Efficacy of Human Papillomavirus Vaccines for Recalcitrant Anogenital and Oral Warts
Abstract
:1. Introduction
2. Materials and Methods
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Righolt, C.H.; Willows, K.; Kliewer, E.V.; Mahmud, S.M. Incidence of anogenital warts after the introduction of the quadrivalent HPV vaccine program in Manitoba, Canada. PLoS ONE 2022, 17, e0267646. [Google Scholar] [CrossRef]
- Kombe, A.J.K.; Li, B.; Zahid, A.; Mengist, H.M.; Bounda, G.-A.; Zhou, Y.; Jin, T. Epidemiology and Burden of Human Papillomavirus and Related Diseases, Molecular Pathogenesis, and Vaccine Evaluation. Front. Public Health 2021, 8, 552028. [Google Scholar] [CrossRef]
- Egawa, N. Papillomaviruses and cancer: Commonalities and differences in HPV carcinogenesis at different sites of the body. Int. J. Clin. Oncol. 2023, 28, 956–964. [Google Scholar] [CrossRef]
- Illah, O.; Olaitan, A. Updates on HPV Vaccination. Diagnostics 2023, 13, 243. [Google Scholar] [CrossRef]
- Egawa, N.; Doorbar, J. The low-risk papillomaviruses. Virus Res. 2017, 231, 119–127. [Google Scholar] [CrossRef]
- Egawa, N.; Egawa, K.; Griffin, H.; Doorbar, J. Human Papillomaviruses; Epithelial Tropisms, and the Development of Neoplasia. Viruses 2015, 7, 3863–3890. [Google Scholar] [CrossRef]
- Ciccarese, G.; Trave, I.; Herzum, A.; Gariazzo, L.; Cozzani, E.; Rebora, A.; Parodi, A.; Drago, F. Dermatological infections in organ transplant recipients: A retrospective study on 222 patients. J. Eur. Acad. Dermatol. Venereol. 2019, 33, E36–E38. [Google Scholar] [CrossRef]
- Trave, I.; Ciccarese, G.; Gasparini, G.; Canta, R.; Serviddio, G.; Herzum, A.; Drago, F.; Parodi, A. Skin cancers in solid organ transplant recipients: A retrospective study on 218 patients. Transpl. Immunol. 2023, 80, 101896. [Google Scholar] [CrossRef]
- de Villiers, E.-M.; Fauquet, C.; Broker, T.R.; Bernard, H.-U.; zur Hausen, H. Classification of papillomaviruses. Virology 2004, 324, 17–27. [Google Scholar] [CrossRef]
- Forman, D.; de Martel, C.; Lacey, C.J.; Soerjomataram, I.; Lortet-Tieulent, J.; Bruni, L.; Vignat, J.; Ferlay, J.; Bray, F.; Plummer, M.; et al. Global Burden of Human Papillomavirus and Related Diseases. Vaccine 2012, 30 (Suppl. S5), F12–F23. [Google Scholar] [CrossRef]
- Herzum, A.; Ciccarese, G.; Drago, F.; Pastorino, A.; Dezzana, M.; Mavilia, M.G.; Sola, S.; Copello, F.; Parodi, A. Cervical, oral and anal Human papillomavirus infection in women attending the Dermatology Unit of a regional reference hospital in Genoa, Italy: A prevalence study. J. Prev. Med. Hyg. 2022, 63, E415–E419. [Google Scholar] [CrossRef]
- Drago, F.; Herzum, A.; Ciccarese, G.; Dezzana, M.; Pastorino, A.; Casazza, S.; Nozza, P.; Rebora, A.; Parodi, A. Prevalence and persistence of oral HPV infection in Italy. J. Eur. Acad. Dermatol. Venereol. 2019, 33, E150–E151. [Google Scholar] [CrossRef]
- Ciccarese, G.; Herzum, A.; Rebora, A.; Drago, F. Prevalence of genital, oral, and anal HPV infection among STI patients in Italy. J. Med. Virol. 2017, 89, 1121–1124. [Google Scholar] [CrossRef]
- Drago, F.; Herzum, A.; Ciccarese, G.; Bandelloni, R. Prevalence of oral human papillomavirus in men attending an Italian sexual health clinic. Sex. Health 2016, 13, 597–598. [Google Scholar] [CrossRef]
- Broccolo, F.; Fusetti, L.; Rosini, S.; Caraceni, D.; Zappacosta, R.; Ciccocioppo, L.; Matteoli, B.; Halfon, P.; Malnati, M.S.; Ceccherini-Nelli, L. Comparison of oncogenic HPV type-specific viral DNA load and E6/E7 mRNA detection in cervical samples: Results from a multicenter study. J. Med. Virol. 2013, 85, 472–482. [Google Scholar] [CrossRef]
- Crosbie, E.J.; Einstein, M.H.; Franceschi, S.; Kitchener, H.C. Human papillomavirus and cervical cancer. Lancet 2013, 382, 889–899. [Google Scholar] [CrossRef]
- Ciccarese, G.; Drago, F.; Copello, F.; Bodini, G.; Rebora, A.; Parodi, A. Study on the impact of sexually transmitted infections on Quality of Life, mood and sexual function. Ital. J. Dermatol. Venerol. 2021, 156, 686–691. [Google Scholar] [CrossRef]
- Herzum, A.; Ciccarese, G.; Occella, C.; Gariazzo, L.; Pastorino, C.; Trave, I.; Viglizzo, G. Treatment of Pediatric Anogenital Warts in the Era of HPV-Vaccine: A Literature Review. J. Clin. Med. 2023, 12, 4230. [Google Scholar] [CrossRef]
- Chesson, H.W.; Dunne, E.F.; Hariri, S.; Markowitz, L.E. The Estimated Lifetime Probability of Acquiring Human Papillomavirus in the United States. Sex. Transm. Dis. 2014, 41, 660–664. [Google Scholar] [CrossRef]
- Drolet, M.; Bénard, É.; Pérez, N.; Brisson, M.; HPV Vaccination Impact Study Group. Population-level impact and herd effects following the introduction of human papillomavirus vaccination programmes: Updated systematic review and meta-analysis. Lancet 2019, 394, 497–509. [Google Scholar] [CrossRef]
- Lei, J.; Ploner, A.; Elfström, K.M.; Wang, J.; Roth, A.; Fang, F.; Sundström, K.; Dillner, J.; Sparén, P. HPV Vaccination and the Risk of Invasive Cervical Cancer. N. Engl. J. Med. 2020, 383, 1340–1348. [Google Scholar] [CrossRef]
- Falcaro, M.; Castañon, A.; Ndlela, B.; Checchi, M.; Soldan, K.; Lopez-Bernal, J.; Elliss-Brookes, L.; Sasieni, P. The effects of the national HPV vaccination programme in England, UK, on cervical cancer and grade 3 cervical intraepithelial neoplasia incidence: A register-based observational study. Lancet 2021, 398, 2084–2092. [Google Scholar] [CrossRef]
- Workowski, K.A.; Bachmann, L.H.; Chan, P.A.; Johnston, C.M.; Muzny, C.A.; Park, I.; Reno, H.; Zenilman, J.M.; Bolan, G.A. Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR Recomm. Rep. 2021, 70, 1–187. [Google Scholar] [CrossRef]
- Li, Y.; Lin, Y.-F.; Wu, X.; Zhou, X.; Tian, T.; Guo, Z.; Fu, L.; Yang, L.; Lu, Z.; Fan, S.; et al. Effectiveness and cost-effectiveness of human papillomavirus vaccination strategies among men who have sex with men in China: A modeling study. Front. Immunol. 2023, 14, 1197191. [Google Scholar] [CrossRef]
- Goodman, E.; Reuschenbach, M.; Kaminski, A.; Ronnebaum, S. Human Papillomavirus Vaccine Impact and Effectiveness in Six High-Risk Populations: A Systematic Literature Review. Vaccines 2022, 10, 1543. [Google Scholar] [CrossRef]
- Pham, C.T.; Juhasz, M.; Sung, C.T.; Mesinkovska, N.A. The human papillomavirus vaccine as a treatment for human papillomavirus–related dysplastic and neoplastic conditions: A literature review. J. Am. Acad. Dermatol. 2020, 82, 202–212. [Google Scholar] [CrossRef]
- Kreuter, A.; Waterboer, T.; Wieland, U. Regression of Cutaneous Warts in a Patient With WILD Syndrome Following Recombinant Quadrivalent Human Papillomavirus Vaccination. Arch. Dermatol. 2010, 146, 1196–1197. [Google Scholar] [CrossRef]
- Kreuter, A.; Wieland, U. Lack of efficacy in treating condyloma acuminata and preventing recurrences with the recombinant quadrivalent human papillomavirus vaccine in a case series of immunocompetent patients. J. Am. Acad. Dermatol. 2013, 68, 179–180. [Google Scholar] [CrossRef]
- Moscato, G.; Di Matteo, G.; Ciotti, M.; Di Bonito, P.; Andreoni, M.; Moschese, V. Dual response to human papilloma virus vaccine in an immunodeficiency disorder: Resolution of plantar warts and persistence of condylomas. J. Eur. Acad. Dermatol. Venereol. 2016, 30, 1212–1213. [Google Scholar] [CrossRef]
- Lee, H.J.; Kim, J.K.; Kim, D.H.; Yoon, M.S. Condyloma accuminatum treated with recombinant quadrivalent human papillomavirus vaccine (types 6, 11, 16, 18). J. Am. Acad. Dermatol. 2011, 64, e130–e132. [Google Scholar] [CrossRef]
- Choi, H. Can quadrivalent human papillomavirus prophylactic vaccine be an effective alternative for the therapeutic management of genital warts? an exploratory study. Int. Braz. J. Urol. 2019, 45, 361–368. [Google Scholar] [CrossRef]
- Dianzani, C.; Neagu, N.; Venuti, A.; Coscarella, G.; Franciscis, B.D.E.; Montini, F.; Zalaudek, I.; Conforti, C. Efficacy of nonavalent human papillomavirus vaccine for recalcitrant warts. Ital. J. Dermatol. Venerol. 2023, 158, 67–68. [Google Scholar] [CrossRef]
- Bossart, S.; Gabutti, M.P.; Seyed Jafari, S.M.; Hunger, R.E. Nonavalent human papillomavirus vaccination as alternative treatment for genital warts. Dermatol. Ther. 2020, 33, e13771. [Google Scholar] [CrossRef]
- Couselo-Rodríguez, C.; Pérez-Feal, P.; Alarcón-Pérez, C.E.; Bou-Boluda, L.; Baselga, E. Clearance of genital warts in a pediatric patient following administration of the nonavalent human papillomavirus vaccine. Int. J. Dermatol. 2021, 60, E377–E379. [Google Scholar] [CrossRef]
- Bossart, S.; Imstepf, V.; Hunger, R.E.; Seyed Jafari, S.M. Nonavalent Human Papillomavirus Vaccination as a Treatment for Skin Warts in Immunosuppressed Adults: A Case Series. Acta Derm. Venereol. 2020, 100, adv00078-2. [Google Scholar] [CrossRef]
- Cyrus, N.; Blechman, A.B.; Leboeuf, M.; Belyaeva, E.A.; de Koning, M.N.; Quint, K.D.; Stern, J.J. Effect of quadrivalent human papillomavirus vaccination on oral squamous cell papillomas. JAMA Dermatol. 2015, 151, 1359–1363. [Google Scholar] [CrossRef]
- Govan, V.A. A novel vaccine for cervical cancer: Quadrivalent human papillomavirus (types 6, 11, 16 and 18) recombinant vaccine (Gardasil). Ther. Clin. Risk Manag. 2008, 4, 65–70. [Google Scholar] [CrossRef]
- Garbuglia, A.R.; Lapa, D.; Sias, C.; Capobianchi, M.R.; Del Porto, P. The Use of Both Therapeutic and Prophylactic Vaccines in the Therapy of Papillomavirus Disease. Front. Immunol. 2020, 11, 188. [Google Scholar] [CrossRef]
- Ferguson, S.B.; Gallo, E.S. Nonavalent human papillomavirus vaccination as a treatment for warts in an immunosuppressed adult. JAAD Case Rep. 2017, 3, 367–369. [Google Scholar] [CrossRef]
- Kenter, G.G.; Welters, M.J.; Valentijn, A.R.; Lowik, M.J.; Berends-van der Meer, D.M.; Vloon, A.P.; Essahsah, F.; Fathers, L.M.; Offringa, R.; Drijfhout, J.W.; et al. Vaccination against HPV-16 Oncoproteins for Vulvar Intraepithelial Neoplasia. N. Engl. J. Med. 2009, 361, 1838–1847. [Google Scholar] [CrossRef]
- Bellone, S.; El-Sahwi, K.; Cocco, E.; Casagrande, F.; Cargnelutti, M.; Palmieri, M.; Bignotti, E.; Romani, C.; Silasi, D.-A.; Azodi, M.; et al. Human Papillomavirus Type 16 (HPV-16) Virus-Like Particle L1-Specific CD8 + Cytotoxic T Lymphocytes (CTLs) Are Equally Effective as E7-Specific CD8 + CTLs in Killing Autologous HPV-16-Positive Tumor Cells in Cervical Cancer Patients: Implications for L1 Dendritic Cell-Based Therapeutic Vaccines. J. Virol. 2009, 83, 6779–6789. [Google Scholar] [CrossRef]
- Egawa, K.; Iftner, A.; Doorbar, J.; Honda, Y.; Iftner, T. Synthesis of Viral DNA and Late Capsid Protein L1 in Parabasal Spinous Cell Layers of Naturally Occurring Benign Warts Infected with Human Papillomavirus Type 1. Virology 2000, 268, 281–293. [Google Scholar] [CrossRef]
- Hu, S.; Xiang, D.; Zhang, X.; Zhang, L.; Wang, S.; Jin, K.; You, L.; Huang, J. The mechanisms and cross-protection of trained innate immunity. Virol. J. 2022, 19, 210. [Google Scholar] [CrossRef]
- Trimble, C.L.; Morrow, M.P.; Kraynyak, K.A.; Shen, X.; Dallas, M.; Yan, J.; Edwards, L.; Parker, R.L.; Denny, L.; Giffear, M.; et al. Safety, efficacy, and immunogenicity of VGX-3100, a therapeutic synthetic DNA vaccine targeting human papillomavirus 16 and E6 and E7 proteins for cervical intraepithelial neoplasia 2/3: A randomised, double-blind, placebo-controlled phase 2b trial. Lancet 2015, 386, 2078–2088. [Google Scholar] [CrossRef]
- Emeny, R.T.; Wheeler, C.M.; Jansen, K.U.; Hunt, W.C.; Fu, T.-M.; Smith, J.F.; MacMullen, S.; Esser, M.T.; Paliard, X. Priming of Human Papillomavirus Type 11-Specific Humoral and Cellular Immune Responses in College-Aged Women with a Virus-Like Particle Vaccine. J. Virol. 2002, 76, 7832–7842. [Google Scholar] [CrossRef]
- Pinto, L.A.; Edwards, J.; Castle, P.E.; Harro, C.D.; Lowy, D.R.; Schiller, J.T.; Wallace, D.; Kopp, W.; Adelsberger, J.W.; Baseler, M.W.; et al. Cellular Immune Responses to Human Papillomavirus (HPV)–16 L1 in Healthy Volunteers Immunized with Recombinant HPV-16 L1 Virus-Like Particles. J. Infect. Dis. 2003, 188, 327–338. [Google Scholar] [CrossRef]
Patient No. | Sex | Age at First Visit in Our STI Center | Site of the Warts | No. of Lesions | Duration (Years) | Comorbidities Affecting the Immune System | Previous Treatments | Current Standard Treatment | 9vHPV Vaccination (yes/not) | Previous 4vHPV Vaccination | Response to Treatment |
---|---|---|---|---|---|---|---|---|---|---|---|
cases (vaccinated patients) | |||||||||||
1 | F | 25 | genitalia | 15 | 2 | none | laser, imiquimod, pophillotoxin | cryotherapy, nitric zinc complex, photodinamic therapy | yes | no | partial |
2 | M | 35 | genitalia | 11 | 5 | none | cryotherapy, imiquimod | cryotherapy | yes | no | complete |
3 | M | 29 | genitalia | 7 | 0.5 | none | imiquimod | nitric zinc complex | yes | no | complete |
4 | M | 46 | genitalia | 1 | 2 | none | imiquimod | cryotherapy | yes | no | complete |
5 | M | 30 | genitalia | 2 | 7 | none | cryotherapy, imiquimod | cryotherapy | yes | yes (2 years earlier) | complete |
6 | M | 64 | tongue | 3 | 2 | HIV infection | surgery | cryotherapy | yes | no | complete |
7 | M | 60 | perianal skin | 2 | 2.5 | HIV infection | cryotherapy | cryotherapy | yes | no | no |
8 | M | 56 | genitalia | 2 | 1 | none | cryotherapy | nitric zinc complex | yes | no | complete |
9 | M | 44 | perianal skin | 6 | 2 | none | imiquimod | imiquimod | yes | no | complete |
10 | F | 17 | perianal skin | 12 | 6 | none | cryotherapy, nitric zinc complex, photodinamic therapy | cryotherapy | yes | yes (5 years earlier) | complete |
11 | M | 22 | genitalia | 12 | 2 | Hodgkin lymphoma (bone marrow transplant 4 months before) | cryotherapy, photodinamic therapy | cryotherapy | yes | no | partial |
12 | F | 51 | tongue and cheek mucosa | 13 | 36 | none | intralesional interferon | cryotherapy | yes | yes (2 years earlier) | no |
13 | M | 29 | genitalia | 13 | 1 | none | cryotherapy | imiquimod | yes | no | partial |
14 | M | 23 | genitalia | 5 | 3 | none | cryotherapy | cryotherapy | yes | no | complete |
controls (not vaccinated) | |||||||||||
1 | F | 35 | genitalia and perianal skin | 3 | 8 | none | surgery, salicylic acid, sinecatechins | nitric zinc complex | no | no | |
2 | M | 28 | genitalia | 10 | 5 | none | cryotherapy, laser | imiquimod | no | complete | |
3 | M | 24 | genitalia | 3 | 1 | none | imiquimod | cryotherapy, nitric zinc complex | no | partial | |
4 | M | 43 | genitalia | 10 | 2 | none | laser, surgery | cryotherapy | no | complete | |
5 | M | 57 | genitalia | 5 | 1 | none | cryotherapy | nitric zinc complex | no | complete | |
6 | M | 63 | genitalia | 2 | 0.5 | gastric lymphoma | surgery | cryotherapy | no | partial | |
7 | M | 59 | perianal skin | 4 | 0.5 | Hodgkin lymphoma (bone marrow transplant 6 months before) | imiquimod | nitric zinc complex | no | no | |
8 | M | 45 | genitalia | 2 | 1 | none | surgery | nitric zinc complex | no | no | |
9 | F | 27 | genitalia | 9 | 0.5 | none | none | sinecatechins, imiquimod | no | no | |
10 | M | 28 | genitalia | 7 | 0.5 | Hodgkin lymphoma (bone marrow transplant 6 months before) | cryotherapy | cryotherapy, imiquimid | no | no | |
11 | F | 40 | genitalia | 10 | 2 | none | surgery | cryotherapy, imiquimod | no | no | |
12 | M | 54 | genitalia | 1 | 0.5 | none | imiquimod | cryotherapy | no | no | |
13 | M | 26 | genitalia | 6 | 0.5 | none | cryotherapy | nitric zinc complex | no | complete | |
14 | F | 40 | genitalia | 7 | 1 | none | imiquimod | cryotherapy | no | no | |
15 | F | 58 | genitalia | 4 | 2 | none | surgery | cryotherapy | no | no |
Variables | Group A (Vaccine + Standard Therapies) | Group B (Standard Therapies) |
---|---|---|
No. of patients | 14 | 15 |
Males | 11 | 10 |
Females | 3 | 5 |
Age (years) | Range: 17–64 (mean age: 39) | Range: 24–63 (mean age: 39) |
No. of lesions | 1–15 (mean: 7) | 1–10 (mean: 5) |
Duration (years) | 0.5–36 (mean: 5) | 0.5–8 (mean: 2) |
Site of Lesions | ||
Genital area | 9 | 14 |
Perianal area | 3 | 2 |
Oral mucosa | 2 | 0 |
Current Standard Therapies | ||
Cryotherapy | 9 | 8 |
Nitrizinc complex | 3 | 6 |
Imiquimod 5% cream | 2 | 3 |
Photodynamic therapy | 1 | 0 |
Comorbidities Affecting the Immune System | ||
Human immunodeficiency virus infection | 2 | 0 |
Hodgkin’s lymphoma (post-bone marrow transplantation) | 1 | 2 |
Group A | Group B | |
---|---|---|
Response at 12 Months | ||
No response | 2 (15%) | 9 (60%) |
Partial response | 3 (21%) | 2 (13%) |
Complete response | 9 (64%) | 4 (27%) |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Ciccarese, G.; Herzum, A.; Serviddio, G.; Occella, C.; Parodi, A.; Drago, F. Efficacy of Human Papillomavirus Vaccines for Recalcitrant Anogenital and Oral Warts. J. Clin. Med. 2023, 12, 7317. https://doi.org/10.3390/jcm12237317
Ciccarese G, Herzum A, Serviddio G, Occella C, Parodi A, Drago F. Efficacy of Human Papillomavirus Vaccines for Recalcitrant Anogenital and Oral Warts. Journal of Clinical Medicine. 2023; 12(23):7317. https://doi.org/10.3390/jcm12237317
Chicago/Turabian StyleCiccarese, Giulia, Astrid Herzum, Gaetano Serviddio, Corrado Occella, Aurora Parodi, and Francesco Drago. 2023. "Efficacy of Human Papillomavirus Vaccines for Recalcitrant Anogenital and Oral Warts" Journal of Clinical Medicine 12, no. 23: 7317. https://doi.org/10.3390/jcm12237317