HPV Home Testing

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A recent University of Michigan study found that around 20% of cervical cancer cases and cervical cancer-related deaths could be avoided if every eligible person was screened. U-M researcher, Dr. Diane Harper is hoping to lower the barriers to cervical cancer screening by making it more convenient and less expensive. How? By empowering patients with the tools and knowledge needed to collect their own samples at home for testing. This approach has the potential to greatly increase the number of people who are screened overall, and would be transformative in advancing health equity and accessibility for cervical cancer screening.

Dr. Diane Harper Profile

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Transcript

Kelly Malcom:

Welcome to The Fundamentals, a podcast where we explore biomedical research here at Michigan Medicine. Research is fundamental to University of Michigan's mission to improve the world. On each episode, we'll meet the people behind the research, learn more about their fields, and the fundamental questions they are trying to answer. I'm Kelly Malcolm, a Science Writer and Communication Strategist for the University of Michigan Medical School. This season we'll start by explaining a little bit of the history behind the questions our experts are asking and get a glimpse into the future of healthcare.

In 1941, George Papanicolaou and Herbert Trout reported that cervical cancer in asymptomatic women could be detected using a vaginal smear. Dr. Papanicolaou is the man for whom the pap smear is named. George's story begins like so many other American stories do, with immigration through New York City. Though he had graduated from medical school at the University of Athens with top honors, upon arrival to the US, he and his wife, Lady Mary Papanicolaou, took the first jobs they could find. Mary became a seamstress and George a rug salesman.

George eventually acquired a position at NYU and Cornell University to study physiology with Mary joining him as a technician. His early research into the reproductive cycle and changes in vaginal and cervical fluid began in Guinea pigs. But it was with the help of his wife, Mary, that he made his landmark discovery about the diagnostic power of the pap smear. For 21 years, Mary provided daily samples of her own vaginal fluid, processing them so that George, who was not a licensed physician and therefore unable to acquire samples from patients, could continue his studies of cellular changes.

Since its invention, the Pap test has led to a massive reduction in the incidence of and deaths from cervical cancer of more than 50%. Caught early, almost all cervical cancers are successfully treated. However, the Pap test can lead to false negative results and has now been replaced by HPV screening, which still requires an uncomfortable cervical swab.

According to the National Cancer Institute, in 2021, 72.4% of women aged 21 to 65 years were up-to-date with cervical cancer screening. That still leaves many who will not benefit from early detection of this preventable cancer. A recent U of M study found that around 20% of cases and deaths could be avoided if every eligible person was screened. U of M researcher, Diane Harper, Professor in the departments of Family Medicine and Obstetrics and Gynecology, Biomedical Engineering, and Women's and Gender Studies is hoping to lower the barriers to cervical cancer screening by making it more convenient and less expensive.

All right, so we're just going to start with question one. What are some of the barriers to people getting regular cervical cancer screening?

Dr. Diane Harper:

Cervical cancer screening is something women are told that they need, but they don't know what it means. It gets covered up by the GYN exam or it gets covered up by the pelvic exam or it gets covered up by your annual diary. And so, women really have not an idea of what their cervix is, what their organ is, where it is, how do to get to it, what is good about it, what's not good about it. And when you are a young person and you're told to, "Welcome to womanhood, you get your first exam," I would say that virtually less than one out of a million women actually have a good time doing it. And then, I worry about that one.

So it's not a pleasant experience. The speculum has been around for centuries, I hate to say it, and that has been an instrument to be able to literally pry things open to see it so that somebody from the outside can see what's going on inside. And it's not comfortable in any way. It requires a person to be on a table. It requires you to have your bottoms off. You're naked. You have somebody over you that can be looking threatening. Most people aren't. Most people have no intention of being threatening, but they look and feel threatening.

The barriers are for women to psychologically be ready to come in for that exam. Even my most healthy patients say if I am seeing them and say, "Oh, by the way, you're due" say, "Oh, not today, cannot do it today. I'm not ready today to do it." And these are people who are well-educated and understand this. This is not an exam that people are excited about and it's not an exam that people look forward to. It's not an exam that makes them feel empowered by their health. It's something that one of my research subjects said that has always kind of hit my heart. It's like, "Well, we are just resigned to the shame of having to lay there and do it and just get it over with." And I thought, "No one should ever feel that way about something that is important to their health. No one should feel that way." So barriers to screening is, yeah, the ugly speculum exam is the big thing that keeps people from getting screened.

Then there are a lot of other secondary things, things like time, things like, "I'm on my period," things like, "I may or may not have insurance," although it's completely covered under the ACA, so there shouldn't be any out of pocket costs to women, but just the time to come in to do it. The fact of understanding that they need to do it. I will tell you, I was giving a community lecture about cervical cancer screening, and just started with, "What's a cervix and why should we screen it?" And the room was quiet. And then, finally somebody said, "I think you have to have a cervix to have a baby," which is true because it's the cervix that dilates and that's what they would remember.

But that shows that we have done a really poor job in educating women about what the cervix is and how to take power of it, and how to understand what that organ is and how you keep that organ healthy.

Kelly Malcom:

Right.

Dr. Diane Harper:

So I think there are a lot of barriers that are maybe subtle. Maybe only some women get it, maybe all women get it, but people don't voice it. But it's not something that people stand up for and say, "Hey, I need to get my cholesterol checked this year."

Kelly Malcom:

Okay. So tell me more about this self-administered test. Where did the idea for it come from and how did you develop it?

Dr. Diane Harper:

So I think every woman who's had a speculum exam thinks, "There has to be a better way to do this." We all think of it. I just happened to be an engineer before I became a physician, and so I said, "Not only can there be a better way, there should be and we can find it." So early 1995, I was the very first person to publish with NCI the concept of using either a tampon or a swab or something to collect both cells and virus DNA for detection of cervical cancer.

So the first instruments we used were pretty crude. A tampon is not what's going to be used in commercial, hundreds of millions of tests because it requires very intricate processing that's just not meant for large-scale. Using swabs could very well be. And so, then it becomes, "Well, how do you get a swab? How do you make it so that the woman can use it? What kind of swab do you need? Then let's look at the fibers on the end of it. Do you use cotton? Do you use nylon? Do you use..." Now we know that you use something called the flocked swab, which is they make the ends kind of sticky so it can pull out the cells and the DNA that are sitting in there.

We also learned in those first trials over the first probably 10 years that we cannot reliably get cells. And looking at cells, which has been the entire process of cytology since 1949 when Dr. Papanicolaou first had his paper published, that that wasn't going to be possible with self-sampling.

So then, the question became a little bit dormant. We went off and worked on HPV vaccines, and realized that we could, with HPV vaccines, prevent so many cancers. So HPV was obviously the key. It wasn't cytology.

Kelly Malcom:

Right.

Dr. Diane Harper:

It's like if we can prevent it with a vaccine, then we should be able to test for it with an HPV test, and then we should be able to figure out how to treat it with some kind of cure for HPV. And so, that gave the whole process many more legs and many more ways to think about it, because then we were looking for HPV detection. We were looking for type-specific HPVs to figure out can we find the kinds that are most prevalent in women who get cancer? And can we find those types that are not covered in the vaccines that women are protected against even if they are vaccinated?

And the long end of that story is that we can. And here at Michigan, I led a team of both family medicine, of OB/GYN, of public health, of biostatistics, of social work, where we have the largest sample of the US-based population that show that self-sampling compared to speculum-based exams from a clinician is exactly equal. It's equivalent. It is so exciting, because while this has been done, it's not a big surprise. Because it's been done like 13, 14 years ago in Europe, but the United States has been really recalcitrant in picking up and understanding this. They've really kind of been stuck on, "Oh, we have to do things with cytology." And it's like it's always hard to have change.

Kelly Malcom:

Right.

Dr. Diane Harper:

It's always hard to move people forward.

Kelly Malcom:

Right. And cytology, just so people understand, is looking at...

Dr. Diane Harper:

It's looking at cells. It's looking at the shape of cells. It's kind of like abstract art. So trying to figure out, "What does that mean to me today, the way that cell nucleus looks and how it's folded in on itself? Did it have a good night's sleep or is it a little grouchy?" So there's a tremendous subjectivity to cytology. Okay.

Kelly Malcom:

So now, you're looking for actual HPV virus instead.

Dr. Diane Harper:

Yes.

Kelly Malcom:

So what are some of the potential barriers to putting this in practice? I know you said that Europe is already sort of using this. What is the barrier here in the US?

Dr. Diane Harper:

Well, a couple of barriers are that practice patterns are established. Many studies show that it takes physicians in the US 10 to 17 years to change their practice. Please, please not that long for this. Women need this. It is also one of where there are now two companies who have FDA-approved HPV self-collection tests. And you have to have FDA approval in this country in order for clinicians to do that. Some clinicians practice medicine and they do what they're told to do, and their professional organization says, "You shall do this," and that's what they do. And they really don't think much more about it, and in part because it protects them legally in case of any lawsuit that happens of any cancer that would happen that they failed to detect.

But I think that we all know that change has to come by people who are willing to step out of that and willing to say, "Look at all of this data we have. Look at the evidence. Look how tight it is." This is like, "Why are we not empowering women to do this? What now are the downsides of ignoring the advances that we've made, that we know that we've made?" Insurance companies pay for it? That's not an issue. Women want it. Anybody listening to this, tell your doctor you want self-sampling because you can have it if you want it.

But that's not the issue. The issue is to make sure that you're connected to a lab, and that lab is using one of those two FDA-approved HPV screening platforms for self-collection. And so, it really shouldn't be that there are many barriers. The question is getting the pathologists together, getting the OB/GYNs together, the family medicine together, the general internists together, the patients together, the nurse practitioners together so that we're all working on the same page.

Kelly Malcom:

Easy, right?

Dr. Diane Harper:

I'm going to put a quick note, because a lot of people when they think about cervical cancer screening, they think, "Who does cervical cancer screening?" And they immediately go to OB/GYN does cervical cancer screening. And I think it's really important for people to realize it in the "real world" that only about 30% of cervical cancer screens are done by OB/GYNs or their nurse practitioners or their nurse midwives.

There was a really great article just published this year in 2024 by the National Cancer Institute that showed that 60 to 70% of cervical cancer screening is done by family medicine and general internal medicine and their nurse practitioners. And I think that that's important to realize, because when you realize who is actually on the front line and doing the screening, that that should make a difference. Allowing those physicians to feel empowered about screening and offering patients the ability to self-sample before their patients may say, "Hey, you're the only doctor in my community and I don't feel comfortable with you knowing my stuff when we go to church together on Sunday." Right?

Kelly Malcom:

Right.

Dr. Diane Harper:

So it's an ability to offer women a chance to get healthy without the embarrassment and the awkwardness that the speculum exam requires.

Kelly Malcom:

Right. So it sounds wonderful, and I really don't know why it's not in practice, but are there any downsides to this approach?

Dr. Diane Harper:

So I think as with any screening, this is appropriate for average risk asymptomatic women. If you are a woman who has funny bleeding after you have intercourse or your periods aren't regular or you have pelvic pain or you have back pain and you haven't particularly been screened before, you may have cancer. And those are signs and symptoms that we haven't done a good job of telling the population about, somewhat part because our menstrual periods are never quite perfect. So we're not really sure, "What is this?" But I think that the self-sampling is wonderful for that average risk asymptomatic person. But if you are somebody who's having those other symptoms, please, please go to your doctor and they will do a speculum exam. And that is important because that's a different category than is general population screening.

Kelly Malcom:

Does this test change how frequently we'll need to be screened?

Dr. Diane Harper:

Okay, so let's talk a little bit about interval screenings. There is absolutely no reason for a woman to go to an OB/GYN every year if she is an average risk asymptomatic woman, that just there isn't anything there. If she has symptoms, of course, absolutely that's something very different. What we have known since 2012 is that you should not be screening for cervical cancer any more often than every five years, because the HPV is like slow man growing, right? He just takes forever to make changes in your cervix. And so, screening every five years is plenty often. In the small group of women who end up with a pre-cancer, where their pre-cancer is treated, so, "Yay success, we found it, we got rid of it, you're not getting cancer." Those women are at risk because we're not treating the HPV, we're just removing the disease. They're at risk for future development. So they go to an every three year screening pool.

If you are in the cycle where your HPV is positive, but it's not bad enough to do anything, you're probably going to get screened a little more frequently just to see is your HPV doing anything else or is it going away? Because we know 90% of women will clear HPV, but it takes three years to clear it. So that means a few repeated tests on that side. But for most women, please, please, please question your physician if they say you need this yearly. Because that's part of the beauty of this, is that we know it's caused by HPV. We know it's very slow moving, and we know that you're safe for five-year intervals.

Kelly Malcom:

So can I ask a question about cost?

Dr. Diane Harper:

Yes.

Kelly Malcom:

Is it cheaper than your traditional speculum exam?

Dr. Diane Harper:

So let's talk about cost in two ways. Cost to the patient, it makes absolutely no difference because the patient has zero out-of-pocket costs because of the ACA. And it doesn't matter which insurance, whether it's private, Medicaid, or whatever. She does need to have insurance, though. She has no insurance, that's a different ball spark.

Now, the cost to the system, the cost when you're looking at cost-effectiveness analysis, you think about a speculum. We'll start first with a metal speculum because that's what we've had in the past. That metal speculum has to be cleaned by a person who has to do dishes and wash and scrub it, has to wrap it in a plastic material, has to go through an autoclave and autoclave it or through some kind of harsh chemical to kill germs to go with it. It then has to be repackaged and labeled and wait for use again.

When it is used in the room, they need a chaperone. That's a human being. That's a human being who has an hourly wage that has to stand there in the room to help and assist, if for no other reason to be a chaperone and be there for the patient, for the patient's protection. So that's expensive. That's HR expenses, that's expenses of plastic, that's environmental waste. Medical waste is huge. And they would say, "Okay, but we don't use metal speculums anymore. We use plastic lighted speculums. They're a single use." So they're single use. They're plastic. They have a light. Can you see the mountain in the landfill of all these lit used plastic speculums that are sitting there? They're expensive. They're less expensive than buying a metal speculum because that's $50 to $100. A plastic speculum is $5 to $10 each. But nonetheless, it's expensive.

And now we're talking about a Copan FLOQSswab that literally costs cents and is literally smaller than a pencil. So yes, it does have to be disposed of as medical waste, but the amount of volume that it has and the amount of incineration that needs to go with it to make it safe so there is no biological addition to our landfill is so much smaller than any speculum could possibly be.

So when we talk about costs, we have the environmental costs, we can talk about human costs, we can talk about cost to the healthcare system, cost to the woman. The biggest cost is for the woman who doesn't get screened at all.

Kelly Malcom:

Where does the HPV vaccine fit in with all of this?

Dr. Diane Harper:

So HPV vaccinations are most effective and last longest when they're given at the youngest age. So ideally, we'd give it to our kids at nine, but in the United States, no one's going to do that and the CDC started it at 11. And then, in reality, most kids don't even get them at 13. They wait until they're 15. But the good news is if you get it before you're 15, for all these people listening out there, you only need two shots. All right? It's like you don't need all three. HPV vaccinations are approved through the age of 45. So people who missed out on it can still get a shot.

Remember that these are shots that prevent the HPV from getting into your skin. Okay? So kind of think of them as a wetsuit that doesn't allow the HPV infection to get in. Once you have that HPV infection, the vaccine doesn't do anything for you. Okay? So if you've already got it. It's there.

So now it's like, okay. Well, you have great evidence to show that vaccinated as a kid, we have 14 years of extraordinarily good protection that gets the kid to the age of 25, right? The age of 25 is the age we start with our primary HPV screening. We didn't really cover this before, but right now we do 21 to 29 year olds separate from our 30 to 65 year olds. Well, with primary HPV screening, the 21 to 25 year olds, they don't have cancer. They are less than 0.01% of cancers are found in that early of an age group. And so, those are not the people that need to be screened. So we just start screening at 25 and go 25 to 65 for primary HPV screening. So I think that the vaccination makes this beautiful bridge into our age of screening that covers kids when they're in that early sexual exploration phase that gives them some level of protection. Again, it's not against every single type, but it gives them some level of protection of what's there.

Kelly Malcom:

So why is this test important for improving health equity?

Dr. Diane Harper:

Health equity is so important. We know that in the United States, the number of women who get cervical cancer every year has not changed in over 20 years. That means we are not reaching people, or people are getting screened in maybe a mass screening event, but then not getting follow-up. And so, we have got to create a pathway where women get primary HPV screening. Most of those women will be negative and they don't have to worry about anything else. Those that are HPV positive, a small portion of them will immediately go to colposcopy. Another small portion will just come back in a year and retest it. And that very small portion, about 5% of those who test positive, will need to go on for a secondary triage test.

And being able to help women walk through that, understand the reasons why they're doing this, to get to the final end result of screening, which is you either have a pre-cancer or you don't have a pre-cancer. And if you have a pre-cancer, we were successful, we found it. Let's get you treated. If you don't have a pre-cancer, let's get you back into the screening pool and get the process started all over again.

So I think that understanding our communities of color, understanding our communities of difference incomes is huge, because what we see in every single large database is that our Black women, our Hispanic women are less screened. We see that they're not coming in for screening. And in this, there was about a 10-year interval where Black women were ahead of everyone in screening. They had the highest screening rates. But they also had the highest cancer rates, which tells me that they got screened, but nobody helped them follow up with what was going on.

And that's something that we have to stop, something that we have to go on. I'm currently working with Native Americans, and again, we just published that 52% of the women who had cervical cancer in the Native American reservations had not had cervical cancer screening, our Native American population. It just breaks my heart when I see that the appropriate kind of healthcare is not available or not happening, or is offered in a way that is not culturally appropriate or sensitive to what those people's needs are.

We have also, in the process of publishing a paper at looking at our women with physical disabilities, arthritis is a physical disability for many people. But looking at people who are born with physical disabilities, their arms or their legs don't work right, they're in a wheelchair, their pelvis is stuck in a contracted way. 90% of these women are sexually active. HPV is transmitted through skin-to-skin contact. That's all this is, is a skin-to-skin contact. These women deserve to have care. These women deserve... You wouldn't tell them, "We're not going to swab you for a strep throat just because we can't get your mouth open." We're going to help figure out a way to do this.

And in looking at this group of women, they were so overjoyed that someone cared enough to help them understand that they could do it. In this particular study we did, they did it at home, in their own privacy, in their own bathroom, and they felt wonderful about knowing that they could take over that part of their healthcare that previously had been a ritual. I have to think about what kind of clothes I'm going to wear. I have to think about the time I'm going to go. Can my caretaker go with me? Who's going to help me on the table? What if my leg slips? What if they make weird faces at me? What if I smell down there? All of the kinds of things that we are aware of because we're a social being and we want to fit in with society, but society doesn't always let us fit in.

So being able to give this to women who do not have the easy ability to jump up on a table and take their bottoms off is a godsend. They are so excited about having the opportunity to be a part of their own healthcare.

Kelly Malcom:

What are some future opportunities for research or people in this space?

Dr. Diane Harper:

So we've talked a lot about how this woman with a pre-cancer that we found gets treated, and her disease is surgically excised or taken out or scooped out or however you want to call it. But her HPV still is there and her HPV is going to cause new disease at a later time. So what we're working on right now is a cure for HPV. We have a trial going on at Michigan right now, where women who have that pre-cancer lesion and we know which HPV type they have, they can choose to voluntarily enter into the trial. The trial gives them a compensation and covers all their medical costs. And we are using a drug in a vaginal suppository that goes in for her. In our Phase 1 trial, we had a 70% clearance of HPV, which was tremendously high in the short period of time that it was normally there.

So I think the future work of this is that we will get a cure for HPV. My future scenario is you're going in and you get HPV tested every five years or so. If you're positive, you get this drug and you're cured. Right? It's like we don't have to do this colposcopy and this biopsy and this surgical excision.

And so, I'm very excited. This is probably the fourth drug I have worked on. And it's not that the drugs fail, it's that the companies go bankrupt doing the trials. And if another company buys them, they shelve it because they have a different product they want to be selling at the time.

Kelly Malcom:

Right.

Dr. Diane Harper:

So I will say that if enough of us keep working in this field and keep working to try to find a cure for HPV, which we can do, and then work with the Melinda Gates and get them to sponsor and make sure that these drugs come to market and go to the FDA trials, because that will be so good.

I will also say that this isn't just a woman's issue. I have many men come to me and say, "Look, I have this and I've given it to my spouse or my friend or my fiance or my wife and I feel horrible about it. What can I do about it?"

Kelly Malcom:

Right.

Dr. Diane Harper:

And then, I will say, likewise, there are many transgender people who have a cervix, and their transgender from being a woman to being a man means they really don't want to be thinking about that cervix, and they sure don't want a speculum in there. That just is totally against who they are as a person. So finding this self-sampling way to look at it and then finding a cure for it. So I do think that before I die, we will have either a therapeutic vaccine or a therapeutic cure that will help us eliminate the HPV, and then we really can make worldwide progress in eliminating cervical cancer.

Kelly Malcom:

So what are the next steps for your research?

Dr. Diane Harper:

So as I said earlier, we are publishing the paper of the first US-based population trial, which I'm very excited about. But in addition, I am also the Michigan PI for the NCI trial, which is a US-based trial across all populations in the United States: rural, urban, South, North. You pick lots of different races, ethnicities, groups of people. And we are doing a large trial with the FDA-approved self-collection techniques to present the data to the FDA to say, "This is our objective trial that's done, that's not sponsored by the company, that should be able to give you evidence that this is acceptable and should be the preferred screening test for women for cervical cancer going forward." You're not supposed to start your science project off with the conclusion.

Kelly Malcom:

Right.

Dr. Diane Harper:

And I fully will accept that criticism, but we've seen it. We've seen those results so many times in so many other countries that we would be worried if we weren't able to replicate them, like what went wrong with that? So I feel pretty confident to say that it may take us another couple of years before we finally have this trial, the NCI trial out. But it's FDA approved now, so there's no reason why a woman can't ask her doctor now to be screened with a self-screening.

Kelly Malcom:

Okay. And we like to give our guests the opportunity to sort of shout out your collaborators here at Michigan. So are there people that you want to give thanks to or note that have been working with you during this whole process?

Dr. Diane Harper:

Everyone at Michigan has been absolutely wonderful. The Rogel Cancer Center, a shout-out to them. They gave me the seed money to start this US-based population study. I will give shout out to MICHR, which is the Clinical Translational Center that we have here, because all of my work is in translational work. How do we take it from the bench to the bedside, literally to the woman's bedside?

I give a shout-out to the OB/GYN department who have been my collaborators in helping me collect the specimens, to my family medicine colleagues who likewise have given me support and have given me access to their patients and have been supportive of the whole concept. The entire family medicine department now screens with primary HPV screening as our screen. So if you come to us, that's the screen that we are offering now.

I want to give a shout-out to the School of Public Health and to the students of the School of Public Health who have worked with me on my labs and have created infographics and have helped me interview patients and come away with it saying, "Wow, I didn't know all of this was going on."

I want to give a shout-out to my admin, who is so wonderful. Katie, you're awesome. And everybody here, it has just been a really wonderful experience to be able to make this happen at Michigan for the women in Michigan, but for the women everywhere.

Kelly Malcom:

Okay. Thank you so much, Dr. Harper. This has been wonderful. And I know what I'm going to ask for at my next appointment. So yeah, it'll be exciting to get this implemented here in the US and worldwide, really.

Dr. Diane Harper:

Can you imagine? Then you can just... We used to go to the lab and get your blood drawn. Go to the lab, they'll swab your throat. Go to the lab, they'll give you a swab. You go in the bathroom, do your test, and you're done.

Kelly Malcom:

Right. Right.

Dr. Diane Harper:

How awesome is that? So it's very exciting.

Kelly Malcom:

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