Smilow Cancer Hospital at Greenwich CME Series: Gynecologic Oncology Treatment and Care

Transcript

• 00:00We can thank you.
• 00:01Thank you very much.
• 00:03Welcome everybody here this evening
• 00:06and like to introduce ourselves.
• 00:09My name is Peter Ditino.
• 00:11I'm AG1 oncologist practiced in
• 00:13Manhattan for 30 years and moved
• 00:16to Yale about the year and a half,
• 00:18two years ago and work in Greenwich and in
• 00:23New Haven as does Doctor Papadla Hope Walden.
• 00:27Our APN joined us and we now have a
• 00:31Jew in oncologist at Greenwich five
• 00:33days a week available to see patients,
• 00:37available for phone consults
• 00:39or just questions.
• 00:40If you have any questions about any
• 00:43management issues in gynecologic
• 00:44cancer that you want to run by US,
• 00:47one of us was always available to do that.
• 00:50We've done this,
• 00:51put this together really in two ways,
• 00:53is just to bring you some basic
• 00:56knowledge and also as an opportunity
• 00:59to introduce ourselves to you
• 01:01and bring you some of the update
• 01:04information in our field as it may
• 01:06be useful to you as you look around
• 01:09and see what patients would be
• 01:12appropriate for referrals or things
• 01:14that you may need clarification on.
• 01:17And like I say, we will be available,
• 01:19we're available five days a week at Granite.
• 01:23So please don't hesitate to reach out.
• 01:26My charge this evening is to give you
• 01:29some of the basics of where we are in
• 01:32endometrial Cancer Diagnosis management now.
• 01:36And that's what I'd like
• 01:37to give a start with.
• 01:39All right, I'm going to share.
• 01:40You ready for your slides?
• 01:42I am ready. OK, Give me a second
• 01:47and I will get this going.
• 01:54Alrighty. Let me get it into
• 01:58presentation. There you go. There
• 01:59you go. Thank you very much.
• 02:02No, I have no conflicts of
• 02:05interest to report tonight.
• 02:07It's not moving forward for some reason.
• 02:10Hang on, how about now,
• 02:13Now, Yes,
• 02:16hold on. Let's say.
• 02:22So tonight we we're going to be
• 02:25talking about endometrial cancer,
• 02:26early stage and also precancerous condition.
• 02:30I'd like to run through epidemiology,
• 02:32the disparities that exist in endometrial
• 02:35cancer today, the risk factors,
• 02:38prevention and treatment,
• 02:39screening, early diagnosis,
• 02:41prevention and treatment.
• 02:43And if we get through that in time,
• 02:45I will go over a little bit
• 02:47about Lynch syndrome and its
• 02:49relationship to endometrial cancer.
• 02:53It's not letting me move forward.
• 02:55I I'll move it forward for you.
• 02:57OK. So you just say next
• 02:59slide and I'll do it perfect.
• 03:00Endometrial cancer,
• 03:01as you may or might not know,
• 03:04it's estimated there's going to
• 03:05be about 66,000 cases in 2023.
• 03:10It's the third most common cancer
• 03:13that affects women, breast,
• 03:15lung and colon being the top three.
• 03:18And what's been projected to happen
• 03:20in the next three to five years
• 03:23is it colon and and rectal cancer
• 03:25are going to drop to the bottom
• 03:28secondary to the extensive screening
• 03:30programs that are are out there.
• 03:32And what's going to be the third
• 03:35most common cancer to affect
• 03:37women is endometrial cancer.
• 03:397% of all new cancer cases are
• 03:41going to be uterine cancer.
• 03:43It's the first,
• 03:44fourth most common currently
• 03:46and it accounts for about 5%
• 03:49of female related deaths.
• 03:52The next slide please.
• 03:55And as we as we can see here,
• 03:57both the incidence and the mortality
• 03:59of endometrial cancer are increasing.
• 04:02Mortality rates have been rising
• 04:05faster and this is most likely due
• 04:08to the increasing number of high
• 04:10risk subtypes which we're going to
• 04:13discuss as we go through the talk.
• 04:15Next slide please.
• 04:18There are two classifications
• 04:20of endometrial cancer that are
• 04:22are commonly used today.
• 04:24One is the traditional classification
• 04:26and the 2nd is the molecular.
• 04:29The traditional classification has
• 04:32two subtypes, a type one and a type 2.
• 04:36And the way we distinguish that is
• 04:38really phenotypically type one patients,
• 04:40as we'll see tend to be obese.
• 04:42Type 2 patients tend to be very thin.
• 04:45So there's a clear difference.
• 04:47There's been an ongoing move over
• 04:49the last 10 years and a lot of it's
• 04:52been driven by the investigators
• 04:54here at Yale and Smilow towards
• 04:57a molecular classification
• 04:59of endometrial cancer.
• 05:00And I will,
• 05:02I will go over that with
• 05:04you also next slide please.
• 05:07So again the,
• 05:08the profile of type 1 which is
• 05:10going to make up 70 to 80% of all
• 05:13new cases of endometrial cancer,
• 05:15They're going to be obesity,
• 05:17slightly younger aged women,
• 05:19some women that have polycystic ovary
• 05:22disease, unopposed estrogen syndromes,
• 05:25which will lead to endometrial cancer,
• 05:29precast precancerous conditions
• 05:32called hyperplasia, endometrial,
• 05:34hyperplasia or atypical hyperplasia.
• 05:37These are commonly referred to as EIN
• 05:41or AEA endometrial atypical hyperplasia.
• 05:44Endometrioid cancer is the most
• 05:48common pathology and the type ones
• 05:51are going to be associated with
• 05:54estrogen and progesterone receptors,
• 05:56positive K RASP,
• 05:59P10 mutations and occasional
• 06:02mismatch repair gene deficits.
• 06:06Next slide please.
• 06:09Type 2 cancer which is making up
• 06:11between 10 and now almost 25% of all
• 06:14the new cases of endometrial cancer.
• 06:16And again these are going to be
• 06:18women who are very thin and they
• 06:21will have high grade endometrioid
• 06:23cancers or non endometrioid cancers
• 06:26which would be clear cell type or
• 06:28what we call UPSC which is uterine,
• 06:31papillary serous cancers or
• 06:34possibly even carcinosarcomas.
• 06:36These are not hormonally driven cancers.
• 06:40These arise from an endometrial intra
• 06:43epithelial carcinoma referred to as EIC,
• 06:47which is a precursor for specifically
• 06:49for the papillary serous carcinoma
• 06:52which is the most common cell type
• 06:55in type 2. And again most often
• 06:58type 2 will arise in a background
• 07:01of atrophic endometrium on on a
• 07:03sonogram as opposed to a thickened
• 07:07irregular endometrium on sonogram.
• 07:09For type one patients,
• 07:12these will pursue an aggressive clinical
• 07:15course with metastasis at about 60%.
• 07:18Recurrence rates are high in stage 1,
• 07:21about 23 to 25% and again these are an
• 07:24elderly, non obese menopausal women.
• 07:30These are going to be treated
• 07:33much like we treat ovarian cancer.
• 07:36These will get surgical staging and
• 07:38they will be followed with dose intense
• 07:41chemotherapy and vaginal brachytherapy
• 07:43as we'll see next slide please, Oops,
• 07:48sorry, it's OK. There we go, there we go.
• 07:53So again the type one or the OR the
• 07:56estrogen driven, they tend to be low
• 07:59grade tumors diagnosed very early.
• 08:01They have an excellent prognosis.
• 08:04Only 20% on presentation will have
• 08:07local regional spread and only 8%
• 08:10distant metastasis. The type 2.
• 08:13Again higher risk aggressive histologies,
• 08:16more common to have extra uterine
• 08:19disease at the time of diagnosis.
• 08:21They carry worse prognosis and again
• 08:24those are going to be a grade 3
• 08:27endometrioid or or uterine papillary
• 08:30serous cancers or clear cell cancers.
• 08:32Next slide please.
• 08:35When we look at the molecular
• 08:38classifications, this was,
• 08:39this was based on TCGA data and again
• 08:42Yale was a participant in this and
• 08:45this was an effort to they sequenced
• 08:48over 350 cases of endometrial cancer
• 08:50and they were able to put them into
• 08:53four different categories and predict
• 08:57outcome based on these categories.
• 08:59And these are just names,
• 09:01but type in category one we have
• 09:04what we call whole ultra mutated #2
• 09:08is microsate satellite in stable
• 09:11hypermutated #3 is copy number,
• 09:14mutation copy number low and #4
• 09:16is copy number high.
• 09:18And you again typically with the Cirrus
• 09:21and we'll take the next slide please
• 09:26and again why this is important as
• 09:28we know that those patients that have
• 09:31a a pull mutation have an excellent
• 09:34prognosis with rare recurrences and
• 09:37we know that those patients with a
• 09:40high copy number like the serious
• 09:42types have a very poor prognosis.
• 09:45Those we now know can as I said we're
• 09:48treated with chemotherapy like ovarian
• 09:50cancer which includes Taxol and carboplatin.
• 09:53We've now added if they have
• 09:55a her to positivity,
• 09:57we use Herceptin as part of their
• 10:00treatments and the two middle types,
• 10:03the MSI high and copy number low
• 10:07are also now a treatments are
• 10:10available for these and this is
• 10:12where immunotherapy has come in to
• 10:14play a a very large role in this.
• 10:16So this is a new classification,
• 10:19some centers very few in the
• 10:22US have yet adopted this.
• 10:24Then they most people in most centers
• 10:26stay with a type one and type 2.
• 10:29But ultimately the molecular
• 10:31classifications for all cancers are
• 10:33are going to be the way patients are
• 10:36treated not based on the Histology
• 10:38or the site of origin,
• 10:39but they're going to be treated most
• 10:41likely based on their their genomic analysis.
• 10:44Next slide please.
• 10:48So again the the Type 1 low grade
• 10:51is is preceded by a pre invasive
• 10:54condition called hyperplasia
• 10:57classification of by the The Who.
• 11:00You can have hyperplasia without atypia,
• 11:03which is a benign,
• 11:05very benign condition which very rarely
• 11:07progresses to endometrial cancer.
• 11:10And then you have atypical hyperplasia
• 11:13which is a direct precursor to that.
• 11:17About 8% of benign hyperplasia will
• 11:20progress over a period of about eight
• 11:23years or so to endometrial cancer.
• 11:27And when these are identified
• 11:30in type 1 hyperplasias,
• 11:32the vast majority of these can have
• 11:35a chance to be reversed with with
• 11:38hormonal therapy and in many cases
• 11:41avoiding his safely hysterectomies.
• 11:45Next slide please and a type,
• 11:49this is a slide to give you an idea
• 11:51on the the left hand side this is a
• 11:54a normal endometrium and type on the
• 11:58right hand side that you're seeing
• 12:00hyperplasia and what happens is the
• 12:02glands that form begin to crowd on
• 12:04each other and you lose some of the
• 12:07stromal component here and that's how
• 12:09the the the the diagnosis is made
• 12:12and the risk for developing cancer
• 12:14in the in the in the non atypical
• 12:18hyperplasia is 4 to 8% and again
• 12:21those women can be easily treated
• 12:23with either D&C where the lining
• 12:25is scraped or with progestins.
• 12:27Next slide please
• 12:32as we as this hyperplasia progresses
• 12:34you can see what's happened here.
• 12:36The glands have essentially crowded
• 12:38out all of the stroma and you can
• 12:41see how thick the glands are with
• 12:43cytologic abnormalities in the hands
• 12:46and that's what makes a diagnosis of
• 12:49the complex hyperplasia with atypia.
• 12:52Next slide please.
• 12:56And So what we know about
• 12:59these is that the EIN,
• 13:01the atypical hyperplasia,
• 13:03you know if not treated can progress
• 13:07to endometrial cancer within about
• 13:09estimated about 12 months.
• 13:12We also know that when we do
• 13:14hysterectomies on women in the menopausal
• 13:17time who have atypical hyperplasia
• 13:1930 to 40% of the time when the
• 13:21uterus is removed and it's sectioned,
• 13:23we will find a very early grade one cancer
• 13:26at the time of definitive hysterectomy,
• 13:30which in most cases will be cured
• 13:32just with the hysterectomy alone.
• 13:35And the again the EIN and the
• 13:38type 1 endometrial cancers
• 13:39both share the risk factors,
• 13:41symptoms and signs of irregular bleeding,
• 13:44heavy bleeding or postmenopausal bleeding.
• 13:47And again the management is going
• 13:49to be treated with hysterectomy
• 13:51with potential exceptions in in
• 13:53very young patients where we can
• 13:56actually preserve their fertility.
• 13:59Next slide please.
• 14:02And this is endometrial
• 14:05intraepithelial carcinoma.
• 14:07Now this is a precursor to the Type 2
• 14:10aggressive form of of endometrial cancer.
• 14:15OK.
• 14:15And you can see from the slide
• 14:17here that this actually has
• 14:19some hob nailing appearance.
• 14:21This tends to be stained for
• 14:24P53 and this is a precursor
• 14:27directly to the serious type of
• 14:29aggressive endometrial cancer,
• 14:31but it does have a defined
• 14:35precancerous condition.
• 14:36Next slide please.
• 14:41So again, this word that we're talking
• 14:44about 9 hereditary types of type 1
• 14:47endometrial cancer, risk factors,
• 14:49nullaparity, irregular menses,
• 14:51polycystic ovary syndrome as
• 14:54a three times increased lift,
• 14:57lifetime risk endometrial cancer.
• 14:59The mechanisms are believed to
• 15:02be through hypersecretion of LH,
• 15:05increased glucose, hyperinsulinemia,
• 15:07insulin resistance,
• 15:09insulin growth factor,
• 15:11inflammatory responses,
• 15:13exogenous estrogen where women are
• 15:16given post menopausal hormone therapy,
• 15:20but they're just given estrogen without
• 15:23progesterone to balance it drastically
• 15:26increases the risk for endometrial cancer.
• 15:29Tamoxifen can also,
• 15:30if used for prolonged prolonged
• 15:33experiences is reported to
• 15:35actually cause endometrial cancer.
• 15:37Also in addition to a whole host
• 15:40of benign endometrial changes,
• 15:44endogenous estrogen come can come
• 15:47from estrogen producing ovarian
• 15:49tumors called granulosa cell tumors,
• 15:52ovarian stromal hyperthecosis or
• 15:55prolonged in ovulation without periods,
• 15:58which is not uncommon in in
• 16:01polycystic ovary cancer.
• 16:03Driving the base of this,
• 16:05as we alluded to is going to be obesity
• 16:09because in obesity in the fat cells,
• 16:11particularly on the abdominal side,
• 16:14you get peripheral conversion of
• 16:16other hormones into estrogen.
• 16:18And you can see in the bottom that as
• 16:22the BMI increases goes from 2925 to
• 16:262525 to 29, you get a 2 to 3% increase risk.
• 16:29When you go BMI to 30 to 39 the the,
• 16:34the risk goes up to 3.7 / 40, it's 13 times.
• 16:40So there's no question that the, the,
• 16:43the driver behind increasing frequency
• 16:45and endometrial cancer moving to the third
• 16:48most common cancer that affects women
• 16:50in in this country and worldwide is the
• 16:53obesity epidemic that we now live with.
• 16:55And as you plot the number of cases
• 16:58versus the increasing BMI that
• 17:01they're directly directly related.
• 17:03Next slide please.
• 17:09So endometrial cancer, you know prevention,
• 17:12again we can use progestin use and that could
• 17:15be in the form of oral contraceptive pills.
• 17:18We have oral progestins.
• 17:20We have Depo Provera which is given as a IM
• 17:24injection and last for a number of months.
• 17:27We now have what's called a Mirena,
• 17:29which is an IUD,
• 17:30which is impregnated with progesterone
• 17:32which is placed directly into the uterus.
• 17:35It not only prevents conception,
• 17:37but it also the progesterone is absorbed
• 17:40directly into the lining of the uterus and
• 17:43is very effective at reversing hyperplasia.
• 17:45And the effects of these also
• 17:48persist after we stop treatment.
• 17:51We know that bariatric surgery weight loss
• 17:54is consistently demonstrated to decrease
• 17:56the risk of getting endometrial cancer.
• 17:58We now know that the there's evidence
• 18:01in in rodent studies that the GLP,
• 18:04one antagonist,
• 18:05the Ozempic Jaro and so forth,
• 18:10these also actually potentiate in these
• 18:13animal studies the effect of a progesterone.
• 18:16So when you're looking in younger women
• 18:19that are obese that have either early
• 18:22endometrial cancer type one or precursors,
• 18:24which is the atypical hyperplasia with
• 18:27that we're treating either with an IUD,
• 18:29progestins or both.
• 18:32Adding one of these GLP one antagonist
• 18:35Ozempic or the like can also add to the
• 18:40likelihood of reversing their hyperplasia.
• 18:43Next slide please.
• 18:48Endometrial cancer treatment.
• 18:50Endometrial cancer is a surgically
• 18:54staged disease much like breast cancer.
• 18:56So we don't assign a stage until
• 18:59after the surgery has been completed
• 19:02and the surgery is going to
• 19:04consist of removal of the uterus.
• 19:05A simple hysterectomy is all that's required.
• 19:08We remove the fallopian tubes in the
• 19:10ovaries and we do a lymph node evaluation
• 19:13and usually that's going to be a
• 19:16bilateral Sentinel lymph node biopsies.
• 19:18These are surgeries that the the
• 19:20standard of care for is now minimally
• 19:23invasive and that could be laparoscopic,
• 19:26it could be robotic.
• 19:28These are same day surgeries with a
• 19:32recovery time of about 7 to 10 days.
• 19:35There is no place in the treatment of
• 19:38endometrial cancer for musculation,
• 19:41for cutting the uterus up
• 19:44or what's called a supracervical
• 19:46hysterectomy where you remove the top
• 19:49of the uterus and leave the cervix
• 19:51inside too because the lymphatic
• 19:53drainage in endometrial cancer.
• 19:55Not only this goes up through the the fundus
• 19:57to the fallopian tubes in the ovaries,
• 19:59but it can go down towards the cervix, so.
• 20:06Again, it's there are standards of
• 20:09care that are proven to work and
• 20:13then low low risk disease when we
• 20:16preoperatively assess these patients
• 20:18and a pelvic ultrasound is usually
• 20:21sufficient in type one disease,
• 20:23some people prefer to do a baseline
• 20:26CAT scan which is not wrong and in
• 20:29type 2 disease because of the high
• 20:32percentage of metastatic disease,
• 20:34those patients are referred for CT
• 20:37imaging to rule out distant metastatic
• 20:40disease before we do surgical staging.
• 20:43Next slide please,
• 20:47we do the Sentinel lymph nodes.
• 20:49In the past, going back about 10 years ago,
• 20:53we used to do lymphadenectomies or selective
• 20:56lymph node samplings on both sides,
• 20:59but that was associated with anywhere from
• 21:02a a 15 to 25% development of lymphedema.
• 21:07And much like in in breast cancer treatment
• 21:10where they went from removing all the
• 21:12lymph nodes to just a Sentinel node,
• 21:14that's what we currently
• 21:16do for endometrial cancer.
• 21:17They receive a dye right before
• 21:19we do surgery.
• 21:21It identifies the Sentinel lymph
• 21:22node that allows us to take out one,
• 21:25usually one or two lymph nodes on each
• 21:28side and lymphedema has just not heard of.
• 21:31Since that is done,
• 21:33the test has been proven to be
• 21:36effective and it does not miss disease.
• 21:39Next slide please.
• 21:44OK, so where's this give us here.
• 21:47So the in treatment the majority of
• 21:49patients because they're going to have
• 21:51low or intermediate risk surgery alone
• 21:53and most of those patients are going
• 21:55to be curative in a small percentage of
• 21:58them adjuvant radiation in the vagina
• 22:00will be all that's required to give
• 22:03them a low risk of recurrent disease.
• 22:06Advanced stage disease systemic therapy
• 22:09is used including chemotherapy and
• 22:13immunotherapy and increasing populations
• 22:15of of of patients of now being identified
• 22:19who will benefit enormously from the
• 22:22addition of immunotherapy specifically
• 22:24pembro that is sometimes can even be the
• 22:29independent of the biomarkers present.
• 22:33And I think I'm going to I think
• 22:36we're it's I have 628 is that right?
• 22:40You are correct. OK.
• 22:41So I'm going to think I'm going to
• 22:44hold here and if there any quick
• 22:47questions that I can answer that.
• 22:49If not, we'll hold it for the end
• 22:51and I'll introduce the next speaker,
• 22:57nothing yet, so you can go ahead
• 23:00and introduce. OK. The next
• 23:05colleague that it's my pleasure to
• 23:08introduce is Doctor Katya Papadla.
• 23:10She comes to us having finished her
• 23:13fellowship in Gynecologic Oncology
• 23:15at Mount Sinai and she's joined me
• 23:18at Greenwich along with Hope and
• 23:21we're happy to have her and she's
• 23:24available also five days a week.
• 23:27So I'm going to turn it over to her.
• 23:33Hi, everyone. Thank
• 23:34you Doctor Tina for that introduction.
• 23:37I'm super happy to be here and to
• 23:41discuss with all of you today.
• 23:43I'm going to be talking about management
• 23:47of annexal masses and kind of what to do,
• 23:51how to triage them. Let me
• 23:55just see if I can.
• 23:59Can you all see that?
• 24:01OK, so indefla masses management and
• 24:05management of and malignancy risk assessment,
• 24:08I have no disclosures.
• 24:09I just want to say that I'll be
• 24:12using the term female here for
• 24:13the purpose of our discussion,
• 24:15with the acknowledgement that many
• 24:17individuals have ovaries and that
• 24:18gender expression may be different
• 24:20from assigned sex at birth.
• 24:21And EOC will be used to describe
• 24:23cancers of the fallopian tube,
• 24:25ovary and peritoneum.
• 24:28So some background on anexal masses.
• 24:31Approximately 10% of females will undergo
• 24:33surgery for an anexal mass in their lifetime,
• 24:36so in the US this number amounts to
• 24:39about 200 to 300,000 females a year.
• 24:42However, less than 20% of
• 24:44these masses will be malignant,
• 24:47so you know the large majority
• 24:48of them are benign.
• 24:51The prevalence of epithelial
• 24:53ovarian cancers are approximately
• 24:551 case per 2500 females per year.
• 25:00The cumulative lifetime risk of
• 25:02an average aged woman in this
• 25:04country is about one in 78 or 1.3%.
• 25:07The median age and onset is 63
• 25:10years old and a large majority
• 25:1270% are diagnosed after age 55.
• 25:17As you all know there are no
• 25:19validated screening methods for
• 25:22epithelial ovarian carcinomas.
• 25:24Often times these patients present
• 25:26with non specific symptoms and
• 25:29many many females would not become
• 25:31symptomatic until late stage disease.
• 25:32So some of these symptoms are abdominal pain,
• 25:35constitutional symptoms,
• 25:36increasing abdominal size,
• 25:38bloating, urinary urgency.
• 25:39There have been various symptom
• 25:42indices developed in order to sort
• 25:45of standardize how we evaluate
• 25:46these symptoms and what this,
• 25:48you know, what each symptom,
• 25:51what the risk of each symptom being
• 25:53associated with an A carcinoma can be.
• 25:55But the outcomes were really varied
• 25:58with these indices and so it was
• 26:01not recommended to use these.
• 26:03Like I
• 26:03said, sorry to interrupt you.
• 26:05Can you just click somehow
• 26:06your presenter mode went off.
• 26:08Can you click on your
• 26:10screen share share again?
• 26:12Yeah. One second. Bottom. Yeah.
• 26:15Yeah, that's odd. Let me see. Yeah, we
• 26:19could see your presentation,
• 26:20but you were still in your.
• 26:23You weren't in the presenting mode.
• 26:25Oh, there you go. Oh,
• 26:33how's that? Perfect. OK.
• 26:37Yeah. No, thank you for pointing
• 26:38that out. Let's see what was I so,
• 26:47so 70 to 80% because of these non,
• 26:49non specific symptoms 70 to 80%
• 26:52of patients with epithelial brain
• 26:54carcinoma are diagnosed late stage.
• 26:56And we know you know from years of
• 26:58gathering data and from treating
• 27:00these patients that the five
• 27:02year overall survival in these
• 27:04patients is for about 20 to 30%.
• 27:06In contrast, those that are
• 27:08diagnosed with stage 1 disease have
• 27:10a 90 to a 95% probability of cure.
• 27:14So therefore a thorough preoperative
• 27:16risk assessment assessment is really
• 27:18critical in order to triage those the
• 27:21highest risk of cancer and refer them to
• 27:23gynecologic oncologists if indicated.
• 27:29So I wanted to.
• 27:31This table is actually taken from
• 27:34one of the American Academy of
• 27:37Family Practitioners resources
• 27:39on management of annexal masses.
• 27:42Because you know we have many,
• 27:43many primary care providers that
• 27:45we do NS family medicine doctors,
• 27:47internists at CDs patients and are the
• 27:51first line people who are hearing the
• 27:54complaint about pain or an annexal mass.
• 27:57And so this table just looks with
• 27:59the sensitivity and specificity of
• 28:01the presenting symptoms in order to
• 28:03identify patients with ovarian cancer.
• 28:05And you can see that you know sensitivity
• 28:09which really really it refers to
• 28:11the tech's ability to note somebody
• 28:13with who has disease as positive is
• 28:16quite low for all of these symptoms.
• 28:19It really only becomes high when
• 28:21patients are coming in with you
• 28:24know three or four symptoms,
• 28:27you know and similarly really the
• 28:29only ones that have the high positive
• 28:32likelihood ratios that here in that
• 28:34third column are the four or more
• 28:36symptoms or three or more symptoms.
• 28:37And this kind of explains why
• 28:40you know a lot of times,
• 28:41a lot of times these patients do
• 28:42end up kind of not really being
• 28:44diagnosed until later stage.
• 28:48OK. So how do we assess the pelvic mass?
• 28:51Pelvic ultrasound is typically what I think
• 28:53many of us put in as our first order.
• 28:57The sensitivity and sensitivity for
• 28:58the for the pelvic ultrasound in
• 29:00effecting A pelvic mass is pretty good,
• 29:0286 to 84% sensitive and 94 to 96 specific.
• 29:07However it does have a relatively low
• 29:11positive predictive value for malignancy
• 29:1335 to 40% And the pelvic ultrasound
• 29:15is also really subject to you know
• 29:19ultrasonographer subjectivity scale
• 29:20as well as inter observer variability.
• 29:23SO1 Ultrasonographer may not read
• 29:25it the same as another.
• 29:27If the ultrasound is really,
• 29:30you know, it's not a good exam,
• 29:31you're not able to characterize it,
• 29:32then the next step would be an MRI.
• 29:34Pelvis characteristics on ultrasound
• 29:37or MRI that are suggestive of a
• 29:40malignancy include cystic solid lesions,
• 29:43lesions that have thick temptations,
• 29:45papillary expressedances,
• 29:46neural nodules, increased Doppler flow,
• 29:49especially increased Doppler flow
• 29:52at the area of the temptation
• 29:54and the presence of ascites.
• 29:59So interestingly, even though you
• 30:01know we talked about this sort of
• 30:04low positive predictive value for
• 30:06a pelvic ultrasound as per ACOG,
• 30:08there's quote no alternative imaging
• 30:10modality that has demonstrated
• 30:12sufficient superiority to
• 30:13transcendental ultracide stenography
• 30:14in order to justify its routine use.
• 30:17So really it is the best thing
• 30:19we have as the first step for
• 30:21assessing these patients. And
• 30:23I just wanted to
• 30:26show you some examples of ultrasound
• 30:31images in different scenarios and
• 30:33why why this isn't the best and why
• 30:36you know why it can be confusing.
• 30:38So you know on the left side we have a 67,
• 30:41sorry, left upper corner we have a 67 year
• 30:44old female with a mucinous cystadenoma
• 30:47on her final peptiologic diagnosis.
• 30:49You can see on her imaging that she has
• 30:51a thick septation here with Doppler flow.
• 30:54She has a possible posterior
• 30:56mirror nodule and you know,
• 30:59ultimately she's 67, she's post menopausal.
• 31:01So this to me it would be a
• 31:02high risk ultrasound she under.
• 31:04She undergoes surgery and
• 31:05the pathology is benign.
• 31:10On the right hand side you
• 31:11have a patient 25 year old
• 31:13presenting with a night NAL cyst.
• 31:15She has really this kind of,
• 31:17you know, fairly large papillary
• 31:21expresses within a simple cyst.
• 31:23And for her this is a
• 31:24serious borderline tumor.
• 31:28In the lower left hand corner, you know,
• 31:31you can see another ultrasound with a
• 31:34neuronodule and nonvascular septation,
• 31:37some posterior acoustic shadowings, and
• 31:39this patient had a mature cystic teratoma.
• 31:42And then finally on the bottom right
• 31:45hand side, there's a 68 year old
• 31:48with again these thin septations.
• 31:51She has some, you know,
• 31:53cystic and solid lesions at the top,
• 31:55at the top of her ultrasound here and
• 31:58this patient did indeed have a high grade
• 32:01papillary sears carcinoma of the ovary.
• 32:03So you know, I think my point here is
• 32:07just that ultrasounds are very varied.
• 32:09If you're ever concerned, you know,
• 32:11I think pelvic MRI is a good next step,
• 32:14but there's also other tools that
• 32:16we can use in order to assess
• 32:18somebody's risk for cancer.
• 32:21If there's a,
• 32:22if you do have a suspicious complex mask
• 32:24then you can combine the transnational
• 32:26ultrasound with the CA-125 in order
• 32:28to help with the risk assessment.
• 32:30So and we'll talk about this
• 32:31in a little more detail,
• 32:32but just to note that this method
• 32:34is not recommended as cleaning
• 32:36in average risk populations.
• 32:38There's a large trial for the prostate lung,
• 32:40colorectal ovarian cancer screening
• 32:42trial who's the US based randomized
• 32:44control trial that had about 34,000
• 32:46average risk females enrolled
• 32:48between the ages of 7055 and 74.
• 32:51They underwent annual say 125 and
• 32:54transcendental ultrasound versus just
• 32:56the usual care with annual pelvic
• 32:59exams and the positive curiosity
• 33:01value for you know the ultimate
• 33:03diagnosis of an ovarian carcinoma in
• 33:05this population was just about 1%.
• 33:07So this is not something that you would
• 33:10do in you know the average risk patient
• 33:12who's not presenting with you know
• 33:14really concerning clinical symptoms.
• 33:16So just to back up for a second,
• 33:18what is CA 1.5,
• 33:20this is a monoclonal antibody to
• 33:22the Ocarian cancer antigen OC 125.
• 33:24It is elevated in 80% of patients
• 33:27with advanced disease but only 50% of
• 33:29patients with early stage disease.
• 33:31So the way that I,
• 33:32you know tell my patients is that
• 33:35if I'm concerned enough to be
• 33:37ordering a CA-125 for you,
• 33:39even if it's negative,
• 33:40you know it doesn't necessarily
• 33:42mean that you don't have anything.
• 33:43It is poorly sensitive and specific
• 33:46for early stage detection.
• 33:48Specificity does increase with
• 33:50menopausal status.
• 33:51So post menopausal women have an increased
• 33:54specificity compared to pre menopausal women.
• 33:57However, there are many false
• 33:59positive causes including fibroids,
• 34:01PID, endometriosis,
• 34:03adenomyosis, pregnancy,
• 34:04menstruation and even things that are not
• 34:06associated with the gynecologic organs.
• 34:08So kidney disease,
• 34:10CHF, cirrhosis,
• 34:11infections or inflammatory diseases,
• 34:14patients with tuberculosis
• 34:16and other malignancies.
• 34:18So it's always something to keep
• 34:20in mind when ordering this value
• 34:22and overall like a one time
• 34:23measurement is not as helpful as
• 34:25measuring multiple values over time.
• 34:32Before we move on, I just wanted to like
• 34:35again include what the AAFP recommends
• 34:38for assessing an enactable mass.
• 34:41And I think my point of including
• 34:43this here is that the only A level
• 34:46evidence rating that they really
• 34:48were able to to give was that
• 34:51they that they recommend against
• 34:52the routine screening for ovarian
• 34:54cancer with ultrasound C-125.
• 34:57We really don't have a
• 34:58good way to screen for it.
• 35:02Moving on, in addition to CA-125,
• 35:06there is a molecule called HE4 that
• 35:10I think we're using more frequently
• 35:12now when assessing in an exile mask.
• 35:15So this is the human epididymis protein four.
• 35:17It is primarily released by malignant
• 35:20ovarian cells and thus is less
• 35:22frequently elevated in benign neoplasms.
• 35:24It's also thought to be a marker of
• 35:27metastasis and chemo resistance and it
• 35:29has good utility in complementing CA-125.
• 35:32So if you think that a patient is
• 35:33at risk for a false positive CA-125,
• 35:35let's say you have some of the Nyxomas,
• 35:37but she also has chronic kidney disease and
• 35:40she has reason to have a false positive.
• 35:42This adding HD four can improve
• 35:44the specificity of the test.
• 35:46It's also useful in those patients who
• 35:49do not express ACA 125 and studies have
• 35:52found that it has greater sensitivity in
• 35:54early stage disease compared with CA-125.
• 35:59OK, So what are our options
• 36:01for risk assessment?
• 36:02There are there have been various sort
• 36:05of algorithms or calculators created
• 36:07in order to help us as a field really
• 36:09triage who we need to be worried about
• 36:12since we can't really screen for them.
• 36:14So one of the first ones is called the
• 36:17risk of malignancy index of the RMI.
• 36:19This was developed by Dr.
• 36:20Ian Jacobs in 1990 in Australia and
• 36:24had been validated in separate studies
• 36:26in the late 90s and early 2000s.
• 36:29So this the RMI uses a formula to assist
• 36:32the rest the risk score of the patient.
• 36:34So the RMI formula is the menopausal
• 36:37status that you get three points
• 36:39if you're postmenopausal,
• 36:40one point if you're premenopausal
• 36:42or perimenopausal.
• 36:42So that that point number multiplied by
• 36:45the ultrasound score which is assigned
• 36:48based on a number of features like we
• 36:51discussed like solid areas ascites,
• 36:53intraepdotal meths,
• 36:54multiloculated cysts and then
• 36:56also multiplied by the CA-125
• 36:58in units per minute later.
• 37:01So here I want this over here.
• 37:08I played around with it a little
• 37:10bit and what I found is that
• 37:11it's very dependent on the CA-125
• 37:13level and the menopausal status.
• 37:15So in this case you can see
• 37:17these two patients side by side.
• 37:18I kind of plugged in the same cyst
• 37:21characteristics and the same CA-125.
• 37:24Both of them have a low CA-125 of 12.
• 37:26The only thing that was different
• 37:27is that on the left this patient
• 37:29has a pre menopausal status and on
• 37:31the right she's post menopausal.
• 37:34And so you can see that the
• 37:35patient on the left has a low
• 37:37risk score of 36, but anything
• 37:39under 200 is considered low risk.
• 37:41And the patient on the left
• 37:42has sort of an indeterminate,
• 37:44you know, intermediate I should
• 37:45say risk score not not above 200,
• 37:49but I wouldn't say it's, you know,
• 37:50low enough that I would be
• 37:52OK to just watch this person.
• 37:54So that was kind of the number
• 37:56one thing that I noted here.
• 38:00What I also was interesting was
• 38:02like if I change this patient,
• 38:04so now I kept everything the same except
• 38:12I included yes to inter abdominal
• 38:15meths and increased the CA-125 to 45.
• 38:18This patient still had a score of
• 38:22135 and this is in the presence
• 38:25of inter abdominal meths.
• 38:26So you know, I think that this is
• 38:28a study that was probably better,
• 38:30better used when we had less information,
• 38:33less markers available.
• 38:35For example, has a large range
• 38:39in terms of suspicious numbers
• 38:41versus non suspicious values.
• 38:43And you know I'm not sure like I said
• 38:45that I would ignore a postmenopausal
• 38:47woman with multilocular cysts
• 38:48and cystic and solid areas with a
• 38:51score of 108 even though it's well
• 38:53under sort of what they call the
• 38:55threshold is concerning of 200.
• 39:00So the RMI in its validation studies
• 39:03it did relatively well with the
• 39:05sensitivity of 71 to 88% asbestosity
• 39:08of 74 to 97% for identifying cancer.
• 39:11These again are their recommendations.
• 39:13So they're saying you know above
• 39:15200 immediately referred to GYNAC.
• 39:17Between 25 and 200 the intermediate
• 39:19score you can obtain an MRI to further
• 39:21characterize and below 25 is low risk
• 39:23related to its observation repeat
• 39:25the clinical assessment as imaging.
• 39:27And I think what's also interesting
• 39:29about this and note about this is
• 39:31that the ultrasound is really here.
• 39:32So if you don't have an autophonographer
• 39:35who is able to, who has high volume,
• 39:38high expertise in commenting on
• 39:40these architectural features,
• 39:42it really makes it that you cannot
• 39:44calculate the score and it reduces
• 39:46the reproducibility of the score.
• 39:50The next training method, which I
• 39:52think is much more accepted now today,
• 39:54is called the ROBA or risk of
• 39:56ovarian malignancy algorithm.
• 39:57So this uses the menopausal status,
• 40:00the CA-125 and the HE4 to stratify patients
• 40:03into low risk and high risk groups.
• 40:06The nice thing about this is that
• 40:08it is something that is easily
• 40:10repetitive or easily repeated because
• 40:11it does not incorporate imaging.
• 40:14And it does give you a score ultimately
• 40:15to risk stratify your patients.
• 40:17And there have been multiple prospective
• 40:20and retrospective studies demonstrating
• 40:21the effectiveness of this method.
• 40:28So one validation study in 2011 by
• 40:31More ET al, they had 472 patients
• 40:33of which 383 had benign disease
• 40:35and 8989 patients had cancer.
• 40:37The patients presented to either
• 40:39their gynecology and their family
• 40:40practitioner or a general surgeon
• 40:42within Mexil Mass and you can see
• 40:44here that the sensitivity was really
• 40:46excellent in both the post menopausal
• 40:49and the pre menopausal groups.
• 40:51There were actually no epithelial
• 40:52ovarian depression was missed
• 40:54in the pre menopausal group
• 40:56with a sensitivity of 100%.
• 40:57If you look at every group,
• 40:59all women combined,
• 41:00the sensitivity was 93.8% and
• 41:02specificity about 75% with a
• 41:05negative predictive value of 99.0,
• 41:06meaning that it's very good at trashing
• 41:09out the patients that you are confident
• 41:11do not have cancer and it maintained
• 41:14a high negative predictive value of
• 41:1699% even in early stage disease.
• 41:19So this was these were excellent
• 41:22findings and this study went on to
• 41:25outperform RMI in multiple head to
• 41:27What you can do to improve upon this
• 41:30is combining the Romas score with
• 41:33your own clinical risk assessment.
• 41:35So really the question here is how
• 41:36can the initial clinical assessment
• 41:38by a patient's gynecologist or primary
• 41:40provider be optimized using the Rama.
• 41:42So a 2015 study looked at this
• 41:44combination of the clinical
• 41:46assessment with the Rama score.
• 41:48This was a retrospective cohort study.
• 41:50Patients who had had surgery from
• 41:5322,009 to 2013 for a pelvic mass were
• 41:56retrospectively looked at in the study.
• 41:57So essentially what they did is they had
• 42:00a sort of a tumor board process where
• 42:03they prospectively implemented the Romas,
• 42:05Romas score as well as
• 42:06incorporated to patients imaging.
• 42:08So that was part of the clinical
• 42:10risk risk assessment to see how well
• 42:12they did in terms of predicting
• 42:14cancer versus no cancer.
• 42:16So they had about 500 patients of
• 42:18which 79% had benign neoplasms,
• 42:204% had low malignant potential neoplasms,
• 42:246% had stage one to two EOC and 7%
• 42:27had stage 3 to 4 and 4% had a non GYN cancer.
• 42:34They recommended based on their
• 42:36study and using this combination they
• 42:39recommended observation in 38% of women.
• 42:42All patients with invasive disease
• 42:45had actually been recommended for
• 42:47surgery by using this algorithm.
• 42:49So they were really able to successfully
• 42:52identify which patients needed surgery.
• 42:56Of the 315 patients that had surgery,
• 42:59212 had benign disease and 84 had cancer.
• 43:02And ultimately the sensitivity
• 43:04for this method was 100% with a
• 43:07negative predictive value of 100%.
• 43:12And if you would look at the, the,
• 43:15if you take out sort of the low malignant
• 43:19potentials and other cancers for stage
• 43:21one through 4 are so kind of all comers
• 43:24with epithelial ovarian carcinomas.
• 43:25The Roma alone had a sensitivity of 95.3%.
• 43:29So really the point here is that
• 43:31combining that Roma score with your
• 43:33clinical risk assessment in the office,
• 43:35so exam pelvic ultrasound gives you kind of
• 43:39the best method to triage these patients.
• 43:42So here's the bottom line.
• 43:44Roma plus clinical risk assessment with
• 43:46an exam and or ultrasound allowed for
• 43:48a highly sensitive triage of patients
• 43:50with epithelial ovarian carcinoma,
• 43:52no invasive epithelial ovarian carcinoma
• 43:54Patients were assigned to the low risk
• 43:56group in the study and were therefore missed.
• 43:58So none of these patients were missed
• 44:00and also 37% of low risk patients were
• 44:02able to avoid unwarranted surgery,
• 44:03which is is excellent.
• 44:05I mean that's our goal right is to reduce
• 44:07unnecessary procedures in patients and
• 44:09to not miss those who really need it.
• 44:13This is the algorithm for this study.
• 44:15So I apologize it's a little bit small,
• 44:18but on the left side,
• 44:19this is the algorithm of just
• 44:21clinical risk risk assessment alone.
• 44:22So you can see here that you know it,
• 44:27it doesn't, you know,
• 44:28I'll go back to it.
• 44:29I'll do more of a comparison
• 44:30on the right side,
• 44:31you have the clinical risk
• 44:32assessment with the Rama.
• 44:33And so the point here is that when you get
• 44:36to this place where surgery is indicated,
• 44:39you're then able to use that
• 44:41Roma and clinical risk assessment
• 44:43to triage into low risk.
• 44:45So those patients that could have
• 44:47surgery done with their gynecologist
• 44:48versus high risk were then referred
• 44:50to a gynec and can have surgery
• 44:53you know with or without staging
• 44:54depending dependent on the findings.
• 44:57And again the point here is that
• 44:59you know you A avoid unnecessary
• 45:01surgeries in the benign patients and B,
• 45:03you also could avoid patients
• 45:05having to undergo second surgery.
• 45:07So they have,
• 45:08they have their anecsa taken out with
• 45:10their benign gynecologist and then you
• 45:12get the surprise path that it's cancer,
• 45:14you send it to the guide on and then
• 45:16you have a second surgery for a
• 45:18completion staging which may or may
• 45:19not be more challenging based on you
• 45:21know the recent surgery that they just had.
• 45:25There was also study that did a
• 45:27cost analysis of this combined
• 45:29clinical and Roma score.
• 45:31So essentially they basically looked
• 45:33at this clinical assessment alone,
• 45:35Roma alone versus the combination
• 45:37and it looks to see if ordering the
• 45:40Roma test would increase costs.
• 45:42And the bottom line for that is that
• 45:44although the lab costs for Roma
• 45:46did increase by 55%,
• 45:47this was completely offset by
• 45:49a decrease in OR costs.
• 45:51So there was a decrease in 3%
• 45:53laparotomy costs,
• 45:544% laparoscopic costs when you
• 45:58compared the Roma alone with the Roma
• 46:02plus the clinical risk assessment.
• 46:03And overall the total cost decreased
• 46:06by almost 4%.
• 46:07They also had a 63% reduction in
• 46:10repeat surgery secondary to false
• 46:12negative clinical risk assessments.
• 46:15So Roma plus clinical assessment is really
• 46:17good to identify those who need surgery,
• 46:19to identify those who don't need surgery
• 46:21and it does also cost savings in the end,
• 46:24some of the pitfalls of Roma.
• 46:25I think really the most important thing
• 46:27you know any of us can order it because any
• 46:29of us can order this A-125 and the HE4.
• 46:31So it does not have to just
• 46:33be a gynecologic oncologist.
• 46:35However the important thing to note
• 46:37is that there are different platforms
• 46:39for these assays which can lead to
• 46:42different results or cut off points.
• 46:44So for example in the pilot trial they
• 46:46reported these cut off points in percentages.
• 46:48So a role model less than 13.1% with low
• 46:52risk for pre menopausal and less than
• 46:5527.7% with low risk and post menopausal.
• 46:57But every individual health system or
• 46:59hospital has their own lab that they use
• 47:01that report these values differently.
• 47:03So for example I put here another
• 47:05platform that I found online for a
• 47:07different individual health system and
• 47:08here they just kind of reported a number.
• 47:11So for pre menopausal,
• 47:12a score less than 1.14 is low risk and less
• 47:16than 2.99 is low risk for post menopausal.
• 47:19So essentially if you are ordering
• 47:21this task like you if you're in a
• 47:23institution that you can order the Roma
• 47:25and put that into your EMR and order it,
• 47:27it will show you the result based on your
• 47:30platform's specific biomarker cut offs.
• 47:32But if you're calculating yourself
• 47:34with CA-125 and HE4 values,
• 47:36which we can all do because there
• 47:38are Roma calculators online,
• 47:40just make sure that you look at
• 47:41the calculator specific to the
• 47:43method that your lab is using
• 47:47almost done. I just really wanted to
• 47:49touch quickly on the ROCA which is
• 47:51the risk ovarian cancer algorithm
• 47:52for people that are high risk.
• 47:54So these are patients that are age 35
• 47:57with the BRCA one and two mutation.
• 47:59This is a two stage screening
• 48:01strategy using age and change
• 48:03in C-125 over time to assess the
• 48:05risk of epithelial ovarian cancer.
• 48:06And high risk scores are then
• 48:10referred for transvaginal ultrasounds.
• 48:12Really in the initial pilot study,
• 48:16the patients were triaged based on
• 48:19the CA-125 level to whether or not
• 48:23they should just get a repeat CA-125
• 48:25in a year versus in three months
• 48:26or to get a transmission ultrasound
• 48:28and be referred to Gynong.
• 48:33Overall they had about 400 patients.
• 48:37The rate of the three month follow
• 48:39up for AC125 was 5.8% and the rate
• 48:42of the transnational ultrasound
• 48:44and GYNAC referral was about 1%.
• 48:46Ultimately they were able to identify
• 48:48patent patients that had suspicious
• 48:51masses that required surgery.
• 48:55So the rope guide is really not
• 48:57as helpful in the setting of
• 48:58a existing and maxilla mass,
• 49:00but where it does come in to be
• 49:02helpful is in patients that you might
• 49:03be following for BRCA mutations.
• 49:05I know a lot of those patients
• 49:08ultimately establish care with
• 49:09gynec and see us regularly,
• 49:10but I have had patients that you
• 49:13know see me and then six months
• 49:14they see their gynecologist and
• 49:16six months after that they see me.
• 49:17So it's kind of an alternating Co
• 49:19management with the gynecologist.
• 49:21And so you may still be somebody
• 49:24who orders this and really this
• 49:26is helpful in patients with BRCA
• 49:28mutations who are not ready to have
• 49:31definitive risk reducing surgery.
• 49:32So for patients that you know don't
• 49:34want to have their ovaries out yet,
• 49:37it could be useful to do the ROCA
• 49:40risk assessment just to really
• 49:41be able to counsel your patients
• 49:43on when it's time to do this.
• 49:48And lastly, I just wanted to touch on
• 49:50what the joint SGO and ACOG guidelines
• 49:53are for evaluating national masses.
• 49:55So these are direct quotes.
• 49:56Physicians should perform a physical
• 49:58examination including pelvic exam or
• 50:00rectovaginal examination may provide
• 50:03additional information and imaging
• 50:05studies especially transvaginal
• 50:06ultrasonography may be helpful.
• 50:08And once the exam and imaging have
• 50:10detected A pelvic mass that's suspicious
• 50:11for a malignant over a neoplpasm,
• 50:13the present presence of at least one
• 50:16of the below warrants referral to
• 50:18gynecologic oncology postmenopausal women.
• 50:20So elevated C-125 ascites and nodular
• 50:23fixed pelvic mass or evidence of abdominal
• 50:26or distant mass and premenopausal woman.
• 50:28A very elevated C-125 level ascites or
• 50:30evidence of abdominal or distant mass
• 50:36patients with suspicious or persistent
• 50:37complex and necal masses that are
• 50:40requiring surgical evaluation should
• 50:41be referred patients with suspicious
• 50:44mass and strong family history.
• 50:45And then like we reviewed today
• 50:48patients who you have done like aroma
• 50:51and clinical risk assessment for.
• 50:53So again that's CA-125HE4 and menopausal
• 50:56status in combination with your
• 50:58symptoms exam and imaging findings.
• 51:00Those are patients that should be sent.
• 51:02And you know I just I want to say
• 51:04that in reality these exams are
• 51:06often limited and are difficult and
• 51:08it can be really hard to discern
• 51:09what is a malignancy by an office
• 51:11exam or imaging or lab values alone.
• 51:13So the bottom line is that we are
• 51:15happy to see anyone that you're
• 51:17concerned or worried about regardless
• 51:19of you know what SGO and ACOG say
• 51:22is the the the rules for this.
• 51:26So takeaways from my portion.
• 51:29The pelvic exam alone has low
• 51:31sensitivity for diagnosing and exo mass.
• 51:33A normal exam should not rule out
• 51:35further work up in symptomatic females.
• 51:37Transventional ultrasound is the first
• 51:38step As for ACOG but it isn't perfect.
• 51:41So just remember that CA-125 and a
• 51:44transventional ultrasound has low
• 51:45utility in the average with women,
• 51:48but it does have good utility,
• 51:50I mean relatively good utility in
• 51:53high risk like BRCA positive women.
• 51:56The HE4 may help you in certain
• 51:58situations with an indeterminate CA-125.
• 52:01If you suspect A malignancy
• 52:03considering or consider ordering
• 52:05both the CA-125 and the HE4.
• 52:09The Roma plus the clinical risk
• 52:11assessment including imaging is
• 52:13excellent for triaging females with
• 52:14adnexal masses and helps to expedite
• 52:16referrals with Dynonc to provide to
• 52:18prevent unnecessary surgeries in
• 52:20patients with benign neoplasms and to
• 52:22avoid second surgery sympos with cancer.
• 52:24If your lab does not offer Roma,
• 52:26you can calculate it yourself
• 52:27using online Roma calculators,
• 52:29but just be sure to use those specific
• 52:31to your FDA approved lab values.
• 52:36I just wanted to give
• 52:38everyone my contact info.
• 52:39If you have any questions,
• 52:41this is my cell, this is our office.
• 52:43If you want to send patients or
• 52:45have questions about a patient,
• 52:46this is their office number.
• 52:47This is my e-mail.
• 52:49My full name is Katya Ani Katyayani
• 52:52but I go by Katya and you can
• 52:54also send me an epic message.
• 52:55I'm check that kind of
• 52:57like a little bit too much.
• 52:59So I will respond my references
• 53:03and I think probably we could
• 53:05save questions until the end.
• 53:07Unless somebody has something
• 53:08burning right now.
• 53:14I think we're good. We can go on to perfect.
• 53:19And then I guess I will.
• 53:21I will do my introduction since
• 53:23Doctor Tino introduced me.
• 53:24I will introduce Hope Walden who
• 53:26is our lovely nurse practitioner.
• 53:29She is has a super cool combination of her
• 53:33NP school and also a surgical fellowship.
• 53:37So we are really lucky to have her
• 53:39because she's able to really be helpful
• 53:41in clinic and also in the operating room.
• 53:44And so she will be talking to you
• 53:47about cervical cancer screening.
• 53:49Well, that
• 53:49was lovely. Thank you so much.
• 53:53I'm also saying now that the
• 53:57vacuum is going in the office,
• 53:59so if you hear that, I apologize.
• 54:01Hopefully it's pretty good
• 54:02and there won't be an issue.
• 54:04But just before I start,
• 54:06everyone can see my screen.
• 54:07There's no issues with my PowerPoints.
• 54:11You're good, good.
• 54:12OK, perfect.
• 54:13So Yep, I will be discussing cervical
• 54:17cancer and heavily focused obviously on HPV.
• 54:21And before we get into it,
• 54:22I always like to revert back to the basics.
• 54:25So this is a healthy cervix.
• 54:27It's derived from the Mullerian
• 54:29ducts which fused to form uterus,
• 54:31cervix and upper vagina.
• 54:33This explains the way in which
• 54:36cervical cancer spreads.
• 54:38Since the upper vagina and cervix
• 54:40share a common embryological origin,
• 54:42the upper vagina is affected
• 54:44before the lower vagina.
• 54:46It connects the vagina to the
• 54:47uterine body and the cervix helps
• 54:49prevent infection from ascending
• 54:51into the uterus and fallopian tubes.
• 54:54Here you can see the cervix.
• 54:57It's a tubular structure composed of
• 54:59stromal tissue lined by squamous epithelium.
• 55:01The cervix is approximately 4 centimeters
• 55:03in length and three centimeters in diameter.
• 55:06This can vary by age,
• 55:07pregnancy,
• 55:08and menopause.
• 55:10In the picture to the right you can see
• 55:12or my screen I should see the right.
• 55:14But over here if you can see my arrow
• 55:16delineated by the blue line is the
• 55:19columnar glandular epithelia and
• 55:21that lines the endo cervical canal.
• 55:23Next in red you can see the squamous
• 55:26epithelia which lines the ecto cervix,
• 55:28and then you can see the squamo columnar
• 55:31junction, also known as the SCJ.
• 55:34And this is the point of which the
• 55:37columnar epithelia and squamous
• 55:39epithelium needs.
• 55:40The SCJ is dynamic and moves during
• 55:43early adolescence and during first pregnancy.
• 55:46The original SCJ originates in the
• 55:50Endo cervical canal and as the cervix
• 55:52diverts during the times I just mentioned,
• 55:54the SCJ comes to lie on the Ecto cervix
• 55:58and becomes a new SCJ and you can see
• 56:01that with the dotted line versus the new.
• 56:04And then next we have
• 56:05the transformation zone.
• 56:06So this is the epithelium between
• 56:08the original and new SCJ.
• 56:10It's the area where all nearly
• 56:13all cervical neoplasia occurs.
• 56:14Squamous metaplasia in the cervix
• 56:17refers to the physiological replacement
• 56:19of the inverted columnar epithelia
• 56:21on the ecto cervix by newly formed
• 56:24squamous epithelia from the sub
• 56:26columnar reserve cells and that again
• 56:29averse within the transformation zone.
• 56:32So a brief history of HPV in 1949.
• 56:36The first description of HPV was
• 56:39provided by Strauss and all who
• 56:41used an electron microscope to
• 56:44examine aqueous extracts of water
• 56:46wart tissues in 1963.
• 56:48The physical properties of HPVDNA
• 56:51were described in the study
• 56:53by Crawford and Crawford,
• 56:54and it wasn't until the 1920s that
• 56:56a role of HPV in cervical cancer was
• 56:59postulated for the first time by this
• 57:02gentleman professor Harold Zuhausen.
• 57:05He's a German virologist,
• 57:07also known as the father of virology.
• 57:10He subsequently isolated and
• 57:11cloned different strains of HPV.
• 57:13His research concluded that patients
• 57:15infected with HPV 16 and 18 were at an
• 57:18increased risk of developing cancer,
• 57:20and he won a Nobel Prize for
• 57:22Medicine or Physiology in 2008.
• 57:24Sadly, he passed away May 2023. So this
• 57:32before we can move on, is what is HPV?
• 57:35As most of us know HPV stands
• 57:37for the Human Papilloma virus.
• 57:40The picture on the left you
• 57:42can see here is the HPV genome.
• 57:44It's approximately 8000 base pair circular
• 57:48double stranded DNA genome in case in
• 57:51a non enveloped isocahedral capsid.
• 57:53It has seven to nine open reading
• 57:57frames divided into 3 regions.
• 57:59So you have your your listed
• 58:01E or early region.
• 58:03It's in a purple or maroon,
• 58:04not sure how it's coming across
• 58:07and it contains the E 12456
• 58:09and seven open reading frames.
• 58:12The core proteins E1 and Two have
• 58:14key roles in viral DNA replication
• 58:17and amplification and regulating
• 58:19A viral transcription.
• 58:20The accessory proteins E456 and Seven.
• 58:24These proteins facilitate the
• 58:26different stages of the vegetative
• 58:29virus life cycle primarily by forming
• 58:31virus post interactions to alter
• 58:34environment of the keratinocyte to
• 58:37support viral replication and enable
• 58:39invasion of host antiviral defenses.
• 58:42And for the high risk HPVS which we
• 58:46focus on a lot on the key players of
• 58:50oncogenesis are the oncoproteins E6 and E7.
• 58:56So the L or late region delineated
• 58:59in blue contains the structural
• 59:01proteins L1 and L2 genes.
• 59:03The L1 and L2 proteins form the
• 59:05capsid as well as L2 having a role
• 59:08in delivery of the viral genome to
• 59:10the nucleus upon infection and viral
• 59:13genome encapsidation during capsid assembly.
• 59:16And then finally the non coding
• 59:18region which is here in red and that
• 59:21is your long control region LCR and
• 59:24it contains regulatory elements.
• 59:26This region contains binding sites
• 59:28for a plethora of transcription
• 59:30and regulatory factors that either
• 59:32activate or repress the early
• 59:33or late and late promoters,
• 59:36the origin of replication to
• 59:38which E1 protein binds as well as
• 59:40multiple binding sites for viral E2
• 59:43proteins and the right hand picture.
• 59:45This is for again our high risk HPV proteins,
• 59:50oncoproteins E6 and E7.
• 59:53So
• 59:56HPV increases basal cell proliferation
• 59:58and forces basal cell to.
• 01:00:01Tolerate mutations through these two
• 01:00:04proteins and E6 inhibits P53 and E7
• 01:00:10retinoblastoma, also known as RB,
• 01:00:13which you'll see here you can see my cursor.
• 01:00:18The E6 protein blocks the binding of
• 01:00:21transcription factor P53 to the promoter
• 01:00:24of pro apoptopic genes through its
• 01:00:26binding with ubiquitin ligase E6AP.
• 01:00:29That's inducing its proteosomal degradation.
• 01:00:33Again, E7 onco protein induces the RB
• 01:00:37degradation for promoting S phase entry.
• 01:00:41The E7, excuse me,
• 01:00:45because of this, this protein,
• 01:00:48the P53 and your RB proteins,
• 01:00:54they're critical in the cell
• 01:00:57cycle checkpoint proteins.
• 01:00:58So with these not being around,
• 01:01:00it really prevents the protection
• 01:01:04that it's needed again,
• 01:01:06the way it looks as proliferation begets
• 01:01:09mutation and mutation begets proliferation,
• 01:01:12immune system escape.
• 01:01:13So over time with repeated
• 01:01:15and chronic infections,
• 01:01:16the basal cell develops sufficient
• 01:01:19mutations that become malignant.
• 01:01:23So HPV types and it spreads,
• 01:01:26there are hundreds of HPV genotypes
• 01:01:29and there are about 12 to 15
• 01:01:32high risk HPV serotypes that
• 01:01:34cause several types of cancers.
• 01:01:36The two again we focus on heavily are
• 01:01:39HPV 16 and 18 as they are the two
• 01:01:43cervical cancer inducing HPV serotypes
• 01:01:45responsible for 70% of cervical cancer.
• 01:01:51It typically HPV resolves within 9 to 12
• 01:01:54months and can almost clear within two years.
• 01:01:58But during productive cervical HPV infection,
• 01:02:01low grade cytological abnormalities
• 01:02:03may clinically be detectable
• 01:02:05and screening usually transient.
• 01:02:07However, the carcinogenic HPV 16 and
• 01:02:1018 infections that persist beyond 12
• 01:02:12months increase the likelihood of
• 01:02:15precancerous or cancerous lesions,
• 01:02:16although not all persistent
• 01:02:19infections progress.
• 01:02:20In the United States,
• 01:02:21the median age of cytologically
• 01:02:24detected precancer cervical lesions
• 01:02:26occurs approximately 10 years after
• 01:02:28the median age of sexual debut.
• 01:02:31HPV can enter a latent state.
• 01:02:34Additionally,
• 01:02:34there's evidence for cervical viral
• 01:02:36reactivation in some populations,
• 01:02:38including females with HIV and older females.
• 01:02:42However,
• 01:02:43it's unknown whether all or any subset
• 01:02:45of HPV infections become latent and
• 01:02:48whether re emergent HPV infections
• 01:02:50carry significant cancer risk.
• 01:02:53So here I have a couple listed.
• 01:02:55Of the genotypes you have your excuse me,
• 01:02:58cutaneous which is your non genital warts.
• 01:03:03These types have a predilection for
• 01:03:05cutaneous epithelium and are found
• 01:03:08in planter warts, common warts,
• 01:03:10flat warts, butcher warts.
• 01:03:11These are types HPV,
• 01:03:14types 1-2 and four for your plantar.
• 01:03:16Flat warts is types 3 and 10,
• 01:03:19and the butcher warts is 7 and two,
• 01:03:22the analogenital epithelium.
• 01:03:23These HPV types have a predilection
• 01:03:26for the analogenital keratinized
• 01:03:28skin and mucous membranes infection.
• 01:03:30So these common sites are your penis,
• 01:03:33scrotum, perineum, **** canal,
• 01:03:36perianal region, vaginal introitus,
• 01:03:39***** and cervix for your genital
• 01:03:43warts HPV 6:00 and 11:00.
• 01:03:46And these are benign **** genital warts.
• 01:03:49And then the squamous intrapathidal
• 01:03:51lesions and or carcinoma of the vagina,
• 01:03:54***** cervix, **** or penis.
• 01:03:56And that's your high risk HPV types,
• 01:03:5816 being the most common and having
• 01:04:02the highest risk of progression
• 01:04:04of cervical cancer.
• 01:04:06Other mucosal services,
• 01:04:08HPV 16 can infect the oral mucosa and
• 01:04:10it's been associated with squamous cell
• 01:04:13carcinoma of the oral cavity.
• 01:04:16Again, related disease in the
• 01:04:18female is your cervical cancer.
• 01:04:20It's the fourth most common cancer
• 01:04:22among females with approximately
• 01:04:24570,000 cases of invasive cervical
• 01:04:26carcinoma diagnosed and 311,000
• 01:04:29cervical cancer deaths annually.
• 01:04:35What are the risk factors
• 01:04:36and how can we prevent it?
• 01:04:38So risk factors for HPV multiple
• 01:04:41sex partners not using a form
• 01:04:43of sexual barrier methods.
• 01:04:45So male or female condoms
• 01:04:49age, young age at start of sex,
• 01:04:51particularly under the age of 18, excuse me.
• 01:04:54And then cigarette smoking
• 01:04:56alter cervical secretions,
• 01:04:58which increases the chance that an HP
• 01:05:00and V infection will be established and
• 01:05:02worsen the chance that it will be cleared.
• 01:05:04And then lastly, but not least,
• 01:05:06your STISA study performed by
• 01:05:08Abreu and ET al.
• 01:05:09In 2016 took a hundred 838 women
• 01:05:14aged 18 to 68 screened using Pap
• 01:05:18smears for cervical abnormalities
• 01:05:20such as HPV non HPVSTDS and they
• 01:05:24used PCR and MCRMPCR methods.
• 01:05:27They were looking for Chlamydia gonorrhea,
• 01:05:29Mycoplasma genitalium,
• 01:05:32Trichomonas vaginalis,
• 01:05:35HSV one and two,
• 01:05:36and then Truconoma Palladium.
• 01:05:40What they found was that
• 01:05:44the primary pathogens
• 01:05:46associated with high risk HPV
• 01:05:50were the chlamydia and gonorrhea.
• 01:05:52Increased risk for all grade
• 01:05:54of cervical abnormalities,
• 01:05:55mainly for high grade serious
• 01:06:00squamous intraepithelial lesions,
• 01:06:02suggesting a possible synergenic
• 01:06:04synergenistic action in
• 01:06:06cervical lesions progression.
• 01:06:09And how can we prevent this
• 01:06:11so safe sex practice?
• 01:06:12That's condoms, monogamy,
• 01:06:15waiting until you're older,
• 01:06:18and then, of course, vaccination.
• 01:06:21I'm not gonna spend too much time on this
• 01:06:23slide just cause for the sake of time,
• 01:06:25but this just gives us a brief overview
• 01:06:29starting from 1951 with Henrietta Lacks.
• 01:06:31For those of you this, that's the one.
• 01:06:33The one thing I will bring
• 01:06:34up is Henrietta Lacks.
• 01:06:35She was a woman who developed cancer in a
• 01:06:39cervical cancer in at her at the age of 30.
• 01:06:42She had sought treatment at John Hopkins
• 01:06:44University with Doctor George Gay,
• 01:06:47and he took a sample of what later
• 01:06:49became known as the He lost sales,
• 01:06:51named after Henrietta Lacks.
• 01:06:53And this is really what sparked
• 01:06:57the profound impact that she had
• 01:06:59on major scientific discoveries,
• 01:07:00not only just with the link
• 01:07:02between HPV and cervical cancer,
• 01:07:04but the polio vaccine.
• 01:07:09So here we're gonna discuss the
• 01:07:13vaccination guidelines so the CDC you
• 01:07:16can see here commit Advisory Committee
• 01:07:19on Immunization Practice so that ACIP
• 01:07:24what they list here on the right hand side,
• 01:07:27routine vaccination at age 11
• 01:07:29or 12 can be started at age 9.
• 01:07:32Vaccination for everyone through age 26
• 01:07:34is not adequately vaccinated when younger,
• 01:07:37and then vaccination is not recommended
• 01:07:39for everyone older the age of 26.
• 01:07:41Some adults 27 to 45 might decide to
• 01:07:43get the HPV vaccine if they did not get
• 01:07:47it adequately when they were younger.
• 01:07:49And then vaccination in this age range
• 01:07:50provides less benefit for several reasons,
• 01:07:52including that most people at this
• 01:07:55age point have already been exposed
• 01:07:58to HPV and the vaccine prevents new
• 01:08:01HPV and obviously does not treat
• 01:08:03existing HPV infections or disease.
• 01:08:05Your dosing schedule is A2 dose
• 01:08:08schedule and it's recommended
• 01:08:10for most persons starting in the
• 01:08:12series before their 15th birthday.
• 01:08:14The 2nd dose of HPV vaccine should be
• 01:08:16given 6 to 12 months after the first dose,
• 01:08:18and adolescents who received 2 doses
• 01:08:20less than five months apart will
• 01:08:22require a third dose of HPV vaccine.
• 01:08:253 doses of HPV vaccine are recommended
• 01:08:28for teens and young adults who started
• 01:08:30the series at age 15 through 26 and
• 01:08:33for immunocompromised persons the
• 01:08:35schedule is 01 to two and six months.
• 01:08:383 doses like I mentioned immunocompromised
• 01:08:42persons between ages 9 through 26
• 01:08:45and then this chart here to the left
• 01:08:49are the three HPV vaccines licensed
• 01:08:52in the United States.
• 01:08:54The one exclusively being used
• 01:08:56and moved to is the 9 valent HPV
• 01:09:01as it's covering the most
• 01:09:05HPV infections.
• 01:09:09Contra indicate contraindications
• 01:09:11and precautions if you have a
• 01:09:14severe allergic reaction such as
• 01:09:18anaphylaxis to Saccharomyces cerevese
• 01:09:20and probably butchering that,
• 01:09:22but that's essentially Baker's use.
• 01:09:24That is an absolute contraindication.
• 01:09:27If you have a hypersensitivity to that
• 01:09:29moderate or severe acute illness,
• 01:09:32you would just hold off until it has run
• 01:09:35its course and you can give the vaccine
• 01:09:37and then minor acute illness such as
• 01:09:39diarrhea or upper respiratory infection,
• 01:09:40you can give it without any concern.
• 01:09:43HPV vaccine is not recommended for
• 01:09:46use during pregnancy and should
• 01:09:48be delayed until after pregnancy.
• 01:09:50There's no study proving that it's harmful.
• 01:09:53However, it is recommended to
• 01:09:55wait until after the pregnancy,
• 01:10:00so screening for cervical
• 01:10:02cancer in the United States.
• 01:10:04As I mentioned before,
• 01:10:05HPV 16 and 18 are responsible
• 01:10:07for 70% of cervical cancers,
• 01:10:08and this can be prevented by
• 01:10:10regular screening of women and
• 01:10:12the vaccination of children.
• 01:10:13Your Pap test begins at age 21 regardless
• 01:10:16of your onset of sexual activity,
• 01:10:18and it recurs every three years.
• 01:10:21Co testing starts at age 30 and
• 01:10:25screening shifts to the code testing,
• 01:10:26which is the Pap test with HPV
• 01:10:29testing every five years until age
• 01:10:3160 fives if they have been negative.
• 01:10:33Pap testing before 21 or starting
• 01:10:36HPV before 30 increases unnecessary
• 01:10:39procedures that are both painful and
• 01:10:42can capitalize on future fertility.
• 01:10:45You can see here this is the
• 01:10:50USPSTF versus the ACS guidelines
• 01:10:54for cervical cancer screening.
• 01:10:56So the American College of
• 01:10:58Obstetrics and gynecologist ACOG
• 01:11:00joined the American Society of
• 01:11:02Colposcopy and Cervical Pathology.
• 01:11:05So the ASCCP and the Society
• 01:11:07of Gynecological Oncology,
• 01:11:09SGO and endorsing the
• 01:11:12USPUSPSTF, which is the US Preventative
• 01:11:14Service Task Force Cervical
• 01:11:15Cancer Screening recommendation.
• 01:11:17So what would be followed was this.
• 01:11:19And then this is the American Cancer Society
• 01:11:25moving on cytology outcomes.
• 01:11:28So now you've done your Pap test,
• 01:11:31you've done your HPV Co testing.
• 01:11:33What do the results mean?
• 01:11:37So some cytology outcomes you have are
• 01:11:40negative for intraepithelial malignancy.
• 01:11:42This means the specimen was adequate
• 01:11:44for evaluation and there's no
• 01:11:47epithelial abnormalities identified.
• 01:11:48Next you have what's referred to as Ascus
• 01:11:51cells that display abnormalities more
• 01:11:53marked than simple reactive changes,
• 01:11:55but do not display squamous
• 01:11:57intrapithelial lesion.
• 01:11:58In some cases these lesions are associated
• 01:12:01with cervical intrapithelial neoplasma,
• 01:12:04also neoplasia,
• 01:12:04also known as sin,
• 01:12:06and we'll get into that later.
• 01:12:08You have your low grade squamous
• 01:12:11intrapithelial lesions.
• 01:12:11These lesions are associated with
• 01:12:13HPV and tend to be associated with
• 01:12:16transient changes that regress over time.
• 01:12:19Atypical squamous cells cannot exclude high
• 01:12:23grade squamous interepithelial lesions.
• 01:12:25These cells are likely consist of a
• 01:12:27mixture of true high grade squamous
• 01:12:29interepithelial lesions and other
• 01:12:31findings that mimic such lesions.
• 01:12:34You have atypical glandular
• 01:12:36cells not otherwise specified.
• 01:12:38This was formerly known as Agus and has
• 01:12:41recently changed to either endocervical AEC,
• 01:12:44endometrial or not otherwise specified.
• 01:12:48And then your high grade squamous
• 01:12:50intraepithelial lesion lesions
• 01:12:51associated with high risk types
• 01:12:53of HPV and that have high risk
• 01:12:56of progression to CIN or cancer.
• 01:12:59And last but not least carcinoma,
• 01:13:01squamous cell cancer,
• 01:13:03adenocarcinoma.
• 01:13:04So squamous cell carcinoma is
• 01:13:06the ectoservice caused by HPV and
• 01:13:08then adenocarcinoma of the cervix,
• 01:13:12the endocarcinoma Cervix,
• 01:13:15the endocervix is a malarian malignancy.
• 01:13:20It's a cancer derived from the
• 01:13:21descendants of the malarian ducts.
• 01:13:22As we talked at the very,
• 01:13:24very beginning,
• 01:13:24why it was important to make that
• 01:13:27note of this malarian malignancy,
• 01:13:29the simple columnar epithelium that
• 01:13:32invaginates upon itself to form these glands.
• 01:13:35It is a mucinous phenotype
• 01:13:38for malaria malignancies,
• 01:13:39commonly encountered as a mucinous
• 01:13:41variant of ovarian epithelial tumors,
• 01:13:46and it's rare but obviously dangerous.
• 01:13:53So here we are,
• 01:13:55cervical interactive neoplasm CIN.
• 01:13:58There are three different grades,
• 01:14:011-2 and three, and they go from low grade
• 01:14:03with mild atypical cellular changes.
• 01:14:06Of the lower 3rd.
• 01:14:08CIN 2, which is your high grade
• 01:14:12moderately atypical change
• 01:14:13confined to the basal 2 cells 2,
• 01:14:16excuse me, 2/3 of the epithelium.
• 01:14:18And then three which is your
• 01:14:20high grade lesion with severely
• 01:14:21atypical cell changes.
• 01:14:22And that it's encompassing more
• 01:14:25than 2/3 of the epithelial thickness
• 01:14:27and includes both thickness lesions
• 01:14:31for syn 1.
• 01:14:35Excuse me,
• 01:14:38yes. So a patient's risk for progression
• 01:14:41to cancer related is related to in
• 01:14:43large part by age and your same grade.
• 01:14:45So ages greater younger than 25 years
• 01:14:49have a low risk of developing cervical
• 01:14:51cancer in patients 25 and older.
• 01:14:53And again, the same grade has a low C1 has
• 01:14:58a low potential versus a Syn 3 and Syn 2,
• 01:15:00which have higher potential for progression
• 01:15:02and a lower potential for regression.
• 01:15:10So what do we do?
• 01:15:12So the 2019 American Society of
• 01:15:15Copaci and Cervical Pathology
• 01:15:18ASCCP put out this really,
• 01:15:20really great app which I'll get into
• 01:15:22and I'm going to hope I can show you.
• 01:15:24But essentially in collaboration
• 01:15:28with multiple professional societies
• 01:15:30and government organizations,
• 01:15:31the United States and Canada
• 01:15:34published practice changing consensus
• 01:15:36guidelines regarding the evaluation
• 01:15:38and management of cervical dysplasia.
• 01:15:40The consensus recommendations
• 01:15:41are based on the principle of
• 01:15:44equal management for equal risk.
• 01:15:46So earlier today I think Jenny
• 01:15:48might be on the call.
• 01:15:50You know she's like well this is what we
• 01:15:52got for our Pap smear HPV Co testing test.
• 01:15:56What does this mean?
• 01:15:57And it takes in a lot of
• 01:15:59things as far as well,
• 01:16:00have they been HPV positive in the past?
• 01:16:04What are their histories?
• 01:16:05It's more than just what it is today.
• 01:16:06It takes into the whole
• 01:16:08account of the person.
• 01:16:09So again,
• 01:16:09this means the same current screening
• 01:16:11results may lead to a different
• 01:16:13management recommendation for one
• 01:16:14patient versus another patient,
• 01:16:16depending on the past testing results.
• 01:16:18So I'm gonna see if I can bring
• 01:16:21over this screen so you can see,
• 01:16:24Can everyone see this now?
• 01:16:25I
• 01:16:27don't know if anyone can see yeah
• 01:16:31so this you can actually download
• 01:16:33as an app for providers, nurses,
• 01:16:35whomever or if you just want to play around
• 01:16:38with it and you literally just plug in
• 01:16:41exactly what it is that is popping up.
• 01:16:43So you know age 3065,
• 01:16:48they came in for routine screening
• 01:16:49and this is a pick your own.
• 01:16:51So if you pick one,
• 01:16:51the other one clicks off.
• 01:16:52So let's say routine screening.
• 01:16:54Next what it came back,
• 01:16:56their HPV was positive.
• 01:16:58Ours are usually always genotyped
• 01:17:00and we'll say that these were
• 01:17:02present And then cytology,
• 01:17:04what did it came come back as?
• 01:17:05So we'll just say ask as does
• 01:17:08the patient of previous and will
• 01:17:10say no and then it will map out
• 01:17:12exactly what it is confirming
• 01:17:13these are exactly what you put in.
• 01:17:15And then it tells you recommendation.
• 01:17:16Colposcopy risk,
• 01:17:18intermediate risk of CIN 3 plus is 9%.
• 01:17:23So it's a really great tool.
• 01:17:24Again you can put on your phone.
• 01:17:26For me who's new to gynecology oncology,
• 01:17:30it's a great resource and I love it.
• 01:17:33So I highly encourage but
• 01:17:35like it recommended.
• 01:17:36So colposcopy it can be diagnostic and
• 01:17:39therapeutic colposcopy with extensional
• 01:17:40biopsy which we've done here in the office.
• 01:17:43So you have your Ecto cervical and
• 01:17:46endo cervical curetage excision,
• 01:17:47your loop electrical excision procedure
• 01:17:50known as the LEAP and then your ablation.
• 01:17:53So your cryotherapy cold knife
• 01:17:55and CO2 lesia all my own time.
• 01:17:59OK,
• 01:18:00so finally what is the future
• 01:18:02of cervical cancer?
• 01:18:03So in 20-30 The Who hopes to
• 01:18:06meet milestones on path to
• 01:18:08eliminating cervical cancer
• 01:18:12after meeting with meeting the 907090
• 01:18:16targets through a global focus on
• 01:18:18vaccination screening and treatment,
• 01:18:20The Who hopes to eradicate
• 01:18:22vaccine preventable cervical
• 01:18:24cancer within the next century.
• 01:18:2690% of girls fully vaccinated
• 01:18:28with HPV vaccine by age 1570%
• 01:18:30of women initially screened with
• 01:18:32high performance testing by age 35
• 01:18:34and a secondary test at age 45.
• 01:18:36And 90% of pre cancers treated and 90%
• 01:18:40of invasive cancers managed strategies
• 01:18:42towards the elimination of cervical
• 01:18:45cancer as a global public health problem.
• 01:18:50The guiding principles life course and public
• 01:18:53health approach social justice and equality,
• 01:18:55integrated people centered health
• 01:18:58services and then the challenges that
• 01:19:01we face limited supply of the vaccine,
• 01:19:04cost and affordability of the
• 01:19:06vaccine and delivering treatment,
• 01:19:08the methods of which we deliver it and
• 01:19:13then quality pathology and last but
• 01:19:16certainly not least, therapeutic vaccines.
• 01:19:18So therapeutic HPV vaccines deliver
• 01:19:21tumor antigen to stimulate an immune
• 01:19:24response to eliminate tumor cells.
• 01:19:27Vaccine antigens delivery platforms are
• 01:19:30diverse and include DNARNA peptide proteins,
• 01:19:33viral vectors, microbial vectors
• 01:19:35and antigen presenting cells.
• 01:19:37Randomized randomized control trials
• 01:19:39have demonstrated that therapeutic
• 01:19:42HPV vaccines are efficacious in
• 01:19:44patients with cervical with syn.
• 01:19:46In patients with HPV mediated malignancies,
• 01:19:49evidence of efficacy is limited.
• 01:19:51However,
• 01:19:52numerous ongoing studies evaluating
• 01:19:54updated therapeutic HPV vaccines in
• 01:19:57combination with immune checkpoint
• 01:19:59inhibition and other therapies
• 01:20:02exhibit significant promise.
• 01:20:05So here are my references and I will stop
• 01:20:09sharing and hopefully that gives us an.
• 01:20:125 minutes for questions.
• 01:20:13I'm sorry.
• 01:20:14No, it's great. Thank you.
• 01:20:16The information is amazing
• 01:20:18and very well appreciated.
• 01:20:20We have two questions in the Q and
• 01:20:25AI will just shout them out there.
• 01:20:26I think the first one came in
• 01:20:28while Doctor Datina was talking.
• 01:20:30How do you feel about
• 01:20:32ultrasound screenings annually?
• 01:20:38And don't forget that you're on.
• 01:20:39Yeah, there you go. I
• 01:20:41I think that there's there's really no no
• 01:20:45proven role for it for annual screening.
• 01:20:47I think it will end up with this as Doctor
• 01:20:51Paddle already said it end up to far
• 01:20:55more unnecessary surgery being performed.
• 01:20:59I think when you couple it with the
• 01:21:01symptoms the patient has or your index of
• 01:21:05suspicion based on your physical exam,
• 01:21:07the patient's personal history,
• 01:21:08the the then the use of a sonogram,
• 01:21:11I think is is God value.
• 01:21:13But just to say I'm going to
• 01:21:16send somebody for one every year,
• 01:21:18it's just a waste of healthcare resources,
• 01:21:24OK. And our other question is,
• 01:21:29do you see artificial intelligence
• 01:21:31leading us to an earlier
• 01:21:33diagnosis of ovarian cancer?
• 01:21:38They're actually interestingly
• 01:21:39there was there's a new study
• 01:21:41that's gonna be published in
• 01:21:43the Gynon March 2024 edition,
• 01:21:46the Gynon Journal looking at
• 01:21:51like a very preliminary study
• 01:21:52out of Georgia Tech I believe.
• 01:21:54And they are looking at using AI plus like
• 01:21:58a combination of a number of metabolic,
• 01:22:03I guess indices that can be
• 01:22:05tested in the blood to see if
• 01:22:07they can come up with a A profile.
• 01:22:09So what they're doing,
• 01:22:10my understanding of what they're doing
• 01:22:12is that they're taking patients that
• 01:22:14they have that have known ovarian
• 01:22:15cancer versus nothing and they're
• 01:22:17trying to establish some kind of
• 01:22:19score based off of this metabolic
• 01:22:21profile that they're building.
• 01:22:23So I I think that there is going to
• 01:22:26be a role for it but there are also a
• 01:22:29lot of I think downsides of AI that
• 01:22:31we you know we have to remember in the
• 01:22:36future as we apply them to our patients.
• 01:22:39I I look out look
• 01:22:40out for that article. I I
• 01:22:42I would, I would add to that and
• 01:22:44and just say that the one of the
• 01:22:46programs that that that I brought
• 01:22:48with me to Yale is early screening
• 01:22:51for ovarian and endometrial cancer.
• 01:22:54And and there we use a form of what's
• 01:22:56called machine learning which is a a,
• 01:22:59a type of AI.
• 01:23:00And we had done all of these studies
• 01:23:03and collected all this data and didn't
• 01:23:05think we had anything worthwhile
• 01:23:07until we met with the bioinformatics
• 01:23:10specialist and they began to train
• 01:23:13our systems using machine learning.
• 01:23:15And then we discovered things that
• 01:23:17we never thought was visible in
• 01:23:19this data and it wasn't visible
• 01:23:21until we use these systems.
• 01:23:22So I think they can just add an
• 01:23:26enormous amount for analyzing large,
• 01:23:28large sums of data.
• 01:23:30But it as Doctor Papadla just alluded
• 01:23:33to you you have to train these
• 01:23:35systems and that means you've got to,
• 01:23:37they've got to see huge amounts of
• 01:23:39data and you also have to be very
• 01:23:42careful about overfitting your data for
• 01:23:44what what you're really looking for.
• 01:23:47But I don't think there's any
• 01:23:48question is these systems undergo
• 01:23:50refinement that these are going
• 01:23:52to become part part of pretty much
• 01:23:54everything we do in medicine.
• 01:23:55They read mammograms better
• 01:23:58than most radiologists today.
• 01:23:59You know there's a lot of places where
• 01:24:02they're they're already doing that.
• 01:24:05They're going to be reading our CAT
• 01:24:07scans or your radiology is going to
• 01:24:09be looked at with AI because again it
• 01:24:11it has of the capacity to to process
• 01:24:14through data and refine it into
• 01:24:17very interesting ways for patients.
• 01:24:20So yeah, I think that's a,
• 01:24:21it's a great question
• 01:24:25and we have one last one.
• 01:24:26What is the role of uterine
• 01:24:28transplant in young patients
• 01:24:30with endometrial cancer?
• 01:24:36It's it's been, it's
• 01:24:38been used, it's been,
• 01:24:40it's it's highly experimental.
• 01:24:42I, I don't remember where
• 01:24:44exactly it was done,
• 01:24:45but I I just don't believe
• 01:24:48it's anything that's really
• 01:24:50taken off to my knowledge
• 01:24:56and that's what I'd have to say about that.
• 01:25:00I think it was somewhere in the UK,
• 01:25:02but I agree I've seen animal studies,
• 01:25:06but I don't know how well they
• 01:25:07translate into human at this point.
• 01:25:12OK. So thank you everybody so much.
• 01:25:15I'm going to end with one more
• 01:25:17comment that we had in the Q&A
• 01:25:19that said thanks so very much.
• 01:25:21We have a lot of worried women and we
• 01:25:23appreciate this talk and you being here.
• 01:25:26So I will second that.
• 01:25:27And thank you so much for your time.
• 01:25:29Thanks everybody for hanging in with
• 01:25:31us and spending your evening with us.
• 01:25:35Thank you.
• 01:25:36Have a great night. Thank
• 01:25:38you. Have a good night. Thank you.