Shared from the 2/6/2022 San Francisco Chronicle eEdition

The other vaccine hesitancy

Resistance to HPV vaccinations offer lessons for COVID-19

Heather A. York 1989

Studying “horned” rabbits led to the discovery that viruses can cause cancer.

In the heart of San Francisco’s Mission District is Paxton Gate, a strange little shop that specializes in “curiously mind-expanding treasures and oddities” and is stuffed to the ceiling with taxidermy mounts of springbok, gazelle, wildebeest, moose and a giraffe with a graceful, 6-foot long neck. Beneath the mounts are natural artifacts of every imaginable kind, from spectacular collections of butterflies and moths, to skulls, teeth and even the baculum (penis bone) of a red fox.

It was here that I took a day-long taxidermy workshop in which I learned to create that most delightful of imaginary animals: the jackalope. Iconic in American popular culture, the jackalope is that strange rabbit hybrid you’ve seen unaccountably sporting antlers. Jackalope hoax taxidermy mounts date to the 1930s, and since that time the weird bunny has spawned a vast industry of kitsch, one tacky postcard, oven mitt and snow globe at a time. The horned rabbit is so prolific that its image now appears in books, songs, films, video games and visual art, not to mention on cans of beer and bottles of wine and on human biceps in the form of tattoos.

But the least known and most fascinating thing about the jackalope is that it is related to “horned” rabbits, which actually do exist. During the medieval and early Renaissance periods, the horned rabbit was incorrectly taxonomized by naturalists as Lepus cornutus, a distinct species. The rabbit’s “horn” is in fact a keratinous carcinoma, a sometimes cancerous growth caused by infection from the Shope papillomavirus, named for Richard E. Shope, the virologist who was the first to identify the cause of the rabbits’ strange growths. Shope’s pioneering studies of horned rabbits in the 1930s advanced medical science by providing the first mammalian model of a virus-induced cancer. The work that followed from those studies, carried out by researchers, including Nobel laureates Peyton Rous and Harald zur Hausen, proved what was once a controversial proposition: Viruses cause some types of cancer.

Among the oldest and most common viruses, papillomaviruses infect a wide range of species. The human papillomavirus, or HPV, infection is so common that most sexually active people will get the virus; the Centers for Disease Control and Prevention estimates that 43 million Americans had HPV infections in 2018. Because HPV is so common and most infections are benign, it is likely that you have had HPV without knowing it. However, HPV can cause premalignant lesions or warts that may ultimately lead to cancer, which often develops decades after infection. HPV can cause cancer of the cervix, vagina, vulva, anus, penis and also oropharyngeal cancers such as cancer of the throat, tonsils or mouth. It is estimated that HPV causes around 50% of penile cancers, 70% of vulvar cancers and 80% of anal cancers.

The cervical cancer statistics are truly startling: 99.7% of cervical cancers contain DNA from high-risk types of HPV. Despite the resistance of the scientific community to the findings of early virus researchers like Shope and Rous, we now know that roughly 11% of cancer deaths worldwide are caused by viruses, which are the second most important risk factor for cancer, behind only tobacco use.

Thanks to the work of several generations of epidemiologists, virologists and oncologists, a safe and effective HPV vaccine was developed and approved for use in 2006. The nine-valent Gardasil 9 vaccine, which protects against nine different strains of potentially harmful HPV, was approved in 2014. The expanded coverage it offers means that the vaccine now protects against cervical, vulvar, vaginal, anal and oropharyngeal cancers, as well as genital warts.

According to CDC guidance, the ideal age for administration of the vaccine is 11 to 12, before children have been exposed to HPV strains that render the vaccine less effective, though it may be given as early as 9 and is recommended for everyone through 26 years of age. (It may also be administered to those 27 through 45, based on discussions between the patient and their doctor.)

The CDC, Food and Drug Administration and a wide range of professional medical societies, including the American Academy of Family Physicians, have endorsed its use. The HPV vaccine is also on the World Health Organization’s Model List of Essential Medicines, those drugs deemed so safe and effective as to be considered essential to a functional health care system.

Despite the existence of this remarkable vaccine, HPV-caused cancers remain a significant cause of mortality. GLOBOCAN worldwide cancer estimates for 2020 are sobering. In that year, 58,000 people died of cancers of the vagina, vulva, anus and penis. Another 177,757 lost their lives to oral cavity cancers. While improved screening, in the form of Pap tests, has substantially reduced the incidence of terminal cervical cancer in developed countries, the disease still killed 341,831 people. In much of the world, this mortality is driven by a lack of access to the HPV vaccine. However, even in the U.S., where the vaccine is widely available, the CDC estimates that each year about 19,400 women and 12,100 men experience cancers caused by HPV, and more than 4,000 women die of cervical cancer. In addition to the terrible human costs, the monetary price is also stunning. In 2018 alone, the direct medical cost of treating HPV infections in the U.S. was around $16 billion.

But if the HPV vaccine is safe, effective and accessible, why are so many of us still suffering from and being killed by HPV-caused cancers? While the answer is complex, a few major factors are clear.

Awareness of the importance of getting the HPV vaccine appears to be low among young people. One study that examined Los Angeles County college students’ awareness of HPV-related disease and vaccination found that about two-thirds of the male and half of the female respondents surveyed were unaware that the HPV vaccine is recommended through age 26. Less than half knew that they could get the vaccine at the college student health center or neighborhood clinics.

There also remains a substantial problem of hesitancy and resistance to the HPV vaccine, which has historically been the most often refused of common vaccines. One of the primary reasons for this resistance stems from the fact that the vaccine was initially marketed as a protection against sexually transmitted infections rather than as a cancer preventative. Many parents bristled at the idea of giving an anti-STI vaccine to their 11- or 12-year-old. However, the crucial point, which parents sometimes misunderstand, is that the vaccine should be given to kids at this age not because they are sexually active, but rather before they are sexually active.

Although HPV vaccination rates have improved over the 15 years the vaccine has been available, they remain far too low. The most recent CDC data indicate that just over half of adolescents in the U.S. are up to date with HPV vaccination

(58.6% in 2020), leaving millions of young women and men vulnerable to cancers that are largely preventable. Moreover, in the story of the HPV vaccine we see a parable of our current predicament with respect to the COVID-19 vaccine. In both cases, a lethal combination of lack of awareness, miscommunication and mistrust has caused too many people to risk their lives, as well as the lives of their family, friends and neighbors. The fact that the study of real-life jackalopes ultimately led to development of the safest and most effective anti-viral cancer vaccine ever devised is a scientific miracle. That so many of us are failing to benefit from the protection it offers is nothing less than a tragedy occurring in slow motion.

Michael P. Branch is the Foundation Professor at the University of Nevada, Reno. His new book is “On the Trail of the jackalope: How a Legend Captured the World’s Imagination and Helped Us Cure Cancer.”

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