- Letter to the Editor
- Open Access
HPV vaccines and cancer prevention, science versus activism
© Tomljenovic et al.; licensee BioMed Central Ltd. 2013
Received: 9 January 2013
Accepted: 21 January 2013
Published: 1 February 2013
The rationale behind current worldwide human papilloma virus (HPV) vaccination programs starts from two basic premises, 1) that HPV vaccines will prevent cervical cancers and save lives and, 2) have no risk of serious side effects. Therefore, efforts should be made to get as many pre-adolescent girls vaccinated in order to decrease the burden of cervical cancer. Careful analysis of HPV vaccine pre- and post-licensure data shows however that both of these premises are at odds with factual evidence and are largely derived from significant misinterpretation of available data.
The recent Editorial by Silvia de Sanjosé*  is problematic from a variety of perspectives. Mainly, it attempts to portray a complex issue as a simple dichotomy between supposedly unjustified “anti-HPV vaccine activism” and alleged absolute science which has presumably provided indisputable evidence on HPV vaccine safety and efficacy.
In spite of much unwarranted and premature optimism, the fact is however that HPV vaccines have not thus far prevented a single case of cervical cancer (let alone cervical cancer death). Instead, what the clinical trials have shown is that HPV vaccines can prevent some of the pre-cancerous CIN 2/3 lesions associated with HPV-16 and HPV-18 infection, a large fraction of which would spontaneously resolve regardless of the vaccination status [2–4]. For example, in adolescent women aged 13 to 24 years, 38% of CIN 2 resolve after one year, 63% after two and 68% after three years . Moreover, the validity of CIN 2 being a cancer precursor is questionable due to high misclassification rates and poor intra- and inter-observer reproducibility in diagnosis, as well as high regression rates [6–9]. According to Castle et al.  CIN 2 is the least reproducible of all histopathologic diagnoses and may in part reflect sampling error. While CIN 3 is a more reliable marker for cancer progression than CIN 2, the use of this marker is not without caveats [2, 10].
reliability of surrogate-markers (i.e., whether they can accurately measure what they are purport to measure);
efficacy against oncogenic HPV strains not covered by the vaccine;
possibility of increased frequency of infections with these types;
efficacy in women acquiring multiple HPV types;
effects in women with pre-existing HPV infections
It is also noteworthy that Merck’s HPV vaccine Gardasil received priority Fast Track approval by the U.S. Food and Drug Administration (FDA) after a 6-month review process, despite the fact that it failed (and still continues to fail) to meet a single one of the four criteria required by the FDA for Fast Track approval. Gardasil is demonstrably neither safer nor more effective than Pap screening combined with the loop electrosurgical excision procedure (LEEP) in preventing cervical cancers, nor can it improve the diagnosis of serious cervical cancer outcomes . In this regard, Gerhardus and Razum have recently noted that the “…unwarranted confidence in the new HPV vaccines led to the impression that there was no need to actually evaluate their effectiveness” .
Similarly, the notion that HPV vaccines have an impressive safety profile can only be supported by highly flawed design of safety trials [2, 13] and is contrary to accumulating evidence from vaccine safety surveillance databases and case reports which continue to link HPV vaccination to serious adverse outcomes (including death and permanent disabilities) [2, 4, 14]. For example, compared to all other vaccines in the U.S. vaccination schedule, Gardasil alone is associated with 61% of all serious adverse reactions (including 63.8% of all deaths and 81.2% cases of permanent disability) in females younger than 30 years of age .
Although a report to a vaccine safety surveillance system does not by itself prove that the vaccine caused an adverse reaction, the unusually high frequency of adverse reactions related to HPV vaccines reported worldwide, as well as their consistent pattern (i.e. nervous system-related disorders rank the highest in frequency), points to a potentially causal relationship . Furthermore, matching the data from vaccine surveillance databases is an increasing number of case reports documenting similar serious adverse reactions associated with HPV vaccine administration, with nervous system and autoimmune disorders being the most frequently reported in the medical literature [15–24].
In summary, the optimistic claims that HPV vaccines will prevent cervical cancers and save lives, and that they are extremely safe, rest on assumptions which are misinterpreted and presented to the public as factual evidence. We thus conclude that further reduction of cervical cancers might be best achieved by optimizing cervical screening (which carries no serious health risks) and targeting other factors of the disease rather than by the reliance on vaccines with questionable efficacy and safety profiles [2, 25].
HPV vaccines have not been demonstrated to prevent any cervical cancers so why are they being promoted as cervical cancer vaccines?
If the majority of HPV infections and a great proportion of pre-cancerous lesions clear spontaneously and without medical treatment and are thus not a reliable indication of cancer later in life, then how can these end-points be used as a reliable indicator of the number of cervical cancer cases that will be prevented by HPV vaccines?
Can a passive monitoring system such as that used by most vaccine surveillance systems world-wide allow the medical regulatory agencies to make accurate estimates on the real frequency of HPV-vaccine related adverse reactions?
Can an accurate estimate of the real frequency of HPV-vaccine related adverse reactions be made if appropriate follow-up and thorough investigation of suspected vaccine related ADRs is not conducted but instead, these cases are a-priori dismissed as being unrelated to the vaccine?
Why are women not informed of the fact that in some circumstances (i.e., prior exposure to vaccine-targeted and non-targeted HPV types), HPV vaccination may accelerate the progression of cervical abnormalities [4, 26–28]?
How can women make a fully informed decision about whether or not to consent to vaccination if crucial information regarding HPV vaccine efficacy and safety is not being disclosed to them?
- de Sanjose S: HPV prevention series. Infect Agent Cancer. 2012, 7 (1): 37-10.1186/1750-9378-7-37.PubMedPubMed CentralView ArticleGoogle Scholar
- Tomljenovic L, Shaw CA, Spinosa JP: Human Papillomavirus (HPV) Vaccines as an option for preventing cervical malignancies: (How) effective and safe?. Curr Pharm Des. 2012, CPD-EPUB-20120924-13-Epub ahead of printGoogle Scholar
- Tomljenovic L, Shaw CA: Who profits from uncritical acceptance of biased estimates of vaccine efficacy and safety?. Am J Public Health. 2012, 102 (9): e13-e14. 10.2105/AJPH.2012.300837.PubMedPubMed CentralView ArticleGoogle Scholar
- Tomljenovic L, Shaw CA: Human papillomavirus (HPV) vaccine policy and evidence-based medicine: are they at odds?. Ann Med. 2011, 10.3109/07853890.2011.645353.Google Scholar
- Moscicki AB, Ma Y, Wibbelsman C, Darragh TM, Powers A, Farhat S, Shiboski S: Rate of and risks for regression of cervical intraepithelial neoplasia 2 in adolescents and young women. Obstet Gynecol. 2010, 116 (6): 1373-1380. 10.1097/AOG.0b013e3181fe777f.PubMedPubMed CentralView ArticleGoogle Scholar
- Castle PE, Schiffman M, Wheeler CM, Solomon D: Evidence for frequent regression of cervical intraepithelial neoplasia-grade 2. Obstet Gynecol. 2009, 113 (1): 18-25.PubMedPubMed CentralView ArticleGoogle Scholar
- Castle PE, Stoler MH, Solomon D, Schiffman M: The relationship of community biopsy-diagnosed cervical intraepithelial neoplasia grade 2 to the quality control pathology-reviewed diagnoses: an ALTS report. Am J Clin Pathol. 2007, 127 (5): 805-815. 10.1309/PT3PNC1QL2F4D2VL.PubMedView ArticleGoogle Scholar
- Castle PE, Schiffman M, Wheeler CM, Wentzensen N, Gravitt PE: Impact of improved classification on the association of human papillomavirus with cervical precancer. Am J Epidemiol. 2009, 171 (2): 155-163.PubMedPubMed CentralView ArticleGoogle Scholar
- Carreon JD, Sherman ME, Guillén D, Solomon D, Herrero R, Jerónimo J, Wacholder S, Rodríguez AC, Morales J, Hutchinson M, et al: CIN2 is a much less reproducible and less valid diagnosis than CIN3: results from a histological review of populationbased cervical samples. Int J Gynecol Pathol. 2007, 26 (4): 441-446. 10.1097/pgp.0b013e31805152ab.PubMedView ArticleGoogle Scholar
- Schiffman M, Rodriguez AC: Heterogeneity in CIN3 diagnosis. Lancet Oncol. 2008, 9 (5): 404-406. 10.1016/S1470-2045(08)70110-4.PubMedView ArticleGoogle Scholar
- Gerhardus A, Razum O: A long story made too short: surrogate variables and the communication of HPV vaccine trial results. J Epidemiol Community Health. 2010, 64 (5): 377-378. 10.1136/jech.2009.090183.PubMedView ArticleGoogle Scholar
- Tomljenovic L, Shaw CA: Too fast or not too fast: the FDA’s approval of Merck’s HPV vaccine gardasil. J Law Med Ethics. 2012, 40 (3): 673-681.PubMedView ArticleGoogle Scholar
- Tomljenovic L, Shaw CA: No autoimmune safety signal after vaccination with quadrivalent HPV vaccine Gardasil?. J Intern Med. 2012, 272 (5): 514-515.PubMedView ArticleGoogle Scholar
- Souayah N, Michas-Martin PA, Nasar A, Krivitskaya N, Yacoub HA, Khan H, Qureshi AI: Guillain-Barre syndrome after Gardasil vaccination: data from vaccine adverse event reporting system 2006–2009. Vaccine. 2011, 29 (5): 886-889. 10.1016/j.vaccine.2010.09.020.PubMedView ArticleGoogle Scholar
- Mendoza Plasencia Z, Gonzalez Lopez M, Fernandez Sanfiel ML, Muniz Montes JR: Acute disseminated encephalomyelitis with tumefactive lesions after vaccination against human papillomavirus. Neurologia. 2010, 25 (1): 58-59. 10.1016/S0213-4853(10)70023-2.PubMedView ArticleGoogle Scholar
- Wildemann B, Jarius S, Hartmann M, Regula JU, Hametner C: Acute disseminated encephalomyelitis following vaccination against human papilloma virus. Neurology. 2009, 72 (24): 2132-2133. 10.1212/WNL.0b013e3181aa53bb.PubMedView ArticleGoogle Scholar
- DiMario FJ, Hajjar M, Ciesielski T: A 16-year-old girl with bilateral visual loss and left hemiparesis following an immunization against human papilloma virus. J Child Neurol. 2010, 25 (3): 321-327. 10.1177/0883073809349322.PubMedView ArticleGoogle Scholar
- Pugnet G, Ysebaert L, Bagheri H, Montastruc JL, Laurent G: Immune thrombocytopenic purpura following human papillomavirus vaccination. Vaccine. 2009, 27 (28): 3690-10.1016/j.vaccine.2009.04.004.PubMedView ArticleGoogle Scholar
- Melo Gomes S, Glover M, Malone M, Brogan P: Vasculitis following HPV immunization. Rheumatology (Oxford). 2012, 2012-10.1093/rheumatology/kes168.Google Scholar
- Chang J, Campagnolo D, Vollmer TL, Bomprezzi R: Demyelinating disease and polyvalent human papilloma virus vaccination. J Neurol Neurosurg Psychiatry. 2011, 82 (11): 1296-1298. 10.1136/jnnp.2010.214924.PubMedView ArticleGoogle Scholar
- McCarthy JE, Filiano J: Opsoclonus Myoclonus after human papilloma virus vaccine in a pediatric patient. Parkinsonism Relat Disord. 2009, 15 (10): 792-794. 10.1016/j.parkreldis.2009.04.002.PubMedView ArticleGoogle Scholar
- Della Corte C, Carlucci A, Francalanci P, Alisi A, Nobili V: Autoimmune hepatitis type 2 following anti-papillomavirus vaccination in a 11-year-old girl. Vaccine. 2011, 29 (29–30): 4654-4656.PubMedView ArticleGoogle Scholar
- Sutton I, Lahoria R, Tan IL, Clouston P, Barnett MH: CNS demyelination and quadrivalent HPV vaccination. Mult Scler. 2009, 15 (1): 116-119. 10.1177/1352458508096868.PubMedView ArticleGoogle Scholar
- Tomljenovic L, Shaw AC: Death after quadrivalent human papillomavirus (HPV) vaccination: causal or coincidental?. Pharm Reg Affairs. 2012, S12: 001-104172/2167-7689S12-001.Google Scholar
- Tomljenovic L, Shaw CA: Mandatory HPV vaccination. JAMA. 2012, 307 (3): 254-author reply 254–255PubMedView ArticleGoogle Scholar
- Spinosa JP, Riva C, Biollaz J: Letter to the editor response to the article of Luisa Lina Villa HPV prophylactic vaccination: the first years and what to expect from now, in press. Cancer Lett. 2011, 304 (1): 70-10.1016/j.canlet.2011.01.024.PubMedView ArticleGoogle Scholar
- U.S. Food and Drug Administration Vaccines and Related Biological Products Advisory Committee (VRBPAC): VRBPAC Background Document: Gardasil™ HPV Quadrivalent Vaccine. May 18. 2006, [http://www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4222B3.pdf]., VRBPAC Meeting
- Beller U, Abu-Rustum NR: Cervical cancers after human papillomavirus vaccination. Obstet Gynecol. 2009, 113 (2 Pt 2): 550-552.PubMedView ArticleGoogle Scholar
- Mello MM, Abiola S, Colgrove J: Pharmaceutical companies’ role in state vaccination policymaking: the case of human papillomavirus vaccination. Am J Public Health. 2012, 102 (5): 893-898. 10.2105/AJPH.2011.300576.PubMedPubMed CentralView ArticleGoogle Scholar
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