To the editors of the Pan African Medical Journal
Human papilloma virus (HPV) is the most common sexually transmitted virus and it is
estimated that about 75% of sexually active women and men will acquire a genital HPV
infection at some time.[1] There is an advance clinical association between HPV and
HIV-1[2, 3] and it has been suggested that HPV may also facilitate progression of
HIV-1 disease by recruitment of HIV target cells, such as CD4+ T-cells and macrophages,
into the site of active HPV infection, and by inducing the production of inflammatory
cytokines, including IL-6, TNF- 45; and IL-1, which in turn induce the replication
and reverse transcription of HIV-1 [4].
In view of paucity of studies from Nigeria and in order to provide preliminary information
on the clinical associations between HPV and HIV-1 infections, we conducted a cross
sectional study between May and July 2010 among 63 HIV-1 infected adults seen at Ahmadu
Bello University Teaching Hospital Zaria (ABUTH), Kaduna State, Nigeria, and 26 HIV-negative
apparently healthy adult controls living in Zaria, Northern Nigeria. After obtaining
demographic and clinical data, including sexual history, we assayed serum IgG antibodies
to HPV by ELISA (Weifang Kanghua Biotech Co. Ltd, China) and CD4 cell counts by flow
cytometry. Ethical approval for the study was obtained for the institutional review
board of ABUTH and all study participants gave consent for the study. Data was analysed
using SPSS 17. For all analyses, P<0.05 was taken as statistically significant.
Of the 63 HIV-infected patients, 40 (63.5%) were females, 55 (87.4%) were ever married
and 15 (23.8%) had 3 or more lifetime sexual partners. Of the 26 HIV negative controls,
13 (50%) were females, 17 (65.4%) were never married, and 19 (73.1%) had 1 to 2 lifetime
sexual partners while 7 (28%) had no previous sexual intercourse. The mean ages and
standard deviation (Ranges) of the HIV positive and negative study participants were
36 ± 8.6years (20-57years) and 34 ± 10.7 years (21-56 years) respectively, (p > 0.05,
student's t test).
With regard to IgG HPV antibody serostatus, 1(3.8%) of the 26 HIV-negative participants
and 26 (41.3%) of the 63 HIV-positive patients were HPV IgG seropositive. The HIV-positive
patients were about 18 times more likely to be HPV seropositive than the HIV-negative
adults (OR 17.6, 95% CI 2.2-138, p=0.0006). The only HIV-negative HPV seropositive
participant was a 28year old male single civil servant who had two lifetime sexual
partners. Among HIV-infected patients, univariate and multivariate (using logistic
regression) analyses (Table 1), revealed that CD4 cell count was the only independent
variable associated with HPV seropositivity. Patients with CD4<200cells/ul (indicative
of AIDS) had 5 times more likelihood of been HPV IgG seropositive than those with
CD4 cell count ≥200cells/ul (0R 5.1, 95% CI 1.3-20.8, p=0.022). Only three (11.5%)
of the 26 HPV seropositive patients had clinical evidence of anogenital and facial
warts. Papanicolaou (Pap) smears were not done.
Table 1
Associations Between HPV IgG Seropositivity And Clinical Variables Of HIV-Infected
Adults from Zaria, Northern Nigeria
Variable
Univariate analyses
Multivariate analyses
N (%)
OR
95% CI
P value
Adjusted OR
95% CI
P value
Age group (yrs)
>0.05
18-40*
17 (37.8)
1
1
>0.05
1
0.3-4.1
>40
9 (50)
1.7
0.6-5.0
1.1
Gender
>0.05
Male
10(43.5)
1.2
0.4-3.3
>0.05
0.86
0.2-3.2
Female*
16 (40)
1
1
1
Marital status
>0.05
Never married*
2 (25)
1
1
>0.05
1
1
Ever married
24 (43.6)
2.3
0.4-12.5
3.4
0.5-23.4
Lifetime number of sexual partners
>0.05
1-3*
19 (39.6)
1
1
>0.05
1
1
>3
7(46.7)
1.3
0.4-4.3
1.8
0.4-8.1
HIV clinical stage
>0.05
Early HIV (stage 1/2)*
7 (35)
1
1
>0.05
1
1
Late HIV (stage 3/4)
19 (44.2)
1.5
0.5-4.4
1.1
0.3-3.6
CD4 category (cells/ul)
0.022
CD4 ≥ 200*
16 (33.3)
1
1
0.02
1
1
CD4<200
10 (66.7)
4.0
1.2-13.7
5.1
1.3-20.8
*
NB:=reference variable, N=number, OR=odds ratio, CI=confidence interval, p >0.05=not
significant
This study from Zaria, Northern Nigeria has shown that cumulative HPV infection detected
by assay of serum IgG antibodies to HPV occurs more frequently in HIV-infected patients
than in HIV-negative healthy adults. This finding is in agreement with studies from
other African countries [5–7], and may be attributed to poor clearance of HPV infection
in HIV-infected patients relative to HIV-negative adults [3, 8] and the fact that
both HIV and HPV infections share similar route and risk factors for infection [2].
It is noteworthy that IgG HPV seropositivity was independently associated with features
of advanced immunosuppresion or AIDS (CD4<200cells/ul). This finding may be due to
the positive correlation between immune status and HPV clearance, as patients with
significant immunosuppresion are less likely to clear HPV infection and consequently
develop persistent HPV infection with continually detectable HPV antibodies [3, 8].
Alternatively, it is probably that HPV infection facilitated the progression of HIV
to AIDS in our patient through mechanisms previously described [4]. In agreement with
our findings, various prospective and cross sectional studies from other parts of
the world have also shown that among HIV-1 infected patients, active, chronic and
persistent HPV infection is more common in those with features of significant immunosuppresion
AIDS defined as CD4<200cells/ul [3, 6, 7, 9].
In Nigeria, there are more than 3.1 million HIV-infected people [10] and about 23.7%
of women and 73% of men of the general population harbour HPV genital infection [11].
In view of the high rates of both HPV and HIV infection in Nigeria, it is necessary
for future prospective studies to be undertaken in Nigeria using larger sample sizes
and more specific assays, such as assay of high risk HPV serotypes and HPV DNA, to
shed further light on the associations between HPV and HIV/AIDS.
In conclusion, cumulative HPV infection is high in HIV-infected patients from Zaria,
Northern Nigeria, especially among AIDS patients. These findings support the need
for routine and early screening of all HIV infected patients for HPV infection in
Nigeria, as well as routine clinical evaluation of all HIV-infected patients for HPV-related
manifestations.