OMOLADE PROPOSAL


INCIDENCE AND PREDICTORS OF PRECANCEROUS CERVICAL LESIONS AMONG HIV POSITIVE WOMEN IN JOS, PLATEAU STATE 

Principal Investigator: Daniel, Grace Omolade

Department of Nursing Science, University of Jos

Co- Investigators: Drs’ Shuaibu S and Shinku F

E mail:gracemola2002@yahoo.co.uk, gracemola2002@gmail.com,gdanielgo@unijos.edu.ng

Phone Number: 08036285950

Purpose of the research: To investigate the incidence and predictors of precancerous cervical lesions among HIV positive women on Antiretroviral therapy in Jos, Plateau State

Date of commencement: January 2017

Mentor: Prof. Oche Agbaji and Dr Abraham Ajayi

 

a.      Abstract

Background

The Human Immuno-Deficiency Virus / Acquired Immune Deficiency Syndrome (HIV/AIDS) is evidently now a reality in Nigeria as it has and is still ravaging families and communities1. There are 16 million (15.2 million–16.9 million) women aged 15 years and older living with HIV; 80% live in sub-Saharan Africa. In sub-Saharan Africa, where about two-thirds of the global disease burden resides, 57% of adults living with HIV are women2. HIV-positive women are at increased risk of acquisition and/or persistence or reactivation of cervical infection with Human papilloma virus (HPV)3,4,5. Cervical cancer poses a major public health threat to women in many low and medium resourced countries in South and Central America, Sub-Saharan Africa, South and Southeast Asia, where it is still the leading type of cancer among women6,7. Cervical cancer (CC) is the second most common cancer affecting women worldwide, after breast cancer8. In 2008, the number of new cases of cervical cancer was estimated at 530,000 and 275,000 deaths were attributed to this disease. Most of these new cases (86%) and deaths (88%) occurred in developing countries mainly in sub- Saharan Africa and South-East Asia8. In Nigeria, the national incidence of cervical cancer is 250/100,0009.

Since the inception of the HIV epidemic, the United States CDC has classified Cervical Cancer, Kaposi Sarcoma and Non-Hodgkin’s Lymphoma as AIDS Defining Cancers because of their close association with HIV infection10. Women with HIV have high rates of cervical abnormalities (30% to 60%) and cervical dysplasia (11% to 60%)11,12 that are more difficult to treat.13 HIV-infected women have a fivefold risk of developing CIN, compared with uninfected women.14 Once these women develop cervical cancer, the cancer may be aggressive, and treatment may be ineffective,15 accounting for high rates of CIN recurrence16.

Cervical cancer screening recommendations among HIV-positive women are further complicated by frequent vaginal infections that result in inflammation or bleeding that obscures the specimen and limits the accuracy of the reading. The incidence of invasive cervical cancer is likely to rise with increasing numbers of HIV-infected women or with high-risk oncogenic types of HPV, especially since many of these women are poor and do not receive adequate health care. Improvements in antiretroviral therapy have dramatically reduced HIV-related mortality from common opportunistic infections, such as Pneumocystis carinii pneumonia.17 As a consequence, malignancies, including cervical cancers, are likely to be an increasing cause of death among HIV-infected women.

 

Because both HIV infection and HPV infection are sexually transmitted, the 2 infections are often found together18,19. In addition, as a result of HIV-induced immune impairment, there is also an increased probability that HPV infection will become persistent in HIV-infected women18 and evolve into precancerous and cancerous lesions of the cervix uteri 20,21,22. Effective screening and early treatment of precancerous cervical lesions are, thus, key factors in preventing cervical cancer in both HIV-infected and HIV-uninfected women23.Cervical cancer is preventable if precancer is diagnosed early through screening and cured through treatment; it takes a long time for a human papilloma virus (HPV) infection to progress to precancer but less time in HIV-positive women.HPV causes cellular changes in the surface tissue of the cervix long before the development of cancer. Antiretroviral therapy reduces the risk of progression to cervical cancer in women with cervical abnormalities only modestly. Studies have shown that persistent HPV infection may lead to CIN of grade 1, which is likely to resolve without treatment in the majority of cases. In a minority of women infected with HPV who develop CIN grade 1, lesions will progress to moderate (2) grade or severe (3) grade or to a precancerous lesion involving cervical glandular cells, called adenocarcinoma in situ (AIS).If untreated, CIN2–3 has a high probability of progressing to squamous cell cancer, and AIS has a high probability of progressing to adenocarcinoma (cervical cancer).24Since an inexpensive diagnostic test exists for easy diagnosis of precancerous cervical lesions, most mortality related to cervical cancer is avoidable. Hence this study is aimed at determining the prevalence of precancerous cervical lesions among HIV positive women who have been on ART.

SUBJECTS AND METHODS

Study Setting: Study will be carried out in the Jos University Teaching Hospital (JUTH) and Bingham University Teaching Hospital (BUTH).

Study population: HIV positive women older than 18 years

Screening Procedure

After obtaining informed consent, nurses obtained demographic and clinical information on all participants and examined the introitus and vulva, noting any abnormalities. A vagina speculum will be introduced to the vagina for a proper view of the cervix. During a Pap smear, an extended-tip wooden spatula or brush is used to gather cells from the outer opening of the cervix and the endocervix in what is called the transformation zone. The entire transformation zone will be sampled as this is where almost all high-grade lesions develop in the cervix. The sample will then be smeared onto a glass slide and immediately fixed with a solution to preserve the cells. The slide will be sent to a cytology laboratory where it is stained and examined using a microscope to determine whether the cells are normal and to classify them appropriately, using the Bethesda classification.

Ethical Consideration

Ethical clearance will be obtained from the research and ethics committee of JUTH and BUTH, informed consent will also be obtained from each of the participants before commencement of the study.

Statistical Analysis

Data will be processed and analysed using SPSS version 22.0. Quantitative data will be presented using frequency table and mean respectively. Pearson correlation will be used to determine the relationship between selected sociodemographic factors and the appearance of precervical cancer lesions among the respondents. A 95% confidence interval and p value of <0.05 will be considered statistically significant.

 

b. NIH-FORM BIOSKETCH

 

BIOGRAPHICAL SKETCH

NAME POSITION
DANIEL, GRACE OMOLADE        

Lecturer II, College of Medicine, University of Jos 

COMMON USER NAME GRACE

 

EDUCATION/TRAINING
INSTITUTION AND LOCATION    DEGREE MM/YY FIELD OF STUDY

Ahmadu Bello University, Zaria Nigeria

University of Ibadan, Ibadan Nigeria

BNSc

MSc

09/2004

05/2014

Nursing

Maternal and child health 

 

A.    Personal Statement

The goal of the proposed research is to assess the prevalence of precancerous cervical lesions among HIV positive women who have been on ART in JUTH and BUTH. Specifically we plan to assess the relationship between factors like age, marital status, level of education, ethnicity, occupation, religion, socioeconomic status ie Employment status income and the appearance of cervical lesions.

I am a young lecturer with a growing interest in research and passion to develop myself to a level where I could conduct various researches of international standard that will impact positively on the health of HIV positive women in plateau state, Nigeria and the world at large. 

I have conducted and published a number of researches and have been co author in some others. As a result of these previous experiences, I am aware of the importance of frequent communication among a research team thereby constructing a realistic research plan, timeline and Budget. I have chosen (Drs Samaila Shuaibu and Francis Shinku) who will provide additional expertise in Oncology and anatomy.

I have participated in the data analysis and Manuscript writing workshops organized by the Medical Education Partnership in Nigeria to further strengthen my research capability especially with the use of the SPSS. I have also attended the case based teaching method and Grant proposal writing.

In Summary, I have stated my passion for research and willingness to carry out productive research in an area of high prevalence of HIV and my modest experiences have prepared me to lead the proposed project.

B. Peer-reviewed Publications

1.  Daniel, G., Emmanuel, A., Achema, G. and Gimba, S. (2011). Knowledge and Practice of Breast Self Examination Among Female Undergraduates of University of Jos, Biological and Environmental Journal for the Tropics, 8 (2): 60 – 63

2. Daniel, G.O and Modupe, O.O (2013) Nursing Informatics: A key to improving Nursing Practice in Nigeria. International Journal of Nursing and Midwifery, 5(5): 90 – 98.

3. Daniel G.O, Modupe O. and Eleri G. (2015) Mothers’ Validation of Midwives care in the management of labour pain in two Hospitals in Plateau State, Nigeria. International Journal of Nursing and Midwifery, 7 (1): 1 – 8

4. Daniel, G.O.; Okoli, N.; Kumzhi, P.R.; Wina, F.; Ari, E.; Onyejekwe, G. (2016) Awareness and use of family planning methods among men in Mista Ali District, Jos, Plateau State, Nigeria. African Journal of Midwifery and Women’s Health, 10 (3): 120-125

5. Ajayi, A.D.,Daniel, G.O., Ari, E., Wina, F and Okezue G.A (2016) Psychosocial effects of pregnancy on teenage mothers in Angwan Rukuba community, Jos, Plateau State, Nigeria. African Journal of Midwifery and Women’s Health, 10(2): 3-8

 

C. BUDGET

PROPOSED BUDGET FOR THE STUDY

ITEM                                         QUANTITY                                UNIT COST(#)                  TOTAL COST(#)

 

 

CONSUMABLES/MATERIALS:

Sterile Gloves                                 8 Packs                                     5,000/Pack                      40,000.00

Sterile Cotton Wool                        5 Packs                                     1,600/Pack                       8,000.00

Gauze                                            3 Packs                                      8,000/Pack                      24,000.00

Ethanol                                           2 Gallons                                   6,500/Gallon                   13,000.00

Disposable Speculum                    4 Packs                                      35,000/Pack                    140,000.00

Slide                                               8 Packs                                      750/Pack                         6,000.00

Cytology Brush                               4 Packs                                      6,000/Pack                      24,000.00

Coppling Jar                                   100 Pieces                                 800/Pack                         80,000.00

Jik                                                    3 Gallons                                   850/Gallon                      2,550.00

Buckets                                            2                                               1600/Bucket                    3,200.00

Cover Slip                                        8 Packs                                     550/Pack                         4,400.00

LABORATORY ANALYSIS:

Reading of Samples                    332 Subjects                             5500/Subject                      1,826,000.00

PERSONNEL:

Research Assistant                          2                                       25,000 X 12months             600,000.00

GRAND TOTAL                                                                                                                     2,771,150.00

 

D. BUDGET JUSTIFICATION

Principal Investigator: Daniel, Grace Omolade

Project Title: Incidence and predictors of precancerous cervical lesions among HIV positive women on Antiretroviral therapy in Jos, Plateau State.

Personnel:

Mentor: Prof. Oche Agbaji and Dr Abraham Ajayi. Will provide scientific support and supervision throughout the duration of the research. No salary requested

Principal Investigator: Daniel, Grace Omolade. Will oversee all aspects of the research- protocol design, recruitment, data collection, analysis and interpretation of results. No salary requested

Co-Investigators: Drs S. Shuaibu and Dr F. Shinku. Will be involved in data collection, analysis and interpretation of results. No salary requested

Research Assistants: Will coordinate research logistics, data collection and laboratory investigations, allowance per month is N25,000

Others:

Publication cost: Research findings will be published in a peer-reviewed Journal

Travel Cost: Research findings will be presented at a conference

E. Project Narrative

This is a study on incidence and predictors of precancerous cervical lesions among HIV women on ART in Jos. It also assesses the predictors of precancerous lesions among HIV positive women using the following parameters: age, marital status, level of education, ethnicity, occupation, religion, socioeconomic status ie Employment status and income. The results of this study will reveal how many HIV positive cases are prone to cervical cancer despite the fact that they are on ARV’s and will also provide information on factors that could predict the occurrence of pre-cervical cancer lesions among women with HIV, this will help to understand apart from screening other preventive strategies towards cervical cancer. Finally, as a nurse, the findings of this study will also help to improve our counselling and education of HIV women in the best way to prevent cervical cancer.

F. Research Plan

This study aims to determine the incidence and predictors of precancerous cervical lesions among HIV women on ART.

Specific Aims

i.                    To determine incidence of precancerous cervical lesions among HIV positive women on ART

ii.                  To determine factors influencing the occurrence of precancerous cervical lesions among HIV positive women on ART

Background and Significance

Cervical cancer is the second most common cancer in women globally and accounts for 13% of all female cancers.25 Rates of cervical cancer in sub-Saharan Africa are among the highest in the world.26 In Nigeria, it is the second most common female cancer after breast cancer, with an age standardized incidence rate of 34.5 cases per 100,000 women in 201027. Two thirds of the world’s cases of HIV infection are found in sub-Saharan Africa, where a shortage of resources and biological factors work synergistically to increase women’s lifetime risk for developing cervical cancer.28 Cervical cancer has a high incidence and is a rapidly progressive illness among human immunodeficiency virus (HIV)-infected women. This cancer has received increasing attention since 1993 following its addition to the list of AIDS-defining illnesses monitored by the Centers for Disease Control and Prevention (CDC). HIV-infected women are at high risk of contracting oncogenic strains of HPV and developing cervical intraepithelial neoplasia (CIN), following immune suppression and risky sexual practices.2 In 2005, there were almost 260,000 deaths from cervical cancer and more than 500,000 new cases worldwide. HIV-positive women have a higher prevalence and incidence of cervical precancerous lesions than HIV negative women. Nigeria has the largest number of HIV/AIDS cases in West Africa29. Studies also have shown that Nigeria has a high prevalence of HPV among HIV positive women. The Papanicolaou (Pap) smear is one of the most essential screening tools for the early diagnosis of cervical cancer and has been found to be the most effective preventive measure.31 The value of cervical cancer screening in reducing the risk of cervical cancer and mortality has been established, and the risk of developing cervical cancer can be reduced by 80% through regular screening30.

In HIV-infected women, there is an increased risk of HPV infection and squamous intraepithelial lesions (SIL), the precursor of cervical cancer. The incidence of cervical cancer among women with AIDS has not decreased in high-resource countries since the introduction of antiretroviral therapy. Thus, HIV-infected women remain at a continued substantial risk for cervical cancer, even if they receive antiretroviral therapy. This is a problem for us in Nigeria which is still a developing Nation. This study is therefore aimed at determining the Incidence and predictors of precancerous cervical lesions among HIV positive women on ART. This study will assist policy makers to develop guidelines for prevention strategies for cervical cancer among HIV-infected women which is largely based on limited evidence. Understanding the predictors of precancerous cervical lesions among HIV positive women will also help in education and counselling of such women on how to prevent cancer of the cervix.

ii. Design and Methods

Study Setting

Two (2) Teaching Hospitals will be used for this study(Jos University Teaching Hospital(JUTH) and Bingham University Teaching Hospital (BUTH)). The Jos University Teaching Hospital is a 500 bed capacity hospital that serves about 8 states within the North central and part of North eastern Nigeria. The Bingham University Teaching Hospital Located in Jos North, serves the central part of Jos and other nearby neighbouring states.

Study Population

The study population will consist of HIV positive women older than 18 years of age, presenting at the HIV clinic of both JUTH and Bingham University Teaching Hospitals.

Study Design

Cross-sectional study where associations between exposure variables and outcome will be determined. Sample size is determined to be 332 based on a 95% confidence Level, 5% confidence interval, a normal distribution of 50% and a 10% attrition rate.

Sampling Technique

All HIV positive women who visit the screening clinics of both JUTH and BUTH, who met the inclusion criteria and have consented to the study will be recruited every clinic until the sample size is met. This is estimated to take approximately a period of 12 to 24 weeks.

Inclusion criteria

HIV positive women above 18 years old

Exclusion criteria

Women who are pregnant

Screening procedure

Each woman who consented to the study will be enrolled after obtaining informed consent. A self administered questionnaire will be used to obtain socio demographic and relevant clinical history. Introitus and vulva will be cleaned and noted for any abnormalities. A vagina speculum will be introduced to the vagina for a proper view of the cervix. During a Pap smear, an extended-tip wooden spatula or brush is used to gather cells from the outer opening of the cervix and the endocervix in what is called the transformation zone. The entire transformation zone will be sampled as this is where almost all high-grade lesions develop in the cervix. The sample will then be smeared onto a glass slide and immediately fixed with a solution to preserve the cells. The slide will be sent to a cytology laboratory where it is stained and examined using a microscope to determine whether the cells are normal and to classify them appropriately, using the Bethesda classification:negative for intraepithelial lesion or malignancy (‘normal’), low-grade squamous intraepithelial lesion (LSIL) (corresponding to HPV infection, mild dysplasia or cervical intraepithelial neoplasia (CIN) 1) and high-grade squamous intraepithelial lesion (HSIL) (corresponding to moderate and severe dysplasia, carcinoma in situ or CIN 2 and CIN 3). A finding of LSIL or HSIL is defined as an abnormal result. Any woman with an abnormal result will be referred to a gynaecologist for further evaluation and treatment.

Study Outcomes

The primary outcome measure will be the detection of precancerous cervical lesions among the women investigated. This can be defined as the appearance of atypical squamous cells or squamous intraepithelial Lesions (SIL) which can be further classified as either low grade (LSIL) or high grade (HSIL).

The secondary outcome measure will be appearance of lesions which correspond to moderate and severe dysplasia or carcinoma insitu.

Ethical Consideration

Ethical clearance will be obtained from the research and ethics committee of the Jos University Teaching Hospital before the commencement of the study.

Statistical Analysis

Data will be processed and analyzed using SPSS version 22. Findings will be presented using mean, standard deviation, frequencies and percentages. To determine predictors of cervical cancer lesions among the women, a multivariate logistic regression analysis will be used. Level of significance is set at a P value of α=0.5

 

 

 

 

 

 

 

 

 

References

1.      Ojo S.S, Agara, J.J anf Pojwan MA Cultural practices and prevalence of HIV/AIDS among Nigerian women: A case study of Lafia, Nigeria. Research on Humanities and Social Sciences. 2015; 5(18): 12

2.      Maiman M et al: Management of cervical neoplasia in human immunodeficiency virus-infected women. Monogr Natl Cancer Inst 1998; 23:43-49,

3.      Minkoff H, Feldman J, Dehovitz J, Landesman S, Burk R. A longitudinal study of human papillomavirus carriage in human immunodeficiency virus infected and human immunodeficiency virus-uninfected women. Am J Obstet Gynecol, 1998; 178: 982–986.

4.      Sun XW, Kuhn L, Ellerbrock TV, Chiasson MA, Bush TJ, et al. Human papillomavirus infection in women infected with the human immunodeficiency virus. N Engl J Med, 1997; 337: 1343–1349.

5.      Phelan DF, Gange SJ, Ahdieh-Grant L, Mehta SH, Kirk GD, et al. Determinants of Newly Detected Human Papillomavirus Infection in HIV Infected and HIV-Uninfected Injection Drug Using Women. Sex Transm Dis, 2009. 36: 149–156

6.      Ferlay BF, Bray F, Pisani P, Parkin DM. GLOBOCAN 2002:Cancer Incidence, Mortality and Prevalence Worldwide. IARC Cancer Base No. 5 Version 2 .O. IARC Press, Lyon. Available at: http:wwwdep. iarc.fr

7.      Parkin DM, Whelan SL, Ferlay J, Storm H. Cancer Incidence in Five Continents, Volumes I to VIII IARC Cancer Base No. 7, Lyon, 2005. http://www.iacr.com.fr/statist.htm

8.      Ferlay J, Shin H, Bray F, Forman D, Mathers C, Parkin DM: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010, 127(12):2893–2917.

9.      Adewole IF, Edozien EC, Babarinsa IA, Akang CE. Invasive and in situ carcinoma of the cervix in young Nigerians. A clinicopathologic study of 27 cases. Afr. J. Med. Sci. 1997. 26:191-193.

10.  Mbulaiteye SM, Bhatia K, Adebamowo C, Sasco AJ: HIV and cancer in Africa: mutual collaboration between HIV and cancer programs may provide timely research and public health data. Infectious Agents and Cancer 2011, 6(1):16.

11.  Maiman M et al: Management of cervical neoplasia in human immunodeficiency virus-infected women. Monogr Natl Cancer Inst 1998, 23:43-49

12.  Goldie SJ et al: The costs, clinical benefits, and cost-effectiveness of screening for cervical cancer in HIV-infected women. Ann Intern Med 1999, 130:97-107.

13.  Palefsky JM et al: Cervicovaginal human papillomavirus infection in HIV-positive and high-risk HIV-negative women. J Natl Cancer Inst 1999, 91:226-236.

14.  Boccalon M et al: Intra-epithelial and invasive cervical neoplasia during HIV-infection. Eur J Cancer 1996, 32A:2212-2217

15.  Palefsky JM et al: Human papillomavirus infection and anogenital neoplasia in human immunodeficiency virus-positive men and women. Monogr Natl Cancer Inst 1998, 23:15-20.

16.  Maiman M et al: Prevalence, risk factors, and accuracy of cytologic screening for cervical intraepithelial neoplasia in women with the human immunodeficiency virus. Gynecol Oncol 1998, 68:233-239

17.  Pallela FJ et al: Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N Engl J Med 1998, 338:853-860

18.  Strickler HD, Burk RD, Fazzari M, et al. Natural history possible reactivation of human papillomavirus in human immunodeficiency virus-positive women. J Natl Cancer Inst 2005, 97:577-6.

19.  Clifford GM, Gonçalves MA, Franceschi S. Human papillomavirus types among women infected with HIV: a meta-analysis. AIDS 2006, 20:2337-44.

20.  Frisch M, Biggar RJ, Goedert JJ. Human papillomavirus-associated cancers in patients with human immunodeficiency virus infection acquired immunodeficiency syndrome. J Natl Cancer Inst 2000, 92:1500-10.

  1. Dal Maso L, Franceschi S, Polesel J, et al. Risk of cancer in persons with AIDS in Italy, 1985–1998. Br J Cancer 2003, 89:94-100.
  2. Mbulaiteye SM, Katabira ET, Wabinga H, et al. Spectrum of cancers among HIV-infected persons in Africa: The Uganda AIDS-Cancer Registry Match Study. Int J Cancer 2006,118:985-90.
  3. International Agency for Research on Cancer (IARC). IARC handbooks of cancer prevention, cervix cancer screening. Lyon, France: IARC Press; 2005.volume 10
  4. WHO position paper 2009

25.  WHO Cervical cancer, human papillomavirus (HPV), and HPV vaccines: Key points for policy-makers and health professionals. Geneva, 2007

26.  Sasco AJ, Jaquet A, Boidin E, Ekouevi DK, Thouillot F, Lemabec T, et al., et al. The challenge of AIDS-related malignancies in sub-Saharan Africa. 2010, 5: e8621

27.  Jedy-Agba E, Curado MP, Ogunbiyi O, Oga E, Fabowale T, Igbinoba F, Osubor G, Otu T, Kumai H, Koechlin A: Cancer incidence in Nigeria: A report from population-based cancer registries. Cancer Epidemiology. 2012, 36 (5):

28.  Global Report: UNAIDS Report on the Global AIDS Epidemic 2010. Geneva: UNAIDS; 2010

29.  Sagay AS, Kapiga SH, Imade GE, Sankale JL, Idoko J and Kanki PHIV infection among pregnant women in Nigeria. International Journal of Gynecology and Obstetrics 2005, 90, 61—67

30.  Stewart BW, Kleihues P (Eds). Cancers of the female reproductive tract. In: World Cancer Report, International Agency for Research on Cancer. IARC Press, Lyon, France 2003.

31.  World Health Organization. Comprehensive cervical cancer control: A guide to essential practice. Geneva, Switzerland 2006b. 272 p.

 

 

 

 

 

 

 

INCIDENCE AND PREDICTORS OF PRECANCEROUS CERVICAL LESIONS AMONG HIV POSITIVE WOMEN IN JOS, PLATEAU STATE

 

Principal Investigator: Daniel, Grace Omolade

 

Department of Nursing Science, University of Jos

 

Co- Investigators: Drs’ Shuaibu S and Shinku F

 

E mail:gracemola2002@yahoo.co.uk, gracemola2002@gmail.com,gdanielgo@unijos.edu.ng

 

Phone Number: 08036285950

 

Purpose of the research: To investigate the incidence and predictors of precancerous cervical lesions among HIV positive women on Antiretroviral therapy in Jos, Plateau State

 

Date of commencement: January 2017

 

Mentor: Prof. Oche Agbaji and Dr Abraham Ajayi

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

a.      Abstract

Background

The Human Immuno-Deficiency Virus / Acquired Immune Deficiency Syndrome (HIV/AIDS) is evidently now a reality in Nigeria as it has and is still ravaging families and communities1. There are 16 million (15.2 million–16.9 million) women aged 15 years and older living with HIV; 80% live in sub-Saharan Africa. In sub-Saharan Africa, where about two-thirds of the global disease burden resides, 57% of adults living with HIV are women2. HIV-positive women are at increased risk of acquisition and/or persistence or reactivation of cervical infection with Human papilloma virus (HPV)3,4,5. Cervical cancer poses a major public health threat to women in many low and medium resourced countries in South and Central America, Sub-Saharan Africa, South and Southeast Asia, where it is still the leading type of cancer among women6,7. Cervical cancer (CC) is the second most common cancer affecting women worldwide, after breast cancer8. In 2008, the number of new cases of cervical cancer was estimated at 530,000 and 275,000 deaths were attributed to this disease. Most of these new cases (86%) and deaths (88%) occurred in developing countries mainly in sub- Saharan Africa and South-East Asia8. In Nigeria, the national incidence of cervical cancer is 250/100,0009.

Since the inception of the HIV epidemic, the United States CDC has classified Cervical Cancer, Kaposi Sarcoma and Non-Hodgkin’s Lymphoma as AIDS Defining Cancers because of their close association with HIV infection10. Women with HIV have high rates of cervical abnormalities (30% to 60%) and cervical dysplasia (11% to 60%)11,12 that are more difficult to treat.13 HIV-infected women have a fivefold risk of developing CIN, compared with uninfected women.14 Once these women develop cervical cancer, the cancer may be aggressive, and treatment may be ineffective,15 accounting for high rates of CIN recurrence16.

Cervical cancer screening recommendations among HIV-positive women are further complicated by frequent vaginal infections that result in inflammation or bleeding that obscures the specimen and limits the accuracy of the reading. The incidence of invasive cervical cancer is likely to rise with increasing numbers of HIV-infected women or with high-risk oncogenic types of HPV, especially since many of these women are poor and do not receive adequate health care. Improvements in antiretroviral therapy have dramatically reduced HIV-related mortality from common opportunistic infections, such as Pneumocystis carinii pneumonia.17 As a consequence, malignancies, including cervical cancers, are likely to be an increasing cause of death among HIV-infected women.

 

Because both HIV infection and HPV infection are sexually transmitted, the 2 infections are often found together18,19. In addition, as a result of HIV-induced immune impairment, there is also an increased probability that HPV infection will become persistent in HIV-infected women18 and evolve into precancerous and cancerous lesions of the cervix uteri 20,21,22. Effective screening and early treatment of precancerous cervical lesions are, thus, key factors in preventing cervical cancer in both HIV-infected and HIV-uninfected women23.Cervical cancer is preventable if precancer is diagnosed early through screening and cured through treatment; it takes a long time for a human papilloma virus (HPV) infection to progress to precancer but less time in HIV-positive women.HPV causes cellular changes in the surface tissue of the cervix long before the development of cancer. Antiretroviral therapy reduces the risk of progression to cervical cancer in women with cervical abnormalities only modestly. Studies have shown that persistent HPV infection may lead to CIN of grade 1, which is likely to resolve without treatment in the majority of cases. In a minority of women infected with HPV who develop CIN grade 1, lesions will progress to moderate (2) grade or severe (3) grade or to a precancerous lesion involving cervical glandular cells, called adenocarcinoma in situ (AIS).If untreated, CIN2–3 has a high probability of progressing to squamous cell cancer, and AIS has a high probability of progressing to adenocarcinoma (cervical cancer).24Since an inexpensive diagnostic test exists for easy diagnosis of precancerous cervical lesions, most mortality related to cervical cancer is avoidable. Hence this study is aimed at determining the prevalence of precancerous cervical lesions among HIV positive women who have been on ART.

SUBJECTS AND METHODS

Study Setting: Study will be carried out in the Jos University Teaching Hospital (JUTH) and Bingham University Teaching Hospital (BUTH).

Study population: HIV positive women older than 18 years

Screening Procedure

After obtaining informed consent, nurses obtained demographic and clinical information on all participants and examined the introitus and vulva, noting any abnormalities. A vagina speculum will be introduced to the vagina for a proper view of the cervix. During a Pap smear, an extended-tip wooden spatula or brush is used to gather cells from the outer opening of the cervix and the endocervix in what is called the transformation zone. The entire transformation zone will be sampled as this is where almost all high-grade lesions develop in the cervix. The sample will then be smeared onto a glass slide and immediately fixed with a solution to preserve the cells. The slide will be sent to a cytology laboratory where it is stained and examined using a microscope to determine whether the cells are normal and to classify them appropriately, using the Bethesda classification.

Ethical Consideration

Ethical clearance will be obtained from the research and ethics committee of JUTH and BUTH, informed consent will also be obtained from each of the participants before commencement of the study.

Statistical Analysis

Data will be processed and analysed using SPSS version 22.0. Quantitative data will be presented using frequency table and mean respectively. Pearson correlation will be used to determine the relationship between selected sociodemographic factors and the appearance of precervical cancer lesions among the respondents. A 95% confidence interval and p value of <0.05 will be considered statistically significant.

 

b. NIH-FORM BIOSKETCH

 

 

 

BIOGRAPHICAL SKETCH

                                                                POSITION TITLE

NAMELecturer II, College of Medicine, University of

DANIEL, GRACE OMOLADE         Jos.

 

 

COMMON USER NAME

GRACE

EDUCATION/TRAINING

INSTITUTION AND LOCATION    DEGREE  MM/YY  FIELD OF STUDY

Ahmadu Bello University, Zaria,           BNSc              09/2004                   Nursing

Nigeria

University of Ibadan, Ibadan, Nigeria   MSc                 05/2014Maternal and Child Health

 

 

A.    Personal Statement

The goal of the proposed research is to assess the prevalence of precancerous cervical lesions among HIV positive women who have been on ART in JUTH and BUTH. Specifically we plan to assess the relationship between factors like age, marital status, level of education, ethnicity, occupation, religion, socioeconomic status ie Employment status income and the appearance of cervical lesions.

I am a young lecturer with a growing interest in research and passion to develop myself to a level where I could conduct various researches of international standard that will impact positively on the health of HIV positive women in plateau state, Nigeria and the world at large. 

I have conducted and published a number of researches and have been co author in some others. As a result of these previous experiences, I am aware of the importance of frequent communication among a research team thereby constructing a realistic research plan, timeline and Budget. I have chosen (Drs Samaila Shuaibu and Francis Shinku) who will provide additional expertise in Oncology and anatomy.

I have participated in the data analysis and Manuscript writing workshops organized by the Medical Education Partnership in Nigeria to further strengthen my research capability especially with the use of the SPSS. I have also attended the case based teaching method and Grant proposal writing.

In Summary, I have stated my passion for research and willingness to carry out productive research in an area of high prevalence of HIV and my modest experiences have prepared me to lead the proposed project.

B. Peer-reviewed Publications

1.  Daniel, G., Emmanuel, A., Achema, G. and Gimba, S. (2011). Knowledge and Practice of Breast Self Examination Among Female Undergraduates of University of Jos, Biological and Environmental Journal for the Tropics, 8 (2): 60 – 63

2. Daniel, G.O and Modupe, O.O (2013) Nursing Informatics: A key to improving Nursing Practice in Nigeria. International Journal of Nursing and Midwifery, 5(5): 90 – 98.

3. Daniel G.O, Modupe O. and Eleri G. (2015) Mothers’ Validation of Midwives care in the management of labour pain in two Hospitals in Plateau State, Nigeria. International Journal of Nursing and Midwifery, 7 (1): 1 – 8

4. Daniel, G.O.; Okoli, N.; Kumzhi, P.R.; Wina, F.; Ari, E.; Onyejekwe, G. (2016) Awareness and use of family planning methods among men in Mista Ali District, Jos, Plateau State, Nigeria. African Journal of Midwifery and Women’s Health, 10 (3): 120-125

5. Ajayi, A.D.,Daniel, G.O., Ari, E., Wina, F and Okezue G.A (2016) Psychosocial effects of pregnancy on teenage mothers in Angwan Rukuba community, Jos, Plateau State, Nigeria. African Journal of Midwifery and Women’s Health, 10(2): 3-8

 

C. BUDGET

PROPOSED BUDGET FOR THE STUDY

ITEM                                         QUANTITY                                UNIT COST(#)                  TOTAL COST(#)

CONSUMABLES/MATERIALS:

Sterile Gloves                                    8 Packs                                        5,000/Pack                         40,000.00

Sterile Cotton Wool                        5 Packs                                     1,600/Pack                       8,000.00

Gauze                                                   3 Packs                                        8,000/Pack                      24,000.00

Ethanol                                                 2 Gallons                                     6,500/Gallon                   13,000.00

Disposable Speculum                   4 Packs                                      35,000/Pack                    140,000.00

Slide                                                      8 Packs                                         750/Pack                             6,000.00

Cytology Brush                                  4 Packs                                         6,000/Pack                      24,000.00

Coppling Jar                                        100 Pieces                                 800/Pack                               80,000.00

Jik                                                           3 Gallons                                     850/Gallon                      2,550.00

Buckets                                                    2                                                 1600/Bucket                   3,200.00

Cover Slip                                        8 Packs                                          550/Pack                               4,400.00

LABORATORY ANALYSIS:

Reading of Samples                    332 Subjects                             5500/Subject                      1,826,000.00

PERSONNEL:

Research Assistant                          2                                       25,000 X 12months             600,000.00

GRAND TOTAL                                                                                                                     2,771,150.00

 

D. BUDGET JUSTIFICATION

Principal Investigator: Daniel, Grace Omolade

Project Title: Incidence and predictors of precancerous cervical lesions among HIV positive women on Antiretroviral therapy in Jos, Plateau State.

Personnel:

Mentor: Prof. Oche Agbaji and Dr Abraham Ajayi. Will provide scientific support and supervision throughout the duration of the research. No salary requested

Principal Investigator: Daniel, Grace Omolade. Will oversee all aspects of the research- protocol design, recruitment, data collection, analysis and interpretation of results. No salary requested

Co-Investigators: Drs S. Shuaibu and Dr F. Shinku. Will be involved in data collection, analysis and interpretation of results. No salary requested

Research Assistants: Will coordinate research logistics, data collection and laboratory investigations, allowance per month is N25,000

Others:

Publication cost: Research findings will be published in a peer-reviewed Journal

Travel Cost: Research findings will be presented at a conference

E. Project Narrative

This is a study on incidence and predictors of precancerous cervical lesions among HIV women on ART in Jos. It also assesses the predictors of precancerous lesions among HIV positive women using the following parameters: age, marital status, level of education, ethnicity, occupation, religion, socioeconomic status ie Employment status and income. The results of this study will reveal how many HIV positive cases are prone to cervical cancer despite the fact that they are on ARV’s and will also provide information on factors that could predict the occurrence of pre-cervical cancer lesions among women with HIV, this will help to understand apart from screening other preventive strategies towards cervical cancer. Finally, as a nurse, the findings of this study will also help to improve our counselling and education of HIV women in the best way to prevent cervical cancer.

F. Research Plan

This study aims to determine the incidence and predictors of precancerous cervical lesions among HIV women on ART.

Specific Aims

i.                    To determine incidence of precancerous cervical lesions among HIV positive women on ART

ii.                  To determine factors influencing the occurrence of precancerous cervical lesions among HIV positive women on ART

Background and Significance

Cervical cancer is the second most common cancer in women globally and accounts for 13% of all female cancers.25 Rates of cervical cancer in sub-Saharan Africa are among the highest in the world.26 In Nigeria, it is the second most common female cancer after breast cancer, with an age standardized incidence rate of 34.5 cases per 100,000 women in 201027. Two thirds of the world’s cases of HIV infection are found in sub-Saharan Africa, where a shortage of resources and biological factors work synergistically to increase women’s lifetime risk for developing cervical cancer.28 Cervical cancer has a high incidence and is a rapidly progressive illness among human immunodeficiency virus (HIV)-infected women. This cancer has received increasing attention since 1993 following its addition to the list of AIDS-defining illnesses monitored by the Centers for Disease Control and Prevention (CDC). HIV-infected women are at high risk of contracting oncogenic strains of HPV and developing cervical intraepithelial neoplasia (CIN), following immune suppression and risky sexual practices.2 In 2005, there were almost 260,000 deaths from cervical cancer and more than 500,000 new cases worldwide. HIV-positive women have a higher prevalence and incidence of cervical precancerous lesions than HIV negative women. Nigeria has the largest number of HIV/AIDS cases in West Africa29. Studies also have shown that Nigeria has a high prevalence of HPV among HIV positive women. The Papanicolaou (Pap) smear is one of the most essential screening tools for the early diagnosis of cervical cancer and has been found to be the most effective preventive measure.31 The value of cervical cancer screening in reducing the risk of cervical cancer and mortality has been established, and the risk of developing cervical cancer can be reduced by 80% through regular screening30.

In HIV-infected women, there is an increased risk of HPV infection and squamous intraepithelial lesions (SIL), the precursor of cervical cancer. The incidence of cervical cancer among women with AIDS has not decreased in high-resource countries since the introduction of antiretroviral therapy. Thus, HIV-infected women remain at a continued substantial risk for cervical cancer, even if they receive antiretroviral therapy. This is a problem for us in Nigeria which is still a developing Nation. This study is therefore aimed at determining the Incidence and predictors of precancerous cervical lesions among HIV positive women on ART. This study will assist policy makers to develop guidelines for prevention strategies for cervical cancer among HIV-infected women which is largely based on limited evidence. Understanding the predictors of precancerous cervical lesions among HIV positive women will also help in education and counselling of such women on how to prevent cancer of the cervix.

ii. Design and Methods

Study Setting

Two (2) Teaching Hospitals will be used for this study(Jos University Teaching Hospital(JUTH) and Bingham University Teaching Hospital (BUTH)). The Jos University Teaching Hospital is a 500 bed capacity hospital that serves about 8 states within the North central and part of North eastern Nigeria. The Bingham University Teaching Hospital Located in Jos North, serves the central part of Jos and other nearby neighbouring states.

Study Population

The study population will consist of HIV positive women older than 18 years of age, presenting at the HIV clinic of both JUTH and Bingham University Teaching Hospitals.

Study Design

Cross-sectional study where associations between exposure variables and outcome will be determined. Sample size is determined to be 332 based on a 95% confidence Level, 5% confidence interval, a normal distribution of 50% and a 10% attrition rate.

Sampling Technique

All HIV positive women who visit the screening clinics of both JUTH and BUTH, who met the inclusion criteria and have consented to the study will be recruited every clinic until the sample size is met. This is estimated to take approximately a period of 12 to 24 weeks.

Inclusion criteria

HIV positive women above 18 years old

Exclusion criteria

Women who are pregnant

Screening procedure

Each woman who consented to the study will be enrolled after obtaining informed consent. A self administered questionnaire will be used to obtain socio demographic and relevant clinical history. Introitus and vulva will be cleaned and noted for any abnormalities. A vagina speculum will be introduced to the vagina for a proper view of the cervix. During a Pap smear, an extended-tip wooden spatula or brush is used to gather cells from the outer opening of the cervix and the endocervix in what is called the transformation zone. The entire transformation zone will be sampled as this is where almost all high-grade lesions develop in the cervix. The sample will then be smeared onto a glass slide and immediately fixed with a solution to preserve the cells. The slide will be sent to a cytology laboratory where it is stained and examined using a microscope to determine whether the cells are normal and to classify them appropriately, using the Bethesda classification:negative for intraepithelial lesion or malignancy (‘normal’), low-grade squamous intraepithelial lesion (LSIL) (corresponding to HPV infection, mild dysplasia or cervical intraepithelial neoplasia (CIN) 1) and high-grade squamous intraepithelial lesion (HSIL) (corresponding to moderate and severe dysplasia, carcinoma in situ or CIN 2 and CIN 3). A finding of LSIL or HSIL is defined as an abnormal result. Any woman with an abnormal result will be referred to a gynaecologist for further evaluation and treatment.

Study Outcomes

The primary outcome measure will be the detection of precancerous cervical lesions among the women investigated. This can be defined as the appearance of atypical squamous cells or squamous intraepithelial Lesions (SIL) which can be further classified as either low grade (LSIL) or high grade (HSIL).

The secondary outcome measure will be appearance of lesions which correspond to moderate and severe dysplasia or carcinoma insitu.

Ethical Consideration

Ethical clearance will be obtained from the research and ethics committee of the Jos University Teaching Hospital before the commencement of the study.

Statistical Analysis

Data will be processed and analyzed using SPSS version 22. Findings will be presented using mean, standard deviation, frequencies and percentages. To determine predictors of cervical cancer lesions among the women, a multivariate logistic regression analysis will be used. Level of significance is set at a P value of α=0.5

 

 

 

 

 

 

 

 

 

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