Gardasil 4vHPV Vaccine Package Insert
Found 45001 cases where Vaccine is HPV4 and Manufacturer is MERCK & CO. INC.
March 20, 2018 – Post-licensure safety monitoring of quadrivalent human papillomavirus vaccine in the Vaccine Adverse Event Reporting System (VAERS), 2009–2015 “We identified 92 reports of death. Sixty-one were hearsay reports which included no medical information that could be verified. Two additional reports mentioned a cause of death (‘‘pontine glioma”; ‘‘died from bone cancer…”), but there was no patient or contact information provided. We were able to verify 29 reports of death from autopsy reports, death certificates, or medical records. Of these verified death reports, the median age was 16 years (range 10–37 years), the median time from vaccination was 13 days (range 0–968 days), 20 (69.0%) were in females, and 9 (31.0%) were in males. In 13 (44.8%) verified death reports, 4vHPV was given alone. In the remaining 16 reports, two to four total vaccines were given, including hepatitis A, meningococcal conjugate, Tdap, varicella, and live attenuated inactivated influenza.
March 7, 2018 – Evaluation on the persistence of anti-HPV immune responses to the quadrivalent HPV vaccine in Chinese females and males: Up to 3.5 years of follow-up “Administration of a 3-dose regimen of qHPV vaccine induces durable anti-HPV 6, anti-HPV 11, anti-HPV 16, and anti-HPV 18 responses among Chinese subjects for at least 3.5 years after vaccination.” Comment: 3 doses of one of the HPV vaccines is causing untold adverse events is only “effective” for 3.5 years?
February 23, 2018 – Assessment of Quadrivalent Human Papillomavirus Vaccine Safety Using the Self-Controlled Tree-Temporal Scan Statistic Signal-Detection Method in the Sentinel System “On scanning diagnoses of 1.9 million 4vHPV recipients, two statistically significant categories of adverse event were found: cellulitis on Days 2–3 after vaccination and “other complications of surgical and medical procedures” on Days 1–3. Cellulitis is a known adverse event. Clinically-informed investigation of electronic claims records of the patients with “other complications” did not suggest any previously unknown vaccine safety problem.”
February 7, 2018 – Quadrivalent human papillomavirus vaccination in boys and risk of autoimmune diseases, neurological diseases and venous thromboembolism “Altogether 7384 boys received at least one dose of the qHPV vaccine at age 10–17 years. Overall, RRs were close to unity for the combined groups of autoimmune diseases (RR = 0.96; 95% CI: 0.71–1.28,) n = 46 cases in qHPV-vaccinated boys had neurological diseases (RR = 0.67; 0.41–1.10, n = 16), as well as for venous thromboembolism (RR = 0.88; 0.33–2.35, n = 4). After taking multiple testing into account, none of the 52 individual outcomes studied appeared to occur in excess among qHPV-vaccinated boys.” Comment: And with a stroke of a pen, the 46 injured boys were negated. Who is paying for care for these boys?
January 30, 2018 – Analysis of Memory B-Cell Responses Reveals Suboptimal Dosing Schedule of a Licensed Vaccine (full text) “Anamnestic Ab responses have been observed following a booster dose administered 60 months postvaccination in young women who received the quadrivalent HPV (4HPV) vaccine series, demonstrating that the HPV vaccines generate B-cell memory (Bmem).”
May, 2016 – Immunogenicity, Tolerability, and Safety in Adolescents of Bivalent rLP2086, a Meningococcal Serogroup B Vaccine, Coadministered with Quadrivalent Human Papilloma Virus Vaccine. “Conclusions: Concomitant administration of bivalent rLP2086 and HPV-4 elicits robust immune responses to both vaccines without increasing reactogenicity compared with bivalent rLP2086 alone. Concurrent administration may increase compliance with both vaccine schedules.” Comment: Here are the adverse events reported within this study which claims no increasing reactogenicity without a true placebo is not an adequate comparison. Other Adverse Events Combining these adolescent vaccines increases the risk of adverse events… to make more profit from drug sales prescribed for side effects.
April 2016 – Immunogenicity of Human Papillomavirus Recombinant Vaccine in Children with CKD “Conclusions: Antibody response to the quadrivalent recombinant HPV vaccine was robust and sustained in girls and young women with chronic kidney disease and on dialysis. A less robust response to the vaccine was observed among those with a kidney transplant. Additional study is needed to determine if vaccination before kidney transplantation or an alternative vaccination regimen would benefit transplant recipients.” Comment: Why give a HPV vaccine to a child who already has a devastating disease?
February 3, 2016 – Use of the nonavalent HPV vaccine in individuals previously fully or partially vaccinated with bivalent or quadrivalent HPV vaccines (full text) “Simultaneously, antibody responses to HPV-6, 11, 16, and 18 were non-inferior to those generated by the 4vHPV vaccine. Consequently, efficacy for 9vHPV against persistent infection and disease related to HPV types 6, 11, 16, or 18 can be inferred to be comparable to that of 4vHPV [17]. Finally, immunization with 9vHPV was shown to be well tolerated and safe in the pivotal RCT, and although it resulted in more adverse local reactions than vaccination with the 4vHPV vaccine, as expected due to the higher dose of antigen and/or adjuvant, more than 90% of these reactions were mild to moderate in intensity. Comment: GARDASIL 9 vaccine contains 500 mcg of aluminum (provided as AAHS) and 9.56 mg of sodium chloride.
January 2, 2016 – Absence of venous thromboembolism risk following quadrivalent human papillomavirus vaccination, Vaccine Safety Datalink, 2008–2011 “We identified 313 potential cases of VTE among HPV4 vaccinees, and 291 (93%) had sufficient medical records for review. Of these, we confirmed 156 embolisms (54%) cases. VTE was uncommon among males (n = 3) and 9–12 year olds (n = 4). Nearly all confirmed cases (97%) had at least one known risk factor for VTE, including hormonal contraceptive use, obesity, and hypercoagulability. Sixteen (10%) confirmed cases occurred in the 1–60 days following HPV4 exposure. The risk of VTE varied from 1.47 in the 1–7 days following HPV4 exposure to 0.92 in the 1–60 days following vaccination. It was not possible to calculate a stratified IRR for males due to small sample size; the other risk factors evaluated did not significantly affect the risk of VTE after HPV4 exposure.”
January 2016 – New Concerns about the Human Papillomavirus Vaccine “It has recently come to the attention of the College that one of the recommended vaccines could possibly be associated with the very rare but serious condition of premature ovarian failure (POF), also known as premature menopause. There have been two case report series (3 cases) published since 2013 in which post-menarcheal adolescent girls developed laboratory documented POF within weeks to several years of receiving Gardasil, a four-strain human papillomavirus vaccine (HPV4).
August 2015 – A link between human papillomavirus vaccination and primary ovarian failure: a current analysis ” Recent findings: An increasing number of cases of primary ovarian failure post-HPV4 are being reported. Possible mechanisms for the suspected effect of HPV on female reproductive function are a toxic effect or an autoimmune response. The trigger could be the vaccine immunogen contents or the adjuvants, the latter are used to increase the immune reaction. The adjuvant in HPV4 contains aluminum. Animal models have shown aluminum exposure to inhibit expression of female reproductive hormones and to induce histologic changes in the ovaries. Specific genetic compositions may be more susceptible to developing an autoinflammatory syndrome after exposure to an environmental factor.”
August 2015 – Evaluation of the Long-Term Anti-Human Papillomavirus 6 (HPV6), 11, 16, and 18 Immune Responses Generated by the Quadrivalent HPV Vaccine (full text) “The development of preinvasive cervical intraepithelial neoplasia grades 2 and 3 (CIN2 and CIN3) to invasive cancer (from incident high-risk HPV infections) takes 10 to 15 years minimum and 20 to 25 years on average. Because of this, the ability of vaccine-induced immunity to prevent cervical preinvasive lesions and cancer in preadolescent girls is best measured years after immunization.”
June 22, 2015 – Chorioamnionitis following vaccination in the Vaccine Adverse Event Reporting System “The three most common vaccines in these reports were 2009 H1N1 inactivated influenza, quadrivalent human papillomavirus (HPV4), and Tdap vaccines in 32%, 29% and 26% of reports, respectively. In all, 58 had at least one reported risk factor for chorioamnionitis. Chorioamnionitis was identified in 3 reports of spontaneous abortions and 6 stillbirths, 6 reports of preterm birth (two of whom died) and 16 reports of term birth; maternal outcomes included two reports of postpartum hemorrhage and one report of maternal admission to the intensive care unit. No maternal deaths were Reported.”
May 21, 2015– Orthostatic intolerance and postural tachycardia syndrome as suspected adverse effects of vaccination against human papilloma virus“Twenty-one of the referred patients fulfilled the criteria for a diagnosis of POTS. All (100%) patients had orthostatic intolerance, 94% nausea, 82% chronic headache, 82% fatigue, 77% cognitive dysfunction, 72% segmental dystonia, 68% neuropathic pain.”…”In a population referred for symptoms of orthostatic intolerance and other symptoms consistent with autonomic dysfunction that began in close temporal association with a quadrivalent HPV vaccination, we identified a 60% prevalence of POTS. Further work is urgently needed to elucidate the potential for a causal link between the vaccine and circulatory abnormalities and to establish targeted treatment options for the affected patients.”
February 2015 – Pain in Adolescent Girls Receiving Human Papillomavirus Vaccine With Concomitantly Administered Vaccines (full text) “Nonetheless, anecdotal reports suggest that HPV hurts more than other vaccines. In clinical investigations, injection site pain following HPV is generally assessed by the use of daily diary cards completed by either the participant or their parent up to 7 days after vaccination.”…”In our study, young girls reported a modestly higher pain score in the arm where HPV4 was administered in the period immediately following receipt of HPV4 when contrasted to the pain score in the arm where other vaccines were concomitantly administered.”
January 15, 2015 – Safety of quadrivalent human papillomavirus vaccine (Gardasil) in pregnancy: Adverse events among non-manufacturer reports in the Vaccine Adverse Event Reporting System, 2006–2013 “We found 147 reports after HPV4 vaccine administered to pregnant women. The most frequent pregnancy-specific AE was spontaneous abortion in 15 (10.2%) reports, followed by elective terminations in 6 (4.1%). Maternal fever was the most frequent non-pregnancy-specific AE in 3 reports. Two reports of major birth defects were received. No maternal deaths were noted. One-hundred-three (70.1%) reports did not describe an AE. This review of VAERS non-manufacturer reports following vaccination with HPV4 in pregnancy did not find any unexpected patterns in maternal or fetal outcomes. Comment: 15 of 147 reports of miscarriages not a pattern?
December 23, 2014 – A case-control study of quadrivalent human papillomavirus vaccine-associated autoimmune adverse events ” It was observed that cases with the serious adverse autoimmune events (SAAEs) of gastroenteritis, arthritis, systemic lupus erythematosus, vasculitis, alopecia, or CNS conditions were significantly more likely than controls to have received HPV4 vaccine (median onset of autoimmune symptoms from 6 to 55 days post-HPV4 vaccination).” Comment: This is not only significant in terms of the conditions but the fact that the MEDIAN onset of these symptoms can be up to 55 days? Note that many “safety” studies follow subjects for only 4 to 14 days.
October 2014– Attribution of 12 High-Risk Human Papillomavirus Genotypes to Infection and Cervical Disease “A total of 10,656 women ages 15 to 26 years and 1,858 women ages 24 to 45 years were enrolled in the placebo arms of one of three clinical trials of a quadrivalent HPV vaccine. We estimated the cumulative incidence of persistent infection and the proportion of CIN/AIS attributable to individual carcinogenic HPV genotypes, as well as the proportion of CIN/AIS lesions potentially preventable by a prophylactic 9-valent HPV6/11/16/18/31/33/45/52/58 vaccine.”
June 2014 – A case of lipoatrophy following quadrivalent human papillomavirus vaccine administration (full text) “A 27-year-old woman presented to the dermatology clinic with a circular depression on her right arm without any local symptoms or previous inflammation. She had no medical problems and was not taking any medication. This was diagnosed as lipoatrophy, the term describing the localized loss of fat tissue. This may occur as a result of subcutaneous injections. She reported a history of three intramuscular Gardasil injections on a 0-, 2-, and 6-month-schedule in the same arm, with the last injection given 9 months before the appearance of the lesion.”… “We estimate that the injection was subcutaneous instead of intramuscular and that the aluminum granulations found in the macrophages correspond to the adjuvant found in the vaccine.”
May 2014 – Human Papillomavirus Prevalence in Oropharyngeal Cancer before Vaccine Introduction, United States “A candidate 9-valent vaccine that includes types in the existing quadrivalent vaccine (HPV types 6, 11, 16, and 18) and 5 additional high-risk types (31, 33, 45, 52, and 58) is in clinical trial. Supported by evidence that existing vaccines effectively reduce oral HPV infections, these formulations may also reduce the incidence of oropharyngeal cancers.” Comment: HPV Vaccines have a long list of adverse events. Click here to view Gardasil. For Cervarix here
January 15, 2014 – The influence of free quadrivalent human papillomavirus vaccine (HPV4) on the timely completion of the three-dose series “Grant sponsorship of at least one HPV4 dose among adults did not predict three dose on-time completion (OR = 1.56, 95%CI: 0.80, 3.06). Neither was adult grant sponsorship of HPV4 significant when analyzing exclusive payor sources vs. a combination of payor sources (OR = 0.72, 95%CI: 0.10, 5.17). Conclusions: Free HPV4 vaccine does not influence the on-time completion rates among adults.”
January 8, 2014 – Systematic review of human papillomavirus vaccine coadministration “Our review included 9 studies, 4 of quadrivalent HPV vaccine and 5 of bivalent HPV vaccine; coadministered vaccines included: meningococcal conjugate, hepatitis A, hepatitis B, combined hepatitis A and B, tetanus, diphtheria, acellular pertussis (Tdap), and inactivated poliovirus vaccines. Studies varied in methods of data collection and measurement of immunogenicity and safety. Non-inferiority of immune response and an acceptable safety profile were demonstrated when HPV vaccine was coadministered with other vaccines.“
November 18, 2013 – The Role of Media and the Internet on Vaccine Adverse Event Reporting: A Case Study of Human Papillomavirus Vaccination “Compared with MNQ, HPV4 had more coverage in the print media and Internet search activity, which corresponded with the frequency of VAERS reports. In February 2007, we observed a spike in print media for HPV4. Although media coverage waned, Internet search activity remained stable and predicted the rise in HPV4-associated VAERS reports.“
October 9, 2013 – Autoimmune, neurological, and venous thromboembolic adverse events after immunization of adolescent girls with quadrivalent human papillomavirus vaccine in Denmark and Sweden: cohort study (full text) “Exposure to qHPV (Gardasil) vaccine was significantly associated with Behcet’s syndrome, Raynaud’s disease, and type 1 diabetes.”
September 2013 – HPV Vaccination of Boys in Primary Care Practices “Although most physicians support HPV4 for boys, physician education and evidence-based tools are needed to improve implementation of a vaccination program for males in primary care settings.“
August 7, 2013 – Safety and immunogenicity of the quadrivalent HPV vaccine in female Systemic Lupus Erythematosus patients aged 12 to 26 years (pdf) “Patients were observed in the clinic for 30 minutes after each vaccine dose for acute allergic reactions or syncope.HPV vaccine-related side effects were evaluated systematically, including but not limited to pain, erythema, swelling and itching at the injection site, fever, fatigue, arthralgias, myalgias, headache, dizziness, syncope, influenza-type symptoms, and signs and symptoms of an acute allergic reaction including dyspnea and hives. At study entry and at months 2, 4, 6 and 7, patients were clinically evaluated, and physical examination and laboratory data were recorded. Clinical manifestations of SLE were carefully analyzed and a SLEDAI score was calculated at each of the clinic visits.”…”Nine of 27 patients (33.3%) had a mild-moderate flare during the study period, typically with symptoms similar to those they experienced in flares before vaccine administration. Five had arthralgias, 4 had a rash, 2 had pleuritis, and 1 had peripheral neuropathy. One of the patients with rash had a severe cutaneous flare after sun exposure, three months after her second HPV vaccine. She was treated with rituximab as this medication had successfully controlled her lupus disease activity a few years earlier. Of 12 patients with history of lupus nephritis, two of four with Class IV nephritis experienced worsening renal function during/after the study and **progressed to renal failure** within 18 months of the completion of the study.”
August 1, 2013 – HPV vaccine update Immunization rates low despite excellent effectiveness, safety profile (full text) “Among the 21,194 reports in females following HPV4 administration, 92% were classified as “non-serious.” Among non-serious adverse events, the most commonly reported generalized symptoms are syncope (fainting), dizziness, nausea, headache, fever and urticaria (hives); the most commonly reported local symptoms are injection site pain, redness and swelling. Among the 8% of HPV4 VAERS reports coded as “serious,” headache, nausea, vomiting, fatigue, dizziness, syncope and generalized weakness are the most frequently reported symptoms.”
July 30, 2013 – Immunogenicity of Quadrivalent HPV Vaccine Among Girls 11 to 13 Years of Age Vaccinated Using Alternative Dosing Schedules: Results 29 to 32 Months After Third Dose “Our findings also suggested that 2 doses of HPV vaccine delivered at 0 and 12 months might afford similar protection. Evidence supporting dosing flexibility could be important for national HPV vaccination policies.” Comment: They’ll never drop the third dose; too much money at stake.
April 2013 – Human Papillomavirus Vaccine Initiation and Awareness: – U.S. Young Men in the 2010 National Health Interview Survey “HPV vaccination initiation among men aged 18–26 years in 2010 was low. HPV and HPV vaccine awareness were also low, and messages in this area directed to men are needed. Since ACIP published a recommendation for routine use of HPV4 among men/boys in December 2011,continued monitoring of HPV vaccination uptake among men aged 18–26 years is useful for evaluating the vaccination campaigns, and planning and implementing strategies to increase coverage.”
May 2012 – Hypersensitivity reaction to human papillomavirus vaccine due to polysorbate 80. “A 17-year-old girl reported generalized urticaria, eyelid angioedema, rhino-conjunctivitis, dyspnoea and wheezing 1 h after third intramuscular administration of quadrivalent human papillomavirus vaccine (Gardasil). She was treated with antihistamine, and corticosteroids with prompt relief of rhinitis and dyspnoea, while urticaria and angioedema lasted 24 h. Intradermal test with Gardasil, which contains polysorbate 80 (PS80), resulted positive, while skin tests with the bivalent vaccine were negative. Prick test performed with PS80 resulted positive in the patient and negative in ten healthy controls. The CD203 basophil activation test result was negative for PS80 at all the tested dilutions and specific IgE was not found. As flu vaccine was recommended, the authors’ skin tested two flu vaccine, one containing PS80 (Fluarix, GSK), which resulted positive and another flu vaccine with no adjuvant or preservative (Vaxigrip, Sanofi Pasteur MSD), which gave negative results. The patient then received Vaxigrip without adverse reactions.”
May 2012 – Human Papillomavirus Immunization Is Associated with Increased Expression of Different Innate Immune Regulatory Receptors “Finally, a significant increase in the expression of NKG2D, NKp30, and NKp46 by NK and CD3+ CD56+ lymphocytes was detected after quadrivalent HPV (type 6/11/16/18) vaccine immunization. Our data indicate that HPV immunization is associated with significant changes in the expression and function of different innate immune receptors, including ILT2, which may participate in the protective effect of HPV vaccines.
May 2012 – Human Papillomavirus Immunization Is Associated with Increased Expression of Different Innate Immune Regulatory Receptors “Finally, a significant increase in the expression of NKG2D, NKp30, and NKp46 by NK and CD3+ CD56+ lymphocytes was detected after quadrivalent HPV (type 6/11/16/18) vaccine immunization. Our data indicate that HPV immunization is associated with significant changes in the expression and function of different innate immune receptors, including ILT2, which may participate in the protective effect of HPV vaccines.
December 2012 – Safety of Quadrivalent Human Papillomavirus Vaccine Administered Routinely to Females (pdf) “This study has limitations. First, we could only detect new-onset conditions requiring ED visits or hospitalizations within 60 days after vaccination; it was not designed to investigate long-term safety outcomes or risk of HPV4-associated recurrence/progression of disease. Second, despite its large size, this study may have had insufficient power to detect very rare conditions.”
December 2012 – Detection of human papillomavirus L1 gene DNA fragments in postmortem blood and spleen after Gardasil vaccination—A case report (open access) “DNA in the postmortem blood and splenic tissue obtained at autopsy of a formerly healthy teenage girl who suffered a sudden unexpected death in sleep 6 months after 3 intramuscular injections of a quadrivalent HPV vaccine, Gardasil.”
September 27, 2011 – Comparing bivalent and quadrivalent HPV vaccines “Competing interests: Vaccine was provided for CVT by GSK Biologicals, under a clinical trials agreement with NCI. GSK also provided support for aspects of the trial associated with regulatory submission needs of the company under FDA BB-IND 7920. Douglas Lowy and John Schiller from NCI are named inventors on US government owned HPV vaccine patents that are licensed to GSK and Merck, and so are entitled to limited royalties as specified by federal law. None of the other NCI and Costa Rica co-authors have any potential conflicts of interest to report.”
September 22, 2011 – VAERS Line List Report Vax Type: HPV4 (pdf) – 1874 pages of VAERS reports on HPV vaccine side effects.
February 3, 2011 – Efficacy of Quadrivalent HPV Vaccine against HPV Infection and Disease in Males (full text) Comment: This is one of the cornerstone articles that allowed the use of Gardasil in boys. All researchers listed had signficant ties to a vaccine manufacturer or the vaccine’s manufacturer, Merck.
- “Supported by Merck by grants (M01-RR-00079 and UL1 RR024131, to Dr. Palefsky) from the National Center for Research Resources and by a grant (RO1 CA098803, to Dr. Giuliano) from the National Institutes of Health.
- Drs. Giuliano, Ferris, Moreira, Penny, and Palefsky report receiving grant support from Merck, either personally or through their institution;
- Dr. Penny reports receiving grant support from GlaxoSmithKline;
- Dr. Goldstone reports receiving grant support from Qiagen;
- Drs. Giuliano, Ferris, Moreira, Hillman, and Chang report receiving speaking fees or fees for board membership from Merck;
- Dr. Moi reports that his institution has received funding from Merck;
- Dr. Penny reports having stock or stock options in AstraZeneca;
- Dr. Palefsky reports receiving consulting fees from GlaxoSmithKline;
- Drs. Giuliano, Palefsky, Goldstone, Moreira, Moi, and Chang report receiving travel reimbursement from Merck;
- Dr. Bryan reports having an approved, filed, or pending patent related to subject matter discussed in this article;
- Dr. Bryan, Dr. Marshall, Dr. Vuocolo, Dr. Barr, Dr. Haupt, Mr. Radley, and Dr. Guris are employees of Merck and own Merck stock or stock options.
- No other potential conflict of interest relevant to this article was reported.”
May 2010 – Gardasil® – The New HPV Vaccine: The Right Product, the Right Time? A Commentary (full text) – In the United States, as of the end of 2008, there were 12,424 reports of adverse events following immunization (AEFIs). Seven hundred and seventy-two reports (6.2% of all reports) described serious AEFIs, including 32 reports of death. Disproportional reporting of syncope and venous thromboembolic events were noted with data mining methods (Slade et al. 2009). These findings must be interpreted against the limitations (possible underreporting) of a passive reporting system. Both CIC and NACI have accepted the vaccine as safe, and neither recommended a post-marketing surveillance campaign. In the absence of long-term data about the vaccine’s safety, that acceptance seems premature.
March 12, 2010 – FDA Webinar Human Papillomavirus (HPV) Quadrivalent & Bivalent Vaccines Global Parental Concerns Regarding Safety and Efficacy of Gardasil & Cervarix (pdf) – Justifying Gardasil
January 29, 2010 – Currently Approved Prophylactic HPV Vaccines (free registration) Vaccine composition.
| Cervarix (GlaxoSmithKline) | Gardasil (Merck) | |
| Vaccine type | HPV-16 and HPV-18 VLP
L1 capsid component |
HPV-6/11/16/18 VLP
L1 capsid component |
| Concentration | 20 µg HPV-16
20 µg HPV-18 |
20 µg HPV-6
40 µg HPV-11 40 µg HPV-16 20 µg HPV-18 |
| Adjuvant | AS04:
500 µg aluminum hydroxide, 50 µg 3-deacylated monophosphoryl lipid A |
Alum:
225 µg aluminum hydroxyphosphate sulfate |
| Recombinant technology substrate system | expression system in cells | Yeast expression system inSaccharomyces cerevisiae |
January 2009 – CNS demyelination and quadrivalent HPV vaccination “We report five patients who presented with multifocal or atypical demyelinating syndromes within 21 days of immunization with the quadrivalent human papillomavirus (HPV) vaccine, Gardasil.”
August 19, 2009 – Postlicensure safety surveillance for quadrivalent human papillomavirus recombinant vaccine. (full text) Review and describe adverse events following immunization (AEFIs) reported to VAERS, a national, voluntary, passive surveillance system, from June 1, 2006, through December 31, 2008. Additional analyses were performed for some AEFIs in prelicensure trials, those of unusual severity, or those that had received public attention. Statistical data mining, including proportional reporting ratios (PRRs) and empirical Bayesian geometric mean methods, were used to detect disproportionality in reporting.
December 2009 – Gardasil needs a new consent form – Recently evaluated the 12,424 reports submitted to the VAERS between 1 June 2006 and 31 December 2008 concerning the risks of Gardasil administration. Reported serious adverse events included venous thromboembolism, Guillain–Barré syndrome, autoimmune disorders, pancreatitis, anaphylaxis, transverse myelitis, motor neuron disease and death. Venous thromboembolism was statistically associated with Gardasil injection.
January 2009 – CNS demyelination and quadrivalent HPV vaccination “We report five patients who presented with multifocal or atypical demyelinating syndromes within 21 days of immunization with the quadrivalent human papillomavirus (HPV) vaccine, Gardasil.”
September 9, 2008 – Anaphylaxis following quadrivalent human papillomavirus vaccination. (full text) Pre-existing allergen sensitization is biologically plausible for several components of the quadrivalent HPV vaccine. Natural HPV infection does not cause viremia; however, HPV virus-like particles are highly immunogenic when injected. It is unclear whether some people may produce an IgE response to injected HPV antigens. One small trial injected participants (n = 30) with HPV type 11 virus-like particles and found no increase in IgE levels; however, data from a study of rhesus macaques (n = 10) suggests it is possible. Because the age group targeted by the HPV vaccination program was 15 years and older, many women may have already been exposed to HPV, because the median age of first sexual intercourse in Australia is 16 years. There is potential for residual amounts of yeast proteins to be in the HPV vaccine. Although hypersensitivity to yeast is a documented phenomenon, there have been infrequent reports of anaphylaxis or hypersensitivity reactions following the receipt of yeast-containing vaccines.
January 30, 2008 – Safety and immunogenicity of co-administered quadrivalent human papillomavirus (HPV)-6/11/16/18 L1 virus-like particle (VLP) and hepatitis B (HBV) vaccines “HPV-vaccine matched placebo consisted of the same adjuvant alone and was visually indistinguishable from vaccine L1 VLP vaccine (GARDASIL®, Merck Research Laboratories, West Point, PA, USA) contained type 6 (20 mcg), type 11 (40 mcg), type 16 (40 mcg), and type 18 (20 mcg) L1 VLPs, and 225 mcg of aluminum adjuvant.”
April 18, 2007 – Gardasil – the Cervical Cancer Vaccine? “If HPV alone caused cervical cancer than the number of cases in the U.S. would be the same as the number of women with HPV infections. Since only a relatively small percentage of HPV infected women get cervical cancer this raises the question whether a vaccine against HPV is the right target at all? In fact, according to the text Cancer: Principles & Practice of Oncology, “In most studies, HPV status was not a strong independent prognosticator of outcome in cervical cancer patients; however there appears to be a trend for HPV-negative tumors to do worse …those tumors containing HPV DNA tend to be of an early stage and low grade.” This suggests that if the goal is to reduce deaths from cervical cancer the target should not be HPV at all because the tumors without HPV actually “do worse.”
October 15, 2007 – HiFi DNA Tech files lawsuit against FDA A lawsuit was filed Oct. 12 in U.S. District Court against the U.S. Department of Health and Human Services (HHS) and the U.S. Food and Drug Administration (FDA) related to reclassification of HPV DNA tests from class III to class II devices. The inaction by both agencies hinders introduction of new and affordable HPV testing to improve women’s health care.
December 1, 2006 – A National Survey of Pediatrician Knowledge and Attitudes Regarding Human Papillomavirus Vaccination (full text) “Pediatricians’ intentions regarding recommending a quadrivalent HPV vaccine for female and male patients in various age groups are illustrated in Fig 1. Respondents were more likely to recommend HPV vaccination to older compared with younger adolescents (Cochran-Armitage test for trend: females, P < .0001; males, P < .0001). Within each age group, respondents were more likely to recommend vaccine to female versus male patients (McNemar’s test for paired data: P < .0001 for the comparison within each age group).”
November 30, 2006 – CSL to fund Gardasil booster “BIOTECHNOLOGY company CSL has promised to help fund a booster to the cervical cancer vaccine Gardasil if its effectiveness diminishes in time.”
November 23, 2006 – Merck Launches National Advertising Campaign For GARDASIL®, Merck’s New Cervical Cancer Vaccine “The full public health benefit of reducing the burden of cervical cancer and HPV disease may be achieved through broad public awareness and vaccination with GARDASIL, which is the driving force behind One Less,” said Bev Lybrand, vice president & general manager, HPV Franchise, GARDASIL, Merck Vaccine Division.”
November 22, 2006 – The making of Gardasil Merck producing vaccine at Pennsylvania plant that was (briefly) the biggest biotech plant in the world.
November 19, 2006 – Cancer vaccine manufacturer drops price THE cervical cancer vaccine Gardasil could be approved for inclusion on the national immunizationn register by the end of the week after its manufacturer agreed to drop its price.”
November 15, 2006 – Most women in the dark about HPV “Younger women, those with higher education levels, and those exposed to more health information were more likely to have heard about HPV. ”But the only factors associated with having accurate knowledge — knowing that it could lead to cervical cancer — was an abnormal Pap test or testing positive on an HPV test,” Tiro said.”
November 1, 2006 – Comparison of the Immunogenicity and Reactogenicity of a Prophylactic Quadrivalent Human Papillomavirus (Types 6, 11, 16, and 18) L1 Virus-Like Particle Vaccine in Male and Female Adolescents and Young Adult Women (full text) “There was 1 death and 1 nonfatal serious AE outside the 15-day postvaccination period, which are described in more detail in the text.”
October 7, 2006 – Should HPV vaccines be mandatory for all adolescents? – “Who will fund these routine immunizations? Reassuringly, Gardasil has been added to the US Vaccines for Children Program that provides free immunizations to those that most need them, and the UK Department of Health is also considering government funding. But, even with these resources, the debate remains over who should be immunized. Contrary to the FDA’s recommendations, there is growing support for the vaccination of both boys and girls. Modeling studies have shown that a female-specific approach would be only 60—75% as effective at reducing HPV prevalence in women as strategies that target both sexes.”
October 2006 – Schoolgirls must have compulsory sex disease jabs, say doctors “This is the first legislation of its kind in the USA, and a decision from which the EU members states should take heed,” said the editorial. There is also growing support for the vaccination of boys. They too can carry human papillomavirus (HPV), the virus spread by sexual intercourse that can trigger cervical cancer. Studies have shown that a female-only vaccination would be only 60-75% as effective as strategies targeting both sexes.”
September 2006 – A content analysis of news coverage of the HPV vaccine by U.S. newspapers, January 2002-June 2005. “Detailed information about HPV, however, was frequently missing which could lead to an incomplete picture or lack of understanding of the complexity of HPV and cervical cancer. As a major source of medical information, the media can be particularly important in educating policymakers and the general public about new scientific advances.”
July 25, 2006 – It’s Not Just Religious Conservatives Who Oppose Mandatory HPV Vaccination“So the story was already written before the Food and Drug Administration announced its approval last month of Gardasil, Merck’s new vaccine against the human papillomavirus, a sexually transmitted virus linked to cervical cancer. Most of the reporting has depicted Christian conservatives as once again playing politics with the FDA’s approval process, just as they did with Plan B. Never mind that the Family Research Council and Focus on the Family, two leading social conservative groups, actually issued press releases supporting FDA approval of Gardasil.”
June 25, 2006 – Hype About New HPV Vaccine is More Good Marketing than Good Medicine “The drug company behind the vaccine is already promoting it as a cure-all solution. The ad campaign, titled ‘Tell Someone,’ has created false hope among women that this new vaccine will make the HPV problem go away,” says Marcy Holmes, a practitioner at Women to Women.”
June 5, 2006 – Merck’s $4 billion PR problem ” Merck (Research) is appealing to states to make the vaccine mandatory for all children who attend public schools. A mandate from the states, which control vaccination policies, would make Gardasil a guaranteed blockbuster. That’s crucial for the nation’s fourth-largest drugmaker, which is still struggling to replace revenues lost after the 2004 withdrawal of its blockbuster arthritis medicine, Vioxx, in addition to shrinking sales of its cholesterol drug Zocor, as it faces generic competition this summer. Gardasil is almost certain to be approved by the FDA, say analysts, who place the medicine’s annual peak revenue potential in the $2 to $4 billion range. Those estimates assume states will make Gardasil mandatory. The shots are given three times over a six month period, and will cost anywhere between $300 and $500. The vaccine lasts for up to five years.”
May 18, 2006 – FDA CBER Vaccines and Related Biological Products Advisory Committee Meeting Transcripts (pdf)
May 18, 2006 – VRBPAC Background Document Gardasil™ HPV Quadrivalent Vaccine VRBPAC Meeting (pdf)
May 16, 2006 – Merck’s dance with the religious right Drug giant close to approval for a controversial anti-cancer vaccine for youngsters.
April 03, 2005 – Cancer Vaccine Will Be a Hard Sell. “One drug maker, Merck, says it will try to convince states to require vaccination before children as young as 12 can enter school.”
April 2005 – Report of the Consultation on Human Papillomavirus vaccines (pdf) WHO “The International Biological Study on Cervical Cancer recruited women with cervical cancer in 22 countries, and multi-center case-control studies recruited women with cervical cancer in 10 countries in Africa, the Americas, Asia and Europe. PCR-based methods were used for the detection and typing of HPV DNA in cells from tumor biopsies and/or cervical Pap smears. Results from these studies have shown that HPV is a necessary cause of cervical cancer and that high parity, long-term use of oral contraceptives and tobacco smoking are important cofactors.”
February 2005 – Parental attitudes about sexually transmitted infection vaccination for their adolescent children.
November 29, 2004 – “A Vaccine Every Woman Should Take” Two drug companies are closing in on shots against HPV, the leading cause of cervical cancer.
July 2004 – Early assessment of the efficacy of a human papillomavirus type 16 L1 virus-like particle vaccine. “The incidence of HPV infection was observed to be 0 cases per 100 person-years at risk in the vaccine group, and 5 cases per 100 person-years at risk in the control group. These results support the institution of larger efficacy trials for HPV L1 VLP vaccines.”
July 2004 – Recommending STI vaccination to parents of adolescents: the attitudes of nurse practitioners. “Generally, participants were amenable to recommending STI vaccines. Conjoint analysis indicated that AAP recommendation, infection, and patient age most strongly influenced ratings.”
August 2003 – Preventative and therapeutic vaccines for cervical cancer “Key Issues: A prophylatic human papillomavirus (HPV) vaccine would have its greatest impact in developing countries. Therefore, it is critical to developing a new generation HPV virus-like (VLP)-based vaccine that is cheap and simple to produce, distribute and administer. It is important to determine the longevity of protection provided by VLP vaccination. There are at least 15 high-risk HPV genotypes that are etiologic agents of cervical carcinoma A Key issue is the development of a single vaccine capable of preventing infection by all these oncogenic genotypes.”
August 2003 – Cervical cancer vaccine may lose effectiveness during ovulation “Given these findings, the authors say that it will be important to determine whether the vaccine will be as effective at protecting ovulating women from HPV16 infections as it appears to be for women taking oral contraceptives.”
June 2003 – Progress in prophylactic and therapeutic vaccines for human papillomavirus infection. “The duration of protection of virus-like particle (VLP) vaccines in humans is not known. This is a key issue since it will dictate the frequency with which booster immunizations will be indicated.”
April 2003 – Absorption-enhanced 3,3’-Diindolylmethane (DIM): Human Use in HPV-related, Benign and Pre-cancerous Conditions. “Human use of this preparation at higher doses has demonstrated treatment-related resolution of moderate and severe cervical dysplasia in preliminary open-label testing. A still higher dose, about 10 times above that possible from dietary exposure to diindolylmethane (DIM) from vegetable sources, has resulted in the control of laryngeal papillomas and resolution of cutaneous and plantar warts in preliminary human testing. The clearing of HPV-related lesions is consistent with DIMs previously described, apoptosis-promoting and chemopreventive activity.”
September 2002 – Vitamin A, carotenoids, and risk of persistent oncogenic human papillomavirus infection. “Higher levels of vegetable consumption and Vitamin A were associated with a 54% decrease risk of HPV persistence (adjusted odds ratio, 0.46; 95% confidence interval, 0.21-0.97). Also, a 56% reduction in HPV persistence risk was observed in women with the highest plasma cis-lycopene concentrations compared with women with the lowest plasma cis-lycopene concentrations”
2002 – Content of folic acid and free homocysteine in blood serum of human papillomavirus-infected women with cervical dysplasia. “Significantly lower levels of folic acid and higher levels of free homocysteine were observed in the blood serum of HPV-positive patients with CIN III. The correlation was found between serum concentrations of folic acid and free homocysteine in both groups.”
December 2001 – Indole-3-Carbinol and Diindolylmethane Induce Apoptosis of Human Cervical Cancer Cells and in Murine HPV16-Transgenic Preneoplastic Cervical Epithelium. – “Estradiol reduced the percentage of these late-stage apoptotic cells in the cervical epithelium of transgenic, E2-treated mice, but this reduction was prevented by I3C. These data confirm the proapoptotic action of I3C on transformed cells in vitro, extend the observations to cervical cancer cells and to DIM and show for the first time that dietary I3C results in increased apoptosis in target tissues in vivo.”
February 1999 – Fish oil constituent docosahexa-enoic acid selectively inhibits growth of human papillomavirus immortalized keratinocytes “Fish oil omega 3s inhibited growth of HPV16 immortalized cells [cell culture].”
1997 – Content of alpha-tocopherol in blood serum of human Papillomavirus-infected women with cervical dysplasias.“A statistically significantly lower level of alpha-tocopherol was observed in the blood serum of HPV-positive patients with cervical intraepithelial neoplasia. The risk of dysplasia was four times higher for an alpha-tocopherol level < 7.95 mumol/l.”
August 1994 – Human papillomavirus vaccines: a warty problem. “In favor of success is (a) the relative simplicity of the HPV genome (only two proteins in the viral coat, and a small number of other genes), (b) the lack of genetic variability within types and stability of the genome, and (c) the encouraging results with vaccines against animal PVs. However, it is difficult to provide evidence of the efficacy of HPV vaccines because of the inability to propagate the virus in culture or in animal models and because of the incomplete understanding of the natural history of HPV infection.”
1987 – “Genital human papillomavirus infections and cancer: Memorandum from a WHO Meeting (pdf) “There is increasing evidence from molecular biology and clinical investigations that infection with specific types of human papillomavirus (HPV) is associated with anogenital cancers, especially cancer of the cervix uteri. Human papillomavirus types 16 and 18 have been found in the majority of cervical cancers investigated; specific viral mechanisms appear to be involved in the malignant conversion of these tumors. However, evidence from epidemiological investigations is still inconclusive. Concerted efforts to study the etiology and natural history of lower genital tract neoplasia and its association with HPV, together with the development of vaccines against specific viral types, are needed in order to make it possible in the future to prevent cervical and other anogenital cancers.”
1986 – Human papillomavirus (HPV) infections of the female genital tract and their associations with intraepithelial neoplasia and squamous cell carcinoma. “So far, HPV 16 and HPV 18 seem to be the only HPV types with DNA capable of existing integrated in the host cell DNA. At the moment, cervical (and other) HPV lesions are the subject of intense study utilizing epidemiologic, morphologic, immunohistochemical, biochemical, and molecular biologic methods (recombinant gene technology) to provide further evidence of the suggested causal relationship between HPV and cancer.”