Another anti-cancer vaccine is on the horizon

Studies show that the interruption of an intermediate-stage CIN strongly suggests that the HPV vaccine will halt progression to cancer.

Issue: September 1, 2006

ByPhilip A. Brunell, MD

Yet another anti-cancer vaccine, one for the human papillomavirus (HPV), was approved. The first question is, what is the other?

The answer to that question is the vaccine that we give to every infant, hepatitis B vaccine (HBV). As pediatricians, we are unlikely to see the effect of anti-cancer vaccines as the time between infection and malignancy is usually measured in decades, so we are unaware of the beneficial effects of immunization. Liver cancer, which is the most common malignancy globally, has been profoundly affected by the widespread use of HBV vaccine. This malignancy is much more common among Asians. The decrease in hepatic malignancies after the widespread use of HBV vaccine in Taiwan has been a quite dramatic proof of concept: Virus vaccines can prevent certain types of cancer.

It is well to be reminded at this time of the new recommendation for the use of hepatitis vaccine (MMWR. 2005;54[RR-16]:1-23). Specifically, the status of hepatitis B vaccine is to be reviewed for all children at the 11- to 12-year visit and additional immunization should be administered as needed. Special attention should be given to older adolescents, particularly those born in areas of the world with intermediate or high prevalence, including adoptees. Hepatitis B is sexually transmitted. The risk is increased in gay men and in those with more than one sexual partner. It is estimated that the prevalence in the United States is 0.2%, or 1:500.

Philip A. Brunell, MD [photo]
Philip A. Brunell

The most recent anti-cancer vaccine is that against HPV, some strains of which can be found in almost all cervical cancers. The FDA has already approved Gardasil from Merck, and Cervarix (GlaxoSmithKline) is far along the development pipeline. The vaccines both are killed, genetically engineered and express a single protein, L1, which is highly immunogenic.

The HPV group is composed of more than 100 virus types that are associated with a variety of neoplasms, including papillomas and cervical cancers. There are about 30 different types that infect the genital tract, some types producing cervical cancer and others causing papillomas. The two most common types, producing 70% to 80% of cervical cancers, are 16 and 18, which are contained in both vaccines. The Merck product contains, in addition, types 6 and 11, which are the main types responsible for genital papillomas (Am J Epidemiol. 2003;157:218-226).

The progression from infection to cancer usually occurs over decades. The peak incidence of cervical cancer is in the fifth decade, while infection occurs most commonly in the second and third decade. In one study, 3,262 women between the ages of 18 and 25 were studied, and there was a prevalence of all HPV types of 26.9%. In women with one lifetime partner, the figure was 14.3%. High-risk types were detected in 20%. About 10% were infected with types in current candidate vaccines (Sex Transm Dis. March 27, 2006). The initial infection may fade out, progress to cervical intraepithelial neoplasm (CIN), which also may be reversible, or go on to produce cervical cancer. The high-risk strains are more likely to progress, while the low-risk strains often regress. Pap smear screening is currently used to detect these changes. It is recommended that women first be tested three years after their sexual debut or at age 21. For older women, a combination of HPV testing and Pap smears is recommended.

Some estimates are that there may be as many as 40 million individuals infected with HPV in the United States, occurring at a rate of about 6 to 10 million per year. They are readily acquired. In one study of college women, 40% had acquired an HPV infection with one type or another within three months of the initiation of sexual intercourse. Condoms are believed to offer some protection. Sexual debut in high school students occurs early: 30% by age 16 and about two-thirds by graduation. Many have had multiple sex partners. Thus if these vaccines are to be effective, they must be given early.

The vaccines tested have been very effective. The assessment of efficacy involves immunogenicity, protection against specific types by virus isolation and protection against CIN by histological examination. By these parameters, they generally have been between 90% and 100% effective (Lancet Oncol. 2005;6:271-278; Lancet; 2004;364:1767-1768).

Effect on cervical cancer will take longer to evaluate, but studies show that the interruption of an intermediate stage CIN strongly suggests that progression to cancer will be interrupted. The duration of protection against infection or CIN is still uncertain, but according to recent data, the vaccines were almost 100% effective and safe after four years (Lancet. 2006;367:1247-1255).

There is some concern about the reaction of the FDA to this vaccine, which could potentially spare 4,000 lives and prevent 10,000 cancers annually. There is strong objection by certain groups to any intervention that might prevent a condition that would not occur if there were abstinence. Abstinence should be encouraged, but one cannot assure that one’s pristine daughter will not get cervical cancer because of the dalliance of her otherwise pristine husband (paraphrased from a recent issue of the New Yorker magazine). One wonders whether dissenters object to antibiotics, which can treat sexually transmitted diseases, or hepatitis B vaccine, which can prevent chronic liver disease of hepatic cancer. Some believe that AIDS was punishment for irreligious behavior. The beliefs of individuals must be respected, but they in turn must respect the beliefs of others.

This article also appeared in Infectious Diseases in Children, a SLACK Incorporated publication.

For more information:

Philip A. Brunell, MD, is the chief medical editor for Infectious Diseases in Children, a special volunteer at the National Institute of Allergy and Infectious Diseases at the NIH and professor emeritus the University of California, Los Angeles School of Medicine.