In a Nutshell: Biomarkers and Cervical Cancer Treatment

00:00:00:08 – 00:00:22:02
Unknown
Hello and welcome to the webinar: In a Nutshell: Biomarkers and Cervical Cancer Treatment. I’m Aisha McClellan, cervical cancer coordinator at SHARE. Before the program begins, I’d like to tell you a little bit about SHARE. We are a national nonprofit that supports, educates and empowers anyone who’s been diagnosed with breast for chronic larger cancers and provides outreach to the general public about signs and symptoms.

00:00:22:04 – 00:00:48:14
Unknown
For more information about upcoming webinar support groups and our helpline, please visit our website at sharecancersupport.org Now I’d like to hand it over to Dr. Salani to introduce herself. Hi everyone. My name is Ritu Salani. I’m a gynecologist at UCLA where I’m division director and I’m really passionate about cervical cancer and I lead the NCI Task Force on Cervical Cancer and involved with it and NRG, which is our research trial Cooperative group in Cervix.

00:00:48:16 – 00:01:10:06
Unknown
And I am so thrilled to be here. And I just want to thank Cher for having me and putting on a great resource for our patients and caregivers. Thank you all. Okay, so we have a few questions. So how can understanding the specific genetic or molecular features of my cervical cancer help doctors tailor my treatment plan to be more effective?

00:01:10:08 – 00:01:30:22
Unknown
And what kinds of treatments might be recommended based on these features? Yeah. So cervical cancer is unfortunately one of these cancers where we have an opportunity for primary prevention with the HPV vaccine because that’s kind of its root cause. And I think it’s important that we talk about vaccination and also screening, which can detect cervical cancer, cervical dysplasia in earlier stages.

00:01:30:24 – 00:01:50:05
Unknown
Now, unfortunately, many patients may not have access to this or even despite access, may still develop cervical cancer. And there’s a couple of things that are really important to understand about how cervical cancer is treated and how factors may inform that treatment. So first, it’s going to be stage and so imaging is going to be a really important part.

00:01:50:05 – 00:02:06:04
Unknown
Imaging and examination are going to be a really important part of assessing kind of the disease stage. And I’m going to speak a little bit off turn here, but just, you know, a lot of people are just like, just cut it out or just do surgery. And unfortunately, that’s not always the case for cervical cancer, where surgery may actually be more harmful.

00:02:06:06 – 00:02:27:16
Unknown
So understanding the exact stage of your disease and imaging examination will help with that. But then also kind of understanding what that treatment means and why that treatment is important. You want to do things are going to enhance your outcome or give you the best outcome without causing harm or even delaying treatment. When it comes to genetics or molecular features, there’s a couple of things that would be important.

00:02:27:18 – 00:02:53:15
Unknown
One is the HPV status. Not all, but most cervical cancers are HPV positive, and there are different strains of HPV. Now, this may just be kind of more informative at this time, but there are targets being developed, particularly for HPV 16, which is the most common type of HPV infection that occurs with cervical cancer. And so knowing what your tumor kind of pathogenesis or causes can be informative.

00:02:53:17 – 00:03:11:24
Unknown
There are other molecular characteristics in cervical cancer, but we haven’t quite figured out what to do with them just yet. And probably the one that’s most important. We’ll talk a little bit more about it kind of as we get in more advanced stages. Is PD-L1 status or what we translate to what’s called a combined positive score or CPC.

00:03:12:01 – 00:03:41:01
Unknown
And this can help inform the role of immunotherapy in advanced settings, in locally advanced settings like patients who may need chemo and radiation. This may still play immunotherapy may still play a role, but the marker may not be as important because most patients actually carry it or their tumor carries it. I should say grades. What are some of the latest tests or biomarkers that doctors use to predict how well cervical cancer treatment might work for me?

00:03:41:07 – 00:03:58:14
Unknown
And how do these tests help improve my treatment outcomes and quality of life? Well, we always want to find the treatment that’s going to kind of enhance the best outcome without causing toxicities. And this is still a challenge. So I mentioned PD-L1 status. This is a immune marker and it kind of lets us know if immunotherapy will be effective.

00:03:58:16 – 00:04:32:00
Unknown
Most patients do. Most patients tumors do carry this PD-L1 expression. And so immunotherapy can really play a key role. Now, that being said, there are other biomarkers or markers that we may see. I mentioned HPV 16 as a potential target. There are a lot of other biomarkers that are continuing to be explored. And so the really key thing about that is you may be a candidate for a clinical trial based on your biomarker and may have access to a treatment that may be the future of cervical cancer care, but it’s still being understood or explored further to determine if that’s the case.

00:04:32:02 – 00:04:56:00
Unknown
This may include things like Trope two, Trope two, which is kind of something that we’re studying now. We think that based on preliminary studies, it looks like most patients also have this expression, but the rate of expression may be important. So if you’re a high expression versus a medium versus a low and same thing with PD-L1 status, we’re kind of seeing that same high low expression kind of being teased out a little further.

00:04:56:02 – 00:05:18:06
Unknown
There are other markers like tissue factor, which also, you know, fortunately, most cervical cancer tumors express this and it makes it really ripe for multiple targets that are being approved nowadays. There are some other interesting targets that I think we just don’t understand if they’re really driver mutations. And what I mean by that is just because a tumor has those mutations, it doesn’t mean it’s important.

00:05:18:06 – 00:05:51:01
Unknown
It just may be like a like a, you know, pre freeloader mutation just hanging around. And this might include things like PIK three Pi, K3 BRCA, as a matter of fact, which is commonly seen in ovarian cancer or breast cancers. We see these mutations, but we just don’t know if they’re important or not. And so understanding this, you know, participating in clinical trials or, you know, doing lab work and understanding the true kind of driver sense of these is going to be important.

00:05:51:03 – 00:06:11:04
Unknown
What are some ways to detect cervical cancer early? So this is so important. You know, one, getting the HPV vaccine and we recommend this really kind of in the pre-teen ages, so 11 and 12 being the most prime time. But it’s that HPV vaccine is FDA approved up to 9 to 45 years. So that’s probably the most important way.

00:06:11:04 – 00:06:29:23
Unknown
But getting PAP testing, HPV testing is really important. And there’s data that shows that even one PAP HPV test in your lifetime can actually reduce the risk of cervical cancer development. It’s not a perfect test, though, and we know that there may be errors in interpretation or kind of, you know, false negatives, if you will, when the test is done.

00:06:29:23 – 00:06:54:00
Unknown
It doesn’t show anything but just didn’t detect it. Now, HPV testing can enhance that where the virus is shut it, you know, shedding. And that can be detected even kind of with a little bit more accuracy than the cell itself. But that’s really the key. And so it’s really important whether you’ve had the vaccine or not, whether you think you’re high risk or not, to get that kind of routine testing and assessment data has shown that we don’t have to do it every year.

00:06:54:00 – 00:07:10:20
Unknown
When I was first starting out, we used to do this every year and we were probably, you know, creating a lot of anxiety, unnecessary testing and unfortunately unnecessary interventions because of what we thought were abnormal results, which were really kind of self-contained. But now we are doing it kind of, you know, if you have normal results every 3 to 5 years.

00:07:10:20 – 00:07:29:07
Unknown
And I think this is kind of minimizing some of that anxiety and cost associated with it. But you have to remember, and when you’re not doing something yearly, even yearly, it’s hard to remember. But, you know, when you’re doing something once every five years, it can kind of slip. You slip off your radar. So make sure you ask about it every time for getting your mammograms or colonoscopies and other testing.

00:07:29:11 – 00:07:50:05
Unknown
You know, just ask your doctor, hey, am I do for my pap test? And they might tell you, no, you have another couple of years. But missing that is a is a really lost opportunity for me especially, you know, it doesn’t matter which doctor it is. It doesn’t have to be your gynecologic, your gynecologist. It can be any doctor who can tell you if you’re up to date on your pap testing or not.

00:07:50:07 – 00:08:13:01
Unknown
Yes, very, very good point. Are there specific biomarkers that are being researched which might provide new options for treatment in the future? And how might these discoveries impact my current or future treatment plan? So this is a really exciting area. You know, cervical cancer research was kind of at a low level over the last 15 years, but then all of a sudden there’s been an explosion and a really great interest in it.

00:08:13:03 – 00:08:32:08
Unknown
And there’s a couple of reasons why. One, the Tcga, which is kind of like the genome analysis, where they do kind of a gene assessment of cervical cancers to look for mutations came out just about ten years ago, not quite, but close to. And so this is really kind of helped shape our understanding of how we can better treat cervical cancer.

00:08:32:10 – 00:08:52:11
Unknown
And one of the things that came out of that is the immune therapy, which has really revolutionized the management of cervical cancer. And so what they’ve found is that there are some amplifications of immune targets in most cervical cancers. And this May and and we know it’s caused by an infectious agent. So targeting the immune system actually really is logical in this setting.

00:08:52:13 – 00:09:16:12
Unknown
And so, you know, studies were done and it we actually improved patients who have front line metastatic disease so cancer that spread from the cervix to other areas, adding immunotherapy actually improves survival progression free survival meaning how long live you lung, how long you live without the disease and how long you live overall. And this is really a huge advance because we really hadn’t seen this in in quite some time.

00:09:16:14 – 00:09:38:19
Unknown
The other really cool thing was it didn’t harm patients quality of life. As a matter of fact, patients had maintained an excellent quality of life despite getting another therapy. Then what we did is we looked at immunotherapy added to chemo radiation. So kind of in that even earlier front line setting. And we found that that also made an impact in how long patients will live without the disease recovery.

00:09:38:21 – 00:09:58:17
Unknown
And these are really two big advances, but they’re not enough because until we say we’ve cured it, we have to keep working. And so now looking at other combinations of options of therapies, whether it’s immunotherapy combinations, we have a new drug called a certain rapid Dalton, which has new FDA approval. It’s also known as TiVo Tak, and that’s used in second line.

00:09:58:17 – 00:10:26:07
Unknown
But there are some provocative studies of combining that with immunotherapy. And then, you know, HER2 expression is also something that’s been studied. I’ve mentioned the PD-L1 and HPV, but there’s a lot of patients who have HER2 expression that can be even independent of HPV positivity or a cause. And HER2 is really we don’t know the exact rate. It’s not the most common finding in cervical cancer when I’m talking about her to expression.

00:10:26:07 – 00:10:47:20
Unknown
So this is tested on your tumor, but there is a target for it. And in a study we saw really provocative and exciting results using a HER2 antibody drug conjugate in cervical cancer, which was actually better than what we’ve seen across the board. So if you are one of those patients who has that mutation, excuse the expression, it’s something to really talk to your doctor about.

00:10:48:01 – 00:11:12:00
Unknown
So, you know, PD-L1 expression, looking at immunotherapy, HER2 expression, looking at maybe trastuzumab drugs can I mentioned earlier trope two and this is a study that we’re actually just opening up now. So if you have recurrent cervical cancer and you’re looking for trial opportunities, this is something that would be a very interesting option. Most patients have it, but the rate of expression may be important.

00:11:12:00 – 00:11:34:24
Unknown
So kind of looking at low, medium and high and understanding how patients respond to this, I mentioned tissue factor two. So to map Dothan is another area. We don’t test for tissue factor because it’s almost 100% expressed, but it’s also a very interesting option. And then new studies looking at things like NEC did for which is a common target and bladder cancer is also being explored.

00:11:35:01 – 00:11:53:05
Unknown
And this is just the tip of the iceberg. There are lots of other avenues that are kind of being researched, maybe not ready for primetime or even the bedside or clinical trials just yet, but continue to be explored in the lab or the bench setting to look at more opportunities for our patients. there’s one other thing I want to mention.

00:11:53:05 – 00:12:18:18
Unknown
Sorry, I know, but the other thing is the HPV 16 target. So HPV 16 is a common cause. HPV is a common cause, and 16 being one of the more common viruses and looking at vaccine options to target patients with cervical cancer. This has been really exciting and preliminary. And so it’s being further developed, kind of finding the right target group, whether it’s in the recurrent setting or even earlier, is really, really cutting edge.

00:12:18:18 – 00:12:47:20
Unknown
So I think it’s also another exciting area. Now, this super exciting. How often should I expect to have biomarker tests done during my treatment and how will the results of these tests influence my decisions? And influence the decisions of my health care team will make about my care? So these are all fantastic questions. And I think one of the most important things before I answer the question is actually talk to your doctor about what what the testing they’ve done on your tumor and understand it.

00:12:47:20 – 00:13:06:04
Unknown
So, you know, they might say, you have a squamous cell carcinoma or you have an adenocarcinoma that’s a type of cancer. But ask, is it HPV positive? And if it is, they may be able to tell you what type. It’s not always tested. And what other testing have you done in my tumor? What’s my PD-L1 expression or my Cp’s asked this and understand what that may mean.

00:13:06:04 – 00:13:29:00
Unknown
Am I can it for immunotherapy? Why or why not? And then, you know, thinking about biomarker testing, it’s not done routinely. And so biomarker testing we typically are doing on the tumor. So unless there’s a change in the tumor or you’re having a repeat biopsy, the role of repeat biomarker testing is not right. Really clear just yet. Now, as we get more information, there may be new tests that we want to test.

00:13:29:00 – 00:13:50:23
Unknown
So it may not be repeat testing, but adding new testing onto it. So, for instance, if you had cervical cancer five years ago, they may not have done PD-L1 testing. And so this might be something if your cancer comes back, hey, what tumor testing can we do? So know your tumor testing and write it down because you won’t remember and then write down notes on what that actually may represent.

00:13:51:00 – 00:14:13:20
Unknown
Now, there are some other biomarkers that are being explored, and one of the really interesting things is CTE, DNA or CTE. HPV DNA. CTE is circulating tumor. And so what this is, is a blood test to see if you have tumor circulating in your bloodstream. And that might actually tell us if your treatment was effective. We would expect a clearance or if we see signs of recurrence.

00:14:13:20 – 00:14:35:23
Unknown
Now, this is still being explored. We don’t quite understand what the role is in today’s treatment landscape, but it’s being studied. And how great would it be as if you could have a blood test to see if your cancer have responded or if your cancer may be at risk for a higher risk for coming back? And that might inform how we how closely we monitor you or if we initiate when, if and when we initiate treatment for recurrent disease.

00:14:36:00 – 00:14:57:16
Unknown
And so it’s it’s still pretty early, but I think it’s a really exciting avenue for for patients to have another way to kind of monitor their cancer. I’m not ready yet, but, you know, I think I not ready to get the test today. I know circulating tumor DNA, I think is going to really help inform monitoring patients. That sounds amazing.

00:14:57:18 – 00:15:22:03
Unknown
I love it. It sounds like there’s been so many advancements. It’s really exciting. It really is. So what are some key what are some of the main takeaways about this that you would like patients to know? So I think, you know, we’ve had this like really great explosion of New data in cervical cancer, and this is a testament to patients enrolling in clinical trials, which has really helped advance the field, which is pretty, you know, stagnant for about 20 years.

00:15:22:03 – 00:15:43:20
Unknown
And now all of a sudden we’ve had this great explosion and it continues in a good way. Not every test is not every new drug is going to be positive, but I think it’s worth exploring. And we need to learn how to move, how to move the treatment landscape forward in a way that improves outcomes. Is it financially debilitating and is it is it toxic?

00:15:43:20 – 00:16:06:17
Unknown
Meaning, does it impact quality of life? Because as you know, many of these patients are very young. And so we want to make sure that we are able to not only improve quantity of life, but really enhance quality of life. And then I think the other thing to think about is, you know, if you’re watching this, you may actually know or have cervical cancer and we need to reach the patients or the people who don’t.

00:16:06:19 – 00:16:36:16
Unknown
And so talk to your friends and family about getting screening for cervical cancer, getting your kids, grandkids, you know, yourselves, vaccinated, you qualify. I think really primary prevention, preventing the disease or secondary prevention, which is catching the disease before it becomes cancer, is so much better than treatment. And any time we do that, that is a win. So, you know, I always joke like the best thing I could do is put myself out of business and I would be totally fine with that because that means we’ve cured these cancers and we have a long way to go.

00:16:36:18 – 00:16:58:03
Unknown
But starting with kind of grassroots people listening, share it with friends, colleagues and, you know, oftentimes people think cervical cancer is kind of a shameful disease because of the HPV exposure. And it’s not you know, 80% of people are expected to have HPV in their lifetime. And the less we talk about it, the more it’s going to linger.

00:16:58:05 – 00:17:23:03
Unknown
And so I think it’s important we are vocal about it. We are, you know, just raising awareness like this program is and advocating for ourselves, clinical trials, research, understanding, biomarkers, all of these things are the right things to do. Wonderful. my gosh. Thank you so much. You’ve jam jampacked so much in 15 minutes. We really appreciate it.

00:17:23:05 – 00:17:45:03
Unknown
I’ve learned a lot. I a whole page of notes here. Thank you so much. We really appreciate you. Please make sure to check out Cher’s upcoming educational programs and support groups and follow us on social media. This concludes the program today. Thank you. Thanks for having me. And thank you all. Bye bye.