Cancer Answers: Building Awareness of Cervical Cancer with guest Dr. Peter Schwartz, July 19, 2009

Dr. Peter Schwartz, Building Awareness of Cervical
Cancer July 19, 2009Welcome to Yale Cancer Center Answers with Drs. Ed Chu and
Francine Foss, I am Bruce Barber.  Dr. Chu is Deputy Director
and Chief of Medical Oncology at Yale Cancer Center and he is an
internationally recognized expert on colorectal cancer.  Dr.
Foss is a Professor of Medical Oncology and Dermatology and she is
an expert in the treatment of lymphomas.  If you would like to
join the discussion, you can contact the doctors directly. 
The address is canceranswers@yale.edu and
the phone number is 1-888-234-4YCC.  This evening Ed and
Francine welcome Dr. Peter Schwartz.  Dr. Schwartz is the John
Slade Ely Professor of Obstetrics, Gynecology, and Reproductive
Sciences at Yale and Dr. Schwartz is internationally recognized for
his work regarding cervical and ovarian cancers.Chu
 Peter, thanks so much for being with us on the show this
evening.Schwartz
Thank you.  It's a pleasure to be here.Chu
 Let's start off by defining what cervical cancer is.Schwartz
Well, cervical cancer is cancer that starts in the neck of the
uterus.  The uterus, for those who may not be familiar with
anatomy, kind of looks like a pear or a light bulb and the narrow
end, the part that has the threads on the light bulb or where the
stem comes out of the pear, that's the cervix.  Worldwide,
cervical cancer is the second most common cancer women get, here in
the United States though, it's only the 13th most common
cancer.  That's because our Pap Smear Screening Program works,
where as in the underdeveloped world, we don't have an effective
screening for cervical cancer.Foss
Can you tell us at what age women get cervical cancer and who is at
risk for it?Schwartz
Women who are at risk for cervical cancer are women who have been
exposed to the human papillomavirus. The factors that usually are
associated with that are early age of first intercourse, multiple
partners, and in the past, we used to talk about children delivered
before age 18, but clearly the human papillomavirus is what is
involved with the etiology of cervical cancer worldwide.  Now,
we should be careful when we talk about cervical cancer; we are
talking about an invasive cancer.  Invasive cancers can spread
and kill patients, but many-many more women get precancerous
changes which are the changes that we detect with the Pap smear,
those are the changes that we can cure by treatment in the office
or with some simple surgical procedures and we can preserve
fertility.  Invasive cancer of the cervix occurs mainly in
women between age 40 and 50 here in the United States and that is
the disease that the Pap smear screening has dramatically
reduced.2:49 into mp3 file 
http://www.yalecancercenter.org/podcast/july1909-cervical-cancer-awareness.mp3Chu
 Now Peter, other than the human papillomavirus, are there any
other risk factors that one needs to be concerned about?Schwartz
Smoking has been a co-factor associated with cervical cancer and
also alcohol consumption has been associated with cervical cancer,
but the predominant factor associated with cervical cancer and the
precancerous changes are the human papillomavirus infection.Foss
Peter, can you tell us a little bit about human papillomavirus, how
is it spread?Schwartz
Human papillomavirus is a very interesting virus because it has a
predilection for the anogenital area, that is the skin around the
opening of the vagina as well as around the anus, and also for the
mucous membranes, that's the lining of the vagina, and the cervix,
but also it involves the upper airways as well and the digestive
systems.  The anogenital human papillomavirus that we are
concerned about is spread predominantly through intercourse.Chu
 Obviously there has been a great deal of publicity surrounding the
development of a vaccine for the human papillomavirus; can you tell
us a little bit about that?Schwartz
Yes, there is now one vaccine approved in the United States, but
there are two vaccines that have been used worldwide.  What we
have recognized is that the most common types of human
papillomavirus associated with invasive cancer of the cervix are
type 16 and type 18. But we have also recognized that for warts
that appear in the genital and the anal area, as well as cancers of
the vagina and precancerous changes of the vagina, the vulva, and
the anus, type 6 and type 11 are also associated with it.  One
of the vaccines, the type that is approved here in the United
States, is called Gardasil and that one covers both 6 and 11, as
well as 16 and 18.  A second virus, which is used worldwide,
is not yet approved in the United States; it only covers 16 and
18.Chu
 And again, when should the vaccinations be administered?Schwartz
Well, the vaccine is approved for women ages 9 to 26, but we still
think about age 11 or so is the time when young girl should be
vaccinated.  At this moment, it is only approved for
women.  It is not approved yet for men or for boys, although
this seems to be in the works.Foss
Peter, can you clarify for our listeners, if a person already has a
positive human papillomavirus on their Pap smear, for instance,
would they be a candidate for this vaccine, or is this only a
preventive vaccine?Schwartz
This is a preventive vaccine.  There are basically two types
of vaccines, there is a therapeutic5:49 into mp3 file 
http://www.yalecancercenter.org/podcast/july1909-cervical-cancer-awareness.mp3vaccine, which will be used to treat a process, and
therapeutic vaccine which is what the
 Gardasil is used to prevent the process, the infection, from
developing.  Now, the vaccine is approved for women who have
not been exposed to HPV, but there are always issues such as, "What
if I have a precancerous change?" Or perhaps, "I have type 16 and
not type 18, can I benefit by being given the Gardasil?" We really
don't have a lot of data on that, but it's something that could
still be considered on a regular basis.Chu
 Are there any potential side effects or complications resulting
from the vaccine?Schwartz
Well, anytime we administer the vaccine, there is always local
irritation; there can be pain, some burning sensation, or some
itching in that area.  There have been very few systemic
problems that have been reported with the vaccine.  There has
been a rare case of asthma and case of bronchospasm, but in terms
of mortality, which is what we are always worried about, the
mortality rates for young women who have received the vaccine are
no different than control groups.Foss
Given the risk of cervical cancer and the prevalence of HPV in the
population, do you feel that this vaccine should become part of the
regular immunization profile for our children?Schwartz
Absolutely, this has been the single most dramatic development in
my 30 odd years as a gynecologic oncologist.  The idea that a
vaccine can be given to prevent what is a horrendous cancer, should
it develop, just blows my mind.  I recommended it for my own
grand nieces now and I certainly think it is appropriate for young
women.Chu
 Peter, can we talk a little bit about the current methods approved
for screening for cervical cancer?Schwartz
Sure.  The Pap smear has been extremely effective in reducing
the incidence rates of cervical cancer in the United States. 
They were introduced here in Connecticut in 1957 or so.  We
now expect only 120 cases a year of cervical cancer in Connecticut;
in the United States as a whole, only 11,000 new cases of cervical
cancer.  When I went to medical school, it was a number one
cancer in women, today, its number 13; Pap smear screenings really
work.  There have been some developments, however, in Pap
smear screening, including the development of liquid based
cytology, which initially was supposed to be more effective then
the conventional cytology that women have been getting for many
years.  More recent studies suggest it's as affective as the
conventional.  So, it's getting the Pap smear that's critical,
not the type that you get.  Even more recently, however, has
been HPV screening. HPV screening allows us to detect whether or
not there is a so-called, high-risk oncogenic8:57 into mp3 file 
http://www.yalecancercenter.org/podcast/july1909-cervical-cancer-awareness.mp3type of papillomavirus present.  The high-risk oncogenic
types are the ones that are associated with the development of
precancerous and cancerous changes, where as the low-risk oncogenic
types are associated with warts.  The introduction of the HPV
DNA testing for women over age 30 has been quite beneficial and can
allow one, if one has three negative Pap smears or negative Pap
smears in association with negative HPVs, to prolong the interval
between testing for cervical precancerous or cancerous changes.Foss
At what age should a woman start getting Pap smears and how long,
say after menopause, does a woman have to continue the Pap
smears?Schwartz
Well, it's just a bit controversial, but generally speaking, we
recommend that within six months of a teenager beginning to have
sexual intercourse, you should have a Pap smear.  How long you
should continue it has been debated a bit.  Between the age of
60 and 65 have been the recommendations of our national
organizations like the American Cancer Society.  However, we
are noticing that a lot of more women over age 50 are now being
tested positive for HPV, and this group of women in particular are
women who are divorced or lost their partner, and now have new
partners.  While we say 60 to 65, quite honestly, I see no
particular upper limit that we should stop doing Pap smear
screening at this moment.Chu
 Take us through some of the process of the Pap smear.  Are
there any complications associated, what does it entail?Schwartz
Pap smears are a very benign test, but require that an instrument
be inserted into the vagina to expose the cervix so that one can
then use what we call a brush and simply wipe the cervix so that
cells can sluff off the cervix and be captured either in liquid or
a glass slide and that's the whole process and it's really very
simple.Chu
 It doesn't sound like there are really any significant side
effects or complications that can occur from that procedure.Schwartz
No, but sometimes when one uses a brush on the inside lining of the
cervix, you can see some spotting after you have had the Pap smear,
its not a reason to be alarmed, but it can occur.Foss
Peter, you talked about a woman in her 50s who is now HPV
positive.  Is there any role, say for a hysterectomy in such
women, to prevent cancer in the future, or is Pap smear screening
and following the patient adequate to prevent cancer?11:49 into mp3 file 
http://www.yalecancercenter.org/podcast/july1909-cervical-cancer-awareness.mp3Schwartz     
 
 It gets very confusing as to what these abnormal Pap smears and
these abnormal HPV testing's really mean to an individual patient,
but in a postmenopausal woman who has a negative Pap smear but is
HPV positive, meaning the high risk oncogenic type, she needs to be
followed more carefully then somebody who has a normal Pap smear,
but has no high risk HPV present, that woman should be still
followed on an annual basis.  If there is high risk HPV
present, she needs to be colposcoped, and in particular, in
postmenopausal women, the area of concern is called the
transformation zone that's an area where the outside surface of the
cervix, which is lined by squamous cells, meets the glandular cells
of the canal.  In postmenopausal women, this area recedes into
the cervical canal and the colposcopy doesn't always pick up
everything, but if the Pap smear is positive, that patient should
be colposcoped and biopsied as soon as the report is available.Chu
 Can you just clarify one thing, is the HPV test a blood test, or
is that a test done on the fluid that comes out of the Pap
smear?Schwartz
The HPV test is the test that's done on the fluid that's associated
with the Pap smear itself.  It's what's in the container after
the doctor has taken the Pap smear.Chu
 I am just curious, is there any kind of blood test that can be
done to help in this screening process?Schwartz
Not currently.Foss
What about prevention programs here in New Haven?  The
hospital participates in the National Breast and Cervical Cancer
Early Detection Program, can you talk a little bit about that?Schwartz
Yes, that program was originally started in 1990 and it was more of
a screening and early detection program, but in the year 2000, a
law was passed allowing the provision of Pap smears and mammogram
for women who are either under a certain income level or are unable
to provide any kind of health care.  It's a free program and
it allows for both the screening for Pap smears and also for a
mammography, and since 2000, through Medicade, it covers the
payment of the services so that people can be treated free of
charge.  It's done through the State of Connecticut and
Yale-New Haven Hospital was one of several hospitals in the state
where this program was active.Foss
It's great to hear that this is available to women across the state
Peter.  We would like to talk a little bit more in detail
after the break about the treatment of cervical cancer.  You
are14:41 into mp3 file 
http://www.yalecancercenter.org/podcast/july1909-cervical-cancer-awareness.mp3
 listening to Yale Cancer Center Answers and we are here with Dr.
Peter Schwartz discussing the risks and the prevention of cervical
cancer.Foss
This is Dr. Francine Foss and I am joined by my co-host Dr. Ed Chu
and Dr. Peter Schwartz, an expert in gynecologic cancers from Yale
Cancer Center.  Peter, we talked a lot about the risks for
cervical cancer and the role of HPV, but what are the treatment
options for a woman who has cervical cancer?Schwartz
Let's define what we mean by cervical cancer, because a lot of
people are told they have cervical cancer when actually they have
the precancerous change.  For precancerous changes there are
simple procedures one can do in the office, or in an outpatient
surgery center, which remove a piece of the cervix; this is called
a cone biopsy.  It could be done in many ways; with a scalpel,
a laser, or an electrolyzed loop called the LEEP procedure. 
However, when one has invasive cancer of the cervix, one has to be
more aggressive. For early stage cervical cancers the standard
treatment has been an operation called a radical hysterectomy,
which not only removes the cervix but removes a border of normal
tissue that surrounds the cervix; it also removes the upper
vagina.  For more advanced disease, radiation in combination
with chemotherapy is the standard treatment for the management of
cervical cancer.Foss
Is there any role, say for radiation, in some of these patient that
have limited involvement who don't undergo surgery?Schwartz
For limited involvement radiation alone is not generally used;
however, there is an operation called a radical trachelectomy and
partial vaginectomy, which is being done here at Yale. This is an
operation that is designed to hopefully cure cervical cancer and
preserve fertility.  That operation would be used in a select
group of younger aged women.Chu
 Would a woman typically go to their general GYN physician for
these treatments that you17:45 into mp3 file 
http://www.yalecancercenter.org/podcast/july1909-cervical-cancer-awareness.mp3
 are talking about, or would that individual seek medical care from
a specialist like yourself, a GYN oncologist?Schwartz
For the precancerous changes called cervical intraepithelial
neoplasia, our community doctors are trained to take care of that,
and that's where the overlying majority of patients receive care
with community doctors in our community hospitals.  For
invasive cancer of the cervix, that's a different situation, and
that's where they need to see a gynecologic oncologist.Foss
What is the role of CAT scanning, PET scanning, and MRI scanning in
women who have invasive cervical cancer in terms of making a
diagnosis and a treatment plan?Schwartz
We diagnose by simply biopsying in the office, and that gives us
the diagnosis of an invasive cervical cancer.  Once we have
that diagnosis, then the question is how far has the disease
spread? If in the office, using a physical exam by a gynecologic
oncologist, the disease seems to be limited to the cervix, we often
don't do much more diagnostic evaluation.  However, if the
disease seems to extend beyond the cervix, then diagnostic imaging
is important.  The CAT scan can be very helpful in telling us
whether or not there is disease involving lymph nodes, particularly
along the para-aortic area.  It will help us to tell whether
the urinary tract is in anyway involved; we look for things like
ureteral obstruction, deviation, and duplication.  The MRI is
much more effective in looking directly at the local area of the
pelvis, and it tell us whether the disease has extended outside of
the cervix and it can certainly look very well at the pelvic lymph
nodes and tell us whether or not there might be involvement. 
The PET scan is generally used to identify more distant
spread.  So, in early stage cervical cancer, very limited
imaging is necessary, in a more advanced stage, that's where these
other imaging modalities really come into play and that's how we
use it.Chu
 Peter, is there any role for chemotherapy, giving chemotherapy
drugs either before surgery is performed or perhaps giving
chemotherapy drugs once the surgery has been conducted?Schwartz
Giving chemotherapy before definitive surgery is done or radiation
is done is called neoadjuvant chemotherapy, and its something that
has been going on for certainly at least the last 25 years in
cervical cancer management. This is particularly because in the
third world, they see a lot more advanced stage disease then we
see.  Neoadjuvant chemotherapy is most effective in something
called stage 1B2 cervical cancer.  This is when the cancer is
really expanding the cervix beyond 4 cm, but hasn't spread outside
of that area. It would appear that neoadjuvant chemotherapy can
shrink the cervix down and then allow the surgeons to do radical
hysterectomies.  So that's the one place where neoadjuvant
chemotherapy appears to be effective.  Once the diagnosis is
made and radiation is going to be given, cisplatin20:59 into mp3 file 
http://www.yalecancercenter.org/podcast/july1909-cervical-cancer-awareness.mp3
 chemotherapy is usually given as a single agent on a weekly
basis.  There have been four different studies that have shown
that for patients receiving primary radiation therapy,
platinum-based chemotherapy in combination with radiation is the
most effective way to treat people. There has been a study that
showed for those women who have had radical hysterectomies, but
have bad prognostic features when the pathologist examines the
specimen, those patients who would then get postoperative radiation
if one adds chemotherapy, also benefit from the combination of the
chemotherapy with platinum, cisplatin and the radiation.Foss
What are the complications for women of having a combination of
chemotherapy and radiation?Schwartz
The complications don't seem to be increased significantly. What
the issue with radiation is that it can irritate the bowel and it
can irritate the bladder.  Typically patients who receive
radiation or chemoradiation tend to have loose stool and diarrhea,
which during radiation therapy the real therapist will put them on
diet and give them medications to control that.  They also
will have to void, pass urine more frequently during the
radiation.  For the most part, that clears following
completion of the chemoradiation.Foss
What about the role of biological agents? We have heard a lot of
about the HER2/neu antibodies, and breast cancer, and the
antibodies that are targeting the EGF receptor, and various kinds
of solid tumors, do any of those apply to the treatment of cervical
cancer?Schwartz
At this moment, to my knowledge, there are none approved; however,
there is a research program that is being conducted by the
Gynecologic Oncology Group, which is now an international study
group but its based in the United States, and we are participants
in the GOG study and are looking at EGFR its epidermal growth
factor receptor inhibitors in recurrent cervical cancer.  It's
still experimental at this point.Chu
 Peter, how significant a problem is a recurrence of cervical
cancer?Schwartz
Well, it's a real problem.  Basically, in Connecticut, we see
two groups of women.  One who have had fairly reasonable Pap
smear screening surveillance and they tend to be found with early
stage cervical cancer and are usually cured with a radical
hysterectomy. Then we get another group, and it's the larger group
of women, who have declined to have Pap smear screening; they come
in with invasive disease that's advanced.  Early stage
disease, stage I disease, has roughly a 90% cure rate.  Once
we start to see that the disease has spread outside of the uterus,
the cure rates decline dramatically.  When the spread is just
limited outside the pelvis, stage 2B, it has about a 60% cure rate,
when its spread to the pelvic sidewalls, stage23:58 into mp3 file 
http://www.yalecancercenter.org/podcast/july1909-cervical-cancer-awareness.mp3
 3B, then we are talking about between 30% and a 50% cure rate,
which means that 50% to 70% of the patient's are going to recur.
And with stage IV disease, which we still see in Connecticut, in
women who have neglected to have Pap smears, almost every one of
them is going to recur.Foss
When we talk about neglecting to have Pap smears, we probably
should have talked about this at the beginning, but are there any
symptoms that those women experience?  If you just go on
without a Pap smear and you are developing cervical cancer, how
would you know?Schwartz
That's a great question.  Typically, the belief of
gynecologists was that women with invasive cancer have symptoms,
and women with pre-invasive disease don't have symptoms. 
Women with invasive disease experience bleeding because the tumor
grows and outstretches its blood supply, and they tend to bleed.
They can have vaginal discharge, and this is due to secondary
infection by the bacteria in the vagina that causes malodorous
discharge. They can also have pain as the tumor invades the nerves
in the pelvic sidewall and pain can radiate down their legs;
sciatic pain is classic with advanced stage cervical cancer. 
We did a study, however, looking at precancerous changes in the
cervix and early cervical cancer, and we found that about the same
proportion of our patient's had bleeding spontaneously or after
sex, who had carcinoma in situ which are precancerous changes, one
step before invasive cancer.  So, abnormal vaginal bleeding,
particularly bleeding after having intercourse, is a very-very
serious warning that there could be a problem of cervical cancer or
precancerous change.Chu
 What percentage of women, in the State of Connecticut and in the
United States, still are not getting screened for cervical
cancer?Schwartz
Back in the 1980s we reported on women who had cervical cancer who
had been getting annual Pap smears and had what we call rapidly
invasive cervical cancer. That led to a very large program project
where we looked at every case of cervical cancer in Connecticut
between 1985 to 1990, and what we found was that the invasive
cancers, about 25%, occurred in women who had Pap smears that were
read as normal within three years of the diagnosis of cancer. 75%
either had not had Pap smears or had stopped having Pap smears once
they had delivered their last child.  So, we found that a
large percentage of patients who developed the cancer don't have
Pap smears, what we don't know is overall how many women don't have
Pap smears.Chu
 Do you have a sense of, in 2009, if we have gotten better in terms
of bringing down that number from 75% to hopefully a much lower
number?26:55 into mp3 file 
http://www.yalecancercenter.org/podcast/july1909-cervical-cancer-awareness.mp3Schwartz
I don't have a feeling that it's changed very much, to tell you the
truth.  When I look at what goes on in our service, I think
that this is the best reason for Gardasil, for the cervical
vaccine.Foss
In terms of understanding the biology of these kinds of cancers,
GYN cancers, I understand that you have a very active research
program in your department called Discovery to Cure, can you tells
us a little bit about that?Schwartz
Well, the Discovery to Cure program it is about ten years old now.
It was originally designed to study ovarian cancer, then we moved
into uterine cancer, and now Dr. Alessandro Santin has jointed
faculty. Dr. Santin is, among many other things, interested in
vaccine therapy for cervical cancer. He is in a phase II trial now
looking at a vaccine that he has developed for cervical
cancer.  So, the Discovery to Cure program is marching on and
we are taking on more and more diseases as we are able to afford
investigators and laboratory research.Chu
 And are there any clinical trials that you and your colleagues are
currently involved with focusing on developing new therapies for
say, advanced recurrent cervical cancer?Schwartz
At this moment the only one that we are actively involved with is
the gynecologic oncology group trial that uses molecularly targeted
therapy, and Dr. Santin is the principal investigator for the
gynecologist oncology group in that trial.Foss
And as we get close to summer, I just wanted to put in a plug for
your program, because I know that you do take on high school
students to work in the research labs along with senior
investigators and that is a tremendous program, hopefully to
interest some young people in going into science in the future.Schwartz
Exactly right, it's a great program.  Dr. Gil Mor runs that
program now for us and is supported through the Discovery to Cure
mechanism. It's just one of the things; we are not only interested
in laboratory research, we are interested in education. It starts
in the high school, and we have college students as well working in
the lab, medical students, and graduate students. It's a lot of
information that we try to provide to a lot of different
people.Chu
 It's amazing how quickly the time has gone. Peter, we look forward
to having you back on a future show to give us an update on what's
going on with cervical cancer and all of the other GYN cancers that
you are involved in.29:34 into mp3 file 
http://www.yalecancercenter.org/podcast/july1909-cervical-cancer-awareness.mp3Schwartz
Thank you very much.  It's a pleasure.Chu
 You have been listening to Yale Cancer Center Answers and we would
like thank our special guest expert Dr. Peter Schwartz for joining
us this evening.  Until next time, I am Ed Chu from the Yale
Cancer Center wishing you a safe and healthy week.If you have questions or would like to share your comments, go
to yalecancercenter.org where you can also subscribe to our podcast
and find written transcripts of past programs.  I am Bruce
Barber and you are listening to the WNPR Health Forum from
Connecticut Public Radio.