1023collaborative

Methods 277 young women (mean age 20·2 years [SD 1·7]) were randomly assigned to quadrivalent HPV (20 É g type 6, 40 É g type 11, 40 É g type 16, and 20 É g type 18) L1 virus-like-particle (VLP) vaccine and 275 (mean age 20·0 years [1·7]) to one of two placebo preparations at day 1, month 2, and month 6. For 36 months, participants underwent regular gynaecological examinations, cervicovaginal sampling for HPV DNA, testing for serum antibodies to HPV, and Pap testing. The primary endpoint was the combined incidence of infection with HPV 6, 11, 16, or 18, or cervical or external genital disease (ie, persistent HPV infection, HPV detection at the last recorded visit, cervical intraepithelial neoplasia, cervical cancer, or external genital lesions caused by the HPV types in the vaccine). Main analyses were done per protocol. Findings Combined incidence of persistent infection or disease with HPV 6, 11, 16, or 18 fell by 90% (95% CI 71-97, p<0·0001) in those assigned vaccine compared with those assigned placebo. Interpretation A vaccine targeting HPV types 6, 11, 16, 18 could substantially reduce the acquisition of infection and clinical disease caused by common HPV types. AUTHOR DISCUSSION We have shown that a multivalent vaccine is efficacious against HPV types that cause cancer and genital warts. Over 35 months’ follow-up, incidence of persistent infection associated with HPV 6, 11, 16, or 18 decreased by 89% in women allocated active vaccine who had at least one dose (ie, the modified intention-to-treat population) compared with those allocated placebo. Vaccine efficacy was 90% in the per-protocol efficacy population, suggesting that the vaccine was protective even during the vaccination period. For example, during the course of vaccination (day 1 through month 7), three women assigned active vaccine and five women assigned placebo were detected with HPV 18 DNA. Of these, only one was verifiable persistent infection (in the placebo group). Thus, one woman allocated placebo and no women allocated active vaccine developed persistent HPV 18 infection during the vaccination period. Furthermore, efficacy with regard to clinical disease associated with HPV 6, 11, 16, or 18 was 100%.

Methods Study design A phase II randomised, multicentre, double-blind placebo-controlled study of a quadrivalent HPV (type 6, 11, 16, and 18) L1 VLP vaccine was done in two parts. Part A was a sequential dose-escalation safety assessment, in which participants, investigators, and staff were blinded as to assignment of vaccine or placebo, but not to assignment of doses in the active-treatment group. Part B was a fully blinded dose-ranging assessment of immunogenicity and efficacy. Study procedures for individuals in part A and part B were identical. The results presented in this article are from part B. 1158 women aged 16-23 years were recruited in Brazil, Europe, and the USA. The study enrolled healthy women, who were not pregnant, had no previous abnormal Pap smears, and reported a lifetime history of four or fewer male sex partners. Enrolment of virgins was restricted to women who were 18 years or older and who were seeking contraception. This study did not exclude women with previous HPV infection. Participants were required to use effective contraception during the trial. The active quadrivalent vaccine was a mixture of four recombinant HPV type-specific VLPs (Merck Research Laboratories, West Point, PA, USA) consisting of the L1 major capsid proteins of HPV 6, 11, 16, and 18 synthesised in Saccharomyces cerevisiae.10,14,16 The four VLP types were purified and adsorbed onto amorphous aluminium hydroxyphosphate sulfate adjuvant. The placebo consisted of the same adjuvant and was visually indistinguishable from vaccine. Three preparations of a quadrivalent HPV types 6, 11, 16, and 18 L1 VLP were used. The three preparations were : 20 É g type 6, 40 É g type 11, 40 É g type 16, and 20 É g type 18, with 225 É g aluminium adjuvant ; 40 É g type 6, 40 É g type 11, 40 É g type 16, and 40 É g type 18, with 225 É g aluminium adjuvant ; and 80 É g type 6, 80 É g type 11, 40 É g type 16, and 80 É g type 18, with 395 É g aluminium adjuvant. The study had two placebo groups with adjuvant doses of 225 É g or 450 É g for appropriate safety comparisons. 0·5 mL vaccine or placebo was given by intramuscular injection at day 1, month 2, and month 6. After vaccination, participants were observed for 30 min. Temperatures were also recorded orally every day in the evening for 5 days after vaccination, and the participant noted adverse events by standard diary card for 14 days after vaccination. Gynaecological examination was done at day 1 and at months 7, 12, 24, and 36. A ThinPrep™ Pap test (Cytyc, Boxborough, MA, USA) and external genital, lateral vaginal, and cervical swabs for PCR analysis of HPV were obtained from all participants at day 1 and at months 7, 12, 18, 24, 30, and 36. Biopsy samples of external genital lesions identified during the study were taken, and serum samples were obtained at day 1 and months 2, 3, 6, 7, 12, 18, 24, 30, and 36. This study was done in accordance with national or local requirements for ethics-committee review, informed consent, and other statutes or regulations regarding the protection of the rights and welfare of those participating in biomedical research. All individuals, or their parents or legal guardians, gave written informed consent after review of the protocol procedures. The aim of the study was to assess a quadrivalent HPV L1 VLP vaccine in terms of the composite primary endpoint of persistent infection associated with HPV 6, 11, 16, or 18, or cervical or external genital disease compared with placebo. Women with persistent infection were defined as those who had the same vaccine-HPV-type DNA in cervicovaginal samples obtained 7 months after vaccination as those obtained from two or more consecutive visits (required to be 4 months or longer apart unless at least one tissue sample was diagnosed as cervical disease by a panel of pathologists), or as those who had vaccine-HPV-type DNA detected in a sample recorded during the last visit before being lost to follow-up. HPV-associated disease was defined as a tissue sample diagnosed as CIN by a panel of pathologists 7 months after vaccination ; vulval intraepithelial neoplasia ; vaginal intraepithelial neoplasia ; external genital warts ; or cervical, vulval, or vaginal cancer with vaccine-HPV-type DNA detected in tissue from, or in a swab of, the same lesion and in cervicovaginal samples obtained at the visit before the biopsy visit.

AHRP's stated rationale for objecting to a policy mandating Merck's HPV vaccine in 11 year old girls [Link] is validated by an internationally recognized expert in the field who tested the vaccine in clinical trials.Dr. Diane M. Harper, a lead researcher in the development of the human papilloma virus vaccine, who says giving the drug to 11-year-old girls "is a great big public health experiment." Dr. Harper, a scientist, physician, professor and the director of the Gynecologic Cancer Prevention Research Group at the Norris Cotton Cancer Center at Dartmouth Medical School in New Hampshire, said: "It is silly to mandate vaccination of 11- to 12-year-old girls There also is not enough evidence gathered on side effects to know that safety is not an issue." All of her trials have been with subjects ages 15 to 25. "This vaccine has not been tested in little girls for efficacy. At 11, these girls don't get cervical cancer - they won't know for 25 years if they will get cervical cancer."

She believes the ideal way of administering the new vaccine is to offer it to women ages 18 and up. At the time of their first inoculation, they should be tested for the presence of HPV in their system. If the test comes back negative, then schedule the follow-up series of the three-part shots.

But if it comes back positive? "Then we don't know squat, because medically we don't know how to respond to that," Harper said.

WASHINGTON, DC, October 5, 2007 (LifeSiteNews.com) - Judicial Watch, the public interest group that investigates and prosecutes government corruption, yesterday released new documents obtained from the U.S. Food and Drug Administration (FDA) under the provisions of the Freedom of Information Act, detailing a total of as many as eleven deaths related to Merck's HPV vaccine Gardasil.  Those deaths resulted between June 8, 2006 - when the vaccine received approval from the U.S. Food and Drug Administration (FDA) - and August 2007 when the latest data was available. The adverse reports coming from the HPV vaccine are increasing daily at an alarming rate.  A LifeSiteNews.com report which scanned a publicly available database of adverse affects coming from the HPV vaccine found 3,137 adverse effects reported on September 28, 2007.  Today the US Government's Vaccine Adverse Event Reporting System (VAERS) lists 3,779 adverse effects.  52 of the cases were deemed "life threatening" and 119 required hospitalization. In one case highlighted by Judicial Watch a 17 year old girl who was vaccinated in June 2007 died the very day she was vaccinated.  According to the report, she "was vaccinated with a first dose of Gardasil…During the evening of the same day, the patient was found unconscious (lifeless) by the mother. Resuscitation was performed by the emergency physician but was unsuccessful.  The patient subsequently died." Other serious reported side effects associated with Gardasil include paralysis, Bells Palsy, Guillain-Barre Syndrome, and seizures.  Says one report: "Initial and follow-up information has been received from a physician concerning an "otherwise healthy" 13 year old female who was vaccinated with her first and second doses of Gardasil.  Subsequently, the patient experienced…paralysis from the chest down, lesions of the optic nerve…At the time of the report, the patient had not recovered." "In light of this information, it is disturbing that state and local governments might mandate in any way this vaccine for young girls," said Judicial Watch President Tom Fitton.  "These adverse reaction reports suggest the vaccine not only causes serious side effects, but might even be fatal." The toll from the HPV vaccine may be greater still.  Judicial Watch filed its request on August 20, 2007, and received the adverse event reports from the FDA on September, 13 2007, in what the agency described as a "partial response." On October 3, 2007, Judicial Watch filed a new lawsuit against the FDA for its failure to fully respond to Judicial Watch's FOIA request as required by law.

Vienna, Virginia - The National Vaccine Information Center (NVIC), the nation's leading vaccine safety and informed consent advocacy organization, is urging state legislatures to investigate the safety and cost of mandating Merck's HPV vaccine (GARDASIL) for all pre-adolescent girls before introducing legislation amending state vaccine laws. In an analysis of reports made to the federal Vaccine Adverse Event Reporting System (VAERS) since the CDC's July 2006 universal use recommendation for all young girls, NVIC found reports of loss of consciousness, seizures, joint pain and Guillain-Barre Syndrome. In a separate evaluation of costs for young girls being vaccinated in private pediatrician offices, NVIC discovered that parents living in the Washington, D.C. area will be paying between $500 and $900 to have their daughters receive three doses of GARDASIL. "GARDASIL safety appears to have been studied in fewer than 2,000 girls aged 9 to 15 years and it is unclear how long they were followed up. [1] VAERS is now receiving reports of loss of consciousness, seizures, arthritis and other neurological problems in young girls who have received the shot," said NVIC President Barbara Loe Fisher. "At the same time, parents who take their daughters to private pediatricians are going to be shocked to find that they will be paying two to three times the widely publicized $360 cost for the three-dose series. The cost is going to break the pocketbooks of parents and break the banks of both insurance companies and taxpayers, when the reality is that almost all cases of HPV-associated cervical cancer can be prevented with annual pap screening of girls who are sexually active." Between July 2006 and January 2007, there have been 82 reports of adverse events filed with VAERS following receipt of GARDASIL by girls and boys ranging in age from 11 to 27 years. Reaction reports have come from 21 states, including Virginia and the District of Columbia. All but three of the reports were for adverse events which occurred within one week of vaccination and more than 60 percent occurred within 24 hours of vaccination. "The most frequent serious health events after GARDASIL shots are neurological symptoms," said NVIC Health Policy Analyst Vicky Debold, RN, Ph.D. "These young girls are experiencing severe headaches, dizziness, temporary loss of vision, slurred speech, fainting, involuntary contraction of limbs (seizures), muscle weakness, tingling and numbness in the hands and feet and joint pain. Some of the girls have lost consciousness during what appears to be seizures." Debold added "The manufacturer product insert should include mention of syncopal episodes, seizures and Guillain-Barre Syndrome so doctors and parents are aware these vaccine adverse responses have been associated with the vaccine."

HPV is the most common sexually transmitted infection in the U.S. and most persons naturally clear the infection from the body without symptoms. [3] However, many years of chronic HPV infection is associated with a higher risk of pre-cancerous changes in the cervix that can lead to cancer unless diagnosed and treated promptly. High risk factors for chronic HPV infection include smoking, long-term use of oral contraceptives and co-infection with HIV, herpes and chlamydia. [4] There has been a more than 70 percent drop in cervical cancer deaths in American women since the 1950's due to routine pap smears and nearly all cervical cancers can be prevented with regular pap smear screening and treatment. [5]

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