Cervical carcinoma in Kampala, Uganda, and the relationship with human immunodeficiency virus and human papillomavirus infections

Introduction: Cervical carcinoma is the commonest tumour in Ugand an women. However, very little is known in the Ugandan population about HPV types associated with invasive cervical cancer, the relative risk of cervical cancer associ ated with different HPV types, and whether the risk of cervical cancer associated with HPV infecti on s modified by HIV infection. Furthermore, the nature of HPV negative invasive cervical cancer , especially adenocarcinoma, is yet to be described and studied to find if the use of differe nt types of cervical samples can influence the studies’ results. Objectives: To study HPV types associated with invasive cervic al cancer. To estimate the relative risk for infections with different HPV typ es, and whether this is modified by HIV infection. To describe the nature of HPV negative c ancer, especially adenocarcinoma, and study if the use of different invasive cervical cancer sa mples can influence the studies’ results. Subjects and Methods: We conducted studies using 186 archival cases of c ervical carcinoma diagnosed between 1967 and 1980, 316 new incident c ases of cervical cancer and exfoliated cervical cells from 314 control women from Uganda b etween September 2004 and December 2006. HPV testing was done using the SPF10 LiPA tec hnology. In paper I, we assessed the prevalence and HPV types. For Article II, we used d ifferent antibodies to clarify the nature of HPV negative adenocarcinomas. In Article III, we es timated the odds ratio (OR) of cervical cancer for different HPV infections as well as for HIV infection. In Article IV, we compared HPV detection in formalin-fixed paraffin embedded ( FFPE) and fresh samples. Results: In Article I, Out of the 186 cases of confirmed invasive cervical cancer in the study paraffin blocks, 114 were positive for HPV DNA. Spe cific HPV genotypes were identifiable in 109 cases: HPV 16, 18, 31, 35, 39, 44, 45, 51, 52 a nd 70. These occurred as single infections in 105 cases (96.3%) and as multiple infections in 4 c ases (3.7%). HPV 16 or 18 accounted for 80% (84/105) of cases with a single infection. In Article II, Among the 13/25 HPV negative ADC samples, five w re positive for CEA, suggesting endocervical origin, and three were vime ntin positive (one had a mucinous endocervical histological pattern and two were ADC, not otherwise specified, most likely of endometrial origin). In Article III, we found a high relative risk of both squamous cell carcinoma and adenocarcinoma of the cervix with HPV 16 and 18 , and moderate relative risk with HPV 45. Concurrent infection with HIV did not increase the relative risk with these three HPV types, but was associated with a statistically borderline incr eased relative risk of squamous cervical carcinoma only with low-risk types and multiple inf ections with HPV types. Article IV showed comparable HPV detection in both fresh and FFPE tissue by the SPF10 LiPA method, with complete agreement for 59.7%, partial agreement 5.3% and complete disagreement 35.0%. Conclusion: Most cervical carcinomas in Uganda are associated with high-risk HPV types, and concurrent infection with HIV has little impact. Bo th archival and fresh samples are suitable for HPV detection, and the use of antibodies may be use ful in the characterization of HPV negative cervical adenocarcinomas.