School Celebrates "Keerti Shah Day" with Lecture Series (web article)

Recognizing his profound contributions to research and education at the School over the past 50 years, the Department of Molecular Microbiology and Immunology has proclaimed October 7 to be Keerti Shah Day. The Day will feature a broad array of scientitic talks. Dr. Shah's career has spanned the departments of Pathobiology, Immunology and Infectious Diseases, and now Molecular Microbiology and Immunology (MMI) and he twice served as interim chair of MMI.

Keerti V. Shah, MBBS, MPH ’57, DrPH ’63, has been the foremost contributor to the epidemiologic studies that have led to our current understanding that an infectious disease—human papillomavirus [HPV]—is the origin of cervical cancer, a major cause of death in women, particularly in developing countries. Dr. Shah, professor of Molecular Microbiology and Immunology, and his colleagues have also recently shown that infection with HPV contributes to the development of some types of head and neck cancers. Now a vaccine has been developed that is able to prevent these infections and cancers." In May, the Office of Communications and Public Affairs spoke with Dr. Shah about the significance of this new vaccine.

Question: What is significant about this HPV vaccine?

Answer: Cervical cancer, or squamous cell carcinoma of the cervix, is unusual in that it is the only major cancer we know of that is solely caused by a virus. Human papillomaviruses are responsible for 100 percent of cervical cancers worldwide.

HPVs have been known for a hundred years but it was difficult to work with them until recently because they could not be grown in cell cultures. After recombinant DNA technology came into use in the 1980s, the viral DNAs were cloned and characterized and the relationship between HPVs and cervical cancer was established. Highly effective vaccines were developed. Progress was very rapid.

There are more than 100 different HPV types. Many of the HPV types cause common skin warts, but 30 to 40 types are known to infect the genital tract. About 80 percent of all adults will become infected with one or more genital HPVs during their lifetime. Most of the infections are harmless but a few go on to actually develop into cervical cancer. About a dozen of the genital HPV types are associated with cervical cancer. Specifically, two HPV types, HPV 16 and 18, are responsible for nearly 70 percent of cervical cancers. The new vaccine provides protection against types 16 and 18, as well as types 6 and 11, which cause genital warts.

The HPV vaccine requires a series of injections to create a strong protective antibody response. The vaccine consists of the main viral proteins of the four HPV types and is not infectious. The greatest benefit will be for those who have not yet been infected with HPV. The vaccine may also provide some protection to people who have already been infected with HPV but have not developed any illness.

Question: How big a problem is cervical cancer?

Answer: HPV is the most common sexually transmitted infection. Cervical cancer is the most prevalent form of cancer among women in developing countries. There are about 500,000 new cases of cervical cancer worldwide each year and about 250,000 deaths. In the U.S. and other developed countries, the number of deaths from cervical cancer is small because of widespread use of the Pap smear test, which detects pre-cancerous cells on the cervix. Treatment of pre-cancers is very effective.

Question: Who would get the vaccine?

Answer: Initially, the vaccine will probably be recommended to preteen girls. This age group would be less likely to be sexually active and therefore less likely to be infected with HPV. Women in their twenties may also wish to receive the vaccine.

Some groups may object to the vaccine out of fear that a vaccine that prevents a sexually transmitted disease will promote promiscuity or that it is unnecessary for girls who are not sexually active. However, several conservative groups have endorsed the vaccine.

It has not been determined whether insurance will cover the cost of the vaccine. The market place will decide how widely the vaccine will be utilized. I think it will be widely accepted as an attractive solution for preventing a serious form of cancer.

Question: Can men benefit from the vaccine?

Answer: There are no data on how effective the vaccine is in men. Obviously, men do not get cervical cancer, but they can get cancer of the penis, which is also caused most often by HPVs. However, cancer of penis is extremely rare. Men and women can develop genital warts, which could be prevented by the Gardasil™ vaccine. There are more than a million cases of genital warts in the United States annually.

Question: How soon will we see the benefits of this vaccine?

Answer: It is worth noting, that it may take many years until we see a reduction of cervical cancer from the vaccine. Most cervical cancers occur when women reach their 40s and 50s, so it may be 25 years before we can measure a reduction in cervical cancers. Reduction in genital warts and in cervical pre-cancers will be seen quite quickly.

Question: Aside from preventing cervical cancer, are there other potential benefits from use of the vaccine?

Answer: The vaccine will also prevent a rare but serious HPV-related disease called respiratory papillomatosis. The illness causes benign tumors to form in the respiratory tract. These tumors are not malignant, but some children may develop the disease at the age of 1-2 years and require hundreds of surgeries to keep the airway open. Mothers who have genital warts can transmit the disease to their children during birth. As I mentioned, the Gardasil™ vaccine developed by Merck also provides protection against HPV types 6 and 11, which cause genital warts. By preventing genital warts, the chance of spreading the virus from mother to child would be practically zero.

The viruses that cause cervical cancer also cause some cancers of the tonsils. These are more frequent in men. The vaccine is expected to prevent these cancers also.

Question: What will be next?

Answer: Glaxso Smith Kline also has an HPV vaccine, which would only protect against cervical cancer. Eventually, researchers hope to develop an oral vaccine, which will be easier to administer than the current series of injections.

Some researchers here at Johns Hopkins are working on an HPV vaccine that would provide broad immunity against all HPV types. Such a vaccine would use another HPV protein from a single papillomavirus, which produces antibody response against all HPV types.

There is also a line of research to develop an HPV-based therapeutic vaccine to destroy existing cancers. Therapeutic vaccines have been successful in animals, but have not yet been demonstrated to work in humans. Hopkins researchers are testing these vaccines for both cervical and tonsillar cancers. —Tim Parsons