The battleground of two Infections and a cancer: Human Papilloma Virus, premalignant lesions of the cervix and their interaction with Human Immunodeficiency Virus in southwestern Nigeria

University dissertation from Division of Social Medicine and Global Health

Abstract: Background: The highest numbers of HIV-infected women are in sub- Saharan Africa, where the natural progression of HIV disease in the absence of treatment results in death before the onset of invasive cervical cancer. With improved access to treatment, several studies outside West Africa demonstrated an increased risk of pre-invasive cervical lesions among HIV-infected women and the positive impact of treatment on the outcome. Given the various HIV strains in Nigeria and other West African countries, a different outcome may be expected. Unfortunately, limited information exists on the subject in the sub-region. Aim: To study the effect of HIV infection on the burden of premalignant lesions of the cervix; assess the diagnostic accuracy of direct visual inspection of the cervix; and contribute to policy formulation and the development and implementation of effective cervical cancer prevention and control programme in Nigeria. Method: The studies (I-V) were conducted among adult women of known HIV status in south-western Nigerian (2011- 2012). Study I, a randomised control study among 1140 women, determined the effect of HIV infection on the test performance of direct visual inspection of the cervix in detecting cytology - diagnosed squamous intraepithelial lesions. Studies II and III utilised data generated in Study I to determine the interaction between HIV infection, antiretroviral therapy, and precancerous lesions of the cervix. Study IV, a cross-sectional study, assessed the acceptability of cervical cancer screening among 1517 HIV- positive women. Study V prospectively determined the outcome of follow- up after a positive cervical cancer screening test. Results: Visual inspection with Lugol’s iodine was found to be inferior to visual inspection with acetic acid and inadequate as a cervical cancer screening tool in cases of severe immune deficiency (specificity of 66.9% and negative predictive value of 50.0%). The prevalence of high risk HPV and squamous intraepithelial lesions were 19.6% and 8.4%, respectively. HPV 16 (3.9%), 35 (3.5%) and 58 (3.5%) were most frequently found. HIV positive women were found to be at increased risk of high risk HPV infection (OR: 1.8; 95% CI: 1.4 - 2.2) and squamous intraepithelial lesion (OR: 5.4; 95% CI: 2.9 - 8.8). Antiretroviral drugs was found to protect against high risk HPV infection (OR: 0.4; 95% CI: 0.3- 0.5) and development of squamous intraepithelial lesions. Although only 56.2% of HIV positive women were aware of cervical cancer screening, the test was acceptable to 79.8% of them. Among the 108 women who screened positive during outreach cervical cancer screening, 47.2% defaulted from follow -up as a result of transportation and cost- related issues and an anticipated long waiting time at the referral centre. Poorly educated women (OR: 3.1, CI:2.0 – 5.2) and those residing more than 10 km from the clinic (OR: 2.0, CI:1.0 – 4.1) were most likely to default. Conclusion. Precancerous lesions of the cervix were found to be higher in HIV positive women, especially severely immuno-compromised ones and those not on treatment. Cervical cancer screening is acceptable to women but default from follow - up after positive screening was high, especially among poorly educated rural women. Visual inspection with Lugol’s iodine was found to be inadequate for cervical cancer screening in cases of severe immune deficiency. The current strategy needs to be changed to one that will integrate cervical cancer prevention into HIV care as well as to improve access services for poorly educated rural women.