Tom Cox, MD, is the Director of the Women’s Center at the University of California, Santa Barbara’s Student Health Service. He was hired in 1986 as a colposcopist to serve the needs of the university’s female undergraduate and graduate population. Prior to working at UCSB, Dr. Cox ran a private obstetrics and gynecology practice in Marin County, CA.
Dr. Cox estimates that 70 percent of his time is occupied by his university work. The other 30 percent is spent in various functions related to women’s health. Dr. Cox is the Executive Medical Director for the National HPV and Cervical Cancer Prevention Center, which is part of the American Social Health Association. He is also the Clinical Advisor for the National Cancer Institute’s HPV Vaccine Trial in Costa Rica. And for the past six years he has been on the Steering Committee for the National Cancer Institute trial studying how to best manage minor Pap abnormalities, including HPV testing. In September he will moderate a conference organized by the American Society for Colposcopy and Cervical Pathology that will establish universal guidelines for Pap management. Dr. Cox is on the Board of the ASCCP.
MedTech1: Could you walk me through a typical day as Director of the Women’s Center?
Dr. Cox: At the university I see women undergraduate and graduate students for gynecologic problems. We have several nurse practitioners and occasionally another doctor who also work in the women’s section of the health center. I am generally referred the more complicated cases and the colposcopies. My job, the job I was hired for in 1986, is to manage women with abnormal Pap smears including colposcopy and surgical treatment when necessary.
MedTech1: Were you in private practice previously?
Dr. Cox: Yes, I had an OB/GYN practice in Marin County, CA, for eight years.
MedTech1: What brought you to the university?
Dr. Cox: I loved what I did but I was not thrilled with night and weekend calls. Because I was out delivering babies I couldn’t be with my family as much as I wanted to be. So I started in the early 1980s looking for something different and ended up taking quite a detour. I sold my practice in 1984 and moved with my family to a plantation we purchased a few years earlier in the Fiji Islands. We ran a coconut and vanilla plantation for the next couple of years, and I took care of the surrounding local population, providing free medical care out of a clinic in our home.
Eventually this job came up at the University of California in Santa Barbara, my wife’s hometown. The job advertised for a colposcopist, and I had always enjoyed the colposcopy aspect of my practice more than anything. So I took the job for that reason. Also, at the time it was a 9-month job, so my family and I could spend three months a year in Fiji on our plantation and nine months working. Eventually the nine-month aspect disappeared and the job has been full-time since 1988.
MedTech1: I did not realize there would be such a specific need for a colposcopist at a university.
Dr. Cox: The age group that I work in is at very high risk for getting genital warts and other manifestations secondary to human papilloma virus (HPV) such as cervical cell changes. Beginning in the mid- to late-1980s we saw a very significant increase in those manifestations in young women. That was why the University looked for somebody to put in the colposcopy position. At that time, the Women’s Center had two or three doctors and several nurse practitioners working mostly with this problem. Now we have a significantly lower number of practitioners who have to spend time with women on these issues. The reasons for the decrease in HPV manifestations are not entirely clear.
MedTech1: Is it due at least in part to safer sex education?
Dr. Cox: I would like to think so, however studies performed on women in this age group show that approximately one-quarter of college women are positive for HPV at any point in time. In a study done by Rutgers University, they got several hundred women to come in every three months for three years to be tested for HPV. The researchers found that over a three-year period, 60 percent of the women were positive for HPV at some point. The virus is very, very common. But for some reason the manifestations of it, at least in our setting, do not seem to be as common as they were in the late 1980s.
Fortunately, most women do not get anything really significant from HPV. A small percent of these women actually get genital warts and probably about 5 to 6 percent get cervical manifestations of HPV. Most of these cervical manifestations are low-grade and are the manifestation of acute HPV infection. Immunity still has a very good opportunity of getting rid of those changes without any real consequences to the woman.
Most young women who have HPV are not at any real significant risk. The problem is that about .5 percent of all women get high-grade changes on Pap smears, and about 1.5 percent get high-grade changes on the cervix proven by biopsy. Those changes, if untreated, could over time turn into cervical cancer. The basic reason for colposcopy is to pick up those high-grade changes and treat them so the woman is not at risk later in life.
MedTech1: Is the colposcopic exam similar to the exam for taking the Pap smear?
Dr. Cox: It’s not very different, at least in terms of how you approach looking at the cervix. You put the speculum in and visualize the cervix just as you would for a Pap. The difference is that you put vinegar on the cervix during colposcopy, which not only cleans the mucus off but also dehydrates the cells on the cervix. Abnormal cells have larger nuclei and are denser than normal cells when dehydrated, so when you shine a strong light on them through the colposcope, the light bounces back much whiter than the surrounding tissue. Not uncommonly, there are blood vessel changes which you can see in the area of abnormality due to increased rate of cell growth. The combination of the density of the tissue, the whiteness that is reflected back, and the blood vessel changes allow you to determine whether biopsy is necessary.
Fortunately for most women, biopsies are not very uncomfortable. There is not nearly as significant a nerve supply on the cervix as there is in most of the rest of the skin. After the procedure, a pathologist reads the biopsy and determines if there are changes related to HPV and, if so, whether they are low- or high-grade. Then the clinician and the patient can decide together how to approach those changes. If they are low-grade, usually the patient is given the opportunity to either treat them as you would treat high-grade disease or not do anything and see if immunity will resolve the problem. In that case, we would just follow up closely with Pap smears. If low-grade disease is treated, it is usually frozen by a procedure called cryotherapy, or cryo for short.
High-grade disease is always treated. You can call it “pre-cancerous” because it has a significant enough potential of eventually going on to cancer. There are two levels of high-grade disease: CIN2 and CIN3, or moderate and severe dysplasia. CIN3, or severe dysplasia, is a true pre-cancer. It has a very high risk, if left long enough, to become invasive cancer. CIN2, which is part of high-grade disease, is on the borderline between CIN1 and CIN3 in terms of risk. A lot of CIN2 will regress spontaneously, and some will go on and persist. In this country, almost everybody with CIN2 is treated.
MedTech1: Are most women with HPV unaware that they have the virus?
Dr. Cox: Yes. HPV is such a common virus that statistically the risk of getting exposed is somewhere in the range of 15 percent per new partner. There is no other STD (sexually transmitted disease) that comes even close to that in terms of the risk of acquiring it. Luckily, it is a fairly low-risk virus. Some would argue it is the only STD that causes cancer, but that is not actually true. Hepatitis B can cause liver cancer, and HIV can make one susceptible to a whole range of cancers.
HPV is a virus that is proven to be necessary for cervical cancer and several other lower genital tract cancers to develop: penile cancer, 80 percent of vaginal and 50 percent of vulvar cancer, anal cancer. A good deal of those cancers are related to the virus.
MedTech1: How did you become so involved with HPV testing?
Dr. Cox: I have gotten involved in all my committees through my position with the student health service, which is not a typical route. In the late 1980s I was trying to understand better how to manage women with all of these HPV problems. There was also a change to the way Pap smears were read in the late 1980s and a new Pap reading called Atypical Squamous Cells of Undetermined Significance (ASCUS) was devised, which became a big management headache.
At about the same time, the first commercial HPV test was released on the market. I decided to evaluate whether that HPV test could help understand how to best manage women with this Pap smear abnormality called ASCUS. This study in our health center was published in 1992 and led to another study on ASCUS management with a better HPV test that was published in 1995. Eventually the National Cancer Institute (NCI) trial, which has been called the ASCUS LSIL Triage Study (ALTS), began in 1995. The NCI put $30 million into the ALTS study and the enrollment results were published six months ago. There are multiple other papers coming out from this study on ASCUS management in the next few years.
The dilemma has been how to manage these women with this minor Pap abnormality. A very small percent will have a significant cervical problem, yet most of the women are normal. It’s kind of like looking for the needle in the haystack. How do you find the needle in the haystack without getting stuck looking for it? You don’t really want to colposcope all women with this problem because the majority women are normal and colposcopy is very expensive and produces a significant amount of anxiety. And women do not like the thought of potentially being biopsied.
The other option that has been utilized significantly over the last decade has been to repeat the Pap every six months for two years. If all repeat Paps are normal, the woman can return to annual Paps. But if any repeats are abnormal, then colposcopy is recommended. But most of the studies that have been done recently have shown that repeat Pap delays diagnosis on a significant number of people with significant disease. Also, this method is likely to be more costly than HPV testing follow-up, and may even be more expensive than colposcopy.
The ALTS study showed that if you HPV-tested women with this Pap reading, about half would be HPV positive for types that are known to be associated with cervical cancer. Therefore, you have already taken about 50 percent of the women and told them that they are not at risk. The other 50 percent need colposcopy. About 20 percent of those that are HPV positive may have high-grade disease detected in follow-up. You’ll still find a significant number of women with an ASCUS Pap who are HPV positive who are normal on colposcopy. The majority of those women will return to normal and eventually return to HPV negative state due to their immune response because most people with HPV will clear it from themselves eventually. However, some of those women who are normal at colposcopy and who are also HPV positive are at increased risk for, and will eventually develop, some significant cervical disease if they do not clear the HPV. Therefore, HPV positive women who are not found to have disease at colposcopy still need to be followed more closely. So an HPV positive test in a woman negative at colposcopy still has predictive value.
MedTech1: Are they monitored with more frequent Pap smears?
Dr. Cox: I think Pap smears every six months until they return three normal Pap smears in a row is appropriate. Some people would advocate repeating the Pap and HPV tests in a year instead, which would be a cost-efficient and perhaps more reasonable way to follow these women.
The interesting thing about where we are at this junction in time is that there never have been any national guidelines on how to manage Pap smears. The American Society for Colposcopy and Cervical Pathology, of which I am on the Board, is having a Pap management consensus conference at the NCI’s Bethesda campus in September. The conference will be attended by about 60 organizations which are interested in Pap smear management: the American Cancer Society, the American College of Obstetrics and Gynecology, the Centers for Disease Control, and more. Recommendations are being made on how to manage abnormal Pap smears.
This is a very significant juncture in history for Pap smear management because there has never been a concentrated effort to make guidelines that would be accepted across the nation.
MedTech1: How do you divide your time between the University and your committee work?
Dr. Cox: I have an ideal life. I very much enjoy the patient contact and I like taking care of the students. Yet I love the intellectual side of all these other activities I have had the opportunity to participate in.
MedTech1: What do you see yourself doing in the next five years?
Dr. Cox: I will stay at the University until I retire. And I will continue to be actively involved in all these other functions as well. There is so much out there that needs to be done, but the University provides a home base. I also cannot see my family or myself wanting to leave Santa Barbara. It is the most incredibly beautiful place I have been.
Photo courtesy of University of California, Santa Barbara Student Health Service