Socio-demographic and reproductive determinants of cervical neoplasia in seven sub-Sahara African countries.

BACKGROUND: Since most human papilloma virus (HPV) infections regress without any intervention, HPV is a necessary but may not be a solely sufficient cause of cervical intraepithelial neoplasia (CIN) and cervical cancer. Hence, the influence of cofactors on progression from cervical HPV infection to high-grade CIN and invasive cervical cancer has been a subject of intensive research. OBJECTIVE: We assessed the effect of socio-demographic and sexual reproductive factors on the prevalence of invasive cervical cancer and CIN diagnosed in cross-sectional cervical cancer screening projects carried out in seven sites of different sub-Saharan countries. METHODS: Between January 2000 and August 2007, healthy women aged 25-59 who participated in the screening projects were interviewed for socio-demographic, reproductive, and behavioral characteristics, investigated for disease confirmation with colposcopy, and had biopsies directed from colposcopically abnormal areas by trained local physicians. Odds ratios (ORs) and their 95% confidence intervals (CIs) from logistic regression analyses were used to assess the effect of women characteristics on CIN 1, CIN 2-3, CIN 3, and invasive cancer outcome measures. RESULTS: Among 47,361 women screened and investigated for disease confirmation, CIN 1 was diagnosed in 1,069 (2.3%), CIN 2 in 517 (1.1%), CIN 3 in 175 (0.5%), and invasive cancer in 485 (1.0%). The site-specific prevalence of CIN 2-3 lesions ranged from 0.3 to 5.1% and from 0.2 to 1.9% for invasive cancers. Risk factors for CIN 2-3 were being widowed or separated versus currently married (OR 1.3, 95% CI 1.0-1.7 a); and having had at least four pregnancies versus zero or one pregnancy (OR at least 1.4-fold, 95% CI 1.1-1.8). Risk factors for invasive cancer were being widowed or separated versus currently married (OR 2.0, 95% CI 1.3-3.1); and having had at least three pregnancies versus zero or one pregnancy (OR at least 3.0-fold, 95% CI 2.1-4.2). Additionally, cervical cancer risk increased with increasing age, age at menarche, and age at marriage, while the risk decreased with increasing level of education and in those with some form of employment compared to housewives. CONCLUSION: The exposure of the exocervix and/or the increased levels of estrogen and progesterone for more prolonged periods during pregnancy in multiparous women and the vulnerability of widowed/separated women in society might result in increased risk of cervical neoplasia more so among women exposed to HPV infection. High parity probably explains the persistently high rates of cervical cancer in sub-Saharan Africa.

The identification of Lynch syndrome in Congolese colorectal cancer patients.

BACKGROUND: We aimed to investigate the prevalence of Lynch syndrome as one of hereditary causes of colorectal cancer (CRC) among young Congolese individuals affected by the CRC, and to define methods for diagnosis in Congo Brazzaville. METHODS: We conducted a transversal cohort study of 34 patients having a CRC with a family history for a period of eight years. They were selected among 89 CRCs of any type from the Bethesda guidelines criteria combined with pedigrees. Mismatch repair (MMR) genes alterations were researched by immunohistochemistry (IHC). RESULTS: We identified with the Bethesda criteria a total of 38.2% (34/89) patients having familial CRC with a confidence interval (CI) of 95%=[0.34-0.41]. Only 14.7% (5/34) 95% CI=[0.34-2.32] patients showed MMR immunodeficiency involving firstly MLH1 protein then MSH2 protein. These data account for 5.6% (5/89) 95% CI=[0.15-0.33] of patients affected by Lynch syndrome with an earlier median age of 35 years (range 20 to 47 years). CONCLUSION: The prevalence of Lynch syndrome found in Brazzaville is comparable to that is found in northern countries. The combined Bethesda guidelines, pedigree and IHC is an accessible and good alternative method for the positive diagnosis of Lynch syndrome in current practice in Congo.

[Clinical and outcome characteristics of inflammatory breast cancers in Brazzaville]. / Caractéristiques cliniques et évolutives des cancers du sein inflammatoires à Brazzaville.

T4 breast cancers are a heterogeneous group. We conducted this study to analyze the differences between inflammatory and non-inflammatory T4 breast cancers. In a cross-sectional descriptive study over a period ranging from 2007 to 2010, we collected patients with T4 breast cancer. These patients were divided into two groups: a group of inflammatory breast cancer (IBC) and a group of breast cancer T4 non inflammatory (NIBC). We compared the epidemiological, clinical and outcome characteristics of the two groups. We identified 129 patients with T4 stage out of 343 patients with a diagnosis of breast cancer. Fifty-two IBC and 77 NIBC patients were observed. We did not found any epidemiological difference between the two groups. The two entities differed in tumor size (greater in the IBC group) and skin ulceration (less frequently found in the NIBC group). The only independent prognostic factor for failure of first line chemotherapy was, for both groups, non-compliance treatment intervals. The median overall survival in our study was 9 months in the IBC versus 13 months in the NIBC (p = 0.01, Log-rank test) patients. By multivariate analysis, IBC was the only independent prognostic factor negatively influencing the survival. IBC is a frequent entity in Brazzaville, Congo and displays a poor-prognosis.

[Arrival of patients at advanced stage: tempting to identify responsibility]. / Arrivée des malades cancéreux aux stades avancés: tentative d'identification de responsabilité

JUSTIFICATION: In many publications on cancer in Africa, the majority of patients were seen in advanced stages (III or IV) during the first consultation. So, it was important to look for factors that explain this situation. METHODS: A survey by questionnaire was made in our Medical Oncology Department of University Teaching Hospital of Brazzaville from January to October 2010. The responsibility of advice to go to hospital was codified in Arrival in Advanced Stage (AAS) from the weakest (AAS 1) to the strongest (AAS 8) according to the knowledge in oncology. The impact of organ accessibility and the patient's instruction level were also evaluated. RESULTS: One hundred and ninety-six patients seen in consultation, hospital day and hospitalization were asked and we had gathered the same information in patients' medical files. Our sample was essentially made by women (67,4%). The age of patients were from 21 to 83 years old with average of 53,8. The direct responsibility of the patient was weak (24,4%) by ignorance or fear of diagnosis. The hospital personal, the nurses and physicians who work in private were for a great part: 40,8%. The number of practitioners by category had limited the results because of the difficulty to join them. The medical doctor, specialist or not, were responsible at 25,5%. CONCLUSION: The medical vulgarization, large information, specialization training adapted were the way to choose in the resolution of the problem, which impact on therapeutic result was undeniable.

[Twelve years of working of Brazzaville cancer registry]. / Douze années de fonctionnement du registre des cancers de Brazzaville.

The Brazzaville cancer registry was created in 1996 with the support of the International Agency Research against Cancer (IARC) which is located in Lyon, France. The Brazzaville cancer registry is a registry which is based on population which records new cancer cases occurring in Brazzaville by using Canreg 4.0 Software. Its aim is to supply useful information to fight against cancer to physicians and to decision makers. We conducted this study whose target was to determine the incidence of cancer in Brazzaville during twelve years, from January 1st, 1998 to December 31, 2009. During that period 6,048 new cancer cases were recorded: 3,377 women (55.8%), 2,384 men (39.4%), and 287 children (4.8%) from 0 to 14 years old with an annual average of 504 cases. Middle age to the patient's diagnosis was 49.5 years in female sex and 505.5 years old for male sex. The incidence rate of cancers in Brazzaville was 39.8 or 100.000 inhabitants per year and by sex we observed 49 to female sex and 35.2 for male sex. The first cancers localizations observed to women were in order of frequency: breast, cervix uterine, liver ovaries, hematopoietic system, to men : liver, prostate, hematopoietic system, colon and stomach; to children : retina, kidney, hematopoietic system, liver and bones. These rates are the basis to know the burden of cancer among all pathologies of Brazzaville and the achievement of a national cancer control program.

Genome-wide high-resolution aCGH analysis of gestational choriocarcinomas.

Eleven samples of DNA from choriocarcinomas were studied by high resolution CGH-array 244 K. They were studied after histopathological confirmation of the diagnosis, of the androgenic etiology and after a microsatellite marker analysis confirming the absence of contamination of tumor DNA from maternal DNA. Three cell lines, BeWo, JAR, JEG were also studied by this high resolution pangenomic technique. According to aCGH analysis, the de novo choriocarcinomas exhibited simple chromosomal rearrangements or normal profiles. The cell lines showed various and complex chromosomal aberrations. 23 Minimal Critical Regions were defined that allowed us to list the genes that were potentially implicated. Among them, unusually high numbers of microRNA clusters and imprinted genes were observed.

[Cytogenomic studies of hydatiform moles and gestational choriocarcinoma]. / Étude cytogénomique de la môle hydatiforme et du choriocarcinome gestationnel.

The complete hydatidiform mole (CHM), a gestational trophoblastic disease, is usually caused by the development of an androgenic egg whose genome is exclusively paternal. Due to parental imprinting, only trophoblasts develop in the absence of a fetus. CHM are diploid and no abnormal karyotype is observed. It is 46,XX in most cases and less frequently 46,XY. The major complication of this disease is gestational choriocarcinoma, a metastasizing tumor and a true allografted malignancy. This complication is infrequent in developed countries, but is more common in the developing countries and is then worsened by delayed care. The malignancies are often accompanied by acquired, possibly etiological genomic abnormalities. We investigated the presence of recurrent cytogenetic abnormalities in CHM and post-molar choriocarcinoma using metaphasic CGH (mCGH) and high-resolution 244K aCGH techniques. The 10 CHM studied by mCGH showed no chromosomal gains or losses. For post-molar choriocarcinoma, 11 tumors, whose diagnosis was verified by histopathology, were investigated by aCGH. Their androgenic nature and the absence of tumor DNA contamination by maternal DNA were verified by the analysis of microsatellite markers. Three choriocarcinoma cell lines (BeWo, JAR and JEG) were also analyzed by aCGH. The results allowed us to observe some chromosomal rearrangements in primary tumors, and more in the cell lines. Chromosomal abnormalities were confirmed by FISH and functional effect by immunohistochemical analysis of gene expression. Forty minimum critical regions (MCR) were defined on chromosomes. Candidate genes implicated in choriocarcinoma oncogenesis were selected. The presence in the MCR of many miRNA clusters whose expression is modulated by parental imprinting has been observed, for example in 14q32 or in 19q13.4. This suggests that, in gestational choriocarcinoma, the consequences of gene abnormalities directly linked to acquired chromosomal abnormalities are superimposed upon those of imprinted genes altered at fertilization.