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Abstract
Two human papillomavirus (HPV) vaccines (Gardasil® and Cevarix™) were launched between 2006∼2007. Clinical trials have been performed in several countries. However, it takes few decades to measure HPV vaccine efficacy for the protection of cervical cancer. Therefore, several surrogate markers such as seroconversion rate, presence of HPV DNA, and cytological/ histological abnormalities have been evaluated. Until now, long-term follow-up data for 5 years (Gardasil) and for 8.4 years (Cevarix) were available from international trials. However, only seroconversion rate at 4 weeks after vaccination and safety were evaluated in Korea. It is necessary to establish a reference laboratory and long-term follow-up monitoring system for the proper evaluation of HPV vaccines in Korea.
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Table 1.
Characteristics of clinical studies included in systemic review by Medeiros (Modified from Medeiros et al. Ref.1)
| Study ID | References | Sex: Enroll No. | Age, yrs | Vaccine valency (HPV Type) | Periods (Area) | Follow-up (Month) |
|---|---|---|---|---|---|---|
| NCT00689741 (HPV-001)a | 4 | F: V 560 P 553 | 15∼25 | Bivalent (16, 18) | 2003.11∼2004.07 (Brazil, Canada, USA) | 44 |
| NCT00122681 (HPV-008)a PATRICIA | 5 | F: V 9,319 P 9,325 | 15∼25 | Bivalent (16, 18) | 2004.05∼2005.06 (14 countries) | 14.8 |
| NCT00128661 (HPV-009)a | 6 | F: V 3,727 P 3,739 | 18∼25 | Bivalent (16, 18) | 2004.06∼2005.12 (Costa Rica) | 12 |
| NCT00365378 (V501-005)b | 7 | F: V 1,193 P 1,198 | 16∼23 | Monovalent (16) | 1998.10∼1999.11 (USA) | 48 |
| NCT00092521 (V501-013)b FUTURE I | 8 | F: V 2,723 P 2,732 | 16∼24 | Quadrivalent (6, 11, 16, 18) | 2002.01∼2003.03 (16 countries) | 36 |
| NCT00092534 (V501-015)b FUTURE II | 9 | F: V 5,305 P 5,260 | 15∼26 | Quadrivalent (6, 11, 16, 18) | 2002.06∼2003.05 (13 countries) | 48 |
Table 2.
Long-term clinical trials of the bivalent and quadrivalent HPV vaccines (modified from Romanowski Ref.2)
| Study identifier | Sex: age (years) | Duration of follow-up currently reported | Planned duration of follow-up | References |
|---|---|---|---|---|
| Head-to-head trials (Bivalent Vs. Quadrivalent vaccine) | ||||
| HPV-010 | F: 18∼45 | 2 years | 4 years | 10, 11 |
| Bivalent vaccine | ||||
| HPV-001/007/023 | F: 15∼25 | Up to 8.4 years after 1st vaccination | ∼ 9.5 years | 12, 13, 14 |
| HPV-014 | F: 15∼55 | 4 years | Completed | 15 |
| HPV-013/025 | F: 10∼14 | 4 years | 10 years | 16 |
| HPV-012 | F: 10∼25 | 4 years | Completed | 17 |
| PATRICIA (HPV-008) | F: 15∼25 | 4 years (average ∼ 3.7 years after 1st vaccination)* | Completed | 18, 19, 20, 21 |
| Quadrivalent vaccine | ||||
| V501-007 | F: 16∼23 | 5 years | Completed | 22, 23 |
| FUTURE I & FUTURE II (V501-013 & 015) | F: 15∼26 | Average ∼ 3.6 years after 1st vaccination* | Completed† | 8, 9, 24, 25, 26, 27 |
* In the PATRICIA and FUTURE trials, case ascertainment for efficacy endpoints began after first vaccine dose in the TVC and ITT populations, and after the third vaccine dose in the ATP-E and per protocol populations (the day after the third dose in PATRICIA, and one month after the third dose in FUTURE).
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