Question

In the 1990s, it was discovered that there was a high correlation rate for patients who had previously had a viral condition called HPV and the later development of cervical cancer. A vaccine was developed and now young people (girls and boys) can receive an HPV vaccine that will protect them against the human papilloma virus and subsequent threat of cancer. However, in order to be effective, the vaccine must be given while the children are still relatively young, for example, eight or 10 years old. A certain segment of the population has condemned the vaccine, saying it is encouraging young girls to be promiscuous, while other members of the medical community are praising it as a great advance that could eradicate cervical cancer, which still claims many lives per year. What are your thoughts about this debate?

Answer 1

Human papillomaviruses (HPVs) are a group of more than 200 related viruses. More than 40 HPV types can be easily spread through direct sexual contact, from the skin and mucous membranes of infected people to the skin and mucous membranes of their partners. They can be spread by vaginal, anal, and oral sex. Other HPV types are responsible for non-genital warts, which are not sexually transmitted.

Sexually transmitted HPV types fall into two categories:

Low-risk HPVs, which do not cause cancer but can cause skin warts (technically known as condylomata acuminata) on or around the genitals and anus. For example, HPV types 6 and 11 cause 90% of all genital warts. HPV types 6 and 11 also cause recurrent respiratory papillomatosis, a disease in which benign tumors grow in the air passages leading from the nose and mouth into the lungs.

High-risk HPVs, which can cause cancer. About a dozen high-risk HPV types have been identified. Two of these, HPV types 16 and 18, are responsible for most HPV-caused cancers.

HPV infections are the most common sexually transmitted infections in the United States. About 14 million new genital HPV infections occur each year. In fact, the Centers for Disease Control (CDC) estimates that more than 90% and 80%, respectively, of sexually active men and women will be infected with at least one type of HPV at some point in their lives. Around one-half of these infections are with a high-risk HPV type.

Most high-risk HPV infections occur without any symptoms, go away within 1 to 2 years, and do not cause cancer. Some HPV infections, however, can persist for many years. Persistent infections with high-risk HPV types can lead to cell changes that, if untreated, may progress to cancer.

High-risk HPVs cause several types of cancer.

• Cervical cancer: Virtually all cases of cervical cancer are caused by HPV, and just two HPV types, 16 and 18, are responsible for about 70% of all cases.
• Anal cancer: About 95% of anal cancers are caused by HPV. Most of these are caused by HPV type 16.
• Oropharyngeal cancers (cancers of the middle part of the throat, including the soft palate, the base of the tongue, and the tonsils): About 70% of oropharyngeal cancers are caused by HPV. In the United States, more than half of cancers diagnosed in the oropharynx are linked to HPV type 16.
• Rarer cancers: HPV causes about 65% of vaginal cancers, 50% of vulvar cancers, and 35% of penile cancers. Most of these are caused by HPV type 16.

High-risk HPV types cause approximately 5% of all cancers worldwide. In the United States, high-risk HPV types cause approximately 3% of all cancer cases among women and 2% of all cancer cases among men.

HPV vaccination can reduce the risk of infection by the HPV types targeted by the vaccine. The Food and Drug Administration (FDA) has approved three vaccines to prevent HPV infection: Gardasil, Gardasil 9, and Cervarix. These vaccines provide strong protection against new HPV infections, but they are not effective at treating established HPV infections or disease caused by HPV. Correct and consistent condom use is associated with reduced HPV transmission between sexual partners, but less frequent condom use is not. However, because areas not covered by a condom can be infected by the virus, condoms are unlikely to provide complete protection against the infection.

Three vaccines are approved by the FDA to prevent HPV infection: Gardasil, Gardasil 9, and Cervarix. All three vaccines prevent infections with HPV types 16 and 18, two high-risk HPVs that cause about 70% of cervical cancers and an even higher percentage of some of the other HPV-associated cancers. Gardasil also prevents infection with HPV types 6 and 11, which cause 90% of genital warts. Gardasil 9 prevents infection with the same four HPV types plus five additional high-risk HPV types (31, 33, 45, 52, and 58).

In addition to providing protection against the HPV types included in these vaccines, the vaccines have been found to provide partial protection against a few additional HPV types that can cause cancer, a phenomenon called cross-protection. The vaccines do not prevent other sexually transmitted diseases, nor do they treat existing HPV infections or HPV-caused disease.

Because none of the currently available HPV vaccines protects against all HPV infections that cause cancer, it is important for vaccinated women to continue to undergo cervical cancer screening. There could be some future changes in recommendations for vaccinated women.

HPV vaccines stimulate the body to produce antibodies that, in future encounters with HPV, bind to the virus and prevent it from infecting cells. The current HPV vaccines are based on virus-like particles (VLPs) that are formed by HPV surface components. VLPs are not infectious, because they lack the virus’s DNA. However, they closely resemble the natural virus, and antibodies against the VLPs also have activity against the natural virus. The VLPs have been found to be strongly immunogenic, which means that they induce high levels of antibody production by the body. This makes the vaccines highly effective.

The VLP technology that is used in the HPV vaccines was developed by NCI and other scientists. NCI licensed the technology to Merck and GSK to develop HPV vaccines for widespread distribution.

Importance
Widespread vaccination with Cervarix or Gardasil has the potential to reduce cervical cancer incidence around the world by as much as two-thirds, while Gardasil 9 could prevent an even higher proportion. In addition, the vaccines can reduce the need for medical care, biopsies, and invasive procedures associated with follow-up from abnormal cervical screening, thus helping to reduce health care costs and anxieties related to follow-up procedures.

Until recently, the other cancers caused by HPV were less common than cervical cancer. However, the incidence of HPV-positive oropharyngeal cancer and anal cancer has been increasing, while the incidence of cervical cancer has declined, due mainly to highly effective cervical cancer screening programs. Therefore, the number of HPV-positive cancers located outside the cervix (non-cervical cancers) in the United States is now similar to that of cervical cancer. In addition, most of the HPV-positive non-cervical cancers arise in men. There are no formal screening programs for the non-cervical cancers, so universal vaccination could have an important public health benefit.

Vaccination is the approved public health intervention for reducing the risk of developing HPV-associated cancers at sites other than the cervix. The combination of HPV vaccination and cervical screening can provide the greatest protection against cervical cancer. It is important that as many people as possible get vaccinated. Not only does vaccination protect vaccinated individuals against infection by the HPV types targeted by the respective vaccine, but also vaccination of a significant proportion of the population can reduce the prevalence of the vaccine-targeted HPV types in the population, thereby providing some protection for individuals who are not vaccinated (a phenomenon called herd immunity). For example, in Australia, where a high proportion of girls are vaccinated with Gardasil, the incidence of genital warts went down during the first 4 years of the vaccination program among young males—who were not being vaccinated at the time—as well as among young females.

Safety
Before any vaccine is licensed, the FDA must determine that it is both safe and effective. All three HPV vaccines have been tested in tens of thousands of people in the United States and many other countries. Thus far, no serious side effects have been shown to be caused by the vaccines. The most common problems have been brief soreness and other local symptoms at the injection site. These problems are similar to those commonly experienced with other vaccines. The vaccines have not been sufficiently tested during pregnancy and, therefore, should not be used by pregnant women.

A recent safety review by the FDA and the Centers for Disease Control and Prevention (CDC) considered adverse side effects related to Gardasil immunization that have been reported to the Vaccine Adverse Events Reporting System since the vaccine was licensed. The rates of adverse side effects in the safety review were consistent with what was seen in safety studies carried out before the vaccine was approved and were similar to those seen with other vaccines. However, a higher proportion of syncope (fainting) and venous thrombolic events (blood clots) were seen with Gardasil than are usually seen with other vaccines. The patients who developed blood clots had known risk factors for developing them, such as taking oral contraceptives. A safety review of Gardasil in Denmark and Sweden did not identify an increased risk of blood clots.