Table 1 Summary of vaccine immunogenicity and efficacy studies conducted in low and middle income countries
Study | Study population | Study vaccine | Study design | Vaccination schedule | Follow-up | Serological assays/HPV DNA assay | Study end points | Main results |
|---|---|---|---|---|---|---|---|---|
Perez et al. (2008) [15] | A total of 6004 healthy female subjects aged 9–24 were recruited from Brazil, Mexico, Colombia, Costa Rica, Guatemala and Peru | Quadrivalent HPV vaccine | Randomised blinded controlled trial | 0,2,6 months | 7 months | cLIA | Geometric mean anti-HPV-6, 11, 16 and—18 antibody titres. Positivity to HPV 6, 11, 16 and 18 by PCR and CIN lesions. Any Condyloma VIN 1 or VaIN | The vaccine was 92.8 and 100 % effective in preventing cervical intraepithelial neoplasia and external genital lesions related to vaccine HPV types, respectively. |
Muñoz et al. (2009) [25] | Multi-center trial Colombia, France, Germany, Philippines, Spain, Thailand, and the USA. Healthy Women aged 24–45 years n = 3819 | Quadrivalent HPV vaccine | Randomised, placebo-controlled, double-blind study | At 0, 2 and 6 months | Mean follow up 2.2 years | HPV multiplex PCR testing | Incidence of cervical and external genital disease related to HPV 6, 11, 16, or 18; and to HPV 16 or 18 alone | The quadrivalent vaccine is effi cacious in women aged 24–45 years not infected with the relevant HPV types at enrolment. |
Medina et al. (2010) [16] | Multi center with Healthy Honduras girls 10–26 years n = 2067 | Bivalent HPV-16/18 vaccine | Randomised controlled observer blind trial (1:1) | at 0, 1, and 6 months | 7 months | ELISA | Safety and immunogenicity | The vaccine was generally well tolerated and immunogenic among these girls.(GMT HPV-16 14,778.0 (95 % CI 12,668.5-17,238.7 and HPV 18 6149.1 (95 % CI 5314.5- 7114.7) |
Bhatla et al. (2010) [19] | Healthy Indian women of an older age group 18–35 years (n = 330) | Bivalent HPV-16/18 Vaccine | Double blinded randomized multi center trial | at 0, 1, and 6 months | 7 months | VLP ELISA | Geometric mean anti-HPV-16 and −18 antibody titres | Vaccine was highly immunogenic and safe in this older population of women (GMT levels HPV-16 10226.5 (95 % CI 8847.1-11821.0) and HPV-18 3953.0 (95 % CI 3421.8-4566.8) |
Neuzil et al. (2011) [27] | Adolescent Vietnam girls 11–13 year n = 903 | Quadrivalent HPV | Open-label, cluster randomized, noninferiority study | 3 doses of quadrivalent HPV vaccine on a standard dosing schedule (at 0, 2, and 6 months) and 3 alternative dosing schedules (at 0, 3, and 9 months; at 0, 6, and 12 months; or at 0, 12, and 24 months. | 1 month after receipt of the third vaccine dose | cLIA | Geometric mean anti-HPV-6, 11,16 and −18 antibody titres | Vaccine administration on standard and alternative schedules was immunogenic and well tolerated. Use of alternative dosing compared with a standard schedule did not result in inferior antibody concentrations. |
Salif Sow et al. (2012) [14] | African girls (Tanzanian and Senegalese) girls and young women, seronegative for human immunodeficiency virus (HIV) 10–25 years (n = 450), placebo (n = 226) | HPV-16/18 AS04-adjuvanted vaccine | Double blinded, randomized controlled (2:1) | at 0, 1, and 6 months | Up to 12 months | VLP ELISA | Geometric mean anti-HPV-16 and −18 antibody titers | The vaccine was highly immunogenic with 100 % seropositive for both anti–HPV-16 and anti–HPV-18 antibodies and safety profile |
Khatun et al. (2012) [18] | Healthy adolescent Bangladesh girls 9–13 years n = 67 | Bivalent HPV-16/18 vaccine | Randomized controlled trial (3:1) | 0, 1, 6 months | 7 months | ELISA | Geometric mean anti-HPV-16 and −18 antibody titres | Vaccine was well tolerated, and highly immunogenic |
Schwarz et al. (2012) [17] | Healthy Girls 10–14 years from 31 centers in Taiwan, Germany, Honduras, Panama, and Colombia | HPV-16/18 AS04-adjuvanted | Open label randomized trial | at 0, 1, and 6 months | Four year follow up | ELISA | Geometric mean anti-HPV-16 and −18 antibody titres | The HPV-16/18 AS04-adjuvanted vaccine produces anti-HPV-16 and anti-HPV-18 antibody titers that are maintained for up to 4 years at higher levels than those in young women in whom vaccine efficacy against cervical lesions was demonstrated. |
n = 1035 | ||||||||
Brown et al. (2013) [22] | Tanzanian females 10–25 years (n = 298) | HPV-16/18 AS04-adjuvanted vaccine | Sub-study nested within a Phase IIIb immunogenicity and safety trial of the HPV-16/18 AS04-adjuvanted vaccine | at 0, 1, and 6 months | Follow up to 12 months | ELISA | Geometric mean anti-HPV-16 and −18 antibody titers | Parasitic infections were common overall, the vaccine induced high HPV-16/18 GMTs, (HPV 16 10,786 EU/mL (95 % CI 9126–12,747), and HPV-18 3701 EU/mL (95 % CI 3156–4340). There was no evidence of a reduction in HPV-16 or HPV-18 GMT at Month 7 or Month 12 follow-up visits among participants with helminths or malaria. |
LaMontagne et al. (2013) [28] | Vietnam girls 11–13 year n = 903 | Quadrivalent HPV vaccine | Open-label, cluster randomized, noninferiority study | 3 doses of quadrivalent HPV vaccine on a standard dosing schedule (at 0, 2, and 6 months) and 3 alternative dosing schedules (at 0, 3, and 9 months; at 0, 6, and 12 months; or at 0, 12, and 24 months. | >2 years follow up | cLIA | Geometric mean anti-HPV-6, 11,16 and −18 antibody titres. | HPV vaccine dose- timing, and extended schedules do not produce inferior immune responses. In addition, 2 doses of HPV vaccine delivered at 0 and 12 months might afford similar protection |
Nakalembe et al. (2014) [21] | Ugandan girls 10–16 years | HPV-16/18 AS04-adjuvanted vaccine | Cross-sectional study follow up on girls vaccinated in 2010 in an HPV demonstration project | 0,1 and 6 months | 18 months post vaccination | Multiplex HPV serology | Median Flourescent intenstity | The AS04-Adjuvanted HPV-16/18 vaccinated girls showed a higher level of antibodies to HPV-16/18(HPV-16 4691 95 % CI: 4438–4958 among the vaccinated compared to 218 95 % CI: 190–252 among the unvaccinated girls; HPV-18 1326 95 % CI: 1470–1776 among the vaccinated compared to 103 95 % CI: 88–121) among unvaccinated girls) and other non-vaccine hrHPV types compared to the unvaccinated girls. |
(n = 404) | ||||||||
LaMontagne et al. (2014) [29] | Ugandan girls 10–17 years | HPV-16/18 AS04-adjuvanted vaccine | Cross-sectional follow-up study. Girls vaccinated in a government-run HPV vaccination demonstration program | 0,1 and 6 months | At month 36 post vaccination | VLP ELISA | Geometric mean anti-HPV-16 and −18 antibody titres | The immunogenicity with less than three doses did not meet a priori non-inferiority thresholds. However, antibody levels measured ≥24 months after last dose were similar to those of adult women where efficacy has been demonstrated (GMTs HPV161-dose = 230 HPV16 2-dose = 808,and HPV16 3-dose = 1607; HPV181-dose = 87, HPV182-dose = 270, and HPV183-dose = 296 EU/mL) The GMT ratio for 2:3 doses was 0.50 for HPV16 and 0.68 for HPV18). |
One dose n = 230, 2 doses n = 808, 3 doses n = 1608 | ||||||||
Skinner et al. (2014) [26] | Phillipines >25 year old women n = 5752 | HPV-16/18 AS 04-adjuvanted vaccine | double-blind, randomised controlled trial | At 0, 1 and 6 months | Mean follow up 40.3 months | HPV DNA | 6-month persistent infection with HPV 16 or HPV 18 (HPV 16/18) or CIN grade 1 or greater (CIN1+) associated with HPV 16/18. | The HPV 16/18 vaccine is efficacious against infections and cervical abnormalities associated with the vaccine types, as well as infections with the non-vaccine HPV types 31 and 45. |