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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HPV testing vs Pap test in cancer screening: Cochrane Systematic review

A negative HPV test is more reassuring than a negative Pap test, as the cytology screening has a higher chance of being false negative thereby missing some women with precancerous lesions and delaying treatment says the result of a Cochrane Systematic review published ahead of print.

Since decades the usual method of screening for cervical cancer is based on cell cytology, but since the etiological relationship between cervical cancer and HPV infection was confirmed along with advent of HPV testing in 1999, the supremacy of these two tests is debated.

Some physician advice Pap and HPV both, especially for women over 30 years old, who are most at risk of cervical cancer, getting both tests provides the best assurance of finding cervical disease before it becomes cancer.

Younger women (20-30) are advised to get HPV test only if their Pap smear looks "inconclusive" or "borderline.”

This systematic review by Cochrane was aimed at determining efficacy of the two tests in detecting precancerous lesions (CIN 2+ and CIN 3+). Literature search for relevant studies till November 2015 identified about 40 studies amounting to a total of 140,000 women between 20 to 70 years old who underwent cervical cancer screening.

Data analysis identified true positives (TP), false positives (FP), true negatives (TN), and false negatives for each screening test (HPV test and cytology) used in each study.

It was seen that HPV test was more sensitive than conventional Pap test and liquid based test in identifying CIN 2+ and CIN 3+, but less specific than Pap test in detecting precancerous lesion.

Data analysis showed that for every 1000 women screened, around 20 women will have precancerous lesions. If HPV test is used, it will correctly identify 16 of the 20 women to be positive for the lesions (but will miss 4 women who have the lesions). The Pap test will correctly identify 12 of the 20 women (but will miss 8 women).

Similarly, for every 1000 women screened, there will be 980 women who will not have precancerous changes. The HPV test will correctly identify 879 women as disease free (but 101 women will be incorrectly told that they have a lesion). The Pap test will correctly identify 951 women (but 29 will be incorrectly told that they have a lesion).

This high false positive rate of HPV testing will lead to high unnecessary referrals and further tests like colposcopy, biopsy and surgery but at the same time it will also identify 50% more women with precancerous changes as compared to conventional cytology.  

The authors concluded that,” Whilst HPV tests are less likely to miss cases of CIN 2+ and CIN 3+, these tests do lead to more unnecessary referrals. However, a negative HPV test is more reassuring than a negative cytological test, as the cytological test has a greater chance of being falsely negative, which could lead to delays in receiving the appropriate treatment.”

Source: Koliopoulos G, Nyaga VN, Santesso N, Bryant A, Martin-Hirsch PP, Mustafa RA, Schünemann H, Paraskevaidis E, Arbyn M. Cytology versus HPV testing for cervical cancer screening in the general population. Cochrane Database Syst Rev. 2017;8:CD008587. doi: 10.1002/14651858.CD008587.pub2. PMID: 28796882

Access the abstract here.