Risk of seropositivity to multiple oncogenic human papillomavirus types among human immunodeficiency virus-positive and -negative Ugandan women.

To understand the prospects for human papillomavirus (HPV) mass vaccination in the setting of a developing country, we studied the co-occurrence of seropositivity to multiple high-risk (hr) HPV types among HIV-positive and HIV-negative Ugandan women. Our seroepidemiological study was conducted among 2053 women attending antenatal clinics. Sera were analysed for antibodies to eight hrHPV types of the α-7 (18/45) and α-9 (16/31/33/35/52/58) species of HPV by using a multiplex serology assay. Our results show that seropositivity for greater than one hrHPV type was as common (18 %) as for a single type (18 %). HIV-positive women had higher HPV16, HPV18 and HPV45 seroprevalences than HIV-negative women. In multivariate logistic regression analysis, age (>30 years) and level of education (secondary school and above) reduced the risk, whereas parity (>5) and HIV-positivity increased the risk for multiple hrHPV seropositivity. However, in stepwise logistic regression analyses, HIV-status remained the only independent, stand-alone risk factor [odds ratio (OR) 1.7, 95 % confidence interval (CI) 1.0-2.8). On the other hand, the risk of HPV16 or HPV18 seropositive women, as compared to HPV16 or HPV18 seronegative women, for being seropositive to other hrHPV types was not significantly different when they were grouped by HIV-status (ORHPV16/HIV+ 12, 95 % CI 4.5-32 versus ORHPV16/HIV- 22, 95 % CI 15-31 and ORHPV18/HIV+ 58, 95 % CI 14-242 versus ORHPV18/HIV- 45, 95 % CI 31-65). In conclusion, seropositivity to HPV16, HPV18 and to non-vaccine hrHPV types is common in Ugandan women, suggesting that there is little natural cross-protective immunity between the types. HIV-positivity was an independent, stand-alone, albeit moderate risk factor for multiple hrHPV seropositivity. HPV mass vaccination may be the most appropriate method in the fight against cervical cancer in the Ugandan population.

Strategies to overcome myelotoxic therapy for the treatment of Burkitt's and AIDS-related non-Hodgkin's lymphoma.

BACKGROUND: Strategies to circumvent or lessen the myelotoxicity associated with combination chemotherapy may improve the overall outcome of the management of patients particularly in resource poor settings. OBJECTIVES: To develop effective non-myelotoxic therapies for Burkitt's Lymphoma (BL) and AIDS-related non-Hodgkin's lymphoma. DATA SOURCES: Publications, original and review articles, conference abstracts searched mainly on Pubmed indexed for medline. DATA EXTRACTION: A systematic review of the clinical problem of combination chemotherapy. Identification of clinical strategies that circumvent or lessen the myelotoxicity of combination cytotoxic chemotherapy. Length of survival, lack of clinically significant (> grade 3) myelosuppression and weight loss were used as markers of myelotoxicity. DATA SYNTHESIS: Review of published experience with some of these strategies including dose-modification of multi-agent chemotherapy; rationale for targeted therapies, and the preclinical development of a mouse model exploring the role of metronomic scheduling substantiate pragmatism and feasibility of these approaches. CONCLUSION: Myelotoxic death rates using multi-agent induction chemotherapy approach 25% for endemic Burkitt's lymphoma and range between 20% to 60% for AIDS-related malignancy. This is mostly explained by the paucity of supportive care compounded by wasting and inanition attributable to advanced cancer and HIV infection making patients more susceptible to myelosuppressive side effects of cytotoxic chemotherapy. Investigations and alternative approaches that lessen or circumvent myelotoxicity of traditional cytotoxic chemotherapy for the management of Burkitt's lymphoma and AIDS-related non-Hodgkin's lymphoma in the resource-constrained setting are warranted. Pertinent pre-clinical and clinical data are emerging to support the need for abrograting the myelosuppressive effects of traditional cytotoxic chemotherapy. This can be achieved by developing targeted anti-viral and other strategies, such as the use of bryostatin 1 and vincristine, and by developing a preclinical mouse model to frame the clinical rationale for a pilot trial of metronomic therapy for the treatment of Burkitt's and AIDS-related lymphoma. Implementation of these investigational approaches must be encouraged as viable anti-cancer therapeutic strategies particularly in the resource-constrained settings.

Anatomical site predilections of non-Hodgkin's lymphoma in human immunodeficiency virus infection: a report on 54 cases.

OBJECTIVE: To identify and describe the primary anatomic sites of non-Hodgkin's lymphoma arising in the setting of Human Immunodeficiency Virus infection. DESIGN: Prospective (ongoing) study. SETTING: Kenyatta National Hospital a referral and teaching hospital in Kenya. SUBJECTS AND METHODS: Patients (n=54) with human immunodeficiency virus with associated non-Hodgkin's lymphoma managed at the Kenyatta National hospital from January 2001 to December 2003. Relevant clinical information obtained by medical history, physical examination and investigations. RESULTS: Of the 54 patients studied 29(54%) were males and 25(46%) females with median age 36 and range 20 to 61 years. Fifty (93%) had high grade and four (7%) intermediate grade lymphoma, the former had 15 (30%) Burkitt's and the rest large cell lymphoma. The stages at diagnosis were IV 35(65%), III 14(26%) and II 5(9%) and all had B symptoms. The primary sites at presentation to the hospital were peripheral nodes 16(30%), abdominal 15(28%), pectoral/chest wall 11(20%), central nervous system eight (15%) and systemic/generalised, four (7%). CONCLUSION: This study demonstrates that there were preferred anatomical sites of involvement by HIV associated non-Hodgkin's lymphomas and the finding of pectoral/ chest involvement in this series may not be coincidental. Further, this study suggests that anatomical sites predilection may be due to the tendency of viral associated malignancies to home to specific anatomic sites and also due to the anatomy of the lymphoreticular system. Studying virus pathogenesis in malignancies should consider also the anatomic sites involved.

Survival of cervix cancer patients in Kampala, Uganda: 1995-1997.

The survival experience of 261 patients with cancer of the cervix registered by the Kampala population-based cancer registry, Uganda, in 1995-1997, is described. Vital status of the subjects was established by active methods including a search of hospital records and house visits. Of the 261 cases, 82 (31.4%) were dead and 105 (40.2%) were alive at the closing date of 31 December 1999; the remaining 74 cases (28.4%) were lost during the follow-up period. Overall observed and relative survival at 3 years was 52.4 and 59.9%, respectively. Of these cases, one-quarter (63) had been treated in the radiotherapy department. These cases had better survival (82.6%) than nontreated patients (78.5%) after 1 year of follow-up, but there was no difference at 3 years. HIV status was not significantly related to prognosis. Stage is an important determinant of survival: cases with distant metastasis had a risk of death some three times that of patients with localised disease. Early detection and prompt treatment should improve overall survival from cervix cancer, in the African context.

Diagnostic implications of genital Kaposi's sarcoma.

Genital Kaposi's sarcoma (KS) before the AIDS epidemic was rarely seen in Uganda although a case was seen in 1973, 1982, 1983 and 1985. Eight cases were seen in 1986 and another 17 cases have been documented since the beginning of 1987. Of the 29 patients, 23 were males, 6 females (M:F = 3.8:1); median age 29 years (range 7-70 years). All except 8 males were under 40 years. Six patients had pure nodular disease, while the rest had mixed clinical type. The external genitalia was involved in nodular disease in 15 patients, 12 had infiltrative disease and 6 had ulcerative disease. Florid and plaque were seen in one case each. Mixed cellularity was typed in 13 patients. 19(70.4%) were positive for HIV serology (ELISA Wellcome kit) of whom 13(61.9%) were males. All females were positive. The patient who presented in 1973 remains alive and disease free 13.5 years making it unlikely that he had AIDS. It appears therefore that genital KS is a feature of HIV associated KS and this mode of presentation is new in Uganda.