Rhodiola for Mild-Moderate Depression

This is a recent article that shows benefit in treating mild-moderate depression. Rhodiola is used by many alternative providers for improved response to stress. SG

Swedish Rhodiola rosea Extract Effective in Treating Mild to Moderate Depression in New Clinical Trial
( Austin , TX , December 19, 2007).

This is the first double-blind, randomized, placebo-controlled study of Rhodiola rosea in patients diagnosed with depression. Patients given the Swedish-made Rhodiola rosea extract showed significant improvements in depression compared to those given placebo.

The trial, published in the Nordic Journal of Psychiatry, utilized a proprietary Rhodiola rosea root extract called SHR-5, a standardized extract used in the product Arctic Root® produced by the Swedish Herbal Institute in Gothenburg, Sweden.*

The 6-week trial was conducted on 89 subjects, aged 18 to 70, who were assessed with clinically significant depression according to two different standard measurements used in psychiatry: the Beck Depression Inventory (BDI, scores greater than or equal to 13) and the Hamilton Rating Scale for Depression (HAMD, scores greater than or equal to 21). Patients were randomly assigned to one of three groups. The first group received 2 tablets once daily (340 mg/day) of SHR-5, the second group received 2 tablets twice daily (680 mg/day) of SHR-5, and the third group was given 2 placebo tablets once daily. (Placebos were described as being identical in appearance to the treatment tablets and contained inactive ingredients with 170 mg of lactose.)

There were no statistically significant differences in the average HAMD and BDI scores among the subjects in the three groups before the herb extract or placebos were given. Following treatment, both groups given SHR-5 experienced statistically significant declines in mean total HAMD scores (from 24.52 to 15.97 in the lower-dose group and from 23.79 to 16.72 in the higher-dose group), as well as statistically significant declines in mean BDI scores (from 12.23 to 7.09 in the lower-dose group and from 10.38 to 4.75 in the higher-dose group). The subjects in the placebo group did not show statistically significant decreases in either the HAMD or BDI scores by the end of the trial.

The study’s authors also measured other effects of the treatment, called secondary efficacy variables. At both dosage levels of SHR-5, people in the HAMD subgroups experienced statistically significant improvements in insomnia, emotional instability, and levels of somatization (the conversion of anxiety into physical symptoms), while such measures did not significantly change in the placebo group. Also, the group given the higher dose of SHR-5 experienced a statistically significant improvement in regards to low self esteem, while the lower-dose group and the placebo group did not experience changes in low self esteem.

The authors concluded that SHR-5 demonstrates clear and significant anti-depressive activity in patients suffering from mild to moderate depression, evident from both overall depression levels as well as from specific symptom levels of depression. They further noted that no adverse effects could be detected in either of the groups given the Rhodiola rosea extract.

Alexander Panossian, PhD, research director of the Swedish Herbal Institute and a co-author of the study, noted that all synthetically-derived, conventional pharmaceutical antidepressant drugs have adverse effects. He added that St. John’s wort (Hypericum perforatum), a popular herbal antidepressant, has been associated with herb-drug interactions, particularly with the pharmaceutical blood-thinner warfarin.

“Because of this drug interaction problem, there is a big demand for new natural antidepressants,” stated Dr. Panossian (e-mail to C. Cavaliere, December 2, 2007). “We have found that our SHR-5 extract of Rhodiola has a significant anti-depressive effect in human and animal studies, with no effect on the pharmacological activity and concentration of warfarin in blood after their oral administration together with SHR-5. It is a very safe extract.”†

Richard P. Brown, MD, associate professor of clinical psychiatry at Columbia University College of Physicians and Surgeons, and a co-author of a comprehensive review of Rhodiola rosea2 and a book on the subject3 likewise commented on the need for new, safe anti-depression medications. “At least 50% of patients given prescription anti-depressants stop them within 3 months due to unpleasant side effects,” said Dr. Brown (e-mail to M. Blumenthal, November 19, 2007). He cited a recent National Institutes of Health-funded multi-center study in which only 30% of patients responded to citalopram, a standard antidepressant medication.4 “Many patients have partial responses and are left with residual symptoms,” he said.

Dr. Brown stated that this clinical trial on SHR-5 has shown promising results: “Two dose levels of Rhodiola rosea [SHR-5 extract] were found to significantly reduce symptoms of depression in patients with mild to moderate depression compared to placebo in this randomized clinical trial. In addition to mood elevation, evidence indicates that R. rosea has numerous other benefits, including enhancement of cognitive function, sexual function, and both mental and physical performance under stress. Additional studies are needed to explore and establish the potential applications of this herbal extract. In the meantime, phytomedicinal researchers and consumers can be encouraged by these findings.”

According to Dr. Panossian, the SHR-5 Rhodiola rosea extract is already widely used and trusted in some areas of the world. “Four hundred million daily doses have been sold in the last 20 years in Scandinavia , where Rhodiola (notably SHR-5) is used as an adaptogen in cases of decreased performance, such as fatigue and sensation of weakness.”

This study was funded by the Swedish Herbal Institute.

About the American Botanical Council

Established in 1988, the American Botanical Council (ABC) is the leading nonprofit, member-based international organization working to educate consumers, healthcare professionals, researchers, educators, industry, and the media on the safe and effective use of herbs and medicinal plants products. ABC is located on a 2.5 acre site in Austin , Texas , where it publishes HerbalGram, a peer-reviewed quarterly journal; HerbClip, a twice-monthly scientific literature review service; and HerbalEGram, a monthly electronic newsletter. ABC is also the publisher of The ABC Clinical Guide to Herbs, a continuing education and reference book, which contains extensive monographs on the safety and efficacy of 29 popular herbs, and the recent The Identification of Medicinal Plants: A Handbook of Morphology of Botanicals in Commerce, a guide to the macroscopic identification of botanical materials for industry quality control laboratories that ABC published in cooperation with the Missouri Botanical Garden. More information is available at http://www.herbalgram.org/. An extensive review of Rhodiola rosea, its traditional uses, and its scientifically-supported modern medicinal properties and uses was published in HerbalGram in 2002.

References

1.
Darbinyan V, Aslanyan G, Amroyan E, Gabrielyan E, Malstrom C, Panossian A. Clinical trial of Rhodiola rosea L. extract SHR-5 in the treatment of mild to moderate depression. Nord J Psychiatry. 2007; 61(5):343-348.
2.
Brown R, Gerbarg P, Ramazanov Z. Rhodiola rosea—a phytomedicinal overview. HerbalGram. 2002;56:40-52.
3.
Brown D, Gerbarg, P. The Rhodiola Revolution. Emmaus , PA : Rodale Press, 2004.
4.
Trivedi MH, Rush AJ, Wisniewski SR, et al. Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry. 2006;163(1):28-40.

Master Cleanse: Yes or No?

I’ve had 5 requests in the past few hours that ask this question. While the Master Cleanse has many loyal fans, and there is little to data to say it is better or worse than any other cleanse, I squirm at the thought of depleted 30-, 40-, and 50-somethings drinking lemon, cayenne and maple syrup for days on end. I favor a cleanse that has sufficient, healthy oils, whole foods and protein to support you and your adrenals. Out of all the cleanses I’ve reviewed, my favorite and what comes closest to what I recommend to my patients is Mark Hyman, MD’s UltraSimple Diet (www.ultrasimple.com). If you are dying to lose a few pounds (or many) or just to cleanse the cabernet and sugar cookies of December out of your system, check it out! It is part of his new program, Ultrametabolism. I believe, unlike the Master Cleanse, this way of cleansing will not send your body into survival mode and lead to yo-yo eating and weight flux.

Mark takes some complicated concepts, such as oxidative stress and the benefits of antioxidants, and makes them very understandable. He calls this “Get the Rust Out” or something like that. More on antioxidants later. I’ve got to go eat dinner with my husband at Café Gratitude and dust off my rust.

Let me know if you've tried the Master Cleanse and how it went for you.

Cheers, SG

HPV Vaccine: Alternative View

Here is Christiane Northrup, MD's perspective on the HPV Vaccine. -- SG
DOES YOUR DAUGHTER NEED THE HPV VACCINE?
Earlier this summer (2006), Merck pharmaceutical received FDA approval to market the first Human Papillomavirus (HPV) vaccine Gardasil, a genetically engineered vaccine that helps prevents four types of HPV viruses, including type 16 infection, one of the most common HPV type viruses implicated in cervical cancer. Other HPV vaccines are in the pipeline. With the approval of Gardasil, HPV and its link to cervical cancer was suddenly front page news around the world with a barrage of media ads marketing the vaccine heavily for women. The CDC quickly recommended vaccinating all women age 9–26 and even beyond. Overnight women with virtually no risk for cervical cancer (the vast majority) were suddenly made to feel vulnerable, thus creating a huge market for the vaccine.
Let me put the issue into much needed perspective. The risk of getting cervical cancer from HPV has been greatly overstated! Fifty to seventy-five percent of all people are exposed to HPV in their lifetimes. The virus clears spontaneously by the immune system within two years in over ninety percent of all women, posing no risk at all.[1-4] Though the vaccine undoubtedly has some value for some women, it is unnecessary, and may even be dangerous, to administer it to millions of girls and women in the United States.

The Numbers Speak for Themselves
There are an average of 9,710 new diagnoses of cervical cancer and 3,700 deaths from the disease in the United States each year, according to the CDC. Of these new cases, 70 percent are related to HPV. That’s about 6,797 cases per year. Over fourteen types of HPV are associated with cervical cancer. Gardasil protects against the HPV strains that are implicated in about 90 percent of cervical cancers, not 100 percent. That further reduces the number of cases of cervical cancer that might potentially be prevented with a vaccine to just under 6,200. And the vast majority of these cases could be prevented with improved nutrition, safe sex, and the kind of screening and early treatment that is already in place!
The HPV vaccine media blitz has overshadowed the fact that the incidence of cervical cancer has already decreased dramatically through routine cervical screening with pap smears and HPV (DNA) testing. For example, the National Health Service of England reports that the incidence of invasive cervical cancer fell by 42 percent between 1988 and 1997 in the U.K because of cervical cancer screening programs. The NHS reports that in 2000, there were 2,424 new cases of invasive cervical cancer, most of which are not fatal.

Abnormal Paps Are Common
Surveys suggest that about four percent of all pap smears will show an abnormality associated with HPV infection, which is known as atypical squamous cells of undetermined significance (ASCUS).[5] In the vast majority, further evaluation will fail to show any abnormality, and no further action is required. (This occurrence of “false positives” with Pap smears led to the development of the ThinPrep® Pap Test, which is more reliable but still not 100 percent accurate.) But five to ten percent of patients initially diagnosed with ASCUS actually have more worrisome cellular changes, known as high-grade, which must be followed closely and treated in some women. [6, 7]
The Department of Pathology, at the University of Alabama in Birmingham reviewed 39,661 pap and HPV tests from January 1, 2002 to December 31, 2003. Of these, 12 percent were diagnosed with ASCUS. High risk HPV (DNA) was detected in only 732 cases! Out of all of these, only six had persistent abnormal pap smears requiring repeat follow-up; five had evidence of cellular abnormalities; and four had low-grade cervical dysplasia or cellular changes associated with HPV. And only one had high-grade dysplasia (a more worrisome type of cellular change that is associated with a higher risk of actual cancer down the line if not treated).
The remaining patients all had negative pap smears. In other words, only a very small percentage of those with high risk HPV were found to have cervical abnormalities—which are not invasive cervical cancer and are treatable! [8]

Vaccines Aren't Entirely Safe
According to the National Vaccine Information Centers (www.909shot.com), “The FDA allowed Merck to use a potentially reactive aluminum containing placebo as a control for most trial participants, rather than a non-reactive saline solution placebo."[9]
Using a reactive placebo can artificially increase the appearance of safety of an experimental drug or vaccine in a clinical trial. Gardasil contains 225 mcg of aluminum and, although aluminum adjuvants have been used in vaccines for decades, they were never tested for safety in clinical trials. Merck and the FDA did not disclose how much aluminum was in the placebo 6.[10]
Whenever you vaccinate an individual, you’re intervening with their immunity. And that’s exactly what happened with Gardasil in the clinical trials. According to the Merck product insert, there was one case of juvenile arthritis, two cases of rheumatoid arthritis, five cases of arthritis, and one case of reactive arthritis out of 11,813 Gardasil recipients. There was also one case of lupus and two cases of arthritis out of the 9,701 patients who received the aluminum containing placebo. Investigators dismissed the total of 102 Gardasil and placebo-associated serious adverse events, including 17 deaths, that occurred during the clinical trials, claiming that they were unrelated. (It’s also not clear how many girls received the Hepatitis B vaccine in addition to Gardasil. Giving a couple vaccines at the same time can increase the risk of adverse outcomes.)
Regardless, there were 102 adverse events in 21,514 women and children who received the vaccine or the aluminum containing placebo. This translates to 474 adverse events per 1 million people getting vaccinated. Conservatively speaking, that’s 14,220 (474 x 30 million) adverse events expected if you were to give the vaccine as recommended to about 30 million women and girls—the approximate number of people in the target market for Gardasil. Is it worth it to make 14,220 girls and women sick in order to possibly prevent 6,200 cases of HPV-related cervical cancer?

The Bottom Line About HPV Vaccines
Remember, it is not HPV per se that causes the cancer. It’s the immune system’s inability to fight the virus that is the issue. The rapid, widespread, and unquestioning acceptance of the HPV vaccine as “the answer” to cervical cancer prevention speaks volumes about our cultural misunderstanding of the root causes of health and disease. On his deathbed, Louis Pasteur, the famous pioneer in the discovery of the role of germs in disease, said that Antoine Beauchamp, his rival, was correct. It was not the germ itself that caused disease, it was the environment, which Beauchamp had claimed all along.
While it is certainly laudable to want to decrease the incidence of invasive cervical cancer even further, and while this vaccine may be useful for some high-risk women and girls, it is far too early to subject millions to yet another vaccine. Especially when there’s so much we can do to shore up an individual’s immunity safely and effectively. (For a complete program on how to do this, read Mother-Daughter Wisdom, Bantam, 2005.)
Gardasil definitely isn’t cost free—it’s a staggering $360 per person. It’s administered in three shots, which must be given over six months. At this time, it doesn’t even guarantee immunity for longer than five years.
Gardasil will not eliminate the need for routine pap smears. And whether or not a woman opts for the vaccine, she should still protect herself from getting a sexually transmitted disease by using condoms, abstaining from intercourse, being discerning about her sexual partners, and also making sure her diet is rich in antioxidant nutrients that help her resist infections of all kinds.
Rather than relying solely on mass immunization programs that treat everyone as though they are at equal risk (which clearly isn’t the case), and which also promote the myth of universal vulnerability, it is far more prudent to optimize a woman’s nutrition and lifestyle so that her immune system is functioning optimally in the first place. This is especially true if she is one of the few who don’t clear HPV rapidly and spontaneously.
Moreover, if a woman has a persistent HPV infection, she has a problem with her immune system. The bottom line is: The depression of her immune system is what's putting her at increased risk for cervical cancer. So while a vaccine might prevent cancer in one location, disease will manifest in another area if the root cause isn’t addressed. This is done by looking at her entire life—body, mind, and spirit.

Money Talks
So who really benefits by vaccinating approximately 30 million girls and women with a vaccine that costs about $360? Industry analysts point out that mandating the HPV vaccine for virtually all girls and women will make Gardasil the blockbuster that Merck needs to boost profits since it was forced to withdraw its arthritis drug Vioxx. I certainly agree. It is no secret that medical schools, researchers, the CDC, and even the FDA itself are increasingly controlled by drug company profits. So is the mainstream media. To learn the facts about this, I recommend the documentary film Money Talks: Profits before Patient Safety.


REFERENCES
1. Ho, G.Y., Bierman R., Beardsley, L., et. al., 1998. Natural history of cervicovaginal papillomavirus infection in young women, N Engl J Med, 338:423-428.

2. Woodman, C.B., Collins, S., Winter, H., et. al., 2001. Natural history of cervical human papillomavirus infection in young women: a longitudinal cohort study, Lancet, 357:1831-1836.

3. Nasiell, K., Nasiell, M., Vaclavinkova, V., 1983. Behavior of moderate cervical dysplasia during long-term follow-up, Obstet Gynecol, 61:609-614.

4. Richart, R.M., Barron, B.A., 1969. A follow-up study of patients with cervical dysplasia, Am J Obstet Gynecol, 105:386-393.

5. Davey, D.D., et. al., 2004. Implementation and reporting rates: 2003 practices of participants in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology. Arch Pathol Lab Med., 128:1224-1229.

6. Manos, M.M., et. al., 1999. Identifying women with cervical neoplasia: using human papillomavirus DNA testing for equivocal Papanicolaou results, JAMA, 281:1605-1610.

7. ASCUS-LSIL Triage Study (ALTS) Group. 2003. Results of a randomized trial on the management of cytology interpretations of atypical squamous cells of undetermined significance. Am J Obstet Gynecol. 188:1383-1392.

8. Adams, A., et. al., 2006. Negative colposcopic biopsy after positive Human Papillomavirus DNA testing: false positive HPV results or false-negative histologic findings, Am J Clin Pathol. 2006;125(3):413-418.

9. Merck & Co., Inc. 2006. Gardasil [Quadrivalent Human Papillomavirus Types 6,11,16,18 Recombinant Vaccine] product insert. Table 6.

10. Food and Drug Administration. May 18, 2006. FDA Background Document for Vaccines and Related Biological Products Advisory Committee: Gardasil HPV Quadrivalent Vaccine.

HPV Vaccine: Conventional View

These are the latest conventional guidelines for the HPV vaccine, recommended routinely for 11-12 year old girls. I will separately post a counterpoint view by holistic gynecologist Christiane Northrup, MD. SG

Guidelines Issued for HPV Vaccine Use to Prevent Cervical Cancer

News Author: Laurie Barclay, MD
CME Author: Penny Murata, MD

January 25, 2007 — The American Cancer Society (ACS) has issued guidelines for the use of the prophylactic human papillomavirus (HPV) vaccine to prevent cervical intraepithelial neoplasia (CIN) and cervical cancer. The new guidelines, published in the January/February issue of CA: Cancer Journal for Clinicians, address who should be vaccinated and at what age, and summarize policy and implementation issues and implications for screening, based on a formal review of the available evidence.
"Cervical cancer screening has successfully decreased squamous cell cervical cancer incidence and mortality," write Debbie Saslow, PhD, of the American Cancer Society in Atlanta, Georgia, and colleagues. The American Cancer Society (ACS) Guideline for the Early Detection of Cervical Cancer was last reviewed and updated in 2002; for the first time, those recommendations incorporated options including liquid-based cytology and human papillomavirus (HPV) DNA testing. Since that time, two vaccines against the most common cancer-causing HPV types have been developed and tested in clinical trials."
A panel of experts reviewed numerous studies published on the efficacy of these vaccines as well as issues related to policy and implementation.
Specific recommendations for HPV vaccination are as follows:
1. Routine HPV vaccination is recommended for girls 11 and 12 years old.
2. Girls as young as age 9 years can receive HPV vaccination.

3. HPV vaccination is also recommended for teenaged girls 13 to 18 years old to catch up on missed vaccine or to complete the vaccination series.

4. The evidence is insufficient at this time to recommend for or against universal vaccination of women 19 to 26 years old in the general population. A decision about whether to vaccinate a woman 19 to 26 years old should be based on an informed discussion between the woman and her healthcare provider regarding her risk for previous HPV exposure and her potential benefit from vaccination. Ideally, the HPV vaccine should be administered before potential exposure to genital HPV through sexual intercourse, because the potential benefit is likely to decrease with an increasing number of lifetime sexual partners.

5. HPV vaccination is not currently recommended for women older than age 26 years or for males.

6. Screening for CIN and cervical cancer should continue in both vaccinated and unvaccinated women, according to current ACS early detection guidelines.
"If duration of immunity is substantial or can be extended adequately through booster vaccinations, the high vaccine efficacy observed in Phase II and III studies suggests that female populations receiving prophylactic immunization will experience a reduction in the morbidity and mortality associated with HPV-related anogenital diseases," the authors write. "The promise of prophylactic vaccines from a broad public health perspective, however, can be realized only if vaccination can be achieved for those groups of women for whom access to cervical cancer screening services is most problematic."
Other screening recommendations are for a preventive healthcare visit, in which vaccination is discussed or offered; this represents an appropriate opportunity to offer Papanicolaou test screening to sexually active patients. HPV testing is not recommended before vaccination.
To foster vaccine implementation and use, the authors recommend public health and policy efforts to ensure access and encourage high HPV vaccine coverage for all racial, ethnic, and socioeconomic groups. To maximize adherence to vaccination recommendations, strategies should include coadministration with other recommended adolescent vaccines, once sufficient safety data are available.
The use of noncomprehensive visits, such as minor illness visits, camp/sports physical visits, and alternative vaccination sites is encouraged for adolescents unable to access comprehensive preventive care.
The guidelines mandate education of providers, policymakers, parents, adolescents, and young women about cervical cancer prevention and early detection, including the need for regular screening even after vaccination.
Recommended research directions consists of ongoing research and surveillance in diverse populations, including research on duration of protective immunity, population- and lesion-based changes in type-specific prevalence for the full spectrum of carcinogenic and noncarcinogenic genital HPV types, changes in Papanicolaou test performance characteristics, changes in screening practices and behaviors, comprehensive surveillance for reproductive toxicities, increasing vaccine coverage and acceptability, and impact on safe sexual behavior.
Other research goals include evaluation of the safety and efficacy of prophylactic HPV vaccine for the prevention of other anogenital cancers and head and neck cancers in males, as well as in females, and designs for sustainable vaccination programs in less-developed countries.
"The protective effect of vaccination that is successfully provided to adolescent and young women who are unlikely to undergo regular Pap [Papanicolaou] screening will be of greater magnitude than that provided to women who will undergo regular screening regardless," the authors conclude. "Even as HPV vaccination for the prevention of cervical cancer is introduced and promoted, it remains critical that women undergo regular screening regardless of whether they have been vaccinated."
CA Cancer J Clin. 2007;57:7-28.
Clinical Context
According to a report by Pagliusi published by the World Health Organization, cervical cancer is the second most common cause of cancer death worldwide. In the December 1999 issue of Clinical Obstetrics and Gynecology, Sawaya and Washington noted that the incidence of cervical cancer would be 2 to 3 per 100,000 even with optimal screening. HPV types 16 and 18 cause 70% of cervical cancers, according to Munoz and colleagues in the February 6, 2003, issue of The New England Journal of Medicine, and 50% to 60% of CIN grade 2 and 3, according to Clifford and colleagues in the July 7, 2003, issue of the British Journal of Cancer.
Two HPV vaccines have been developed to decrease HPV-related cervical, penile, vulvar, vaginal, and anal precancerous and cancerous lesions, genital warts, and laryngeal papillomatosis: Gardasil (Merck & Co, Inc) is a quadrivalent vaccine to prevent HPV types 6, 11, 16, and 18; and Cervarix (GlaxoSmithKline) is a bivalent vaccine to prevent HPV types 16 and 18.
An expert panel organized by the ACS reviewed the published and unpublished data on HPV vaccines and the prevention of cervical cancer and precancerous lesions. Panel members put forth expert opinions in cases of insufficient evidence. The recommendations were discussed and voted on by the ACS Gynecologic Cancer Advisory Group and the National Board of Directors. The ACS guidelines focus mainly on Gardasil, which is licensed by the US Food and Drug Administration.
Study Highlights
• Cervical cancer incidence is higher in some groups because of social, cultural, and healthcare access barriers.
• Progression from HPV infection to invasive cancer takes an average of 20 years.
• Genital HPV transmission usually occurs within a few years after onset of vaginal or anal intercourse.
• Study enrollment criteria limited the lifetime number of sex partners (mean, 2; maximum, 4) and histories of cervical abnormalities.
• 2 Gardasil phase 3 efficacy substudies were conducted on women who complied with vaccine regimen and did not have type-specific HPV infection:
• Females 15 to 26 years old had 100% vaccine efficacy in prevention of HPV 16/18-related CIN 2/3 and adenocarcinoma in situ.
• Females 16 to 23 years old had 100% vaccine efficacy in prevention of HPV 6/11/16/18-related external genital warts, vulvar/vaginal intraepithelial neoplasia, and cervical lesions with follow-up of 1.5 years.
• Results from intent-to-treat analyses of Gardasil included women who received at least a 1 vaccine dose and had current or past HPV infection, according to polymerase chain reaction or serology
• Cervarix had 100% efficacy in preventing HPV 16/18-related CIN in females 15 to 25 years old followed up to 4.5 years
• Safety results for Gardasil and Cervarix from phase 2b randomized controlled trials:
• Injection site adverse events were more common and intense in Gardasil vs placebo subjects (83% vs 73%) and more common in Cervarix vs placebo subjects (94% vs 88%).
• Most common systemic adverse events occurred in 69% of both Gardasil and placebo subjects and in 86% of both Cervarix and placebo subjects.
• Serious vaccine-related events occurred in 5 Gardasil and 2 placebo subjects.
• Up to 0.2% of subjects discontinued study because of adverse events.
• No vaccine-related deaths occurred in Gardasil or Cervarix subjects.
• In women who became pregnant within 30 days' postvaccination, congenital anomalies occurred in 5 of Gardasil group and none of placebo; no data were published for Cervarix subjects.
• Pregnancy registry postmarketing to further evaluate effects has been proposed.
• Duration of vaccine-related HPV immunity is not known.
• Youngest subjects were 9 years old for safety and immunogenicity studies, 16 years old for Gardasil efficacy studies, and 15 years old for Cervarix efficacy studies.
• Insufficient evidence exists to recommend for or against routine vaccination for women 19 to 26 years old, but those who have not had sexual intercourse would benefit from vaccine. Efficacy data for HPV 16/18-related CIN 2/3 in women with more than 4 lifetime sex partners are lacking.
• Male subjects 9 to 15 years old were included in Gardasil safety, immunogenicity, and ongoing efficacy trials; male vaccination might not be cost-effective in cervical cancer prevention, but might be more effective in low-vaccination areas.
• Current cervical cancer screening recommendations should continue.
• Vaccination effects on cervical cancer rates will not be apparent until subjects reach the age of 48 years, the median age of cervical cancer diagnosis.
• HPV testing before vaccination is not recommended.
• Recommendations for vaccine implementation include distribution to underserved areas through free programs and at routine healthcare visits for girls at age 11 or 12 years.
• Limitations of HPV vaccines include lack of protection against all carcinogenic HPV types, noncompliance, and need for studies in HIV-infected people.
Pearls for Practice
• HPV vaccine is recommended routinely for girls 11 and 12 years old and for catch-up for teenaged girls 13 to 18 years old. It can be given to girls as young as 9 years. However, data are inadequate to support universal HPV vaccine for women 19 to 26 years old, but the vaccine is likely less beneficial in females with more lifetime sexual partners.
• Females who are vaccinated and unvaccinated with HPV vaccine should continue to undergo screening for CIN and cancer, as recommended in current ACS guidelines.