FDA broadens the age range of Gardasil 9 to cover individuals 27 through 45 years old

The US Food and Drugs Administration (FDA) extended the use of Merck’s cervical cancer vaccine Gardasil 9 to include men and women aged 27 through 45 years.

"Today's approval represents an important opportunity to help prevent HPV-related diseases and cancers in a broader age range," Peter Marks, MD, Ph.D., director of the FDA's Center for Biologics Evaluation and Research, says in a news release.

"The Centers for Disease Control and Prevention has stated that HPV vaccination prior to becoming infected with the HPV types covered by the vaccine has the potential to prevent more than 90% of these cancers, or 31,200 cases every year, from ever developing," Marks says.

 "The CDC has made increasing HPV vaccination rates a public health priority,” said Jacques Cholat, M.D., president, Merck Vaccines, “and today’s recommendation for GARDASIL 9 is an important milestone in the shared effort to help further reduce the burden of HPV-related cancers and diseases.”

According to CDC, every year about 14 million Americans become infected with HPV; about 12,000 women are diagnosed with, and about 4,000 women die from cervical cancer caused by certain HPV viruses. Additionally, HPV viruses are associated with several other forms of cancer affecting men and women. 

FDA first approved Gardasil in 2006, to prevent certain cancers and diseases caused by HPV Types 6, 11, 16, and 18. Gardasil is no longer available in the US. Gardasil 9 received approval in 2014 for use in girls and women 9 through 26 years of age and boys 9 through 15 years of age for the prevention of the cancers and precancerous lesions of cervix, vulva, vagina, and anus caused by HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58.

The approval is based on results of a study involving 3,200 women, aged 27 through 45 years, followed for an average of 3.5 years, Gardasil was 88 percent effective in the prevention of a combined endpoint of persistent infection, genital warts, vulvar and vaginal precancerous lesions, cervical precancerous lesions, and cervical cancer related to HPV types covered by the vaccine.

"The FDA’s approval of Gardasil 9 in women 27 through 45 years of age is based on these results and new data on long-term follow-up from this study," the FDA said.

Similarly, in men aged 27 through 45 years of age, vaccine effectiveness was inferred based on data described above in women, along with efficacy data of Gardasil 9 in younger men aged 16 through 25 years, and immunogenicity data from a clinical trial in which 150 men, 27 through 45 years of age, received a 3-dose regimen of Gardasil over 6 months.

In all the safety and efficacy of Gardasil 9 was evaluated in a total of 13,000 males and females, the most commonly reported side effect being injection site pain, swelling, redness, and headaches.

The FDA granted the Gardasil 9 application priority review status. This program facilitates and expedites the review of medical products that address a serious or life-threatening condition.

Important Information about GARDASIL 9 (Human Papillomavirus 9-Valent Vaccine, Recombinant)

GARDASIL 9 does not eliminate the necessity for women to continue to undergo recommended cervical cancer screening.

Recipients of GARDASIL 9 should not discontinue anal cancer screening if it has been recommended by a health care provider.

GARDASIL 9 has not been demonstrated to protect against disease from vaccine HPV types to which a person has previously been exposed through sexual activity.

GARDASIL 9 has not been demonstrated to protect against diseases due to HPV types other than 6, 11, 16, 18, 31, 33, 45, 52, and 58.

GARDASIL 9 is not a treatment for external genital lesions; cervical, vulvar, vaginal, and anal cancers; or cervical intraepithelial neoplasia (CIN), vulvar intraepithelial neoplasia (VIN), vaginal intraepithelial neoplasia (VaIN), or anal intraepithelial neoplasia (AIN).

Not all vulvar, vaginal, and anal cancers are caused by HPV, and GARDASIL 9 protects only against those vulvar, vaginal, and anal cancers caused by HPV 16, 18, 31, 33, 45, 52 and 58.

Vaccination with GARDASIL 9 may not result in protection in all vaccine recipients.

FDA press release

Merck news release

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CDC reports a rise in Human papillomavirus(HPV) associated cancers in recent years.

Clinical Pearls:

• HPV associated cancers are on the rise.
• Out of 38,793 HPV-associated cancers diagnosed each year in U.S, nearly 79 % were preventable cancer caused due to HPV strains for which vaccine coverage is available across population.
• Out of all the HPV associated cancer, only cervical cancer is preventable by good screening strategies. No population based screening strategy exist for other HPV associated cancer.

The CDC reported a rise in Human papillomavirus(HPV) associated cancers in recent years’ in its Morbidity and Mortality Weekly Report published on line on July 7, 2016.[1] It is known that HPV is a cause of cervical cancers as well as vulvar, vaginal, oropharyngeal, rectal and anal cancers. 13 known strains of HPV are carcinogenic and persistent infection with these can progress to precancer and cancer.

CDC analyzed the high quality data obtained from population-based cancer registries of National Program of Cancer Registries and the National Cancer Institute’s Surveillance, Epidemiology, and End Results program from 2008–2012, covering approximately 99% of US population.

There was an overall increase in HPV-associated cancer from 10.8 per 100,000 persons during 2004–2008 to 11.7 per 100,000 persons during 2008–2012.

 An average of 38,793 HPV-associated cancers were diagnosed each year during the study span of 5 years. Out of which 23,000 were among females and 15,793 among males. Out of 38,793 at least 30,700(79%) can be attributed to HPV.

Notably, of these 24,600 cancers are attributable to HPV types 16 and 18, which are targeted by all current HPV vaccines, and 28,500 are attributable to high-risk HPV types 31, 33, 45, 52, and 58, all included in the 9-valent HPV vaccine. 

The most common HPV associated cancer was cervical cancer (11,771) in females and oropharyngeal squamous cell carcinomas (15,738) mostly in males.

Only cervical cancer can be prevented with regular screening and follow up, no population based screening strategy exist for other HPV associated cancer. The Healthy People 2020 target for cervical screening is 93%, and the2013 statistics report only 80.7% of women undergo complete screening with wide racial and ethnic disparity.

The authors led by Laura J. Viens, MD, of the Division of Cancer Prevention and Control said “HPV vaccination can prevent infection with HPV types that cause cancer at cervical and other sites," including the anus. "Vaccines are available for HPV types 16 and 18, which cause 63% of all HPV-associated cancers in the United States, and for HPV types 31, 33, 45, 52, and 58, which cause an additional 10%." 

The study has very important public health implication that extending coverage to full US population could prevent future HPV-attributable cancers bringing down the incidence dramatically.

The CDC advisory committee recommends routine HPV vaccination (bivalent, quadrivalent, or 9-valent) for females aged 11-12 through 26 years and quadrivalent or 9-valent for males at ages 11 to 12 through 21 for males if they were not previously vaccinated.

"In order to increase HPV vaccination rates, we must change the perception of the HPV vaccine from something that prevents a sexually transmitted disease to a vaccine that prevents cancer," said Electra Paskett. She is co-director of the Cancer Control Research Program at the Ohio State University Comprehensive Cancer in Columbus.

"Every parent should ask the question: If there was a vaccine I could give my child that would prevent them from developing six different cancers, would I give it to them? The answer would be a resounding yes -- and we would have a dramatic decrease in HPV-related cancers across the globe," Paskett added.

"Ongoing surveillance for HPV-associated cancers using high-quality population-based registries is needed to monitor trends in cancer incidence that might result from increasing use of HPV vaccines and changes in cervical cancer screening practices," the CDC report concluded.

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[1] https://www.cdc.gov/mmwr/volumes/65/wr/mm6526a1.htm?s_cid=mm6526a1_w

Important Policy Updates from American Society of Clinical Oncology (ASCO) supporting HPV Vaccination.

American Society of Clinical Oncology is  the leading professional body committed to decrease the burden of cancer and hence promote any underutilized intervention that have potential to save millions of lives by preventing cancer incidences.

An extremely important policy statement from the American Society of Clinical Oncology (ASCO), published ahead of print on April 11, 2016 regarding the HPV Vaccination

ASCO states that more than 10% of cancers worldwide (more than million cases per year) are caused by viruses with HPV contributing about 600,000 to the pool.

In addition to cervical cancer, HPV is also responsible for causing anal cancer, vaginal cancer, and vulvar cancers, and increasingly of oropharyngeal cancer. It is estimated that HPV is responsible for 60% of all oropharyngeal cancer, 90% of which are caused by HPV 16.

HPV is the cause of nearly all cervical cancers with 70% cases caused by genotype 16 and 18.

HPV additionally causes of 91% of anal cancers, 75% of vaginal cancers, 69% of vulvar cancers, and 63% of penile cancers, with HPV 16 being the predominant oncogenic genotype.

Thus HPV causes cancers in both sexes and oropharyngeal cancer is 3-5 times more common in men.

“With safe and effective vaccines readily available, no young person today should have to face the devastating diagnosis of a preventable cancer like cervical cancer. But unless we rapidly increase vaccination rates for boys and girls, many of them will,” said ASCO President Julie M. Vose, MD, MBA, FASCO.

Vaccination against the HPV virus is incredible preventive strategy, because once the HPV virus becomes incorporated into cells lining the cervix, anus or oropharynx it is impossible to eradicate it and it will remain there for life.

A 2011 National immunization survey reported that only 36% of girls 14% of boys have received the full schedule of immunization needed to protect against the virus.  A study in the same year also showed that some of the states with highest rates of HPV related cancers have the lowest rate of immunization.

Therefore, The ASCO recommendations for increasing vaccination awareness and use are summarized here.

1. Education and raising the awareness among health care providers, public health professionals, policy makers and patients about HPV vaccine and the cancers it causes.
2. Increasing the vaccination rates in society by combining it with other vaccines like eg, Tdap and meningococcal virus) for young adolescents. Distribution of educational pamplets, reminders by e-messaging or mailing should also be considered to bring on increase contacts among Drs and patients.
3. ASCO strongly urges the policy makers and insurance company to increase the vaccination coverage, thereby decreasing out of pocket expenses because vaccination rates are strongly related to these factors.  
4. Addressing critical knowledge gaps through research and development, making vaccinations safe and effective.
5. ASCO strongly believed that oncologists can play a very important role in increasing patients compliance for vaccination. They should keep abreast the recent advances by CDC and WHO regarding vaccination and interact with internists, gynecologists and primary care physicians to raise their awareness and interaction. Play a role in policy making in the society so that leaders can understand the critical role played by vaccines in avoiding cancers.

Bivalent (Cervarix), quadrivalent (Gardasil), and, more recently, nonavalent (nine-valent) vaccines against HPV genotypes (targeting those most commonly causing cancer globally) are approved in the United States and other countries for primary prevention of HPV infections 

The current Advisory Committee for Immunization Practices (ACIP)  Vaccine Recommendations are: 

 Usual Adult Dose for Human Papillomavirus Prophylaxis

Gardasil - women and men:
Cervical, vulvar, vaginal, and anal cancer caused by HPV and genital warts (condyloma acuminata) caused by HPV:
9 years through 26 years: one dose (0.5 mL) intramuscularly once. Repeat dose in 2 months and 6 months for a total of 3 doses.
Cervarix - women:
9 years through 25 years: one dose (0.5 mL) intramuscularly at 0, 1, and 6 months.

Usual Pediatric Dose for Human Papillomavirus Prophylaxis

Gardasil - girls and boys:
9 years or older: one dose (0.5 mL) intramuscularly once. Repeat dose in 2 months and 6 months for a total of 3 doses.
Cervarix - girls:
9 years or older: one dose (0.5 mL) intramuscularly at 0, 1, and 6 months.

Vaccine is usually initiated at 11 to 12 years old; optimally, vaccination should be completed prior to onset of sexual activity.

References.

Bailey HH, Chang LT, DuPont NC, et al: American Society of Clinical Oncology statement: Human papillomavirus vaccination for cancer prevention. J Clin Oncol. April 11, 2016 (early release online).

http://jco.ascopubs.org/content/early/2016/04/07/JCO.2016.67.2014.full#sec-11

http://www.ascopost.com/News/39503

http://www.ascopost.com/issues/april-25-2016/asco-urges-aggressive-efforts-to-increase-hpv-vaccination-and-prevent-cancer/?platform=hootsuite

Kish JK, Rolin AI, Zou Z, et al: Prioritizing US cervical cancer prevention with results from a geospatial model. J Global Oncol. April 11, 2016 (early release online).