Melanie Cole, MS (Host): Welcome to AHN Med Talks, an informative resource for physicians across various specialties as we delve into the latest medical insights and best practices, ensuring you stay at the forefront of your field. I'm Melanie Cole. And today, we're highlighting vulvar dysplasia and when it could be cancerous.

Joining me is Dr. Christopher Morse. He's a gynecologic oncologist with the AHN Cancer Institute at West Penn Hospital. Dr. Morse, thank you so much for joining us today. When we talk about vulvar dysplasia today, what spectrum of disease are we really referring to? How has the terminology evolved in recent years? And why do we think it remains underrecognized, both by patients and at times by clinicians?

Dr. Christopher Morse: Thank you so much for having me today, Melanie. I think vulvar dysplasia is one of those conditions that can often be overlooked. It is not extremely common, but it does have some common symptoms that patients might report to either their gynecologist or perhaps their primary care physician.

But a lot of these symptoms might get misdiagnosed or misclassified as perhaps a urinary tract infection if the patient's complaining of discomfort with urination. But the most important thing is that primary care doctors or gynecologists listen to their patients and perform an exam and, if there's anything visually abnormal, do a biopsy.

Melanie Cole, MS: So then, walk us through, Dr. Morse, the two main pathways of vulvar dysplasia. There's HPV-associated versus non-HPV. Why does that distinction matter clinically when you're making this diagnosis?

Dr. Christopher Morse: So, there's a couple important characteristics or distinctions to make when thinking about vulvar dysplasia. The majority of vulvar dysplasia is HPV-mediated. And we think of those HPV-mediated vulvar dysplasias into two categories, one being low-grade vulvar dysplasia, and the other being high grade.

Typically, low-grade vulvar dysplasia, which is HPV-mediated, is not thought to be pre-malignant, meaning we don't think that, over time, it will become a vulvar cancer, which ultimately is what we're trying to prevent from happening. High-grade vulvar dysplasia, which is also HPV-mediated, is something that, without treatment, over time, can progress to become a vulvar cancer.

In contrast to high and low-grade vulvar dysplasia that is HPV-mediated, we also have a entity called differentiated vulvar dysplasia or differentiated VIN. And that is actually not typically associated with HPV infection and is more commonly associated with underlying vulvar dermatologic conditions such as lichen sclerosus most commonly.

Melanie Cole, MS: So when clinicians see their patients, which patient populations, Dr. Morse, should immediately raise those red flags for progression risk, and why? Tell us a little bit about patients and what are they looking for.

Dr. Christopher Morse: So, one of the first things that we can think about is, in patients who have HPV-related vulvar dysplasia, they tend to be younger. So typically, more in the mid-40s, perhaps early 50s. And classically, those patients are going to present with either a symptom, like a new lesion that they feel they might have itching, burning with urination are common symptoms, or they might report bleeding as well. Those patients are also going to have risk factors for HPV acquisition, such as cigarette smoking, immunosuppression perhaps, or they might have a history of either prior vulvar dysplasia or cervical dysplasia. And so, those are characteristics that we would see in that patient population. In contrast to that, patients who might have differentiated VIN are typically older, and this is not HPV-associated. And so, these patients might have a long history of untreated lichen sclerosus. And those would be risk factors that you would be asking for in this patient population.

At the end of the day, the symptoms that they might present with or report might be the same. And ultimately, a tissue diagnosis or a biopsy is going to be required to kind of sort it all out.

Melanie Cole, MS: Okay. And this is really interesting and not something that every clinician knows about what you're discussing here today. So, what histologic or clinical features would suggest that it may be progressing? If you have diagnosed a patient that it may be progressing towards an invasive cancer, are there specific symptoms that you'd like to mention to other providers, can't-miss signals for malignancy?

Dr. Christopher Morse: Ultimately, the biopsy will be what confirms the diagnosis of either dysplasia or malignancy? Certainly if a patient has a longstanding history of vulvar dysplasia that's gone either undiagnosed or untreated, if the patient has a large lesion on clinical examination that is firm with irregular borders or is bleeding, those would all be things that would make me more concerned that the biopsy might ultimately reveal a malignancy.

Melanie Cole, MS: Along those lines then, Dr. Morse, so how aggressive should clinicians be with biopsy? Do you have some guidance that you could give for when watchful waiting might no longer be appropriate? Are there areas of the vulva that are more likely to harbor malignancy and therefore warrant a lower threshold for biopsy?

Dr. Christopher Morse: I would say, at the end of the day, if a patient has a new lesion or a persistent symptom that can't be explained, I would recommend that clinicians have a very low threshold for performing a biopsy because, ultimately, the biopsy will help guide further therapy and will either prove or demonstrate that the lesion is benign, with no evidence of dysplasia or malignancy, or it'll confirm the underlying suspicion that this is a dysplastic or malignant lesion. And then, the patient can be referred for the appropriate treatment after having a confirmed tissue diagnosis. So if there's ever uncertainty, I always recommend, or if I'm seeing the patient, I always would perform a biopsy.

Melanie Cole, MS: Well, thank you for clearing that up about the threshold. So, how often do you see cancer present in patients who might be previously thought to have stable or lower grade disease?

Dr. Christopher Morse: So certainly, when you do a biopsy, sometimes the pathologist might suggest that there is either a cancer present or concern for malignancy. And then, the other thing is that when you treat vulvar dysplasia, and oftentimes this is treated with surgical excision. There's always the risk of, on your final pathology, detecting an occult cancer within the final specimen, and that's probably in the range of 5-10%.

Melanie Cole, MS: Now, let's talk about therapies available. Tell us what's going on in your field. As, you know, you're always getting more tools in your toolbox, so speak a little bit about the trade-offs between oncologic safety and preservation of vulvar anatomy and function. And individualized treatments, topical therapy, surgical excision, surveillance, speak about all the treatment options available.

Dr. Christopher Morse: Yeah. So when we think about how to treat vulvar dysplasia, you know, certainly, the first and foremost goal is to prevent progression to malignancy. So, starting with low-grade vulvar dysplasia, we don't typically think that this becomes malignant. So often, as long as the patient's not symptomatic, we can recommend observation alone.

If we then think about high-grade vulvar dysplasia, high-grade vulvar dysplasia does have the potential of becoming malignant over time if untreated. So essentially, we think of three different treatment options. One is surgical excision. The second would be ablative therapy with something called CO2 laser ablation. And then, the third would be topical therapy with something called imiquimod.

And when we think about which patient we recommend which treatment for, some important factors or considerations that we might take in mind are the location of the dysplasia, whether it's close to critical structures such as the clitoris, the urethra, or the anus that might be impacted if you were to do surgery, whether there's just a single lesion or whether there's multiple lesions, because the more potential sites that you would have to resect could impact the patient's vulvar anatomy, whether the patient's an appropriate surgical candidate, and then whether or not you're worried that there might be an underlying malignancy. Certainly, if there's ever a concern or a worry that there might be an underlying malignancy, either because of the pathology report or your visual clinical exam of the lesion, then surgical excision is always favored and recommended if feasible.

And finally, with differentiated VIN, there's a higher rate that there might be either a malignancy or progression over time to malignancy. So generally, with differentiated VIN, we typically recommend in that situation moving forward with surgical excision.

Melanie Cole, MS: So when we think of vulvar dysplasia, this disease, any vulvar disease carries a unique emotional and sexual burden, Dr. Morse. How do you address this in clinical practice with your patients so that shared decision-making is how you come up with your treatment modalities?

Dr. Christopher Morse: Yeah. So, important when you're discussing with the patient potential options is asking them whether or not they're sexually active. For some of our older patients who are no longer sexually active, some of the considerations in terms of areas that you may or may not have to resect would become more or less impactful in the decision-making.

But certainly, making sure that you're having an informed discussion with the patient to explore these things as it might impact your decision for surgery or maybe avoiding surgery if certain structures like the clitoris might be impacted and leaning towards a more ablative therapy, like CO2 laser ablation or even a topical therapy like imiquimod.

Melanie Cole, MS: We are hearing more about the HPV vaccination. It's been around a while now. Dr. Morris, how is that impacting vulvar dysplasia and cancer? Are we fully leveraging its benefits? Do you see a connection there? Tell us about the vaccination itself.

Dr. Christopher Morse: So currently, in the United States, the HPV vaccine is targeted against nine different strains of HPV, many of the ones that do cause underlying cervical and vulvar cancer. So, over time, as the uptake of the HPV vaccination increases, we are seeing decreasing rates of both vulvar and cervical dysplasia and malignancy. So, I think, with time and with increased uptake, we are seeing the change over time.

Other things that we can also discuss with our patients are things like smoking cessation, which is very important in patient's ability to clear HPV infection. So, all these things are things that we're discussing with the patient. And oftentimes when we see the patient, initially, we're focusing on the surgical decision-making or the treatment options. But when we get them through their course of, say, seeing them for their postoperative visit, we're making sure that they've received the HP vaccine or. If they haven't and are still eligible for it, making sure that they receive it. And then, also, going over important things like the importance of smoking cessation.

Melanie Cole, MS: Yeah. These are all important points, Dr. Morris. As we wrap up, what's the single most important takeaway that you'd like other clinicians to remember when deciding whether vulvar dysplasia could be cancerous? If you could change one thing about how it's recognized or treated, what would that be and what's that key takeaway?

Dr. Christopher Morse: Yeah. I would say that the key takeaway is that, you know, when patients present with new symptoms or there's a lesion on exam that doesn't have a clear diagnosis, when in doubt, perform a vulvar biopsy to get a tissue diagnosis or refer to your gynecologist or GYN oncologist to help with treatment decision-making. And then, any unexplained symptom, even in the absence of a visible lesion would warrant a biopsy so you can establish the tissue diagnosis and have the patient get the appropriate treatment.

Melanie Cole, MS: You've given us really great straightforward information for other clinicians. Really a lot to think about. Thank you so much, Dr. Morse, for joining us today and to learn more or to refer your patient to Dr. Morse, please call 844-MD-REFER, or you can visit findcare.ahn.org. Thank you so much for listening to this edition of AHN Med Talks with the Allegheny Health Network. I'm Melanie Cole.