A conversation about HPV

Although he is currently working in Pretoria, South Africa, Jeffrey D. Klausner, MD, MPH, public-health infectious-disease expert and associate clinical professor of Medicine at the University of California-San Francisco, made himself available via e-mail to answer some of MLO’s questions on HPV and the newest HPV vaccines. Dr. Klausner was director of STD Prevention and Control Services for the San Francisco Department of Public Health from 1998-2009. He is editor of the textbook Current Diagnosis and Treatment of Sexually Transmitted Diseases and author of more than 250 peer-reviewed articles on HIV and STD prevention and epidemiology, several of which haved appeared previous issues of MLO.

Jeffrey D. Klausner,

MLO: Lately, new advertisements for the HPV (Merck’s GARDASIL, for HPV Quadrivalent Types 6, 11, 16, and 18, and GlaxoSmithKline’s Cervarix for HPV 16 and 18) vaccine have appeared with the suggestion that “boys”/men should be vaccinated as well as “girls”/women — all of them between 9-26 years of age — since two of those strains are believed to be responsible for 70% of cervical and anal cancers, and HPV-associated penile and throat-and-neck cancers, and  the other two cause 90% of genital warts cases.

This suggestion is being made despite the fact that the Centers for Disease Control and Prevention (CDC) and other government forums say boys/men with HPV are not as likely to suffer the types of serious health issues as girls/women do. In fact, the initial approval for Merck’s GARDASIL was based on its use for boys/men to be protected against HPV 6 and 11 (genital warts). Based on your knowledge of HPV and your work within the public-health environment, what would your choice (vaccination or not?) for your patients be and why?

Jeffrey D. Klausner, MD: The HPV quadrivalent vaccine has been shown to be highly protective for boys and girls for the prevention of external genital warts and persistent HPV infection. In girls, the HPV quadrivalent vaccine has also been shown to be protective against pre-cursor lesions to cervical cancer, a major cause of repeat Pap smears, and costly and uncomfortable surgical interventions to treat those cervical lesions. In addition, the HPV quadrivalent vaccine reduces the risk for precursor lesions to vulvar cancer, which, although rare, can be quite disabling.

Given the high effectiveness of the vaccine against cancer-causing HPV subtypes over the long term, vaccination will be very likely to reduce cervical-cancer morbidity and mortality. Since HPV is a sexually transmitted infection, to maximize the public-health benefit, it makes sense to vaccinate both boys and girls. Boys will have the added benefit of reduced incidence of genital warts which, while not life threatening, can be quite unpleasant, stigmatizing, and result in frequent medical visits for treatment. There are strong data that anal HPV infection causes anal cancer, and HPV infection is associated with increased risk for HIV infection. Men who have sex with men in the United States might benefit from HPV vaccination to prevent anal cancer and reduce the risk for HIV infection, although clinical trials have not been done.

Some public-health experts have advocated for routine vaccination
for all boys and girls and also support school-entry requirements that
would mandate students entering 7th grade
be vaccinated
or demonstrate a religious exemption.

MLO:  Do you know if any tests currently exist for identifying the more than 30 types of HPV? Of those 30 types, these vaccines take care of four: HPV 6, 11, 16, and 18. Do you know which of the remaining 26 HPV types would be the next on the list for a vaccine and why? Do you have any knowledge of how and why certain strains of a virus become the focus of vaccine development?

Klausner:  I am not aware of any Food and Drug Administration-cleared tests that exist to identify more than 30 types of HPV. There are certainly different tests available in the research laboratory to identify more than 100 types but none that are commercially available. It is unlikely that HPV-vaccine manufacturers will develop expanded vaccines to target additional HPV types. The current vaccines target the most common types; vaccine development is expensive; and clinical trials take many years and are also quite costly. Trials would have to study the current vaccine versus the expanded vaccine, and the incidence of those less-common HPV types would be low, requiring much larger study-sample sizes, further increasing the cost and complexity of a clinical trial. The current HPV types in the vaccine were selected based on their frequency in the population (6 and 11 quite common) and their strong association with cervical cancer (16 and 18).

MLO: Statistics show that at least 50% of sexually active men and women contract HPV in the United States. What is the prevalence of HPV in other countries, if you know?  Are others of the 30 HPV viruses more likely to show up in populations of other countries?

Klausner: The prevalence of HPV in countries outside the United States is at least as high or higher. HPV is a common virus, easily transmitted during sexual contact. There are multiple studies showing that the lifetime prevalence of HPV in women in several countries is 50% to 70%. The global distribution at present of HPV types seems to be fairly similar with 6 and 11 being the most common and 16 and 18 mostly highly associated with cervical cancer. Some experts are concerned that with the increased use of the vaccine, particularly in Australia and in Northern European countries where vaccination is nearly universal, there might be the expansion of replacement HPV types . HPV types that were rare prior to population-level vaccination now fill the available ecological niche. We have seen that with some pneumococcal subtypes but not necessarily with other bacteria or viruses. HPV surveillance in many countries is ongoing — both to monitor the effectiveness of the vaccine and detect changes in the epidemiolology of HPV.

MLO: What reasons, aside from the “fear of vaccinations” in general, would preclude a parent from having a son vaccinated? Has there been any argument from the public-health sector one way of the other regarding the importance of protecting all children/adults?

Klausner: The current lack of enthusiasm for routine vaccination for boys is due to analyses of cost-effectiveness. Because preventing cervical cancer, abnormal Pap smears, medical visits, and treatment is cost saving, in females the cost-benefit ratio is quite favorable. In boys, however, the benefits are less compelling and cost savings for reduction in external genital warts or penile (or anal cancer) at the population-level are not as great. In my personal opinion, that is shortsighted, and we should be supporting the implementation of preventive measures like effective vaccinations — not only to reduce costs but to keep people healthy and save lives. The vaccine is safe and has not been shown to be associated with a significant frequency of adverse effects. The major reason a parent might not vaccinate a son is cost and, as I have stated, that is pretty shortsighted and a shame that all insurance organizations may not cover HPV vaccination for boys.

Some public-health experts have advocated for routine vaccination for all boys and girls and also support school-entry requirements that would mandate students entering 7th grade be vaccinated or demonstrate a religious exemption. I think when the data from Australia and other countries are published showing the health benefits and cost savings of population-level vaccination, policy makers in the U.S. will be more convinced. The U.S. is a fairly conservative environment when it comes to public-health policy.


  • Human papillomas (warts) were linked to a virus (HPV).
  • Papillomavirus was first isolated in rabbits by Richard Shope; thus the first oncogenic strain was discovered.
  • Georgios Papanicolaou did research on diagnostic cytology of the cervix.
  • Papanicolaou conceives of the smear test for detecting uterine-cancer diagnosis.
  • Papanicolaou’s research was published. First Pap smears were done in Korea.
  • The uterine cancer smear test is named after Papanicolaou (“Pap” test).
  • Pap smears began being used widely.
  • Harald zur Hausen of the German Cancer Research Center linked HPV with cervical cancer.
  • His team isolated several genotypes linked to cervical cancer and genital warts
  • Almost a decade after he began researching the connection between HPV and cervical cancer, zur Hausen discovered that HPV strain 16 is present in some cervical cancer tumors.
  • zur Hausen discovered HPV strain 18 in tumors and then cloned the viruses to make them available to other researchers. Infections with HPV strains 16 and 18 now are known to cause about 70% of all cervical cancer cases.
  • PCR assay found HPV DNA in 99.7% of cervical cancers studies.
  • The U.S. Food and Drug Administration (FDA) approved a hybrid-capture test manufactured by Qiagen as the primary screening tool for detecting HPV cervical infection as an adjunct to Pap testing, and which can be performed during a routine Pap smear. It can detect the DNA of the 18 HPV types that most commonly affect the cervix and distinguish between “low” and “high-risk” HPV types, but it cannot determine the specific HPV types.
  • The FDA approved Gardasil, a vaccine designed to prevent infection with high-risk HPV types16 and 18 that cause most (70%) cervical cancers, and types 6 and 11 that cause most (90%) genital warts.
  • zur Hausen was awarded half of the $14 million Nobel Prize in Medicine for his discovery that HPV was linked to cervical cancer, which eventually led to the development of two vaccines against HPV strains that cause most cases of cervical cancer, which is the second most common cancer among women.
  • A test, called Cervista HPV 16/18, which identifies the specific HPV subtypes 16 and 18, was approved by the FDA.