OBGYN.net Conference CoverageINTERNATIONAL FEDERATION of GYNECOLOGY & OBSTETRICS: Washington DC, USA
Dr. Zvavahera Chirenje: “Good morning, everybody. Like the Chairman said, we are facing a formidable task in gynecological cancers in our part of the world. I think for most of the people attending the conference – obstetricians and gynecologists, it is of note that one of the reasons we face a formidable task is because of the areas we live in. I live in Zimbabwe in Southern Africa, in Harare is where I practice and I work for the University of Zimbabwe. The Committee needs are actually more for general obstetrics especially because of the high maternal mortality which obviously more people are keen to talk about, and the average person who works as a trained doctor in our part of the world is more keen to address the problems of maternal death and mortality very important diagnostic process in the way of bed occupancy and early deaths. The other problem we face as a nation in Zimbabwe is the high prevalence of HIV, which obviously impounds a lot on the maternal transmission policies. I thought I would start with the background; I am part of the Zimbabwe nation Cancer Registry which I’m currently serving as the Treasurer. We have the Zimbabwe Cancer Registry from way in the eighties, which I serve as a member, and one of those registries in Africa is recognized by Leon France in terms of data collection.
This is from our latest data set which basically shows you that out of the 6,000 cases recorded in Harare, there were at least 50% male cancers, about 45% female cancers, and about 3.5 pediatric cases. What we’ll go through here is an elaboration of what sort of female cancer cases we see in the country. The distribution of cancer seen in the 1996 registry was in all 6,000 and out of that 45% were female and pediatric cases. I won’t talk much about pediatric cases but of interest in pediatric cases is that we are seeing a high prevalence of Kaposi’s sarcoma, which was never recorded before the HIV epidemic. Then out of the 3,000 cases of female cancers, the burden of cervical cancer is by far the largest; one in every three of all registered cancers is cervical. We also reported recently in a publication of the International Journal of Cancer that Zimbabwe is one of the highest age standardized rates for cervical cancer at about 53 per 100,000. You will note that lots of countries are recording cases of age standardized rates of about 10-12 per 100,000 and the profile of gynecological malignancies we saw in 1999 constituted cervical cancer about 83%, by far the largest, and ovarian cancer was about 68 cases, about 7.5. Uterine cancer, again, is an extremely rare cancer as you can note compared to most of the countries in the north, and colon carcinoma about 2.1. Vulva cancer is an extremely rare cancer in our situation, and I want to add a word about vaginal cancer. Primarily, vaginal cancer is extremely rare; we spend a considerable amount of time on it because I guess it’s basically a cancer confined to very elderly women. The two cases of note here were one woman was 22 years of age from a neighboring country, which also has a problem with HIV, and she has an HIV disease going on. The second one is a 32-year-old lady, again, with a primary vaginal cancer, and these were actually compiled case reports for International Journal of Cancer. Note that these two vaginal cancers are quite interesting in the sense that these were the first primary vaginal cancers recorded in a period of fifteen years, and both of them are associated with HIV. I’ll talk a bit about cervical cancer because that’s where we spend most of our time in terms of our practice in gynecological cancer. Cervical cancer occurs at peaks ages in Zimbabwe, around 47 years of age. Right here you can see that most of the women who were diagnosed with cervical cancer are at the peak of their lives, their children are young, probably in high school, and it’s a tremendous loss to the economy. The majority of cancer cases are referred from the rural communities.
We have a fairly well defined health sector in Zimbabwe: there’s about 1,500 primary health centers in the country, 52 district hospitals, 8 provincial hospitals, 2 tertiary hospitals, and I work in one of the tertiary hospitals. Our system is fairly effective in the sense that the rural communities are defined by a health center, which is ten kilometers within the confines of the rural areas so the first entry for diagnosis is a rural health center. Then they go to the district hospital before they go to the provincial hospitals. If they’re advanced, then they come to us or if they think they need operative care, they’ll come to us. As you can see, the majority of them by the time they come, 80% of them, are stage II-B and above. I’m hesitant to say that we are lucky in Zimbabwe in the sense that we have two effective radiotherapy centers, and unlike myself, I am the only gynecologist but they list eight radiation oncologists in Harare and two in Bulawayo. They, in fact, cater for quite a few of our neighboring countries, to my knowledge there’s no radiation center in Mozambique. The Zambian situation and Malawi is the same so we see quite a few cases with cervical cancer when you treat from the surrounding countries. Part of the reasons why these ladies come in advanced stages is that there’s basically no screening cervical cytology, at this level, there are no screening facilities. As you know, cytological services are quite expensive, and in a recent study we did on situation analysis for cervical cancer screening, we documented that only 5% of women are ever screened in Zimbabwe. Out of those 5%, they tend to be urban women and they tend to be in private practice, which obviously is not catering for the majority of women in rural areas. So if a case presents to the primary health center with suspicion of cervical cancer, and most of these women present late because the symptoms of cervical cancer as we know in the early stage of the disease are asymptomatic, and once in a while they may have post-coital bleeding but, again, this is contact bleeding when this cancer itself is fragmenting. Once they approach the district hospital, there is a resident medical doctor who has access to histology. The only problem is the histologic process in the two tertiary hospitals in Harare and Bulawayo; it takes a lag time of 4-6 weeks to get the results back to province and to district hospitals. Again, it’s a lack of manpower; there are no pathologists at district or provincial hospitals.
We have eight provincial hospitals, and all the pathologists we have are in the tertiary centers. So that time lag is not to the benefit of the patient, and if you look at the histological diagnosis in 1999, 92% had squamous cell carcinoma, 7 are adenocarcinoma, and the others were mixed. The standard treatment we offer, and you must keep in mind that the operable cases occurring are between 16%-20% each year, is we do a standard external hysterectomy pelvic lymphadenectomy, and we do have a very effective anesthetic cover with good ICU coverage at the tertiary hospitals. But one of the things to keep in mind is that the social culture barriers heavily instructed in the African community is not an easy issue. You sometimes approach women that have elegance and there is almost a 25%-30% default rate because they do not accept a hysterectomy easily and the workload. It makes the practitioner and counseling not fairly adequate to convince these women to have the operation. However, some of them will go back to rural areas and when the disease advances, i.e. they’re now having uncontrollable bleeding, smelly discharge or fistulae in the urine, they’ll come back for palliative care in the central hospital. So radiation therapy by far is the most common mode of treatment, and Harare is a center that has advantages. They have perhaps what you would consider the latest technology in radiotherapy, they’ve got afterload machines, and the success rate of treatment is quite good. I do run a joint clinic with radiation oncologists where we screen cases, and we now have a standard protocol to offer HIV screening for all women who are diagnosed with cervical cancer because we know that the treatment course is quite affected by the level of the disease. Chemoradiation therapy is offered and is a standard treatment now for women with bulky disease. What we have noted over the past years is that quite a few of the young women below 35 years of age with bulky disease are actually HIV positive, and if I can go into what we’ve observed is the relationship between HIV and cervical cancer in the center. We did a cross sectional study which we published in the British Journal of Obstetrics & Gynecology sometime this year, this was a screening study for cervical cancer. Out of the four under 66 women, the prevalence of HPV by probe B was 47%, low grade was 13%, and high grade was 12%. HIV infected women had a three-fold greater AGSL compared to HIV infected. In other words, if you’re HIV infected your chances of high grade was 17% compared to those women who actually had a negative 1, and a prevalence of 5.9. Among these 92 women with HIV virus, treatment for high grades by cryotherapy actually had a significantly low failure rate of 40.5% compared to a lip excision, which had a failure rate of 14% at 12 months. This we think is extremely important in terms of implementing protocols which talk about treatment for cervical pre-cancer which is obviously needed, once you diagnose high grade, we recommend that you should screen for HIV in your community. If you’re going to offer any therapy to these women, you should probably avoid cryotherapy.
We have also done a publication recently where we looked at our data from the Zimbabwe initial Cancer Registry, and as you know in this country in 1993, the AIDS defining CDC regulation stated that a woman who was HIV positive with invasive cervical cancer should be put in the AIDS defining syndrome like somebody with pneumocystic carinii. What we’ve observed over the years is actually that we don’t see any increment in actual cases of cervical cancer on the total registry. In other words, the first slide I showed you which showed about 700 women with cervical cancer in a year, it’s pretty much steady from the eighties and we put this publication to note that what we see is an increment of Kaposi’s sarcoma among women. We also noted that the latency is four months including ovarians are also in the increment but in terms of invasive cervical cancer itself, we don’t see a significant increment, which would parallel the high prevalence of HIV, which now in most clinics is going as high as 25%. However, we noted that HIV infected women develop invasive cervical cancer at virtually a younger age, below 35. Lots of them are very bulky disease, and these are cancers when you do an EA is quite mobile, and it’s confined to the cervix but it can go to diameters of 10-12 cm. This is why we now have a protocol that for all cervical cancer diagnosed by a histologist they should have an HIV screen, and if they’re more than 4 cm, offer them initial radiation therapy by external beam. I do run a joint clinic with a radiation oncologist to actually assess post-radiation therapy and surgical intervention. We have been compiling and we probably have about twelve now. We’ve gone past two years of survival because before that we noticed that it was extremely difficult for an HIV positive cervical cancer case to go beyond two years but a combined modality seems to be the way for it.
The next thing I want to talk about is ovarian cancer. Ovarian cancer is not as common, as I said, as cervical cancer but it’s the second most common cancer in our center. I must say in our publication for the Center we did note that among the white population in our community that the register has actually one of the highest age standardized incidences for ovarian cancer but in terms of actual numbers, we are relatively small. The other thing to note in our population is that ovarian cancer does cause a problem among the young girls who come in with germ cell tumors. They tend to ignore abdominal swelling and the peak age for that in our data is about 18-22. Although they are initially extremely responsive to chemotherapy with the blood therapy, they tend to recur a lot and that’s fairly frustrating. If I may also say, lots of the women from the rural areas still present quite late with advanced stage III cancers, and unlike cervical cancer, we do not have a confined approach. I see them for chemotherapy, in other words, the open policy we still run is that most of the gynecologists do the initial approach and it’s for ovarian cancer, then they’re referred to my team for management for chemotherapy. So we do debulk in surgery and we offer them six courses of platinum contained chemotherapy in both in Harare and the perinatal hospital. The major problem with the platinum based chemotherapy for us is the cost. Over the past few years it has been very difficult, in fact, to offer anything above cisplatinum, Carboplatinum, or Taxol. All of those drugs are available in town but you cannot afford them for government patients so that’s also confounding. But I must say the successful treatment here is fairly poor, most of them are dead of their disease within two years. The other problem we face is choriocarcinoma, it occurs fairly frequently, and we have no facilities to treat this cancer anywhere outside the tertiary hospitals. Lots of them come quite late with advanced disease. I don’t have case presentations here because of the limitation of time but I attended one or two talks on choriocarcinoma management and they talked about surgical management. I think it would be fair to say that I probably do a primary hysterectomy for uncontrolled vagina hemorrhage for many ignored choriocarcinoma from the rural areas, maybe one in every four for four weeks. When they come early, gestational trophoblastic disease is quite responsive. We give them standard modified bed shore, we score them, and we give them the standard chemotherapy. We tend to use methotrexate alone and then we combine it with etoposide for the medium risk and then standard bleomycin, and with the difficult recurrences, we are now adding platinum based therapies.
We’ve had one or two cases where it was difficult, one or two cases where I’ve had to call a cardiothoracic for resection, and one or two cases for irradiation of their brain, and cure rates are difficult because we have problems with defaults. People who come from the rural communities and are very ill, in other words, they’ve got a lot of metastasis, they are coughing blood, they’re quite poorly, and you start them on chemotherapy, they go for 1, 2, or 3 cycles and they’re relatively better, they are stable. To convince them to stay in the urban areas for treatment is extremely difficult for some of them. They go back to their homes and by the time they come back, they’ve got tumor resistance, and then you’re stuck so that’s a big problem although we try hard to get them going. About five years ago we noticed some of the ladies coming in with choriocarcinoma away stage and we didn’t have any routine policy for HIV screening. We had one or two fatalities because induction of chemotherapy with a high risk regiment on an HIV positive patient, your best following an immune system which is depressed and cytotoxic drugs down the road will blast your cells in the bone marrow until you can’t reverse it so we now have standard HIV protocols before you administer any cytotoxin for choriocarcinoma. We have recorded quite some success stories in these young ladies. I conclude that the burden of gynecological cancer in Zimbabwe is mainly cervical cancer, and in the last slide I just talked about the burden of cancers is basically cervical. In Zimbabwe we embarked on a mass screening research protocol several years ago and we published in the LANCET for visual inspection in anticipation that we cannot afford Pap smears. Following the results of our publication in the LANCET, we’ve now gone into operational research where we are doing visual inspection in two public districts in Zimbabwe about 150 kilometers from Harare. What we’re doing there is offering visual inspection and we trained nurse practitioners in the primary health centers, and at district hospital level, we’ve trained district hospital doctors to offer cryotherapy and routine knife cone biopsy. We’ll be reviewing the results in two to three years, we hope following the operational research. In the next two years we’ll be able to have recommendations for the Minister of Health in terms of which we fought for screening of cervical cancer.