Why was the cohort set up?
Globally, cervical cancer is the fourth most common cancer among women, with an estimated
528 000 new cases in 2012.
1
Although it remains a significant public health problem worldwide, the burden of cervical
cancer falls disproportionately on low-resource countries. In the USA, the incidence
rate of cervical cancer was 6.6 per 100 000 in 2012,
1
compared with 23.0 per 100 000 in Nigeria
2
which had about half the population of the USA in 2012.
Persistent high-risk human papillomavirus (hrHPV) infection of the cervix is a necessary
cause of cervical cancer.
3
,
4
About 80% of sexually active individuals become infected with at least one genital
hrHPV in their lifetime. Most of the infections are cleared, but about 10% become
persistent infections.
5–7
The mechanism by which some individuals are able to remain uninfected while some clear
the infection and others remain persistently infected, remains unclear. Of the women
with persistent hrHPV infection, only ∼ 12% go on to develop cervical intraepithelial
neoplasia (CIN)
2
,
3
and cervical cancer.
8
Therefore, several co-factors are required to support the cervical carcinogenesis
induced by persistent hrHPV infection.
7
,
9
Data from Western series suggest that HPV types 16 and 18 account for most of the
cases of cervical cancer in those environments.
4
However, there have been few longitudinal studies of hrHPV infections and their association
with cervical cancer in much of the rest of the world. Given the marked heterogeneity
of types and prevalence of multiple hrHPV infection in many parts of the developing
world, variation in ability of different hrHPV types to establish persistent infection
and concerns about the coverage of existing vaccines, longitudinal studies of large
numbers of women in the general population in different regions of the world, with
information on HPV types and risk factors, are critical to bridging the knowledge
gaps, especially in African populations where such studies are scarce.
10–14
The aetiology of cervical cancer is multifactorial. It is clear that environmental
risk factors such as smoking, age at first sexual intercourse, age at first full-term
pregnancy, high parity and use of oral contraceptives which have been implicated in
persistent hrHPV infection, do not completely explain the association between hrHPV
infection and cervical cancer, and several studies have identified a role for genetics
and heritability in its aetiology.
15–23
These studies suggest that genetic factors contribute to the risk of persistent hrHPV
infection and progression to cervical cancer. A recent review of 15 studies on heritability
of cervical cancer risk suggested that having a first-degree relative with cervical
cancer increases an individual’s risk by 1- or 2-fold.
24
Other reviews concluded that there is a potential role for genetic factors in cervical
cancer in situ and estimated the heritability to be between 11% and 15%.
25–27
Nevertheless, there have been few studies of genetic risks of the different components
of the pathway to cervical carcinogenesis among all populations, particularly in Africans.
An important yet understudied aspect of HPV carcinogenesis is the role of innate immunity
and emerging knowledge about the vaginal microbiome, and the role that these play
in cervical carcinogenesis.
28–34
Vaginal microbiota may affect the risk of persistent hrHPV infection through rich,
complex, dynamic and individual-specific microbial interaction with the host such
as through signalling of host cells that affect inflammatory, immunological, and host-defence
functions.
35
,
36
Specific types of vaginal microbiota may sculpt the cervical cytokines in ways that
influence the persistence of HPV infection or breach the incipient latency of the
persistent hrHPV infection state and drive it towards induction of malignancy in the
cervix.
35
Furthermore, health behaviours, including intravaginal health practice, number of
sexual partners and other factors, may affect the types of vaginal microbiota and
their association with risk of persistent hrHPV infection. There have been few studies
of the vaginal microbiota
37
,
38
and the interaction between the vaginal microbiota and cervical cytokines and their
association with persistent hrHPV infection.
27
,
28
The design of the African Collaborative Center for Microbiome and Genomics Research
(ACCME) HPV and Cervical Cancer Cohort Study enables us to study environmental, microbiomic,
genetic and epigenetic factors associated with persistent hrHPV infection, in order
to improve knowledge of the mechanism of HPV carcinogenesis and discover biomarkers
of persistent hrHPV infection and cervical cancer. We evaluate the epidemiological
determinants of persistent infection, and the genetic and epigenetic changes in hrHPV
as well as in somatic cervical cells and their association with persistent hrHPV infection
and CIN2+. We evaluate the epidemiological determinants of patterns of cervical cytokines
and their association with persistent hrHPV infection. We identify the community state
types and stability of the vaginal microbiota, and their association with persistent
hrHPV infection. We conduct genome-wide association studies (GWAS) to identify the
genetic variants associated with the risk of persistent hrHPV infection and CIN2+.
The ACCME cohort is located in Nigeria. Ethical approval to conduct this study was
obtained from the National Health Research Ethics Committee in Nigeria. All study
participants were informed about the study and were requested to consent before participation.
The informed consent is reiterated at different study visits and new consent is obtained
for specific components of the research project. An ethics and regulatory affairs
coordinator conducts regular audits of the informed consent process and evaluates
the understanding of the informed consent among randomly selected study participants.
This study is funded by the National Institutes of Health.
Who is in the cohort?
There are 36 states, six geopolitical zones and a Federal Capital Territory in Nigeria.
Our study is located in Abuja, the main municipality in the Federal Capital Territory,
which is located in the centre of the country. In general, the socio-demographic characteristics
of women in Abuja, North Central Nigeria, were similar to those of women in the South
East, South South, and South West zones in 2013, but not the North East or North West
which are more rural and the women there are less likely to be educated or employed.
39
We randomly selected seven out of 42 districts in Abuja for our study. The populations
served by these study sites varied from urban city dwellers to semi-rural to rural
people living on farmlands and villages. In each district, we employed extensive community
engagement strategies, to create awareness of the study and ensure that a representative
sample of the target population was enrolled. These strategies included: focus group
discussions and surveys to identify cultural issues, literacy levels and local language;
town hall meetings and community forums to gain input from the general public; participatory
evaluation; and partnerships with community stakeholders to create alliances and ownership
and build trust. We also created awareness of the study through the use of: mass media
including radio and television talk shows; social media including Twitter and Facebook;
interactions with key opinion leaders; and engagement of religious leaders, women’s
advocacy groups, corporate organizations, the Nigerian Federal Ministry of Health
and community members.
In this study, we identified women who were at least 18 years old, had had sexual
intercourse and had no previous history of cervical abnormalities, cervical cancer
or total abdominal hysterectomy, by area sampling in Abuja. Potential participants
were offered HIV testing with voluntary counselling. Those who were HIV-positive were
not eligible to participate in the cohort and were referred to free HIV treatment
programmes. Enrolment into the cohort began in February 2014 in Abuja, Central Nigeria.
How often is follow-up?
Data are collected during the initial visit and at 6, 12, 18 and 24 months. Research
nurses collect epidemiological data using our tablet computer-assisted survey instruments
(TaCASI) directly into a secure web database application—the Research Electronic Data
Capture (REDCap) platform hosted at the Institute of Human Virology (IHVN).
43
Paper copies of the study forms are available to serve as backup for data collection.
Detailed contact information (address and phone numbers) are collected from all participants.
Follow-up visits are scheduled at appropriate times and reminders are sent by text
messages, e-mails and phone calls. Where participants cannot be reached by phone,
home visits are conducted.
What is being measured?
The data collection tools were piloted in a study of 1000 women with similar characteristics
as the participants of the ACCME study. In order to compute socioeconomic status (SES)
in a low-resource environment where income data are sparse, we generated wealth index
data as previously described.
44
In summary, we used principal components analysis (PCA) with varimax rotation to compute
factor scores based on the sum of the ownership of household items weighted by their
factor loading. We sorted the data on the first principal component which had the
highest eigen value, and divided all respondents into three categories based on its
value. Participants with the lowest 40% were categorized as low SES, the middle 40%
were categorized as middle SES and the top 20% were categorized as high SES. The validity
and reproducibility of the wealth index has been examined in previous studies and
it correlates well with other measures of wealth in environments without reliable
expenditure data.
44
We adapted tools for the measurement of alcohol intake, cigarette smoking, tobacco
use, sexual and reproductive health and medical and drug history from the PhenX toolkit
version of 20 September 2013, version 5.6.
45
We obtained self-report of occurrence of diseases such as cancer, diabetes, myocardial
infarction and stroke. We modified the Harvard School of Public Health’s Nurses’ Health
Study II physical activity questionnaire to collect data on physical activity and
we used the Nigerian food frequency questionnaire that we had previously developed
to collect information on dietary intake. Members of the ACCME research group have
used these tools for previous research in Africa.
46–48
We asked participants about their sexual activities in the past 24 h including history
of sexual intercourse (vaginal, anal, oral), use of contraceptives, sex toys and lubricants,
and vaginal symptoms. Given the sensitive nature of some questions, especially those
on sexual history, we ensured the mode and placement of the questions were appropriate,
the interviewers were trained to be culturally and morally sensitive and each interview
was conducted in a relaxed, private setting, sufficiently so to encourage accurate
responses.
Three blood pressure (BP) measurements are taken at least 1 min apart in accordance
with the American Heart Association recommendations,
49
using the automated OMRON® BP760 (HEM-7220-Z) with patients in a sitting position,
not earlier than 15 min after participant arrival at the study site. Standing height,
body weight and waist and hip circumferences were measured in accordance with the
World Health Organization (WHO) Multinational Monitoring of Trends in Cardiovascular
Disease (MONICA) project.
50
Pelvic examinations were performed on all participants and data on any significant
findings in the lower abdomen, the vulva/perineum, vagina, cervix and adnexa were
collected as described.
51
,
52
We performed bivalve speculum examination and measured the vaginal pH using pH paper
(pHydrion®, Micro Essentials Laboratories, Brooklyn, NY) and compared colour change
of the pH paper with the manufacturer-provided colour charts.
53
,
54
All research nurses passed a colour perception test before performing the pH tests.
The data collected by questionnaires and during the Clinical Evaluation, Sample Evaluation
and Testing schedule are outlined in Supplementary Table 1 (available as Supplementary
data at IJE online).
Biological samples including blood and mid-vaginal and ectocervical cell samples are
collected at baseline and during follow-up visits. The blood samples are separated
into plasma, serum, buffy coat, red blood cells and clot. All biological samples are
stored at -80 °C at the ACCME Laboratories, IHVN, Abuja, Nigeria. Germline, somatic
and viral DNAs are extracted using MagNa Pure LC 2.0® and Qiagen Qiacube HT robotic
nucleic acid isolation and purification platforms. Germline DNA is quantitated using
NanoDrop 8000 UV-Vis spectrophotometer at wavelengths of 260 and 280 nm, after which
working dilutions to the 5–10 ng of DNA required per reaction are created.
Cervical exfoliated samples are analysed for any HPV and hrHPV using SPF10 PCR-DEIA-LiPA25,
version 1, according to manufacturer’s instructions. Samples of cervical cytokines
are collected and stored immediately in ice coolers and transported to the laboratory
for storage. Cervical cytokines are measured using polystyrene non-magnetic bead-based
multiplex assay according to manufacturer’s instructions (Bio-Rad® Bio-Plex 200 System®,
Hercules, CA). The vaginal microbial species composition and abundance will be determined
as described by Forney et al.
30
The V1-V3 hypervariable regions of the 16S rRNA genes will be amplified using an optimized
primer set 27F and 533R as recommended by the Human Microbiome Project (HMP) [http://www.hmpdacc.org].
Colposcopy and biopsy will be done for all individuals with persistent hrHPV infection
and clinical features of a cervical lesion suspected to be CIN2+ and for matching
controls. Biopsy samples are handled according to the TCGA [http://cancergenome.nih.gov)]
standard operating procedure. Spot urine samples are collected and tested for glucose,
ketones, specific gravity, blood, pH, protein, nitrites and leukocytes with Multistix®
10 SG reagent strip; the rest are stored in the laboratory at -80 °C. Women with cervical
cancer are biopsied and referred for appropriate treatment. We store fresh frozen
samples and paraffin embedded samples of the cervical biopsy and collect minimal data
from these women; they are not enrolled in the prospective cohort.
Quality assurance and control
Data
Tablet computer-assisted survey instruments (TaCASI) have proved versatile in survey
research that incorporates sensitive questions like those on sexual behaviour.
55–57
We use real-time data entry into secure RedCap databases with in-built logic and error
checks, which enables data managers to review data and follow-up on missing values
and outliers with site research associates promptly.
11
,
12
,
55–59
Laboratory
Two independent pathologists who are blinded to the HPV status of the participants
report on the histological diagnoses. Quality assurance (QA) and quality control (QC)
of HPV genotyping is done in collaboration with DDL diagnostic laboratory. Human genomics
QA/QC is done in collaboration with the Center for Research on Genomics and Global
Health, at the National Human Genome Research Institute. We store digital colposcopy
images on a private cloud server for secondary review.
What has been found?
The focus of this project so far has been on establishing the study population and
obtaining baseline data on known and potential risk factors of hrHPV infection and
CIN2+, which will be used for epidemiological and genomic studies. Some early results
are presented here.
From commencement of enrolment in February 2014 to July 2016, 11 500 women had been
enrolled in the ACCME cohort. The women in this cohort have homogeneous contraceptive,
sexual and reproductive characteristics and health status compared with similarly
aged HIV-negative women, in the general population.
40–42
Many of the women enrolled were in their third or fourth decade of life, the mean
age [standard deviation (SD)] of the participants was 39 (10) years. Most of the participants
were married (77%; 8832/11 500), monogamous and live with their spouses (86%; 7556/8832).
Many participants have had some university education (45%; 5152/11 500) and have professional
jobs (36%; 4175/11 500). Selected socio-demographic characteristics of the study participants
at baseline are shown in Table 1. To date we have tested the baseline samples of all
the study participants for HPV using DEIA, and observed that 42% (4773/11 500) tested
positive (Table 2). Similar tests for HPV have been done in 5349 participants at the
12 months follow-up visit, and we observed that 21% (1107/5349) of these women had
persistent HPV infections. About 16% of the study participants have had oral sex and
< 1% have had anal sex (Table 3). Most participants thought anal sex was unacceptable
for health (57%), religious (53%) and/or cultural (26%) reasons (multiple responses
allowed). Some of the participants reported a history of physician-diagnosed hypertension
(15%), diabetes (2%), hypercholesterolaemia (4%) or heart disease (0.3%) (Table 4).
We found the mean (SD) vaginal pH was 5.2 (0.5); it was similar among HPV-positive
and HPV-negative women. Selected gynaecological characteristics of the study participants
at baseline are shown in Table 5. Our results on sexual health and behaviour provide
important data for studies of associations between these characteristics and HPV-associated
cancers including cervical, head and neck, and anal cancers, and identifies attitudes
and beliefs which may contribute to the social epidemiological risk for other non-communicable
diseases (NCD). The study attrition rate is ∼ 20%.
Table 1
Selected baseline socio-demographic characteristics of women in the ACCME Cohort,
n (%)
Characteristics
Total
Rural
Semi-rural
Urban
n = 11500
n = 1380
n = 5336
n = 4784
Age, years
a
38.8 (9.6)
38.4 (9.9)
37.8 (9.7)
40.1 (9.2)
Age categories, years
18–29
2093 (18.2)
304 (22.0)
1180 (22.1)
609 (12.7)
30–39
4105 (35.7)
462 (33.5)
1926 (36.1)
1717 (36.0)
40–49
3530 (30.7)
398 (28.8)
1494 (28.0)
1638 (34.2)
50–59
1576 (13.7)
186 (13.5)
656 (12.3)
734 (15.3)
≥ 60
196 (1.7)
30 (2.2)
80 (1.5)
86 (1.8)
Tribe
Hausa
862 (7.5)
79 (5.7)
598 (11.2)
185 (3.8)
Ibo
2531 (22.0)
195 (14.1)
875 (16.4)
1461 (20.5)
Yoruba
1322 (11.5)
59 (4.3)
464 (8.7)
799 (16.7)
Other tribes
6785 (59.0)
1047 (75.9)
3399 (63.7)
2339 (50.0)
Religion
Atheist
23 (0.2)
2 (0.1)
11 (0.2)
10 (0.2)
Christian
9545 (83.0)
1208 (87.5)
4173 (78.2)
4164 (87.0)
Eckankar
2 (0.02)
0 (0.0)
0 (0.0)
2 (0.04)
Judaism
2 (0.02)
0 (0.0)
1 (0.01)
1 (0.02)
Muslim
1920 (16.7)
168 (12.2)
1147 (21.5)
605 (12.7)
Traditional
8 (0.07)
2 (0.1)
4 (0.1)
2 (0.04)
Marital status
Cohabiting
23 (0.2)
8 (0.6)
11 (0.2)
4 (0.1)
Divorced/separated
310 (2.7)
33 (2.4)
112 (2.1)
165 (3.4)
Married
8832 (76.8)
1070 (77.5)
4204 (78.8)
3558 (74.4)
Single
1668 (14.5)
148 (10.7)
710 (13.3)
810 (17.0)
Widowed
667 (5.8)
121 (8.8)
299 (5.6)
247 (5.1)
Marital arrangement
Monogamous (live separately)
386 (4.4)
56 (5.2)
131 (3.1)
199 (5.5)
Monogamous (live together)
7556 (85.6)
913 (84.4)
3529 (85.3)
3114 (86.6)
Polygamous (all live together)
628 (7.1)
84 (7.8)
380 (8.9)
164 (4.6)
Polygamous (live separately)
262 (2.9)
28 (2.6)
114 (2.7)
120 (3.3)
Education
No formal schooling
1127 (9.8)
251 (18.2)
779 (14.6)
97 (2.0)
Primary
1069 (9.3)
277 (20.1)
598 (11.2)
194 (4.0)
Secondary
2507 (21.8)
486 (35.2)
1409 (26.4)
612 (12.8)
University
5152 (44.8)
309 (22.4)
2065 (38.7)
2778 (58.1)
Postgraduate
1645 (14.3)
57 (4.1)
485 (9.1)
1103 (23.1)
Occupation
Professional
4175 (36.3)
208 (15.1)
1484 (27.8)
2483 (51.9)
Self-employed
3634 (31.6)
567 (41.1)
1920 (36.0)
1147 (24.0)
Manual
678 (5.9)
195 (14.1)
368 (6.9)
115 (2.4)
Skilled manual
897 (7.8)
149 (10.8)
507 (9.5)
241 (5.0)
Student
747 (6.5)
70 (5.1)
438 (8.2)
239 (5.0)
Unemployed
1369 (11.9)
191 (13.8)
619 (11.6)
559 (11.7)
Socioeconomic status
Low
4600 (40.0)
927 (67.2)
2759 (51.7)
914 (19.1)
Middle
4715 (41.0)
373 (27.0)
1969 (36.9)
2373 (49.6)
High
2185 (19.0)
80 (5.8)
608 (11.4)
1497 (31.3)
a
Mean (standard deviation).
Table 2
Prevalence (%) of HPV infection among women in the ACCME cohort
Persistently DEIA HPV-positive
HPV status
Any HPV
a
Low-risk HPV
b
High-risk HPV+
HPV-positive at baseline
4773 (41.5)
1718 (36.0)
3050 (63.9)
HPV-positive at follow-up visit
c
2305 (43.1)
521 (22.6)
1784 (77.4)
Persistent HPV-positive
1107 (20.7)
139 (12.6)
598 (54.0)
a
Based on DEIA.
b
Results based on LiPA.
c
Follow-up visit at 12 months after baseline, current total n = 5349.
Table 3
Some baseline sexual and reproductive history of women in the ACCME cohort
Characteristics
Total
HPV-negative
HPV-positive
n = 11500
n = 6727
n = 4773
Mean (standard deviation)
Age at menarche
14 (2)
14 (2)
14 (2)
Age at menopause
44 (9)
44 (9)
43 (9)
Age at first vaginal sexual intercourse
20 (4)
21 (4)
20 (4)
Age at first oral sexual intercourse
26 (6)
27 (6)
26 (6)
Age at first anal sexual intercourse
27 (7)
27 (7)
26 (7)
Number of lifetime sexual partners
Vaginal
2.6 (2.6)
2.7 (2.6)
2.8 (2.7)
Oral
1.8 (1.7)
1.6 (1.5)
1.8 (1.8)
Anal
1.3 (1.2)
1.0 (0.6)
1.3 (1.2)
n (%)
Types of sexual experience
a
Vaginal
11500 (100.0)
6727 (100.0)
4773 (100.0)
Oral
1832 (15.9)
1016 (15.1)
816 (17.1)
Anal
69 (0.6)
42 (0.6)
27 (0.6)
First type of sexual experience
Vaginal
9574 (98.3)
5605 (98.4)
3969 (98.1)
Oral
154 (1.6)
8 (1.5)
3 (1.8)
Anal
11 (0.1)
82 (0.1)
72 (0.1)
Oral sex type
a
Fellatio
964 (58.2)
545 (59.3)
419 (56.8)
Cunnilingus
689 (41.6)
371 (40.4)
318 (43.1)
Anallingus
4 (0.2)
3 (0.3)
1 (0.1)
Anal sex type
a
Receptive
195 (94.4)
109 (55.9)
86 (44.1)
Insertive (using objects e.g. sex toys)
1 (0.5)
0 (0.0)
1 (100.0)
Both
9 (5.1)
6 (66.7)
3 (33.3)
Sexual type preferred
None
75 (0.8)
52 (0.9)
23 (0.6)
Vaginal
9363 (97.3)
5484 (97.2)
3879 (96.9)
Oral
14 (2.0)
9 (1.7)
5 (2.4)
Anal
196 (0.2)
99 (0.2)
97 (0.1)
Usual frequency of sexual intercourse
Vaginal
< 1/month
3186 (32.5)
1826 (32.0)
1342 (33.2)
1–3/month
1825 (18.7)
1010 (17.7)
815 (20.2)
1/week
2339 (24.0)
1410 (24.7)
929 (23.0)
2–4/week
2075 (21.3)
1254 (22.0)
821 (20.3)
≥ 5/week
335 (3.5)
202 (3.6)
133 (3.3)
Oral
< 1/month
9208 (95.1)
5392 (95.0)
3816 (95.1)
1–3/month
233 (2.4)
125 (2.2)
108 (2.7)
1/week
101 (1.0)
65 (1.2)
36 (0.9)
2–4/week
105 (1.1)
65 (1.1)
40 (1.0)
≥ 5/week
41 (0.4)
27 (0.5)
14 (0.3)
Anal
< 1/month
9635 (99.6)
5643 (99.6)
3992 (99.6)
1–3/month
25 (0.2)
12 (0.2)
13 (0.3)
1/week
6 (0.05)
3 (0.05)
3 (0.06)
2–4/week
8 (0.07)
7 (0.1)
1 (0.02)
≥ 5/week
4 (0.03)
3 (0.05)
1 (0.02)
Usual gender of sexual partners
Only males, never females
9546 (99.4)
5578 (99.3)
3968 (99.2)
Mostly males, rarely females
54 (0.5)
28 (0.6)
24 (0.7)
Only females, never males
10 (0.1)
5 (0.1)
5 (0.1)
Mostly females, rarely males
7 (1.0)
6 (0.1)
1 (0.1)
Menopausal status
Premenopausal
8049 (82.7)
4704 (82.7)
3345 (82.8)
Postmenopausal
1678 (17.3)
985 (17.3)
693 (17.2)
Ever been pregnant
Yes
8698 (89.1)
5163 (90.4)
3535 (87.3)
No
1061 (10.9)
545 (9.6)
516 (12.7)
a
Multiple responses allowed. HPV results are based on DEIA tests at baseline only.
Given the sensitive nature of the sexual and reproducibility history questions, some
women did not respond. Therefore the total does not sum up to 11 500.
Table 4
Baseline history of selected physician-diagnosed medical conditions among women in
the ACCME cohort, n (%)
Disease
Mean age at diagnosis (years)
Total (%)
Rural (%)
Semi-rural (%)
Urban (%)
n = 11500
n = 1380
n = 5336
n = 4784
Hypertension
Yes
40 (8)
1702 (14.8)
187 (13.5)
630 (11.8)
885 (18.5)
No
–
9798 (85.2)
1193 (86.5)
4706 (88.2)
3899 (81.5)
Diabetes
Yes
43 (8)
219 (1.9)
21 (1.5)
69 (1.3)
129 (2.7)
No
–
11281 (98.1)
1359 (98.5)
5267 (98.7)
4655 (97.3)
Hypercholesterolaemia
Yes
43 (8)
552 (4.1)
108 (7.8)
133 (2.5)
311 (6.5)
No
–
10948 (95.2)
1272 (92.2)
5203 (97.5)
4473 (93.5)
Rheumatic fever
Yes
39 (10)
58 (0.5)
23 (1.7)
21 (0.4)
14 (0.3)
No
–
11442 (99.5)
1357 (98.3)
5315 (99.6)
4770 (99.7)
Heart disease
Yes
40 (10)
35 (0.3)
0 (0.0)
11 (0.2)
24 (0.5)
No
–
11465 (99.7)
1380 (99.8)
5325 (99.8)
4760 (99.5)
TIA/stroke
Yes
42 (9)
35 (0.3)
5 (0.4)
16 (0.3)
14 (0.3)
No
–
11465 (99.7)
1375 (99.6)
5320 (99.7)
4770 (99.7)
Kidney disease
Yes
45 (9)
46 (0.4)
6 (0.4)
11 (0.2)
29 (0.6)
No
11454 (99.6)
1374 (99.6)
5325 (99.8)
4755 (99.4)
Cancer
Yes
41 (10)
23 (0.2)
7 (0.5)
6 (1.1)
10 (1.2)
No
–
11477 (99.8)
1373 (99.5)
5330 (99.9)
4774 (99.8)
Table 5
Selected baseline gynaecological characteristics of women in the ACCME Cohort, n (%)
Gynaecological characteristics
Total
HPV-negative
HPV-positive
n = 11500
n = 6727
n = 4773
Vaginal pH
a
5.2 (0.5)
5.2 (0.5)
5.2 (0.6)
Ectopy observed
Yes
1368 (11.9)
809 (12.0)
559 (11.7)
No
10132 (88.1)
5918 (88.0)
4214 (88.3)
Transformation zone
< 25%
3324 (28.9)
1978 (29.4)
1346 (28.2)
25–50%
4310 (37.5)
2382 (35.4)
1928 (40.4)
51–75%
2901 (25.2)
1823 (27.1)
1078 (22.6)
> 75%
965 (8.4)
544 (8.1)
421 (8.8)
Squamo-columnar junction
Fully observed
8245 (71.7)
4877 (72.5)
3368 (71.1)
Partially observed
2369 (20.6)
1406 (20.9)
963 (20.1)
Not observed
886 (7.7)
444 (6.6)
422 (8.8)
Cervical friability
b
None
10568 (91.9)
6168 (91.7)
4400 (92.2)
Mild
839 (7.3)
511 (7.6)
328 (6.9)
Moderate
93 (0.8)
48 (0.7)
45 (0.9)
HPV status based on DNA enzyme immunoassay (DEIA) test.
a
Mean (standard deviation).
b
Cervical friability: mild, discrete spot of blood on swab; moderate, pink discolouration,
swab soaked.
Training and capacity development
The ACCME project includes a training programme in epidemiology, molecular biology,
data management and analysis. Several pre- and postdoctoral trainees are currently
engaged in the project and are taking the lead in several analyses and publications.
Students and faculty members from Nigerian and US universities and research institutes
have also used the resources of the project for their own research projects.
Future plans?
We will contribute DNA samples from our study participants to the H3Africa Biorepositories
according to the H3Africa guidelines. We are participating in the development of the
H3Africa Consortium Genome Analysis Array chip in collaboration with other H3Africa
projects and Illumina Inc. The resultant chip will be highly informative for genomics
research in African populations. We plan to replicate our genomics findings in other
African cohorts. The combination of somatic and germline mutation analyses in our
study enhances opportunities for gene discovery, understanding of gene functions,
new clinical insights and integrative analysis of cervical cancer. Our research will
also characterize the epidemiology of HPV infection in Nigeria before widespread deployment
of HPV vaccination. We intend to maintain and expand this valuable cohort to include
male partners of the participants and to study other NCDs in future.
What are the main strengths and weaknesses?
The ACCME cohort incorporates a large number of repeated measurements of a wide range
of exposures. There are also strong data and laboratory QA/QC procedures in collaboration
with local and international researchers incorporated into the project, thereby ensuring
high quality of the data. An ethics and regulatory compliance officer independently
monitors research activities at clinical sites and generates reports for the Study
leadership for action. Close collaboration with the NIH-funded West African Bioethics
Training Program [http://bioethicscenter.net)] ensures ongoing training in research
ethics, good clinical and laboratory practices, and responsible conduct of research.
We implement extensive community engagement efforts that include: community rallies;
regular meetings with research participants; circulation of study newsletters that
provide updates about study progress and challenges; and motivational and health education
messages through e-mails, radio, TV and newspapers. The study maintains a webpage,
a Facebook page and an active Twitter account. Study participants are able to contact
the research staff and leadership via phone applications, including Blackberry messenger
and WhatsApp.
A major limitation of longitudinal studies is loss to follow-up. This can be particularly
challenging in low-resource environments where participants have poor history of follow-up
even in clinical care. To improve participant retention in the cohort, we deployed
several strategies including extensive use of mobile health-based interventions such
as automated phone applications that are used to send health tips and visit reminders
to participants before their scheduled appointment, regularly. Thus, we have achieved
a participant retention rate of ∼80%.
Problems associated with conducting research in resource-limited settings that may
affect ACCME include poor infrastructure, inadequate power supply, challenges with
conduct of research in low-literacy environments and lack of trained personnel. To
address these, we: purchased state of the art laboratory equipment with service agreements
for genomic analyses; set up a three-level power backup system with multiple power
generators, inverters and batteries for the laboratory; develop appropriate health
education materials; train and re-train all research staff; and implement schemes
for motivation of staff through regular research meetings and opportunities to attend
international meetings, implementation of mentored research projects and generation
of appropriate health education materials. All of these challenges have contributed
to much higher cost for implementation of this research than anticipated. Nonetheless,
we collaborate with renowned international institutions in the USA, UK and The Netherlands
for ongoing staff training and support.
Can I get hold of the data? Where can I find out more?
Further information is available at [http://h3africa.org/]. Documentation for the
ACCME cohort including the questionnaires, information sent to the participants and
detailed information about the research, is available at [http://h3accme.com/. We
also welcome specific queries and proposals for collaboration, which should be directed
to the scientific director[(sadebamowo@som.umaryland.edu] and the principal investigator
[cadebamowo@som.umaryland.edu] of ACCME.
Supplementary Data
Supplementary data are available at IJE online.
Funding
The ACCME cohort is currently supported by the National Institutes of Health [NIH/NHGRI
grant 1U54HG006947]. The content is solely the responsibility of the authors and does
not necessarily represent the official views of the National Institutes of Health.
Supplementary Material
Supplementary Table S1
Click here for additional data file.