MMBR.00033-08. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lee SA, Belyaeva OV, Wu L, Kedishvili NY. Retinol dehydrogenase 10 but not retinol/sterol dehydrogenase(s) regulates the expression of retinoic acid-responsive genes in human transgenic skin raft culture. J Biol Chem. 2011;286:13550–13560. doi: 10.1074/jbc.M110.181065. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lin KY, Guarnieri FG, Staveley-O’Carroll KF, Levitsky HI, August JT, Pardoll DM, Wu TC. Treatment of established tumors with a novel vaccine that enhances major histocompatibility class II presentation of tumor antigen. Cancer Res. 1996;56:21–26. [PubMed] [Google Scholar]
- Liu Y, You H, Hermonat PL. Studying the HPV life cycle in 3A trophoblasts and resulting pathophysiology. Methods Mol Med. 2005;119:237–245. doi: 10.1385/1-59259-982-6:237. [DOI] [PubMed] [Google Scholar]
- Martinez I, Gardiner AS, Board KF, Monzon FA, Edwards RP, Khan SA. Human papillomavirus type 16 reduces the expression of microRNA-218 in cervical carcinoma cells. Oncogene. 2008;27:2575–2582. doi: 10.1038/sj.onc.1210919. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Maufort JP, Shai A, Pitot HC, Lambert PF. A role for HPV16 E5 in cervical carcinogenesis. Cancer Res. 2010;70:2924–2931. doi: 10.1158/0008-5472.CAN-09-3436. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McKenna DJ, Patel D, McCance DJ. miR-24 and miR-205 expression is dependent on HPV onco-protein expression in keratinocytes. Virology. 2014;448:210–216. doi: 10.1016/j.virol.2013.10.014. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McLaughlin-Drubin ME, Meyers C. Propagation of infectious, high-risk HPV in organotypic “raft” culture. Methods Mol Med. 2005;119:171–186. doi: 10.1385/1-59259-982-6:171. [DOI] [PubMed] [Google Scholar]
- McLaughlin-Drubin ME, Münger K. Oncogenic activities of human papillomaviruses. Virus Res. 2009;143:195–208. doi: 10.1016/j.virusres.2009.06.008. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Melar-New M, Laimins LA. Human papillomaviruses modulate expression of microRNA 203 upon epithelial differentiation to control levels of p63 proteins. J Virol. 2010;84:5212–5221. doi: 10.1128/JVI.00078-10. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Meyers C, Frattini MG, Hudson JB, Laimins LA. Biosynthesis of human papillomavirus from a continuous cell line upon epithelial differentiation. Science. 2002;257:971–973. doi: 10.1126/science.1323879. [DOI] [PubMed] [Google Scholar]
- Moody CA, Laimins LA. Human papillomaviruses activate the ATM DNA damage pathway for viral genome amplification upon differentiation. PLoS Pathog. 2009;5:e1000605. doi: 10.1371/journal.ppat.1000605. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moody CA, Laimins LA. Human papillomavirus oncoproteins: pathways to transformation. Nat Rev Cancer. 2010;10:550–560. doi: 10.1038/nrc2886. [DOI] [PubMed] [Google Scholar]
- Ocadiz-Delgado R, Marroquin-Chavira A, Hernandez-Mote R, Valencia C, Manjarrez-Zavala ME, Covarrubias L, Gariglio P. Induction of focal epithelial hyperplasia in tongue of young BK6-E6/E7 HPV16 transgenic mice. Transgenic Res. 2009;18:513–527. doi: 10.1007/s11248-009-9243-6. [DOI] [PubMed] [Google Scholar]
- Ojesina AI, Lichtenstein L, Freeman SS, Pedamallu CS, Imaz-Rosshandler I, Pugh TJ, et al. Landscape of genomic alterations in cervical carcinomas. 2014. Nature. 2014;506:371–375. doi: 10.1038/nature12881. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Park JW, Shin MK, Lambert PF. High incidence of female reproductive tract cancers in FA-deficient HPV16-transgenic mice correlates with E7’s induction of DNA damage response, an activity mediated by E7’s inactivation of pocket proteins. Oncogene. 2014;33:3383–3391. doi: 10.1038/onc.2013.327. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Park JW, Shin MK, Pitot HC, Lambert PF. High incidence of HPV-associated head and neck cancers in FA deficient mice is associated with E7’s induction of DNA damage through its inactivation of pocket proteins. PLoS One. 2013;8:e75056. doi: 10.1371/journal.pone.0075056. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Peng S, Wang JW, Karanam B, Wang C, Huh WK, Alvarez RD, Pai SI, Hung CF, Wu TC, Roden RB. Sequential cisplatin therapy and vaccination with HPV16 E6E7L2 fusion protein in saponin adjuvant GPI-0100 for the treatment of a model HPV16+ cancer. PLoS One. 2015;10:e116389. doi: 10.1371/journal.pone.0116389. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Regan JA, Laimins LA. Viral transformation of epithelial cells. Methods Mol Biol. 2013;945:449–465. doi: 10.1007/978-1-62703-125-7_26. [DOI] [PubMed] [Google Scholar]
- Sankovski E, Männik A, Geimanen J, Ustav E, Ustav M. Mapping of beta papillomavirus human papillomavirus 5 transcription and characterization of viral-genome replication function. J Virol. 2014;88:961–973. doi: 10.1128/JVI.01841-13. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sarkola ME, Grénman SE, Rintala MA, Syrjänen KJ, Syrjänen SM. Human papillomavirus in the placenta and umbilical cord blood. Acta Obstet Gynecol Scand. 2008;87:1181–1188. doi: 10.1080/00016340802468308. [DOI] [PubMed] [Google Scholar]
- Schütze DM, Kooter JM, Wilting SM, Meijer CJ, Quint W, Snijders PJ, Steenbergen RD. Longitudinal assessment of DNA methylation changes during HPVE6E7-induced immortalization of primary keratinocytes. Epigenetics. 2015;10:73–81. doi: 10.4161/15592294.2014.990787. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shishodia G, Verma G, Srivastava Y, Mehrotra R, Das BC, Bharti AC. Deregulation of microRNAs Let-7a and miR-21 mediate aberrant STAT3 signaling during human papillomavirus-induced cervical carcinogenesis: role of E6 oncoprotein. BMC Cancer. 2014;14:996. doi: 10.1186/1471-2407-14-996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Siolas D, Hannon GJ. Patient-derived tumor xenografts: transforming clinical samples into mouse models. Cancer Res. 2013;73:5315–5319. doi: 10.1158/0008-5472.CAN-13-1069. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Son J, Park JW, Lambert PF, Chung SH. Requirement of estrogen receptor alpha DNA-binding domain for HPV oncogene-induced cervical carcinogenesis in mice. Carcinogenesis. 2014;35:489–496. doi: 10.1093/carcin/bgt350. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stanley MA, Browne HM, Appleby M, Minson AC. Properties of a non-tumorigenic human cervical keratinocyte cell line. Int J Cancer. 1989;43:672–676. doi: 10.1002/ijc.2910430422. [DOI] [PubMed] [Google Scholar]
- Stanley JR, Yuspa SH. Specific epidermal protein markers are modulated during calcium-induced terminal differentiation. J Cell Biol. 1983;96:1809–1814. doi: 10.1083/jcb.96.6.1809. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Steenbergen RD, Parker JN, Isern S, Snijders PJ, Walboomers JM, Meijer CJ, Broker TR, Chow LT. Viral E6-E7 transcription in the basal layer of organotypic cultures without apparent p21cip1 protein precedes immortalization of human papillomavirus type 16- and 18-transfected human keratinocytes. J Virol. 1998;72:749–757. doi: 10.1128/jvi.72.1.749-757.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stelzer MK, Pitot HC, Liem A, Schweizer J, Mahoney C, Lambert PF. A mouse model for human anal cancer. Cancer Prev Res (Phila) 2010;3:1534–1541. doi: 10.1158/1940-6207.CAPR-10-0086. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thomas MK, Pitot HC, Liem A, Lambert PF. Dominant role of HPV16 E7 in anal carcinogenesis. Virology. 2011;421:114–118. doi: 10.1016/j.virol.2011.09.018. [DOI] [PMC free article] [PubMed] [Google Scholar]
- le Tran S, Bergot AS, Mattarollo SR, Mittal D, Frazer IH. Human papillomavirus E7 oncoprotein transgenic skin develops an enhanced inflammatory response to 2,4-dinitrochlorobenzene by an arginase-1-dependent mechanism. J Invest Dermatol. 2014;134:2438–2446. doi: 10.1038/jid.2014.186. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Viarisio D, Decker KM, Aengeneyndt B, Flechtenmacher C, Gissmann L, Tommasino M. Human papillomavirus type 38 E6 and E7 act as tumor promoters during chemically induced skin carcinogenesis. J Gen Virol. 2013;94:749–752. doi: 10.1099/vir.0.048991-0. [DOI] [PubMed] [Google Scholar]
- Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999;189:12–19. doi: 10.1002/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F. [DOI] [PubMed] [Google Scholar]
- Wald AI, Hoskins EE, Wells SI, Ferris RL, Khan SA. Alteration of microRNA profiles in squamous cell carcinoma of the head and neck cell lines by human papillomavirus. Head Neck. 2011;33:504–512. doi: 10.1002/hed.21475. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wang HK, Duffy AA, Broker TR, Chow LT. Robust production and passaging of infectious HPV in squamous epithelium of primary human keratinocytes. Genes Dev. 2009;23:181–194. doi: 10.1101/gad.1735109. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wang X, Meyers C, Wang HK, Chow LT, Zheng ZM. Construction of a full transcription map of human papillomavirus type 18 during productive viral infection. J Virol. 2011;85:8080–8092. doi: 10.1128/JVI.00670-11. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wang X, Tang S, Le SY, Lu R, Rader JS, Meyers C, Zheng ZM. Aberrant expression of oncogenic and tumor-suppressive microRNAs in cervical cancer is required for cancer cell growth. PLoS One. 2008;3:e2557. doi: 10.1371/journal.pone.0002557. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wang X, Wang HK, Li Y, Hafner M, Banerjee NS, Tang S, Briskin D, Meyers C, Chow LT, Xie X, Tuschl T, Zheng ZM. miRNAs are biomarkers of oncogenic HPV infections. Proc Natl Acad Sci U S A. 2014;111:4362–4267. doi: 10.1073/pnas.1401430111. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wang X, Wang HK, McCoy JP, Banerjee NS, Rader JS, Broker TR, Meyers C, Chow LT, Zheng ZM. Oncogenic HPV infection interrupts the expression of tumor-suppressive miR-34a through viral oncoprotein E6. RNA. 2009;15:637–647. doi: 10.1261/rna.1442309. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wilson JL, Dollard SC, Chow LT, Broker TR. Epithelial-specific gene expression during differentiation of stratified primary human keratinocyte cultures. Cell Growth Diff. 1992;3:471–483. [PubMed] [Google Scholar]
- Wilson R, Laimins LA. Differentiation of HPV-containing cells using organotypic “raft” culture or methylcellulose. Methods Mol Med. 2005;119:157–69. doi: 10.1385/1-59259-982-6:157. [DOI] [PubMed] [Google Scholar]
- Xu H, Pirisi L, Creek KE. Six1 overexpression at early stages of HPV16-mediated transformation of human keratinocytes promotes differentiation resistance and EMT. Virology. 2015;474:144–153. doi: 10.1016/j.virol.2014.10.010. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yablonska S, Hoskins EE, Wells SI, Khan SA. Identification of miRNAs dysregulated in human foreskin keratinocytes (HFKs) expressing the human papillomavirus (HPV) Type 16 E6 and E7 oncoproteins. Microrna. 2013;2:2–13. doi: 10.2174/2211536611302010002. [DOI] [PubMed] [Google Scholar]
- You H, Liu Y, Agrawal N, Prasad CK, Edwards JL, Osborne AF, Korourian S, Lowery CL, Hermonat PL. Multiple human papillomavirus types replicate in 3A trophoblasts. Placenta. 2008;29:30–38. doi: 10.1016/j.placenta.2007.08.005. [DOI] [PubMed] [Google Scholar]
- Zhang J, Li S, Yan Q, Chen X, Yang Y, Liu X, Wan X. Interferon-β induced microRNA-129-5p down-regulates HPV-18 E6 and E7 viral gene expression by targeting SP1 in cervical cancer cells. PLoS One. 2013;8:e81366. doi: 10.1371/journal.pone.0081366. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zheng ZM, Wang X. Regulation of cellular miRNA expression by human papillomaviruses. Biochim Biophys Acta. 2011;1809:668–677. doi: 10.1016/j.bbagrm.2011.05.005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- zur Hausen H. Papillomaviruses in the causation of human cancers — a brief historical account. Virology. 2009;384:260–265. doi: 10.1016/j.virol.2008.11.046. [DOI] [PubMed] [Google Scholar]