HPV vaccines: a controversial issue?

Brazilian Journal of Medical and Biological Research (2016) 49(5): e5060, http://dx.doi.org/10.1590/1414-431X20155060 ISSN 1414-431X Review 1/5 HPV vaccines: a controversial issue? A.F. Nicol1, C.V. Andrade2, F.B. Russomano2, L.L.S. Rodrigues3, N.S. Oliveira1,4 and D.W. Provance Jr.5 1 Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, RJ, Brasil Instituto Nacional de Saúde da Mulher, da Crianc¸a e do Adolescente Fernandes Figueira, Fiocruz, Rio de Janeiro, RJ, Brasil 3 Instituto de Saúde Coletiva, Universidade Federal do Oeste do Pará, Santarém, PA, Brasil 4 Hospital Universitário Antonio Pedro, Universidade Federal Fluminense, Niterói, RJ, Brasil 5 Centro de Desenvolvimento Tecnológico em Saúde, Fiocruz, Rio de Janeiro, RJ, Brasil 2 Abstract Controversy still exists over whether the benefits of the available HPV vaccines outweigh the risks and this has suppressed uptake of the HPV vaccines in comparison to other vaccines. Concerns about HPV vaccine safety have led some physicians, healthcare officials and parents to withhold the recommended vaccination from the target population. The most common reason for not administering the prophylactic HPV vaccines are concerns over adverse effects. The aim of this review is the assessment of peer-reviewed scientific data related to measurable outcomes from the use of HPV vaccines throughout the world with focused attention on the potential adverse effects. We found that the majority of studies continue to suggest a positive risk-benefit from vaccination against HPV, with minimal documented adverse effects, which is consistent with other vaccines. However, much of the published scientific data regarding the safety of HPV vaccines appears to originate from within the financially competitive HPV vaccine market. We advocate a more independent monitoring system for vaccine immunogenicity and adverse effects to address potential conflicts of interest with regular systematic literature reviews by qualified individuals to vigilantly assess and communicate adverse effects associated with HPV vaccination. Finally, our evaluation suggests that an expanded use of HPV vaccine into more diverse populations, particularly those living in low-resource settings, would provide numerous health and social benefits. Key words: Human papillomavirus; Vaccination; Adverse events Introduction Vaccination is the most successful method to control infectious diseases in terms of both cost and effectiveness. Human papillomavirus (HPV) belongs to a large family of more than 170 double-stranded DNA viruses of which approximately 40 mucosal types are commonly transmitted mainly via sexual activity. Two prophylactic HPV vaccines have been approved by the Food and Drug Administration (FDA) in the USA: the bivalent Cervarixs (GlaxoSmithKline, Middlesex, UK) for prevention of infection with HPV types 16 and 18 and the quadrivalent Gardasils (Merck Sharp & Dohme, USA) for HPV types 6, 11, 16, and 18. Both HPV vaccines can protect females against cervical pre-cancers (CIN). Several studies have demonstrated that both the bivalent and quadrivalent HPV vaccines are safe (1–3). Each has shown long-term durability for protection against primary infections caused by the types of HPV viruses targeted by the respective vaccines along with a moderate degree of cross-protection against some non-targeted HPV viruses, most notably HPV 31, 33, and 45 (4). However, there are Correspondence: A.F. Nicol: <nicol@ioc.fiocruz.br> Received October 13, 2015 | Accepted November 5, 2015 Braz J Med Biol Res | doi: 10.1590/1414-431X20155060 several ongoing controversies surrounding compliance with the vaccination recommendation, which at times has involved government health agencies. It is important to emphasize that the HPV vaccines are not a therapeutic treatment for any HPV-associated disease that might exist at the time of vaccination, nor will it invariably protect against diseases that are caused by types of HPV not targeted by the vaccines. Furthermore, HPV vaccines are not recommended for females o9 years old or individuals that are pregnant. Lastly, Cervarixs (GlaxoSmithKline) is not licensed for use in males at this time. Despite the efforts by public health agencies in the United States, the coverage of HPV vaccination remains low. Among adolescent females and males aged 13–16 years, only 33.4 and 6.8%, respectively, had received the three recommended doses of the HPV vaccine in 2012 (5). In June of 2013, the Japanese Ministry of Health partially suspended its HPV vaccination program due to several reported adverse events following HPV Controversy with HPV vaccines immunization (6), which demonstrates that immunization programs can be seriously compromised by safety and possible political concerns. However, much of the published scientific data regarding the safety of HPV vaccines could be influenced by conflicts of interest such as receiving advisory board fees and grant support with commercial interests from the competitive HPV vaccine market. Therefore this review aims to examine, independently of the competing vaccine manufacturers, the current evidence from the peer-reviewed scientific literature referring to the potential adverse effects associated with HPV vaccination. Adverse events One systematic review that involved a total of 29,540 individuals showed that the most frequently reported adverse event related to the HPV vaccines was pain and swelling at the injection site followed by fatigue, fever, gastrointestinal symptoms and headaches (7). In Japan, HPV vaccination was recommended by the government in April 2013. However, several adverse effects such as complex regional pain syndrome were reported by the Japanese media, which led to a suspension of both the bivalent and quadrivalent HPV vaccines by the Japanese government two months later, in June 2013. Together with the government decision, the media reports also created distrust in the Japanese public that led to a further decrease in HPV vaccination coverage. Ueda et al. (8) reported that in Japan, between 2012 and 2014, the rate of vaccination against HPV in girls from the 7th grade had plunged from 65.4 to 3.9% and it also decreased significantly for girls in the 8th–10th grades. Another publication from Japan clinically analyzed 44 girls between the ages of 11 and 17 years that complained of several adverse events following HPV vaccination with either the bivalent or the quadrivalent vaccine. Among them, 4 were excluded due to a diagnosis of another disease. Of the remaining 40, the main clinical manifestations reported in the study were: headaches (70%), general fatigue (53%), coldness of the legs (53%), limb pain (50%), limb weakness (48%), difficulty in getting up (48%), orthostatic fainting (43%), decreased ability to learn (43%), arthralgia (43%), limb tremors (40%), gait disturbances (40%), disturbed menstruation (35%) and dizziness (30%). Moreover, a high inci (...truncated)