HPV, or human papilloma virus, is a type of virus that infects the skin and mucosa of the cervix, vagina, vulva, anus, penis, mouth, and throat. There are over one hundred strains of HPV that have been identified. Of these, forty have been associated with low-risk or benign conditions, like genital warts, and fifteen are considered high risk and associated with causing cancer.

HPV infection is often cleared by the healthy immune system in six to eighteen months. It’s the persistent HPV infection that may lead to the development of cancer.

This happens when the HPV DNA inserts itself into the DNA of human mucosal cells, then is triggered by physiological stress in a way that leads to uncontrolled cell growth, or cancer. Infection with HPV occurs during sexual contact, most commonly during vaginal and anal sex, and has been associated with cervical, vaginal, vulvar, penile, anal, and throat cancers.

The quadrivalent HPV vaccine—which protects against four strains—was first approved in 2006. The vaccine that protects against nine strains wasn’t approved until 2014. The HPV vaccination rates in the US are low—now it’s 60 percent on average nationwide.

But even back in 2006, when the vaccine was first approved, an impact on the rates of cervical cancer was not projected until 2020. Once somebody is infected, it’s estimated to take anywhere from ten to fifteen years for cancer to develop. That’s why starting with vaccination in 2006, you should start to see changes in rates in 2020. Unfortunately, it’s still too early to see the benefits of HPV vaccination.

Per the CDC guidelines, girls and boys both should be vaccinated prior to potential exposure. It’s recommended to complete the two-shot series between the ages of nine and fourteen, and after the age of fifteen to complete the three-shot series. The vaccine is approved in people up to the age of forty-five, but the American Cancer Society does not recommend vaccination in those older than twenty-six because there is not yet data supporting a benefit in this age group. [Editor’s note: Condoms also offer protection from genital HPV infections.]

The vaccine has been shown to be safe based on the data in the clinical trials and the post-marketing data that’s been routinely gathered. There are reports of patients with allergies, so patients who have allergies should talk to their doctors before receiving the HPV vaccine. But overall, the HPV vaccine is safe.

There’s now an RNA test as well as a DNA test. The DNA assay tells you whether the virus is there, even if it’s not active—what we call a latent infection. The RNA assay will pick up HPV only if the virus is active.

The HPV RNA assay could give you a false negative. If you have a latent infection, it will tell you you’re HPV negative, but you could still have the DNA present. The HPV RNA assay is automated, it’s less expensive, and it has much higher sensitivity for picking up early cellular changes. So a lot of pathologists switched over to that not realizing that from a screening perspective and a cancer-prevention perspective, we need to know whether the latent HPV infection is present. The screening guidelines from the American Society of Colposcopy and Cervical Pathology (ASCCP) change based on whether HPV is present or not.

I tell patients, “Go back and make sure you’re DNA negative, not RNA negative,” because I don’t want people to think that they’re clear of the infection when it’s really just an RNA negative. A lot of gynecologists don’t even realize that their labs switched assays to the new RNA assay, and many don’t realize the limitations of the HPV RNA assays. If they specifically order HPV DNA tests, then the pathologist has to run that test. But if the gynecologist doesn’t specify, then the pathologist does whatever their standard assay is in the lab. So there’s a big education gap right now.

Our research is about finding a way to clear HPV in people with persistent infections. Over 80 percent of the sexually active adult population in the US has been infected with HPV at one time or another. The majority of people with a healthy immune system will clear the HPV infection within six to eighteen months. But about 10 percent of the population has a persistent infection. We have focused on finding ways to help support the host’s immune function to clear persistent HPV infections.

It’s estimated that there are about 3 million women worldwide with persistent high-risk HPV infections. About 15 percent of those will progress to precancerous or early-stage lesions that can be treated and resolved with proper screening and treatment. It’s a bigger problem in countries where people don’t have access to that screening. Another 1 percent or so of these women will develop cervical cancer.

It’s very fortunate we have the Pap smear, which has had a significant impact on cancer prevention through early detection of cellular changes. That same technology has been adopted in clinical practice—not universally yet—to help screen for anal cancers in recent years. But that is certainly is not a standard of practice yet.

[Editor’s note: Although the prevalence of genital HPV infection is similar across sexes, the development of persistent infections appears to be less common in men. There is a lack of research on HPV infection in trans and nonbinary people.]

If you have a normal Pap and you’re HPV negative, the recommendation is not to be seen again for five years. The ASCCP guidelines for 2020 also recommend primary screening with HPV testing alone. One of the biggest concerns with these new screening guidelines is how the RNA assay can give a false negative. That is a big concern if you really are HPV DNA positive—a lot can happen in five years.

You may think you’re in a monogamous relationship, but you never really know. In our study, we’ve had people say, “I’ve been married for twenty years, I’ve never been with anyone else, nor has my husband, and I have HPV.” Our audience is largely women in their maybe late twenties to mid-fifties. Many of those are married. It’s a difficult population to target STI education toward because they’re like, “I don’t need to worry about that.”

AHCC is a standardized extract of cultured Lentinula edodes mycelia produced by Amino Up Co., Ltd., which developed it in 1992. AHCC is unique because it has primarily the alpha-glucan component. Most of the mushroom extracts are primarily the beta-glucan component. AHCC supports the body’s immune system to clear the infection as it normally would under healthy physiological conditions.

We have completed two pilot studies using AHCC, as well as a phase 2 double-blind placebo-controlled study that was accepted to be presented at the upcoming Central Association of Obstetricians & Gynecologists annual meeting, from October 28 to 31, 2020, and will be given the Dr. George W. Morley Memorial Paper award. It is not yet published but will be after this meeting. In the pilot studies, we had over 50 percent clearance of HPV infections, and that was very encouraging. In the phase 2 study, more than 60 percent of the patients had a durable clearance of the HPV infection.

We think AHCC supplementation helps support a healthy body’s immune response to HPV infection.