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This study was undertaken to determine the prevalence of cervical dysplasia in HIV-positive women attending the antiretroviral clinic of the Jos University Teaching Hospital. 370 women with western blot confirmation of their HIV status were recruited. One result was excluded from analysis due to incomplete data. HIV-status was confirmed by Western Blot assay (Immunetics, Inc, Boston MA).

Quantification of HIV-1 RNA viral load was performed using the

Roche-Ampiclor HIV-1 monitor test, version 1.5(RocheAmpiclor®-Roche Diagnostics, Branchburg, NJ) and results were expressed as the number of RNA copies per milliliter of plasma. Values ≤ 400 copies/ml are regarded as undetectable levels.

CD4+ lymphocyte count was estimated using Flowcytometric methods (Cyflow, Partec, Germany). Results are expressed as cells per cubic millimeter of blood (cells/ mm3).

We collected specimens from the endocervix using a cytobrush and a plastic spatula-Medscan sample collection kit (Medscand Medical AB, Sweden) was used to collect scrapings from the ectocervix. Materials from both the endocervix and ectocervix were smeared on one prelabeled slide and immediately fixed in alcohol. Smears were then transported to the Pathology laboratory where they were stained by a technologist and read by a Pathologist.

The mean age was 33.9 ± 7.4 years. The mean CD4 count was 203± 178cells/mm³. 78.9% had detectable levels of viral load with mean detectable number of viral copies of 157,047 ± 246,054copies/ml of blood. 30.9% had a positive history of ARV use (mean duration of use: 14.7 ±11.5 months). Only 0.3% had ever done a prior Pap smear. Prevalence of abnormal cervical cytology was 68.3% with the following distribution: ACSUS- 57.5%, CIN I-22.2%, CIN II-12.3% and CIN III-7.9%. Viral load >10,000 copies/ml and CD4 count were significantly associated with cervical dysplasia (p = 0.05.) However, presence of HPV changes was identified as the strongest predictor of cervical dysplasia.

In this population, there is a high prevalence of cervical dysplasia among HIV-positive women with significant correlation between CD4 count and viral load >10,000 copies/ml.



CONTENTS                                                                            PAGES DECLARATION                                                                                 i

SUPERVISORS’                                                                                ii

DEDICATION                                                                                    iii ACKNOWLEDGEMENTS                                                                 iv

TABLE OF CONTENTS                                                                    v

LIST OF FIGURES                                                                           viii

LIST OF TABLES                                                                             ix

LIST OF ABBREVIATIONS                                                              x

SUMMARY                                                                                       xii


1.1.     Introduction                                                                               1

1.2    Definition of research problem/justification for study                4

1.3     Relevance of the study                                                             6

1.4    Aims and objectives                                                                  7


2.1     Morphology                                                                               8

2.2     Pathophysiology of dysplasia                                                   9

2.3    Epidemiology and risk factors                                                 11

2.4    HIV, HPV and cervical dysplasia                                            15

2.5    The HIV epidemic                                                                   17

2.6    Life cycle of HIV-1                                                                   24

2.7    Diagnostic tests for HIV                                                           26

2.8    Tests for monitoring disease                                                   27

2.9     Methods of detecting dysplasia                                               31

2.10 Treatment of dysplastic lesions                                               36

2.11 Management of dysplasia in HIV-positive women                   40

2.12 Preventing cervical cancer                                                       42

2.13 Highly active antiretroviral therapy                                           44

2.14 Intervention                                                                              47

2.15 Summary of literature review                                                    50


3.1 Study site                                                                                51

3.2 Study design                                                                           52

3.3 Study population                                                                     52

3.4 Ethical consideration                                                               53

3.5 Sample size determination                                                      53

3.6 Sampling method                                                                    54

3.7 Instrument of data collection                                                   54                        3.8 Data analysis                                                                          57


4.1 Demographic and reproductive characteristics of subjects    58

4.2 Reproductive symptoms of subjects and clinical findings       62

4.3 Immunologic classification/viral load and cytologic findings   66

4.4 Comparison of subjects with and without dysplasia               69 4.5 Independent relationship between variables and cervical      71        dysplasia



5.1 Prevalence of cervical dysplasia                                            74

5.2 Demographic characteristics of subjects                                76

5.3 Frequency of reproductive organ disease                              77

5.4 Risk factors for dysplasia                                                       89

5.5 HPV changes and dysplasia                                               80

5.6 Effect of HAART on cervical dysplasia                               81

5.7 Limitations of the study                                                       82

5.8. Recommendations                                                              82

5.9 Conclusion                                                                          84

REFERENCES:                                                                             86


1.1                                       INTRODUCTION

Cervical cancer, a preventable disease, is the second most common cancer in women worldwide, with about 500,000 new cases and 250,000 deaths each year. Almost 80% of these cases occur in developing countries, which

collectively have only 5% of the global cancer resources1, 2, 3. Cervical cancer is also the leading cause of years-of-life-lost in women in south central Asia, Latin

America, and sub-Saharan Africa. It results in a greater reduction of a woman’s life expectancy than AIDS, tuberculosis, or maternal conditions in Latin America and Europe4. In Nigeria and most other developing countries, it is the most common genital cancer with significant morbidity and mortality5.Cervical cancer is a preventable disease because it is preceded by an easily detectable and preventable pre-invasive disease by a period of about 10-15 years. While the incidence, morbidity and mortality of cervical cancer have declined in developed countries due to organized cancer screening programmes4, 6, 7, there has been little progress in developing countries.

Prior to the introduction of the Papanicolaou (Pap) smear in the early 40’s, the incidence of cervical cancer was 40-50/100,000 women in the USA. With regular screening, recent data show that the incidence in the same country is approximately 8/100,000 women, indicating that cervical cancer is largely avoidable8. In most countries, the incidence of invasive cervical cancer increases with age to reach a maximum in women in their fifties and sixties. Between 8090% of confirmed cases in developing countries occur among women aged 35 years and over8. The highest age standardized incidence rates are found in East Africa, Melanasia, Central America, the Caribbean, South America and Southern

Africa. In all these regions, the rates are over 30 cases per 100,000 women.

Bolivia, Guinea, Guyana, Haiti, Malawi, Nicuaragua, Swaziland, Tanzania, Zambia and Zimbabwe all have rates over 50 cases per 100,000 women3.

Whereas some developed countries have been able to drastically reduce the incidence of cervical cancer through routine screening programmes, the scope and impact of the disease in Nigeria is still largely undefined due to paucity of screening programmes. A recent report from Lagos in southern Nigeria found a prevalence rate of 4.1% in a group of urban women 9. A prevalence of 21.8% was reported in Abuja, the Federal Capital Territory, while a rate of 11.8% was reported from a healthy cohort of women in Jos, the north central part of the

country10, 11.

In recent times, it has been discovered that women infected with the human immunodeficiency virus (HIV) are at increased risk for the development of dysplastic genital lesions12, 13. In a report from Thailand, HIV-infected Thai women appeared to have increased prevalence of abnormal vaginal discharge, squamous intra-epithelial lesions and self-reported history of sexually transmitted disease (STD) 14. Cervical dysplasia or cervical intra-epithelial neoplasia (CIN) is reported in HIV infected women at rates of between 15-40%7, 9, 10. Furthermore, there is a significant risk of short term recurrence (40-60%) following standard therapies for pre-invasive disease. Some evidence also suggests that HIV positive women with atypical squamous cells of undetermined significance (ASCUS) on Pap smear have a higher rate of progression to CIN15.

Invasive cervical cancer in HIV positive women is characterized by high grade tumours with lymph node and often metastatic involvement at the time of diagnosis. The documentation of increased rates of invasive cervical cancer (ICC) prompted the Center for Disease Control (CDC) to add ICC to the AIDS surveillance case definition in 199312.In the setting of HIV infection, 30-60% of Pap smears exhibit cytologic abnormalities and 15-40% has evidence of dysplasia. These rates are about 10 times greater than those observed among HIV negative women15, 16. Abnormal cytology is more common among HIV infected women and is associated with the presence of the human papillomavirus (HPV) infection and the degree of immunosuppression. Both the frequency and severity of abnormal pap smears and histologically documented dysplasia increase with declining CD4 cell counts and higher HIV-RNA levels17. A French study using only Pap smear results found an increased likelihood of progression of cervical abnormalities in HIV positive women18. Another recent study also found an association between progression of abnormal pap smears and high plasma HIV-RNA levels (>100,000 copies /ml) 19.

In the analysis of women in the HIV Epidemiologic Research (HER study),

HIV positive women had an ICC rate of 144/1000-person years compared to 0/1000-person years in HIV negative women20. Women with HIV and cervical cancer tend to be younger than HIV negative women with the same condition. HIV positive women with ICC appear to present at more advanced stages (especially with CD4 count<200/mm³), have metastases to unusual locations (e.g. psoas muscle, clitoris, meninges), have poorer responses to standard therapies, and have shorter intervals to recurrence or death compared with HIV negative women of similar disease stage21.

Sub-Saharan Africa currently bears the brunt of the HIV/AIDS pandemic in all its ramifications. Whereas attempts have been made to characterize the pattern and course of cervical abnormalities and cancer in HIV/AIDS in developed countries, not much is known about the pattern and course of this disease in Nigeria.


1.2   Definition of research problem/justification for the study

Most cases of cervical cancer occur in less developed countries where no effective screening systems are available22-27. In Nigeria, cervical cancer is the most common gynaecologic tumour. Patients often present to the hospital when they can be offered only palliative care. Majority of them are seen in clinical stages III and IV with low probability of long term survival28-30.The Pap smear have proven to be one of the most successful methods of cervical cancer detection available 31, 32. Epidemiological evidence indicates that the rates of cervical cancer have fallen in areas where routine screening programmes have been instituted33-36. The Pap smear is effective because cervical neoplasia has a long pre-invasive phase before the development of invasive disease. Cytological examination can detect pre-invasive lesions which can be adequately treated.

Although some developing countries have introduced routine screening for cervical cancer, not much progress has been made in terms of disease prevention. This is because the technology, infrastructure and expertise required running a screening programme is beyond the reach of the majority of the population who reside mainly in rural areas.

Since the 1994 International Conference on Population and Development in Cairo and the 1995 World Conference on women in Beijing, China, more attention has been given to comprehensive reproductive health for women. The central role of reproduction in the lives of women in many parts of the world is now recognized. Reproductive health has been defined as the “ability to live through the reproductive years and beyond with reproductive choice, dignity and successful child bearing, and free of gynaecological disease and risk”. This definition includes the concepts of choice (a woman’s control over her reproductive process), dignity (social and psychological wellbeing from the process of reproduction), and physical health of the reproductive organs37.       There is little information on the burden of reproductive health problems in developing countries owing to difficulties of access to and quality of health services, as well as to the culture of silence about these disorders37.Cervical cancer is the most common female cancer in sub-Saharan Africa38, and developing countries accounted for 370,000 out of a total of 466,000 cases of cervical cancer that were estimated to occur in the world in the year 200039. Some developing countries that have data on cancer incidence and/or mortality have registered either a stable or slowly declining trend in cervical cancer, most likely due to sociodemographic changes rather than to early detection/prevention measures40.

It has been well established that cervical dysplasia, a precursor of cervical cancer, in HIV positive women is associated with more multifocal lesions and higher incidence, more rapid progression and higher recurrence rates when compared with HIV negative women33.

It is in the light of the statistics above that this study is being carried out to define the prevalence of cervical dysplasia in women infected with HIV in our environment.


1.3 Relevance of the study

Cervical cancer, an AIDS defining illness, is a public health problem, and routine screening should be integrated into the primary health care programme of Nigeria41-43. At the same time, the AIDS epidemic is affecting women and girls in increasing numbers. Globally, just under half of all people living with HIV are female. Females comprise 57% of all people infected with HIV in sub-Saharan Africa, where a striking 76% of young people (aged 15-24years) living with HIV is female. In most other regions, women and girls represent an increasing proportion of people living with HIV, compared with five years ago. Nigeria has the third largest number of people living with HIV in the world (after South Africa and India) with prevalence being highest among young people; particularly women aged 20-29 years44.

The majority of people infected with HIV usually present for primary care with signs and symptoms of either early or advanced HIV disease. Therefore the family physician needs to be in a position to offer good quality care when these patients present, and routine screening for cervical cancer should form a part of a family physician’s practice.


1.4 Aims and objectives of the study

The primary aim of this study was to determine the prevalence of cervical dysplasia in women infected with the HIV at the Jos University Teaching

Hospital. Secondary objectives included the following:

  1. To determine the proportion of early lesions amenable to intervention. ii. To describe common reproductive organ symptoms in women infected with HIV.

iii. To determine the relationship between the degree of cervical dysplasia and immune status in women infected with HIV. iv.           To determine the relationship between the degree of cervical dysplasia and viral load in women infected with HIV.

  1. To be able to, at the conclusion of the study disseminate the information obtained from this study to the medical community.


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