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

Introduction: Cervical carcinoma is the commonest tumour in Ugandan women. However, very little is known in the Ugandan population about HPV types associated with invasive cervical cancer, the relative risk of cervical cancer associated with different HPV types, and whether the risk of cervical cancer associated with HPV infection is 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 different types of cervical samples can influence the studies results.

Objectives: To study HPV types associated with invasive cervical cancer. To estimate the relative risk for infections with different HPV types, and whether this is modified by HIV infection. To describe the nature of HPV negative cancer, especially adenocarcinoma, and study if the use of different invasive cervical cancer samples can influence the studies results.

Subjects and Methods: We conducted studies using 186 archival cases of cervical carcinoma diagnosed between 1967 and 1980, 316 new incident cases of cervical cancer and exfoliated cervical cells from 314 control women from Uganda between September 2004 and December 2006. HPV testing was done using the SPF10 LiPA technology. In paper I, we assessed the prevalence and HPV types. For Article II, we used different antibodies to clarify the nature of HPV negative adenocarcinomas. In Article III, we estimated 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. Specific HPV genotypes were identifiable in 109 cases: HPV 16, 18, 31, 35, 39, 44, 45, 51, 52 and 70. These occurred as single infections in 105 cases (96.3%) and as multiple infections in 4 cases (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 were positive for CEA, suggesting endocervical origin, and three were vimentin 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 increased relative risk of squamous cervical carcinoma only with low-risk types and multiple infections 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. Both archival and fresh samples are suitable for HPV detection, and the use of antibodies may be useful in the characterization of HPV negative cervical adenocarcinomas.

List of scientific papers

I. Odida M, de Sanjose S, Quint W, Bosch XF, Klaustermeier J, Weiderpass E. (2008). "Human papillomavirus type distribution in invasive cervical cancer in Uganda. " BMC Infectious Diseases 8: 85
https://pubmed.ncbi.nlm.nih.gov/18577214

II. Odida M, Lloveras B, Guimera N, Weiderpass E. (2010). "The usefulness of immunohistochemistry in tissue microarrays of Human papillomavirus negative adenocarcinoma of the uterine cervix" BMC Research Notes 3: 54
https://pubmed.ncbi.nlm.nih.gov/20199664

III. Odida M, Sandin S, Mirembe F, Kleter B, Quint W, Weiderpass E. (1970). "HPV types, HIV and invasive cervical carcinoma risk in Kampala, Uganda: a case control study." (Submitted)

IV. Odida M, de Sanjose S, Sandin S, Quiros B, Alemany L, Lloveras B, Quint W, Kleter B, Alejo M, van Doorn LJ, Weiderpass E. (2010). "Comparison of Human papillomavirus detection between freshly frozen tissue and paraffin embedded tissue of invasive cervical cancer." Infectious Agents and Cancer 5: 15
https://pubmed.ncbi.nlm.nih.gov/20846370