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Ethan Lowder, BA, is an MD student Harvard Medical School.

Ethan Lowder, BA, and Alexander Nagrebetsky, MD, MSc, reported that nearly 80% of children fast longer than recommended before surgery.

Experts say most children fast too long before surgery

Articles

She joined the MJH Life Sciences team in December 2019. She graduated from Youngstown State University in 2019 with a bachelor's degree in journalism and a minor in political science. Prior to graduating, Morgan worked as the editor-in-chief of her college newspaper. She went on to work as an assignment editor at a broadcast news station in Youngstown, Ohio, before joining 

 You can reach her at mebert@mjhlifesciences.com.

Women with prior cesarean delivery are more likely to experience severe pain, sleep disturbances, and daily activity disruption postpartum.

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The Menopause Society’s 2025 meeting heads to Orlando with sessions on longevity, hormones, cognition, and care innovation at midlife and beyond.

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Sheth is Associate Professor, Obstetrics, Gynecology and Reproductive Sciences; Associate Medical Director & Director of Colposcopy and Cervical Dysplasia, Women's Center, at Yale New Haven Hospital. 

On this episode of Pap Talk, Sangini Sheth, MD, MPH discusses the latest research in cervical cancer and HPV. 

S3E2: HPV and cervical cancer with Sangini Sheth, MD, MPH

Black women at risk for endometrial cancer favor biopsy-first approaches when provided education, trust, and shared decision-making.

Early biopsy may improve endometrial cancer detection among symptomatic Black women

Women with a history of cervical cancer face nearly double the risk of anal cancer, highlighting the need for tailored screening guidelines.

Cervical cancer linked to increased anal cancer risk

Counties with persistently low cervical cancer screening rates have nearly double the rates of late-stage diagnoses and mortality, study finds.

Lower cervical cancer screening rates linked to higher late-stage diagnoses and mortality

A new study shows that a self-collected cervical cancer screening device is highly accurate, easy to use, and preferred over clinician collection.

Benefits found for self-collected cervical cancer screening

A comparison of 4 ultrasound-based algorithms demonstrated strong performance, with nuanced implications for clinical practice, according to a new study presented at the 2025 ACOG ACSM.

Evaluating diagnostic tools for adnexal masses in novice hands

Ovarian cancer

Jesus Gonzalez Bosquet, MD, PhD, associate professor of obstetrics and gynecology at The University of Iowa, highlighted the efficacy of a machine learning model using blood-based biomarkers to identify ovarian cancer.

Ovarian cancer remains one of the most difficult gynecologic cancers to detect early, and this significantly impacts patient survival outcomes. According to Gonzalez Bosquet, the primary challenge is the lack of effective early screening or detection methods. Current tools, such as ultrasound and tumor markers, have been tested in multiple studies in the United States and abroad, but none have demonstrated consistent accuracy. 

As a result, most patients are diagnosed at advanced stages, when treatment options are limited and survival rates drop significantly. Gonzalez Bosquet noted that 5-year survival rates for early-stage ovarian cancer reach approximately 95%, but this falls between 40% and 50% for patients diagnosed at later stages, underscoring the need for earlier detection strategies.

To address this gap, Gonzalez Bosquet and his team have explored the use of machine learning models to identify ovarian cancer through blood-based biomarkers. Their work focuses on detecting methylated DNA fragments shed by tumors into the bloodstream. Starting with a platform that examined more than 850,000 methylation probes, the researchers used machine learning to narrow the list down to 9 probes that showed strong potential for accurately identifying ovarian cancer. While promising, these findings are still in the pilot phase and require further validation before they can be used in clinical settings.

According to Gonzalez Bosquet, the next step in this research is to confirm whether these methylated probes can be reliably detected in blood samples, not just in surgical tissue specimens. He that his team, in collaboration with Mayo Clinic, has submitted a project aimed at this validation step. If successful, the model will need to be tested in large-scale screening studies involving both patients with and without ovarian cancer to determine its true diagnostic accuracy and clinical value.

Looking ahead, Gonzalez Bosquet envisions practical applications of these artificial intelligence (AI) models that would make them accessible to clinicians worldwide. Once fully developed, the models could be hosted on web-based platforms, allowing physicians to upload data such as imaging scans or blood test results. The system would then provide a risk assessment, ranging from low to high probability of ovarian cancer. This streamlined, user-friendly approach could integrate seamlessly into clinical workflows, offering physicians a powerful tool for earlier and more accurate cancer detection.

Ultimately, Gonzalez Bosquet emphasized that while the technology is still under development, AI-driven models hold great promise in transforming ovarian cancer diagnosis, potentially improving survival rates by identifying the disease before it reaches advanced stages.

Gonzalez Bosquet J, Wagner VM, Russo D, et al. Identifying ovarian cancer with machine learning DNA methylation pattern analysis. 

2025;15(1):20910. doi:10.1038/s41598-025-05460-9

Jesus Gonzalez Bosquet, MD, PhD, discusses how machine learning could improve early ovarian cancer diagnosis by identifying methylated DNA in blood.

Jesus Gonzalez Bosquet, MD, PhD, highlights test for earlier ovarian cancer detection

Miami Cancer Institute's onco-fertility program

Fertility counseling for oncology patients

In a recent interview, Elina Melik-Levine, advanced registered nurse practitioner at Miami Cancer Institute, discussed fertility preservation among patients diagnosed with cancer.

According to Melik-Levine, when cancer treatment is prescribed to patients, providers should discuss options for fertility preservation with their patients. All patients must sign an informed consent forum when receiving cancer treatment, and the forum will always include a paragraph about fertility.

Providers can refer patients with additional fertility-related questions to a fertility doctor or directly to the Miami Cancer Institute, where they will not have to wait long to receive fertility consultation. Since some patients may choose not to seek fertility treatment, they should be referred to an in-house doctor before an outside doctor who may not know what to expect.

There are also socioeconomic factors to consider when recommending fertility care. Fertility coverage is unavailable to most patients in Florida, including care for personal choice and in the setting of cancer treatment. This can lead to difficult conversations between providers and patients.

Fortunately, there are organizations that help ease the financial burden among patients seeking fertility care. These centers help patients obtain grants, loans, and subsidiaries necessary to receive care. Additionally, insurance of fertility coverage among cancer patients has improved over time, indicating improving legislation.

Melik-Levine also discussed Miami Cancer Institute’s onco-fertility program. The goal of the program is for an oncologist to identify when a patient they are seeing for the first time being prescribed cancer treatment is of reproductive age or has expressed an interesting in fertility discussion.

Following this discussion, the provider should refer the patient to the onco-fertility program. This will allow staff such as Melik-Levine to reach out to patients as soon as possible, which is vital since fertility treatment can take 1 to 2 weeks. Patients can also receive a tailored education program discussing their potential care.

Elina Melik-Levine, ARNP, highlights the importance of early discussions about fertility preservation, referral pathways, and addressing socioeconomic challenges in cancer care, emphasizing the role of Miami Cancer Institute's onco-fertility program.

Hi, I'm Celeste Krewson with Contemporary OB/GYN and I'm here with Dr. Minneci to discuss a recent study evaluating an algorithm for identifying benign lesions. Do you want to introduce yourself?

Sure, I'm Peter Minneci, I'm the chair of surgery at Nemours Children's Health Delaware Valley and the lead author on the study.

So, to get started, can you give a brief overview on how benign ovarian masses impact children and adolescents?

Yes. So, ovarian masses can occur in young females and then throughout their life, and the biggest issue is determining whether those masses are benign or malignant. And in children and adolescents, the masses are 90% of the time going to be benign, whereas in adults, they're much more likely to be malignant. So, having a way to identify children and adolescents with ovarian masses and to identify the probability or the likelihood that it's going to be benign, then allows us to do the type of surgery we call an ovary sparing surgery where rather than take the entire ovary out, we can just take out the mass itself and leave the rest of the ovary in place. Which then, is very important because removing ovaries unnecessarily can have sort of lifelong consequences as these children then grow up into adulthood.

And can you expand on these consequences?

Sure. So, an unnecessary oophorectomy, so taking out an ovary that maybe didn't need to come out or losing an ovary pretty much for any reason, can lead to early menopause and premature ovarian failure. And it's the premature ovarian failure which is really critical because the ovaries do more than just reproductive health, they protect women against heart disease, neurologic diseases. So, if you take out an ovary unnecessarily, you can have impaired sexual health, you can have earlier menopause, you have higher rates of neurologic disease and cardiovascular disease, because the hormones that the ovaries present protect against that. You also have reproductive health, you can have harder rates of getting pregnant, and then actually worse responses to in vitro fertilization. And then the hidden risk is if you actually have an ovary taken out early on in life, there's a 10% to 20% chance that another ovarian mass would develop in the other ovary and if it isn't a liquid, then it would have to come out. So essentially, you would have surgical castration at that point.

Thank you for going over that, that definitely makes detection of benign lesions important. So how does this new algorithm identify benign lesions.

So, what it does is it basically takes the way the patient presents, so their symptoms, their radiologic imaging findings, and their laboratory tests, and helps us categorize them in a way so that if certain symptoms aren't there, and the mask looks very specific ways, and the laboratory values are not abnormal, we know that that particular lesion has a very high likelihood of being benign. And it allows the practicing surgeon who's at the bedside to say —quickly kind of following this algorithm —this is likely to be benign, I can do an ovary sparing surgery. And then it also is very sensitive to picking up any lesion that has an increased risk of potentially being malignant. And so, what the algorithm does is if you have an abnormal finding, that puts you into the other part of the algorithm, the high risk algorithm, triage is huge, what we would call a multidisciplinary team discussion, which is that we would, if you have one of these features that increases the risk, then a team of doctors would talk about your case and decide whether you should have the whole ovary out or whether ovary sparing surgery is still reasonable because the likelihood of malignancy is lower. And then the overall impact of the algorithm that we hope is it decreases variability in the care that we were seeing. We were seeing what we would call unnecessary oophorectomy rates for benign disease anywhere from 15% to 75% across institutions. We want to remove that variability and try to standardize it in a way that those who are safer ovary sparing surgery can be quickly identified, and someone who has something that's concerning, would get triaged to a multidisciplinary team discussion with surgeons, gynecologist, medical oncologist, radiologists to look a little more in depth at how they presented, and then determine should they have the ovary out or is it still reasonable to do an ovary sparing surgery?

That's all really interesting, thank you. We're just about ready to wrap up but is there anything you want to add first?

No, I think the biggest thing that I was surprised by with the study and that I was happy with is the real teamwork and collaboration between our different specialties. So, between surgery and gynecology and radiology and medical oncology, and that the algorithm was actually very well followed. It was 95% compliance, which meant that was pretty easy for the practitioners to use.

Well, thank you again for joining me today.

Peter Minneci, MD, MHSc, discusses a study evaluating a new algorithm capable of accurately identifying benign lesions in female patients.

New algorithm to identify benign lesions developed

I'm Dr. Anne Banfield. I currently am the physician, clinical, and administrative director for MedStar St. Mary's Hospital in Southern Maryland. I am currently serving as the ACOG representative on the American Cancer Society's Cervical Cancer Primary HPV Screening Provider Workgroup Roundtable. And my colleagues and I will be presenting on primary HPV screening for cervical cancer this Sunday at the American College of Obstetricians and Gynecologists Annual Clinical and Scientific Meeting.

What were some of the highlights from your presentation at ACOG?

So the American Cancer Society, in conjunction with the US government, put together a roundtable on using primary HPV for cervical cancer screening. About a year and a half ago, they did invite the American College of Obstetricians and Gynecologists along with other stakeholders to be part of that roundtable. And there are multiple workgroups associated with that. Our workgroup in particular is about provider needs. And so we're really working on helping providers have the tools that they need to understand why we're recommending primary HPV screening for cervical cancer, and how they can communicate that to their patients and to colleagues who maybe are not familiar with that concept.

Do you have any clinical pearls for talking to patients about primary HPV screening?

As far as talking to your patients about primary HPV screening for cervical cancer, we really want providers to focus on the efficacy of the test, and how good HPV is and the testing for high risk HPV types at screening our patients and giving us good information about what their long term outcomes can be. Primary HPV screening does give us a lot of information about what we can expect for our patients in the following years. And it allows us to potentially offer that screening to patients who can't make it to an office visit, as we are currently looking at ways for self testing, which opens a whole other door to screening for your patients. So we want our providers to really focus on those sorts of things. As a bonus for providers in the health care system, there is a cost savings associated with going to primary HPV screening, that we don't really want the providers to be focusing on that as a strategy to communicate with their patients.

What are your thoughts on the increasing interest in self-testing for HPV?

So, I think anything that brings access to our patients is a great tool if it can be validated. I currently practice in rural Southern Maryland and prior to this, I practiced in rural West Virginia. Both of those are areas where we don't necessarily have as much accessibility for our patients, to see providers, whether that's a physician or family practice provider, or an AP, as would be ideal. And so if we have tools where those patients can self screen, and have that screening come in in some way to be evaluated, that is an incredible access tool that would then provide and help us to increase the screening for cervical cancer. And we know that cervical cancer screening is nowhere where we'd like it to be. And especially in communities of color. We know it is nowhere near where we where we would like it today.

What are some takeaways from your presentation?

I would say the top takeaways we want folks to see are the efficacy of the testing the way that it can improve potentially accessibility for our patients, and the way that it can be easily integrated now into our systems. What many people don't know is that the platforms that are used to perform the primary HPV screening that are FDA approved, are actually the same platforms that hospitals used to do COVID-19 testing. So many hospitals actually already have the lab infrastructure in place that we can move forward with this testing.

Anne Banfield, MD, discusses the highlights from her presentation on primary HPV screening at the 2023 ACOG Annual Clinical and Scientific Meeting in Baltimore, Maryland. 

The importance of primary HPV screening

Well, thank you so much for joining me today. My name is Morgan Petrocelli with Contemporary OBGYN and Contemporary Pediatrics.

Hi, my name is Dr. Jonathan Miller. I'm a general pediatrician and chief of primary care, pediatrics, at Nemours Children's Health in the Delaware Valley.

Awesome. Well, thank you so much, again, for joining me today. So I kind of want to talk about your abstract that's gonna be presented at the Pediatric Academic Societies. Um, so can you kind of tell me a little bit more about the subject that your abstract is on? And why you chose this topic?

So as a primary care pediatrician, we're really interested in prevention of disease. And one of the diseases that we can prevent now with a vaccine is certain types of cancer that are related to human papillomavirus (HPV). And so we have the HPV vaccine available to us. And it is recommended for all children to get that vaccine, typically at 11 years old. And we are interested in it, it's allowed to be given as early as 9 years. And we're really interested in seeing if we can increase the percentage of our patients that are interested in getting that vaccine and that actually do get that vaccine by trying to start it a little bit earlier, because other folks have had had some success at getting increased uptake of the vaccine when starting at 9 years old. So that's what our project was about.

Can you tell me a little bit more about the results?

Absolutely. So we were looking at two main outcomes. The national HPV vaccine metric specifically looks at what percentage of 13 year old kids are fully vaccinated for HPV. So that was our ultimate goal was looking at 13 year olds. But our project was really about starting the vaccine early. So our initial goal was initiation of the vaccine prior to 11. And when we really when we started this, about 12% of our patients were starting HPV prior to 11 years old. And by the end of our project, which we did over several years, we now have over 42% of our patients starting before 11 years old. So it was a massive increase over what our baseline was. And that led to significant improvements. In the national metric, the 13 year old metric, we started at about 47% of our patients were fully vaccinated for HPV by 13 years old. And by the end of this now we're over 60%. And we're doing better than some national benchmarks. And so we're really proud of this work. And I really do believe that, that early initiation of the vaccine is a major game changer, as far as this is concerned. And that really should, you know, looking forward to thinking about our conclusions. You know, this really should inform the CDC and the Advisory Committee for Immunization Practices recommendations for when we start the vaccines right now, it's recommended to start at 11 years. But you can start it at 9 years, I think these types of studies will eventually lead to us having a recommendation for starting at 9 years.

And what did you find the most interesting about the results?

My primary care network has 20 primary care practices that take care of over 126,000 kids. This is a really large network. And we started with a lot of variability within practices, as well as in providers in how they were recommending the HPV vaccine. In the past, people recommended the vaccine really talking about HPV as a sexually transmitted disease and the implications of that. But now we're really changing to speaking about this as something that's about preventing cancer. And that conversation actually became a little bit easier when you were doing it at 9 and 10 years old than at 11 and 12. Because I think a lot of parents used to say, you know, having this conversation as their child was approaching, you know, sexual activity. And we've sort of been able to take that part out of the conversation, which makes it a little bit more meaningful for parents. I think,

I know you kind of discussed opening up conversation with parents, do you personally have any clinical pearls when it comes to opening up that conversation with parents about getting their children vaccinated against HPV? Especially, a lot of people assume it's just girls who get vaccinated, but it's also available for boys.

Yeah, so this is a vaccine that has been shown to prevent cancer in both men and women. So, it prevents cervical cancer in women, but clearly does a really good job of preventing all types of cancer and throat cancers, for instance, in men are also something that is going to be protected by getting this vaccine. And so what I find is that a lot my patients, they, you know, they have trust in me as their physician, and so that if I have a strong recommendation that their child will really benefit from this, a lot of families are listening to that. And so part of this project was teaching providers to make strong recommendations around this vaccine, to do it at earlier ages, to focus on discussion of cancer. And, we really had excellent results, you know, in making those changes.

And do you have any top takeaways from this abstract that you think people should walk away with when they kind of look at it and digest the information?

Yeah, well, for our practices, one of the changes that we made that was the most successful was updating our electronic medical record, to start to notify us that a child was behind on this vaccine at nine years old instead of 11. And so it was triggering that reminder for all of our providers to say, well, you know, this is a child who's now due for a vaccine where it didn't used to say until 11 years old, that was probably the single biggest factor that allowed us to be successful at doing this. And so, what I would recommend to other pediatricians as they consider something like this, is really think about how you can use your technology to work for you. If you can make those EMR changes, it's going to sort of be built into your system. And that's what leads to change in culture.

Jonathan Miller, MD, pediatrician and chief of primary care, pediatrics, at Nemours Children's Health in the Delaware Valley, spoke about the latest data regarding early HPV vaccination in children as young as 9 at the 2023 Pediatric Academic Societies meeting.

Jonathan Miller, MD, discusses early HPV vaccination in children at PAS 2023

Sarah Crafton, MD, gynecologic oncologist at Allegheny Health Network in Pittsburgh, Pennsylvania, details how sentinel lymph node mapping can help identify the stage of uterine cancers and lead to better patient care.

Sarah Crafton, MD, details how sentinel lymph node mapping can help identify the stage of uterine cancers and lead to better patient care.

A glimpse into sentinel lymph node mapping

Excellent. As we begin to wrap up this conversation, does anybody have any additional comments they'd like to make? Dr Sheth? Dr Hill?

 I ust wanted to comment that we didn't really get a chance to talk about this, but there are, I think, also some studies looking at artificial intelligence and deep learning algorithms to implement some of these technologies that we have for screening; triaging women with HPV related issues is also a kind of an exciting development. Again, we don't have a lot of time to go into it, but a lot of interesting studies are supporting that as a new technology that we can use for helping managing HPV related diseases.

Essentially using visual methods with artificial intelligence trained algorithms?

 Yes, my final thought is we focused a lot today on screening, of course we talked about vaccination, and the final piece is that women who have or people who have abnormal results, a key component of that is the linkage to care to follow up on abnormal results, and I think ultimately the goal of this conversation is to close the gap on cervical cancer or even working towards elimination. The last piece of that is that linkage of care of abnormal results, whatever form of screening, we may be using.

Right, very important points, clearly. Dr Stoler?

 I'd emphasize that last point that the whole purpose of screening is to find the precancer, and if you can't treat the precancer, you're not doing anything with screening. That being said, life is getting a little more complex. We talked about extended genotyping, dual stain, different algorithms. How is the clinician and/or patient supposed to keep this all straight? I think more important than artificial intelligence apply to Pap smears [Papanicolaou tests] as a way of improving the performance of pap smears is the development of information systems and apps like the ASCCP [American Society of Colposcopy and Cervical Pathology] has developed that will essentially allow the app or the program to acquire the data from the patient record. What's the Pap history? What's the HPV test? What's the type? Was dual stain done to then give the clinician more direct guidance? You don't have to remember what the HPV type is. You just need to know whether the patient is safe to get retested in 5 years vs they have to get a colposcopy vs their risk is so high that no matter what the colposcopy shows you might end up treating them anyhow. It's that synthesis of clinical data that we now have so much good data that really says we can more precisely at the individual level synthesize these data and give you a risk that clearly tells the clinician what should happen to the patient. I think we're going to see more and more of that as we go forward because clinicians don't want to really know which test and they don't have time to become necessarily as expert in all the nuances of laboratory testing and data analysis that the data really support.

Excellent. I'd like to thank all of our panel members for a really informative discussion, and I'd like to thank the viewers for watching this 

 viewpoint. If you enjoyed the content please subscribe for the newsletters, E-newsletters, to receive upcoming viewpoints and other great content right into your inbox. Thank you all so much, have a good day.

Drs Emily K. Hill, Sangini S. Sheth, and Mark H. Stoler share practice pearls for HPV and cervical cancer screening and express their hope for emerging testing options.

Key Takeaways for HPV and Cervical Cancer Screening

The other approach to triaging HPV [human papillomavirus] positive women is to do genotyping. I think everyone is aware of the importance of knowing whether a woman is HPV 16 or 18 positive. We already alluded in this conversation about the high rate of cervical cancer precursors in women are HPV 16 positive. It's about 25 of those women will become CIN2 or 3 positive within 3 years of being diagnosed as having HPV 16. What about other genotypes? Some people are discussing extended genotyping which means you would look for other HPV genotypes such as 31 or 35. Dr Hill, are you aware of that data and have any thoughts about it?

 No, I'm sorry I don't know that I have enough expertise to speak on that. I might have to defer to the other panelists.

 I don't know the specific data except to know that there are increasing commercial tests available. I think I just saw something earlier this week that 31 was added to one of the assay journals and I often teach that this is an area that we're going to see change over the course of our clinical careers, the more specific genotyping.

Okay, fair enough. Dr Stoler, you were involved in some of those studies.

 Yes. I think there's more than 1 way to skin this cat, if you want to use that old phrase. The ASCCP [American Society of Colposcopy and Cervical Pathology] has promoted for many years in their guidelines equal management for equal risk. When HPV primary screening was FDA approved, it incorporated partial genotyping, namely HPV 16 and 18 genotyping because of that risk that I've already talked about with particularly HPV 16. If you're HPV 16 positive, you need to get a colposcopy. I don't care what your Pap smear [Papanicolaou test] shows even though Pap smear abnormality will stratify that risk even higher. You have ASC-H and HPV 16. Your risk is so high that you might consider treating the patient without biopsy. What we found out in epidemiological studies over the last 10 years is that the 12 other types that are masked in most of the prior FDA approved assays have differential risks. Just like 16 and 18 have the highest risk, we now know that 31 and 33 in the New Mexico study, (52 if you're in Asia, etc.) have risks that approach the risk of HPV 18. If you're going to take an HPV 18 positive person to colposcopy, why shouldn't you take the HPV 31 positive person to colposcopy? There is an assay on the market today, the Onclarity assay, that has gotten an FDA approval to reveal extended genotyping because it has the capability of unmasking the data that were already there. Other assays don't have that capability, but you can use dual stain to perform equivalently. I think what you're going to see going forward from the NCI [National Cancer Institute] and during guidelines project that's working with practices and manufacturers is that there'll be different ways depending upon which HPV assay is offered in the laboratory to get the right people the colposcopy in their triage step. You might do extended genotyping. You might do dual stain. In some places you might do even a combination, but the point is that not all HPV types are of equal virulence, if you will, in terms of promoting the development of precancer or the rate of transformation to invasive cancer and that we now have that data, so why not use it. I think you're going to see in some practices, HPV extended genotyping where they take into account the other genotypes as a way of improving triage specificity.

Experts in obstetric and gynecologic management provide insight on the role of HPV genotypes in cervical cancer risk.

Role of HPV Genotypes in Cervical Cancer 

As we move to HPV primary screening, the big issue is going to be triage of HPV-positive women. Currently, when we cotest, we use cytology as a triage. If you've got an abnormal cytology, you're managed differently than if you have a negative cytology, depending on whether or not you've got HPV 16 or 18. There are other triage methods which are currently available and under development. One of those is CINtec PLUS which is testing for p16 and Ki-67. P16 is a small molecular way marker for cell cycle progression as is Ki-67. Normal cells will not coexpress p16 and Ki-67 whereas neoplastic cells do. We can use that for cytology as a way of determining whether or not there is a CIN really present or not. Dr Stoler, you were involved in a large study which got FDA approval of CINtec. Can you talk about that?

 The IMPACT trial which led to the FDA approval as well as data retrospectively that you and I have published from the ATHENA study basically looked in the primary HPV screening algorithm at the performance of triage test. Either cytology is a triage at various cut points, ASCUS [squamous cells of undetermined significance] or above, LSIL [low-grade squamous intraepithelial lesion] or above vs dual stain cytology which is performed on the same kind of liquid-based cytology slide but is an immunohistochemical test. What we found in those studies repeatedly is that CINtec PLUS or p16 and Ki-67 dual stain as a scientific name for the procedure outperformed cytology by a significant fraction. Remarkably, it does something that's very rare in laboratory testing. It was 25% to 30% more sensitive meaning it found the CIN 3 in the HPV positive population or the precancers of the HPV positive population more effectively than cytology even at the lowest threshold of cytologic abnormality; it was simultaneously more specific at least in some of the analyses. You had the best of both worlds in terms of triage and the implication of these studies and why it was FDA approved is that in a primary screening algorithm you greatly improved the safety and efficacy of the triage procedure. You get the right patients to go to colposcopy and you don't colposcope or biopsy nearly as many women as you would with a cytology test as triage.

Mark H. Stoler, MD, FASCP, provides insight on the role of dual testing in the management of HPV positive women.

Role of Dual Testing in HPV Positive Triage Management 

Let's move on now to recent advances in screening and looking ahead. How do you all foresee cervical cancer screening guidelines changing as more HPV-vaccinated individuals reach the screening age? Do you think this is just going to get more as time goes on as our vaccination rates increase? Dr Sheth?

I think we may see more interest in the adoption of primary HPV screening so a change in the modality of screening. Two, as we have increased screening rates, we could see the intervals shift and we could see the age change of initiation of screening. It's hard to predict right now because the vaccine has been available to us for over 15 years, and we're still so far from that optimal vaccination rate that it's hard to know when we're going to get there.

What is your feeling about why we're so far from the optimal vaccination rate?

 I think there are a few factors at play. The vaccine has some bad press that is not founded in any science or evidence in terms of side effects. Then there's just a lack of understanding that it is a vaccine and therefore it should be offered and recommended to everyone, so there's often this [attitude of], “Well, who needs it.” Trying to assess risk where, like any preventative measure, the point is for everyone to get it. I think those 2 issues combined have made uptake challenging.

Not surprising. We have vaccine hesitancy in the United States given what we've seen with COVID. Dr Stoler, would you address this issue of the performance of HPV testing vs cytology in vaccinated populations?

Sure, but I want to make a quick comment to what was just said. There's a study that was just published. It was in many of the newspapers last week out of Virginia, where they found that 25% of the population haven't even heard of the HPV vaccine. This is 15 years after FDA approval that every pediatrician and family practice doc should be vaccinating their teenagers and 25% of adults have never heard of it.

Sure, Mark. There's been a lot of discussion about the performance of cytology vs HPV as we get more people vaccinated.

 As I said, screening performance is driven by prevalence. HPV vaccinated individuals with Gardasil 9 have a 90% decrease in the rates of infection for the 7 types that cause 90% of all cervical cancers. In those individuals, the only thing that will work is the more sensitive HPV test. I think in this conversation, whether you're doing cotesting because that's what's available or primary HPV, the important thing is if you're going to screen, you have to do HPV testing. Now, as the vaccination goes through the population, the prevalence will drop particularly the prevalence of the most important HPV types. What you'll see is decreasing rates of HPV in vaccinated individuals and decrease in screen positives, and the first things that will drop out are the most important drivers of cancer screening, which are the most high-risk type 16 and 18 that account for 70% of cervical cancer. Lower sensitivity tests like a Pap [Papanicolaou test] will just perform less and less. It's not only less sensitive. It becomes increasingly less specific. We know that most abnormalities on Pap are already nonspecific ASCUS [squamous cells of undetermined significance] cases. When we take ASCUS out, the performance of Pap testing is quite poor. Yet the meaning of those ASCUS cases for the types that are not included in the vaccine becomes less and less specific. Vaccinated populations will be ahead of the game in that their risk of precancer is decreased by almost 90% or more. They still need some screening for a while until the overall population prevalence drops and that screening has to be molecularly based with HPV.

Drs Sangini S. Sheth and Mark H. Stoler share their thoughts on the adoption of primary HPV screening and how they foresee changes to cervical cancer screening as more individuals get vaccinated.

Gynecologic Oncology

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