Recent Updates on the Management of Human Papillomavirus-related Cancers

Page: [272 - 283] Pages: 12

  • * (Excluding Mailing and Handling)

Abstract

Cervical cancer incidence and mortality rates have been steadily decreasing in developed nations owing to the excellent screening programs executed. However, it still remains one of the most prevalent tumors in developing nations, contributing significantly to cancer-related mortality in females. The major causal factor in the genesis of cervical cancer is recognized to be human papillomavirus (HPV) infection. The female population, particularly in poor countries, is highly susceptible to HPV infections and cervical cancer as a result of the increasing costs posed by widespread cervical screening and HPV vaccination methods. Understanding the roles of HPV oncoproteins (E6 and E7) and non-coding RNAs, along with their many cellular targets, can help us develop targeted drug therapy to manage cervical cancer. In the hunt for novel ways for effective disease control and prevention, new insights and methodologies in molecular biology keep evolving continuously. In the recent past, newer studies have revealed deeper knowledge of HPV-activated molecular signaling pathways as well as prospective targets for early diagnosis, prevention, and therapy of HPV-related malignancies. Also, there has been much new research conducted on genome-editing tools for HPVinduced cervical cancer treatment in conjunction with other treatment strategies, such as immunotherapy and therapeutic vaccines.

Graphical Abstract

[1]
International agency for cancer research. World health organisation.Cervix uteri Fact sheet. Globocan. 2020. Available From: https://gco.iarc.fr/today/data/factsheets/cancers/23-Cervi x-uteri-fact-sheet.pdf
[2]
Small W Jr, Peltecu G, Puiu A, et al. Cervical cancer in Eastern Europe: Review and proceedings from the cervical cancer research conference. Int J Gynecol Cancer 2021; 31(7): 1061-7.
[http://dx.doi.org/10.1136/ijgc-2020-001652] [PMID: 33122244]
[3]
Allemani C, Weir HK, Carreira H, et al. Global surveillance of cancer survival 1995-2009: Analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2). Lancet 2015; 385(9972): 977-1010.
[http://dx.doi.org/10.1016/S0140-6736(14)62038-9] [PMID: 25467588]
[4]
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin 2016; 66(1): 7-30.
[http://dx.doi.org/10.3322/caac.21332] [PMID: 26742998]
[5]
Pogoda CS, Roden RBS, Garcea RL. Immunizing against anogenital cancer: HPV vaccines. PLoS Pathog 2016; 12(5): e1005587.
[http://dx.doi.org/10.1371/journal.ppat.1005587] [PMID: 27196109]
[6]
Bray F, Jemal A, Torre LA, Forman D, Vineis P. Long-term realism and cost-effectiveness: Primary prevention in combatting cancer and associated inequalities worldwide. J Natl Cancer Inst 2015; 107(12): djv273.
[http://dx.doi.org/10.1093/jnci/djv273] [PMID: 26424777]
[7]
Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin 2016; 66(2): 115-32.
[http://dx.doi.org/10.3322/caac.21338] [PMID: 26808342]
[8]
Bruni L, Barrionuevo-Rosas L, Albero G, et al. ICO information centre on HPV and cancer (HPV Information Centre). Human papillomavirus and related diseases in the world. Summary Report. 2017; 27.
[9]
Mallath MK, Taylor DG, Badwe RA, et al. The growing burden of cancer in India: Epidemiology and social context. Lancet Oncol 2014; 15(6): e205-12.
[http://dx.doi.org/10.1016/S1470-2045(14)70115-9] [PMID: 24731885]
[10]
Plummer M, de Martel C, Vignat J, Ferlay J, Bray F, Franceschi S. Global burden of cancers attributable to infections in 2012: A synthetic analysis. Lancet Glob Health 2016; 4(9): e609-16.
[http://dx.doi.org/10.1016/S2214-109X(16)30143-7] [PMID: 27470177]
[11]
Chakravarthi S, Karikalan B. Basaloid squamous cell carcinoma of the oropharynx -brief overview. Inter J Pharm Res 2020; 12(4)
[http://dx.doi.org/10.31838/ijpr/2020.12.04.053]
[12]
Chesson HW, Dunne EF, Hariri S, Markowitz LE. The estimated lifetime probability of acquiring human papillomavirus in the United States. Sex Transm Dis 2014; 41(11): 660-4.
[http://dx.doi.org/10.1097/OLQ.0000000000000193] [PMID: 25299412]
[13]
Winer RL, Hughes JP, Feng Q, et al. Early natural history of incident, type-specific human papillomavirus infections in newly sexually active young women. Cancer Epidemiol Biomarkers Prev 2011; 20(4): 699-707.
[http://dx.doi.org/10.1158/1055-9965.EPI-10-1108] [PMID: 21173170]
[14]
Woodman CBJ, Collins SI, Young LS. The natural history of cervical HPV infection: Unresolved issues. Nat Rev Cancer 2007; 7(1): 11-22.
[http://dx.doi.org/10.1038/nrc2050] [PMID: 17186016]
[15]
Hu Z, Ding W, Zhu D, et al. TALEN-mediated targeting of HPV oncogenes ameliorates HPV-related cervical malignancy. J Clin Invest 2015; 125(1): 425-36.
[http://dx.doi.org/10.1172/JCI78206] [PMID: 25500889]
[16]
Elfström KM, Arnheim-Dahlström L, von Karsa L, Dillner J. Cervical cancer screening in Europe: Quality assurance and organisation of programmes. Eur J Cancer 2015; 51(8): 950-68.
[http://dx.doi.org/10.1016/j.ejca.2015.03.008] [PMID: 25817010]
[17]
Skeate JG, Woodham AW, Einstein MH, Da Silva DM, Kast WM. Current therapeutic vaccination and immunotherapy strategies for HPV-related diseases. Hum Vaccin Immunother 2016; 12: 1418-29.
[18]
Levin C, Sharma M, Olson Z, et al. An extended cost-effectiveness analysis of publicly financed HPV vaccination to prevent cervical cancer in ChinaCancer: Disease control priorities. (3rd ed.). Washington, DC: The International Bank for Reconstruction and Development/The World Bank 2015; Vol. 3: pp. 295-306.
[19]
Zhai L, Tumban E. Gardasil-9: A global survey of projected efficacy. Antiviral Res 2016; 130: 101-9.
[http://dx.doi.org/10.1016/j.antiviral.2016.03.016] [PMID: 27040313]
[20]
Flanagan SM, Wilson S, Luesley D, Damery SL, Greenfield SM. Adverse outcomes after colposcopy. BMC Womens Health 2011; 11(1): 2.
[http://dx.doi.org/10.1186/1472-6874-11-2] [PMID: 21251278]
[21]
Graziottin A, Serafini A. HPV infection in women: Psychosexual impact of genital warts and intraepithelial lesions. J Sex Med 2009; 6(3): 633-45.
[http://dx.doi.org/10.1111/j.1743-6109.2008.01151.x] [PMID: 19170869]
[22]
Kumar S, Jena L, Sahoo M, Kakde M, Daf S, Varma AK. In silico docking to explicate interface between plant-originated inhibitors and E6 oncogenic protein of highly threatening human papillomavirus 18. Genomics Inform 2015; 13(2): 60-7.
[http://dx.doi.org/10.5808/GI.2015.13.2.60] [PMID: 26175664]
[23]
Rietz A, Petrov DP, Bartolowits M, DeSmet M, Davisson VJ, Androphy EJ. Molecular probing of the HPV-16 E6 protein alpha helix binding groove with small molecule inhibitors. PLoS One 2016; 11(2): e0149845.
[http://dx.doi.org/10.1371/journal.pone.0149845] [PMID: 26915086]
[24]
Stutz C, Reinz E, Honegger A, et al. Intracellular analysis of the interaction between the human papillomavirus type 16 E6 oncoprotein and inhibitory peptides. PLoS One 2015; 10(7): e0132339.
[http://dx.doi.org/10.1371/journal.pone.0132339] [PMID: 26151636]
[25]
Liu Y, Henry GD, Hegde RS, Baleja JD. Solution structure of the hDlg/SAP97 PDZ2 domain and its mechanism of interaction with HPV-18 papillomavirus E6 protein. Biochemistry 2007; 46(38): 10864-74.
[http://dx.doi.org/10.1021/bi700879k] [PMID: 17713926]
[26]
Tian YS, Kawashita N, Arai Y, Okamoto K, Takagi T. Pharmacophore modeling and molecular docking studies of potential inhibitors to E6 PBM-PDZ from human papilloma virus (HPV). Bioinformation 2015; 11(8): 401-6.
[http://dx.doi.org/10.6026/97320630011401] [PMID: 26420921]
[27]
Zanier K, Stutz C, Kintscher S, et al. The E6AP binding pocket of the HPV16 E6 oncoprotein provides a docking site for a small inhibitory peptide unrelated to E6AP, indicating druggability of E6. PLoS One 2014; 9(11): e112514.
[http://dx.doi.org/10.1371/journal.pone.0112514] [PMID: 25383876]
[28]
Zanier K, ould M’, hamed ould Sidi A, Boulade-Ladame C. Solution structure analysis of the HPV16 E6 oncoprotein reveals a self-association mechanism required for E6-mediated degradation of p53. Structure 2012; 20(4): 604-17.
[http://dx.doi.org/10.1016/j.str.2012.02.001] [PMID: 22483108]
[29]
Yuan C-H, Filippova M, Krstenansky JL, Duerksen-Hughes PJ. Flavonol and imidazole derivatives block HPV16 E6 activities and reactivate apoptotic pathways in HPV+ cells. Cell Death Dis 2016; 7(1): e2060.
[http://dx.doi.org/10.1038/cddis.2015.391] [PMID: 26794656]
[30]
Malecka KA, Fera D, Schultz DC, et al. Identification and characterization of small molecule human papillomavirus E6 inhibitors. ACS Chem Biol 2014; 9(7): 1603-12.
[http://dx.doi.org/10.1021/cb500229d] [PMID: 24854633]
[31]
Fera D, Schultz DC, Hodawadekar S, et al. Identification and characterization of small molecule antagonists of pRb inactivation by viral oncoproteins. Chem Biol 2012; 19(4): 518-28.
[http://dx.doi.org/10.1016/j.chembiol.2012.03.007] [PMID: 22520758]
[32]
Kontostathi G, Zoidakis J, Makridakis M, et al. Cervical cancer cell line secretome analysis highlights the role of transforming growth factor-beta-induced protein ig-h3, peroxiredoxin-2 and NRF2 on cervical cancer carcinogenesis. BioMed Res Int 2017; 2017: 1-15.
[http://dx.doi.org/10.1155/2017/4180703] [PMID: 28261610]
[33]
Pappa KI, Lygirou V, Kontostathi G, et al. Proteomic analysis of normal and cancer cervical cell lines reveals deregulation of cytoskeleton-associated proteins. Cancer Genomics Proteomics 2017; 14(4): 253-66.
[http://dx.doi.org/10.21873/cgp.20036] [PMID: 28647699]
[34]
Bajan S, Hutvagner G. RNA-based therapeuticS: From antisense oligonucleotides to miRNAs. Cells 2020; 9(1): 137.
[http://dx.doi.org/10.3390/cells9010137] [PMID: 31936122]
[35]
Gutschner T, Hämmerle M, Eißmann M, et al. The noncoding RNA MALAT1 is a critical regulator of the metastasis phenotype of lung cancer cells. Cancer Res 2013; 73(3): 1180-9.
[http://dx.doi.org/10.1158/0008-5472.CAN-12-2850] [PMID: 23243023]
[36]
Arun G, Diermeier S, Akerman M, et al. Differentiation of mammary tumors and reduction in metastasis upon Malat1 lncRNA loss. Genes Dev 2016; 30(1): 34-51.
[http://dx.doi.org/10.1101/gad.270959.115] [PMID: 26701265]
[37]
Kim SS, Harford JB, Moghe M, Rait A, Pirollo KF, Chang EH. Targeted nanocomplex carrying siRNA against MALAT1 sensitizes glioblastoma to temozolomide. Nucleic Acids Res 2018; 46(3): 1424-40.
[http://dx.doi.org/10.1093/nar/gkx1221] [PMID: 29202181]
[38]
Jost I, Shalamova LA, Gerresheim GK, Niepmann M, Bindereif A, Rossbach O. Functional sequestration of microRNA-122 from Hepatitis C Virus by circular RNA sponges. RNA Biol 2018; 15(8): 1-8.
[http://dx.doi.org/10.1080/15476286.2018.1435248] [PMID: 29486652]
[39]
Derrien T, Johnson R, Bussotti G, et al. The GENCODE v7 catalog of human long noncoding RNAs: Analysis of their gene structure, evolution, and expression. Genome Res 2012; 22(9): 1775-89.
[http://dx.doi.org/10.1101/gr.132159.111] [PMID: 22955988]
[40]
Yang J, Meng X, Pan J, et al. CRISPR/Cas9-mediated noncoding RNA editing in human cancers. RNA Biol 2018; 15(1): 35-43.
[http://dx.doi.org/10.1080/15476286.2017.1391443] [PMID: 29028415]
[41]
Connelly CM, Moon MH, Schneekloth JS Jr. The Emerging Role of RNA as a Therapeutic Target for Small Molecules. Cell Chem Biol 2016; 23(9): 1077-90.
[http://dx.doi.org/10.1016/j.chembiol.2016.05.021] [PMID: 27593111]
[42]
Di Giorgio A, Duca M. Synthetic small-molecule RNA ligands: future prospects as therapeutic agents. MedChemComm 2019; 10(8): 1242-55.
[http://dx.doi.org/10.1039/C9MD00195F] [PMID: 31534649]
[43]
Xia C, Liang S, He Z, Zhu X, Chen R, Chen J. Metformin, a first-line drug for type 2 diabetes mellitus, disrupts the MALAT1/miR-142-3p sponge to decrease invasion and migration in cervical cancer cells. Eur J Pharmacol 2018; 830: 59-67.
[http://dx.doi.org/10.1016/j.ejphar.2018.04.027] [PMID: 29704494]
[44]
Xu Y, Zhang Q, Lin F, et al. Casiopeina II gly acts on lncRNA MALAT1 by miR 17 5p to inhibit FZD2 expression via the Wnt signaling pathway during the treatment of cervical carcinoma. Oncol Rep 2019; 42(4): 1365-79.
[http://dx.doi.org/10.3892/or.2019.7268] [PMID: 31524268]
[45]
Zhang J, Lin Z, Gao Y, Yao T. Downregulation of long noncoding RNA MEG3 is associated with poor prognosis and promoter hypermethylation in cervical cancer. J Exp Clin Cancer Res 2017; 36(1): 5.
[http://dx.doi.org/10.1186/s13046-016-0472-2] [PMID: 28057015]
[46]
Hu D, Su C, Jiang M, et al. Fenofibrate inhibited pancreatic cancer cells proliferation via activation of p53 mediated by upregulation of LncRNA MEG3. Biochem Biophys Res Commun 2016; 471(2): 290-5.
[http://dx.doi.org/10.1016/j.bbrc.2016.01.169] [PMID: 26850851]
[47]
Wang TH, Chan CW, Fang JY, et al. 2-O-Methylmagnolol upregulates the long non-coding RNA, GAS5, and enhances apoptosis in skin cancer cells. Cell Death Dis 2017; 8(3): e2638.
[http://dx.doi.org/10.1038/cddis.2017.66] [PMID: 28252643]
[48]
Özeş AR, Wang Y, Zong X, Fang F, Pilrose J, Nephew KP. Therapeutic targeting using tumor specific peptides inhibits long non-coding RNA HOTAIR activity in ovarian and breast cancer. Sci Rep 2017; 7(1): 894.
[http://dx.doi.org/10.1038/s41598-017-00966-3] [PMID: 28420874]
[49]
Ma T, Wang R, Zou X. Dioscin inhibits gastric tumor growth through regulating the expression level of lncRNA HOTAIR. BMC Complement Altern Med 2016; 16(1): 383.
[http://dx.doi.org/10.1186/s12906-016-1360-1] [PMID: 27751178]
[50]
Chang JT-C, Kuo T-F, Chen Y-J, et al. Highly potent and specific siRNAs against E6 or E7 genes of HPV16- or HPV18-infected cervical cancers. Cancer Gene Ther 2010; 17(12): 827-36.
[http://dx.doi.org/10.1038/cgt.2010.38] [PMID: 20885450]
[51]
Gaj T, Gersbach CA, Barbas CF III. ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering. Trends Biotechnol 2013; 31(7): 397-405.
[http://dx.doi.org/10.1016/j.tibtech.2013.04.004] [PMID: 23664777]
[52]
Albert E, Laimins L. Regulation of the human papillomavirus life cycle by DNA damage repair pathways and epigenetic factors. Viruses 2020; 12(7): 744.
[http://dx.doi.org/10.3390/v12070744] [PMID: 32664381]
[53]
Periwal V. A comprehensive overview of computational resources to aid in precision genome editing with engineered nucleases. Brief Bioinform 2017; 18(4): 698-711.
[PMID: 27373734]
[54]
Mali P, Yang L, Esvelt KM, et al. RNA-guided human genome engineering via Cas9. Science 2013; 339(6121): 823-6.
[http://dx.doi.org/10.1126/science.1232033] [PMID: 23287722]
[55]
Fu Y, Foden JA, Khayter C, et al. High-frequency off-target mutagenesis induced by CRISPR-Cas nucleases in human cells. Nat Biotechnol 2013; 31(9): 822-6.
[http://dx.doi.org/10.1038/nbt.2623] [PMID: 23792628]
[56]
Ran FA, Hsu PD, Lin CY, et al. Double nicking by RNA-guided CRISPR Cas9 for enhanced genome editing specificity. Cell 2013; 154(6): 1380-9.
[http://dx.doi.org/10.1016/j.cell.2013.08.021] [PMID: 23992846]
[57]
Hodge LS, Downs LS Jr, Chura JC, et al. Localized delivery of chemotherapy to the cervix for radiosensitization. Gynecol Oncol 2012; 127(1): 121-5.
[http://dx.doi.org/10.1016/j.ygyno.2012.07.097] [PMID: 22796462]
[58]
Caramella CM, Rossi S, Ferrari F, Bonferoni MC, Sandri G. Mucoadhesive and thermogelling systems for vaginal drug delivery. Adv Drug Deliv Rev 2015; 92: 39-52.
[http://dx.doi.org/10.1016/j.addr.2015.02.001] [PMID: 25683694]
[59]
D’Cruz OJ, Samuel P, Waurzyniak B, Uckun FM. Development and evaluation of a thermoreversible ovule formulation of stampidine, a novel nonspermicidal broad-spectrum anti-human immunodeficiency virus microbicide. Biol Reprod 2003; 69(6): 1843-51.
[http://dx.doi.org/10.1095/biolreprod.103.019182] [PMID: 12890726]
[60]
Santin AD, Deng W, Frumovitz M, et al. Phase II evaluation of nivolumab in the treatment of persistent or recurrent cervical cancer (NCT02257528/NRG-GY002). Gynecol Oncol 2020; 157(1): 161-6.
[http://dx.doi.org/10.1016/j.ygyno.2019.12.034] [PMID: 31924334]
[61]
Naumann RW, Hollebecque A, Meyer T, et al. Safety and efficacy of nivolumab monotherapy in recurrent or metastatic cervical, vaginal, or vulvar carcinoma: Results from the phase I/II CheckMate 358 trial. J Clin Oncol 2019; 37(31): 2825-34.
[http://dx.doi.org/10.1200/JCO.19.00739] [PMID: 31487218]
[62]
Chung HC, Ros W, Delord JP, et al. Efficacy and safety of pembrolizumab in previously treated advanced cervical cancer: Results from the phase II KEYNOTE-158 study. J Clin Oncol 2019; 37(17): 1470-8.
[http://dx.doi.org/10.1200/JCO.18.01265] [PMID: 30943124]
[63]
Burtness B, Harrington KJ, Greil R, et al. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): A randomised, open-label, phase 3 study. Lancet 2019; 394(10212): 1915-28.
[http://dx.doi.org/10.1016/S0140-6736(19)32591-7] [PMID: 31679945]
[64]
Grau JF, Farinas-Madrid L, Oaknin A. A randomized phase III trial of platinum chemotherapy plus paclitaxel with bevacizumab and atezolizumab versus platinum chemotherapy plus paclitaxel and bevacizumab in metastatic (stage IVB), persistent, or recurrent carcinoma of the cervix: the BEATcc study (ENGOT-Cx10/GEICO 68-C/JGOG1084/GOG-3030). Int J Gynecol Cancer 2020; 30(1): 139-43.
[http://dx.doi.org/10.1136/ijgc-2019-000880] [PMID: 31645423]
[65]
Zhao Y, Yang W, Huang Y, Cui R, Li X, Li B. Evolving roles for targeting CTLA-4 in cancer immunotherapy. Cell Physiol Biochem 2018; 47(2): 721-34.
[http://dx.doi.org/10.1159/000490025] [PMID: 29794465]
[66]
Lheureux S, Butler MO, Clarke B, et al. A phase I/II study of ipilimumab in women with metastatic or recurrent cervical carcinoma: A study of the Princess Margaret and Chicago N01 Consortia. J Clin Oncol 2015; 33(15) (Suppl.): 3061.
[http://dx.doi.org/10.1200/jco.2015.33.15_suppl.3061]
[67]
Mayadev J, Brady WE, Lin YG, Da Silva DM, Lankes HA, Fracasso PM. A phase I study of sequential ipilimumab in the definitive treatment of node positive cervical cancer: GOG 9929. J Clin Oncol 2017; 35: 5526.
[68]
Callahan MK, Odunsi K, Sznol M, et al. Phase 1 study to evaluate the safety and tolerability of MEDI4736 (durvalumab, DUR) plus tremelimumab (TRE) in patients with advanced solid tumors. J Clin Oncol 2017; 35: 3069.
[69]
Chabeda A, Yanez RJR, Lamprecht R, Meyers AE, Rybicki EP, Hitzeroth II. Therapeutic vaccines for high-risk HPV-associated diseases. Papillomavirus Res 2018; 5: 46-58.
[http://dx.doi.org/10.1016/j.pvr.2017.12.006]
[70]
Nalliah S, Karikalan B, Kademane K. Multifaceted usage of HPV related tests and products in the management of cervical cancer-A review. Asian Pac J Cancer Prev 2015; 16(6): 2145-50.
[http://dx.doi.org/10.7314/APJCP.2015.16.6.2145] [PMID: 25824730]
[71]
Lin K, Doolan K, Hung CF, Wu TC. Perspectives for preventive and therapeutic HPV vaccines. J Formos Med Assoc 2010; 109(1): 4-24.
[http://dx.doi.org/10.1016/S0929-6646(10)60017-4] [PMID: 20123582]
[72]
Huh WK, Dizon DS, Powell MA, et al. ADXS11-001 immunotherapy in squamous or non-squamous persistent/recurrent metastatic cervical cancer: Results from stage I of the phase II GOG/NRG0265 study. J Clin Oncol 2016; 34(15) (Suppl.): 5516.
[http://dx.doi.org/10.1200/JCO.2016.34.15_suppl.5516]
[73]
Basu P, Mehta A, Jain M, et al. A Randomized phase 2 study of ADXS11-001 Listeria monocytogenes-Listeriolysin O immunotherapy with or without cisplatin in treatment of advanced cervical cancer. Int J Gynecol Cancer 2018; 28(4): 764-72.
[http://dx.doi.org/10.1097/IGC.0000000000001235] [PMID: 29538258]
[74]
Safran H, Leonard KL, DiPetrillo TA, et al. ADXS11-001 Lm -LLO Immunotherapy, Mitomycin, 5-fluorouracil (5-FU) and Intensity-modulated radiation therapy (IMRT) for Anal Cancer. J Clin Oncol 2017; 35(15) (Suppl.): e15072.
[http://dx.doi.org/10.1200/JCO.2017.35.15_suppl.e15072]
[75]
Ghamande SA, Platt D, Wheatley D, Rungruang BJ, Janik JE, Khleif S. Phase I study evaluating high-dose treatment with ADXS11-001, a Listeria monocytogenes -listeriolysin O (Lm -LLO) immunotherapy, in women with cervical cancer. J Clin Oncol 2016; 34(15) (Suppl.): e14580.
[http://dx.doi.org/10.1200/JCO.2016.34.15_suppl.e14580]
[76]
Cohen EEW, Moore KN, Slomovitz BM, et al. Phase I/II study of ADXS11-001 or MEDI4736 immunotherapies alone and in combination, in patients with recurrent/metastatic cervical or human papillomavirus (HPV)-positive head and neck cancer. J Immunother Cancer 2015; 3 (Suppl. 2): 147.
[http://dx.doi.org/10.1186/2051-1426-3-S2-P147]
[77]
Le Tourneau C, Delord JP, Cassier P, et al. Phase Ib/II trial of TG4001 (Tipapkinogene sovacivec), a therapeutic HPV-vaccine, and Avelumab in patients with recurrent/metastatic (R/M) HPV-16+ cancers. Ann Oncol 2019; 30 (Suppl. 5): v494-5.
[http://dx.doi.org/10.1093/annonc/mdz253.036]
[78]
Trimble CL, Peng S, Kos F, et al. A phase I trial of a human papillomavirus DNA vaccine for HPV16+ cervical intraepithelial neoplasia 2/3. Clin Cancer Res 2009; 15(1): 361-7.
[http://dx.doi.org/10.1158/1078-0432.CCR-08-1725] [PMID: 19118066]
[79]
Maldonado L, Teague JE, Morrow MP, et al. Intramuscular therapeutic vaccination targeting HPV16 induces T cell responses that localize in mucosal lesions. Sci Transl Med 2014; 6(221): 221ra13.
[http://dx.doi.org/10.1126/scitranslmed.3007323] [PMID: 24477000]
[80]
Pellom ST, Rumfield CS, Morillon YM, Roller N, Brough D, Sabzevari H, et al. Anti-tumor efficacy and immune responsesinduced by a novel therapeutic HPV-specific gorilla adenovirus off-the-shelf immunotherapeutic (PRGN-2009). J Immunol 2020; 204 ((1 Supplement)): 91-6.
[81]
Massarelli E, William W, Johnson F, et al. Combining immune checkpoint blockade and tumor-specific vaccine for patients with incurable human papillomavirus 16-related cancer: A phase 2 clinical trial. JAMA Oncol 2019; 5(1): 67-73.
[http://dx.doi.org/10.1001/jamaoncol.2018.4051] [PMID: 30267032]
[82]
Gerritsen WR, Melief CJ, Welters M, et al. Association of T cell responses after vaccination with HPV16 long peptides for late stage cervical cancer with prolonged survival. J Clin Oncol 2017; 35(15) (Suppl.): 5525.
[http://dx.doi.org/10.1200/JCO.2017.35.15_suppl.5525]
[83]
Greenfield WW, Stratton SL, Myrick RS, et al. A phase I dose-escalation clinical trial of a peptide-based human papillomavirus therapeutic vaccine with Candida skin test reagent as a novel vaccine adjuvant for treating women with biopsy-proven cervical intraepithelial neoplasia 2/3. OncoImmunology 2015; 4(10): e1031439.
[http://dx.doi.org/10.1080/2162402X.2015.1031439] [PMID: 26451301]
[84]
Smalley Rumfield C, Roller N, Pellom ST, Schlom J, Jochems C. Therapeutic vaccines for HPV-associated malignancies. ImmunoTargets Ther 2020; 9: 167-200.
[http://dx.doi.org/10.2147/ITT.S273327] [PMID: 33117742]
[85]
Su JH, Wu A, Scotney E, et al. Immunotherapy for cervical cancer: Research status and clinical potential. BioDrugs 2010; 24(2): 109-29.
[http://dx.doi.org/10.2165/11532810-000000000-00000] [PMID: 20199126]
[86]
Vici P, Pizzuti L, Mariani L, et al. Targeting immune response with therapeutic vaccines in premalignant lesions and cervical cancer: hope or reality from clinical studies. Expert Rev Vaccines 2016; 15(10): 1327-36.
[http://dx.doi.org/10.1080/14760584.2016.1176533] [PMID: 27063030]
[87]
Yang A, Farmer E, Wu TC, Hung CF. Perspectives for therapeutic HPV vaccine development. J Biomed Sci 2016; 23(1): 75.
[http://dx.doi.org/10.1186/s12929-016-0293-9] [PMID: 27809842]
[88]
Choi YJ, Hur SY, Kim TJ, et al. A Phase II, prospective, randomized, multicenter, open-label study of GX-188E, an HPV DNA vaccine, in patients with cervical intraepithelial neoplasia 3. Clin Cancer Res 2020; 26(7): 1616-23.
[http://dx.doi.org/10.1158/1078-0432.CCR-19-1513] [PMID: 31727676]
[89]
Hillemanns P, Petry KU, Woelber L, et al. Abstract CT209: Safety, efficacy and immunogenicity of VB10.16, a therapeutic DNA vaccine targeting human papillomavirus (HPV) 16 E6 and E7 proteins for high grade cervical intraepithelial neoplasia (CIN 2/3): 6-month data from an exploratory open-label phase I/2a trial. Cancer Res 2019; 79(13) (Suppl.): CT209-9.
[http://dx.doi.org/10.1158/1538-7445.AM2019-CT209]
[90]
Alvarez RD, Huh WK, Bae S, et al. A pilot study of pNGVL4a-CRT/E7(detox) for the treatment of patients with HPV16 + cervical intraepithelial neoplasia 2/3 (CIN2/3). Gynecol Oncol 2016; 140(2): 245-52.
[http://dx.doi.org/10.1016/j.ygyno.2015.11.026] [PMID: 26616223]
[91]
Draper LM, Kwong MLM, Gros A, et al. Targeting of HPV-16+ epithelial cancer cells by TCR gene engineered T cells directed against E6. Clin Cancer Res 2015; 21(19): 4431-9.
[http://dx.doi.org/10.1158/1078-0432.CCR-14-3341] [PMID: 26429982]
[92]
Jin BY, Campbell TE, Draper LM, et al. Engineered T cells targeting E7 mediate regression of human papillomavirus cancers in a murine model. JCI Insight 2018; 3(8): e99488.
[http://dx.doi.org/10.1172/jci.insight.99488] [PMID: 29669936]
[93]
Jutz S, Leitner J, Schmetterer K, et al. Assessment of costimulation and coinhibition in a triple parameter T cell reporter line: Simultaneous measurement of NF-κB, NFAT and AP-1. J Immunol Methods 2016; 430: 10-20.
[http://dx.doi.org/10.1016/j.jim.2016.01.007] [PMID: 26780292]
[94]
Lang Kuhs KA, Lin SW, Hua X, et al. T cell receptor repertoire among women who cleared and failed to clear cervical human papillomavirus infection: An exploratory proof-of-principle study. PLoS One 2018; 13(1): e0178167.
[http://dx.doi.org/10.1371/journal.pone.0178167] [PMID: 29385144]