Adjuvant HPV Vaccination to Prevent Recurrent Cervical Dysplasia after Surgical Treatment: A Meta-Analysis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Search Strategy
2.2. Selection of Studies and Methodologic Quality Assessment
2.3. Outcomes
- (1)
- Primary outcomes
- 1.1
- CIN 2+ recurrence: recurrences of CIN 2+ (irrespective of HPV type and HPV 16/18-related) have been extrapolated from the studies.
- 1.2
- CIN 1+ recurrence: recurrences of CIN 1+ (irrespective of HPV type and HPV 16/18-related) have been extrapolated from the studies.
- (2)
- Secondary outcomes
- 2.1
- HPV persistence: the detection of positive HPV test at the first clinical follow-up after surgical treatment.
- 2.2
- CIN 3 recurrence: recurrences of CIN 3 (irrespective of HPV type and HPV 16/18-related) have been extrapolated from the studies.
- 2.3
- Persistence of abnormal cervical cytology: the detection of abnormal cervical cytology at the first clinical follow-up after surgical treatment.
2.4. Statistical Analysis
3. Results
3.1. Study Characteristics
3.2. Risk of Bias
- -
- -
- -
- -
- -
- Incomplete outcome data (attrition bias): All studies reported complete outcome data, thus we rated all them as having low risk of bias for this item.
- -
3.3. Effects of Interventions
3.3.1. Primary Outcomes
CIN 2+ Recurrence
CIN 1+ Recurrence
3.3.2. Secondary Outcomes
HPV Persistence
CIN 3 Recurrence
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Appendix A. Search Strategy (Pubmed/Medline Database)
- Cervical cancer: “uterine cervical neoplasms” [MeSH Terms] OR (“uterine”[All Fields] AND “cervical”[All Fields] AND “neoplasms”[All Fields]) OR “uterine cervical neoplasms”[All Fields] OR (“cervical”[All Fields] AND “cancer”[All Fields]) OR “cervical cancer”[All Fields] (111,287 results)
- Cervical disease: “uterine cervical diseases”[MeSH Terms] OR (“uterine”[All Fields] AND “cervical”[All Fields] AND “diseases”[All Fields]) OR “uterine cervical diseases”[All Fields] OR (“cervical”[All Fields] AND “disease”[All Fields]) OR “cervical disease”[All Fields] (118,317 results)
- Cervical intraepithelial neoplasia: “cervical intraepithelial neoplasia”[MeSH Terms] OR (“cervical”[All Fields] AND “intraepithelial”[All Fields] AND “neoplasia”[All Fields]) OR “cervical intraepithelial neoplasia”[All Fields] (14,638 results)
- Human papillomavirus: “alphapapillomavirus”[MeSH Terms] OR “alphapapillomavirus”[All Fields] OR (“human”[All Fields] AND “papillomavirus”[All Fields]) OR “human papillomavirus”[All Fields] (44,121 results)
- Vaccine: “vaccine”[Supplementary Concept] OR “vaccine”[All Fields] OR “vaccination”[MeSH Terms] OR “vaccination”[All Fields] OR “vaccinable”[All Fields] OR “vaccinal”[All Fields] OR “vaccinate”[All Fields] OR “vaccinated”[All Fields] OR “vaccinates”[All Fields] OR “vaccinating”[All Fields] OR “vaccinations”[All Fields] OR “vaccination’s”[All Fields] OR “vaccinator”[All Fields] OR “vaccinators”[All Fields] OR “vaccine’s”[All Fields] OR “vaccined”[All Fields] OR “vaccines”[MeSH Terms] OR “vaccines”[All Fields] OR “vaccine”[All Fields] OR “vaccins”[All Fields] (409,438 results)
- Vaccination: “vaccin”[Supplementary Concept] OR “vaccin”[All Fields] OR “vaccination”[MeSH Terms] OR “vaccination”[All Fields] OR “vaccinable”[All Fields] OR “vaccinal”[All Fields] OR “vaccinate”[All Fields] OR “vaccinated”[All Fields] OR “vaccinates”[All Fields] OR “vaccinating”[All Fields] OR “vaccinations”[All Fields] OR “vaccination’s”[All Fields] OR “vaccinator”[All Fields] OR “vaccinators”[All Fields] OR “vaccine’s”[All Fields] OR “vaccined”[All Fields] OR “vaccines”[MeSH Terms] OR “vaccines”[All Fields] OR “vaccine”[All Fields] OR “vaccins”[All Fields] (409,438 results)
- 1 OR 2 OR 3 (144,114 results)
- 5 OR 6 (409,438 results)
- 5 AND 7 AND 8 (6503 results)
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Study, Year | Study Design | N. of Patients Age (Years) | Primary Endpoint | HPV Vaccine Type and Time of Vaccination | Surgical Treatment |
---|---|---|---|---|---|
Joura et al., 2012 [37] | Post-hoc-pooled analysis of 2 RCT (FUTURE I and II) Follow-up 2.5 years (median) | 1066 15–26 | CIN 2+ (HPV-type independent) | Quadrivalent at day 1, month 2, and month 6 after surgery | LEEP (84.7%), cervical conization (12.5%), cryotherapy (0.7%), and other n.a. (2.1%) |
CIN 2+ (HPV 16, 18) | |||||
CIN 1+ (HPV-type independent) | |||||
CIN 1+ (HPV 16, 18) | |||||
CIN 3 (HPV-type independent) | |||||
Kang et al., 2013 [38] | Retrospective case-control Follow-up 3.5 years (median) | 737 20–45 | CIN 2+ (HPV-type independent) | Quadrivalent at week 1, month 2, and month 6 after surgery | LEEP |
CIN 2+ (HPV 16, 18) | |||||
CIN 1+ (HPV-type independent) | |||||
CIN 1+ (HPV 16, 18) | |||||
Garland et al., 2016 [39] | Post-hoc analysis of a RCT (PATRICIA) Follow-up 4 years | 454 15–25 | CIN 2+ (HPV-type independent) | Bivalent at months 0, 1, and 6 after surgery | LEEP |
CIN 2+ (HPV 16, 18) | |||||
CIN 1+ (HPV-type independent) | |||||
CIN 1+ (HPV 16, 18) | |||||
Hildesheim et al., 2016 [40] | Subgroup analysis of a RCT Follow-up 27.3 mo (median) | 311 18–25 | CIN 2+ (HPV-type independent) | Bivalent, 3 doses over 6 months after surgery | LEEP |
CIN 2+ (HPV 16, 18) | |||||
CIN 1+ (HPV-type independent) | |||||
CIN 1+ (HPV 16, 18) | |||||
Ghelardi et al., 2018 [41] | Prospective case-control (SPERANZA project) Follow-up 4 years | 344 18–45 | CIN 2+ (HPV-type independent) | Quadrivalent at day 30, month 2, and month 6 after surgery | LEEP |
CIN 1+ (HPV-type independent) | |||||
Pieralli et al., 2018 [42] | RCT Follow-up 3 years | 178 <45 | CIN 2+ (HPV-type independent) | Quadrivalent at months 0, 2 and 6 after surgery | Conization (83%), other n.a. (17%) |
CIN 1+ (HPV-type independent) | |||||
Ortega-Quinonero et al., 2019 [43] | Retrospective Follow-up 2 years | 242 18–65 | CIN 2+ (HPV-type independent) | Bi-/Quadrivalent, first dose 0-1 months before or 0-1 months after surgery, other 2 doses over 6 months | LEEP |
CIN 2+ (HPV 16, 18) | |||||
Sand et al., 2020 [44] | Prospective cohort | 17128 17–51 | CIN 2+ (HPV-type independent) | Bi-/Quadrivalent, first dose 0-3 months before or 0-12 months after surgery | Conization |
Petrillo et al., 2020 [45] | Retrospective Follow-up 2 years | 285 32–47 | CIN 2+ (HPV-type independent) | Bi-/Quadrivalent, first dose 0-1 months after surgery | LEEP |
CIN 1+ (HPV-type independent) | |||||
Del Pino et al., 2020 [46] | Prospective Follow up 22.4 mo median | 265 26–64 | CIN 2+ (HPV-type independent) | Bivalent at 0, 1 and 6 months after surgery Quadrivalent at 0, 2 and 6 months after surgery | Conization |
Bogani et al., 2020 [47] | Retrospective, multicenter Follow-up 5 years | 300 18–89 | CIN 2+ (HPV-type independent) | Bi-/Quadrivalent | LEEP |
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Di Donato, V.; Caruso, G.; Petrillo, M.; Kontopantelis, E.; Palaia, I.; Perniola, G.; Plotti, F.; Angioli, R.; Muzii, L.; Benedetti Panici, P.; et al. Adjuvant HPV Vaccination to Prevent Recurrent Cervical Dysplasia after Surgical Treatment: A Meta-Analysis. Vaccines 2021, 9, 410. https://doi.org/10.3390/vaccines9050410
Di Donato V, Caruso G, Petrillo M, Kontopantelis E, Palaia I, Perniola G, Plotti F, Angioli R, Muzii L, Benedetti Panici P, et al. Adjuvant HPV Vaccination to Prevent Recurrent Cervical Dysplasia after Surgical Treatment: A Meta-Analysis. Vaccines. 2021; 9(5):410. https://doi.org/10.3390/vaccines9050410
Chicago/Turabian StyleDi Donato, Violante, Giuseppe Caruso, Marco Petrillo, Evangelos Kontopantelis, Innocenza Palaia, Giorgia Perniola, Francesco Plotti, Roberto Angioli, Ludovico Muzii, Pierluigi Benedetti Panici, and et al. 2021. "Adjuvant HPV Vaccination to Prevent Recurrent Cervical Dysplasia after Surgical Treatment: A Meta-Analysis" Vaccines 9, no. 5: 410. https://doi.org/10.3390/vaccines9050410