Oral human papillomavirus infection and genotyping in a cohort of people living with HIV

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Journal of Immunoassay and Immunochemistry
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Oral human papillomavirus infection and
genotyping in a cohort of people living with HIV
O.F Adebayo, F.J Owotade, O.A Folarin, O.A Oninla & E.O Oyetola
To cite this article: O.F Adebayo, F.J Owotade, O.A Folarin, O.A Oninla & E.O Oyetola (23 Dec
2024): Oral human papillomavirus infection and genotyping in a cohort of people living with
HIV, Journal of Immunoassay and Immunochemistry, DOI: 10.1080/15321819.2024.2441778
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Oral human papillomavirus infection and genotyping in
a cohort of people living with HIV
O.F Adebayo
a
, F.J Owotade
a
, O.A Folarin
b
, O.A Oninla
c
, and E.O Oyetola
a
a
Department of Oral Medicine and Oral Pathology, Obafemi Awolowo University, Ile-Ife, Nigeria;
b
African
Centre of Excellence for Genomics of Infectious Diseases (ACEGID), Redeemers’ University, Ede, Nigeria;
c
Department of Dermatology and Venereology, Obafemi Awolowo University Teaching Hospitals
Complex Ile-Ife, Nigeria
ABSTRACT
This study is aimed at determining the prevalence of oral HPV
infection and the risk indicators for oral HPV carriage in people
living with HIV. Data on socio-demographics, sexual behavioral
practices, and lifestyle practices of the participants were col-
lected from 66 people living with HIV. The HIV parameters of
each study participant were obtained from clinical records. Oral
rinses obtained from each participant were subjected to HPV
ELISA antigen test for screening and extracted DNA was sub-
jected to nested PCR and whole-genome sequencing for geno-
typing. Approximately 36% (10 of 28) HIV-positive individuals
had oral HPV carriage with one person carrying oncogenic type,
HPV16. In addition, 80% (8 of 10) of those with HPV positivity by
PCR are females, but with no statistically signicant association.
The CD4 count showed no signicant association with oral HPV
carriage in HIV positive individuals; however, age at rst sex is
a determinant of oral HPV infection in people living with HIV
with positive association observed on both bivariate analysis
and logistic regression (AOR: 150.49, 95% CI: 1.40–16,155.47,
p = 0.036).
KEYWORDS
HPV; HIV; ELISA; PCR;
oncogenic; co-infection; risk
indicators; genotyping
Introduction
HPV infection is the most common sexually transmitted disease and it
accounts for about 4.5% of global human cancer burden including anogenital
and oropharyngeal cancers.
[1,2]
HPV infection is usually transient in nature
and cleared by the immune system.
[3,4]
The persistence of oral HPV with high-
risk HPV may be a critical factor for the development of HPV-related
cancers.
[4,5]
Factors that fuel persistent oral HPV infection include being
male, older age, immunodeficiency states such as HIV infection, smoking,
immunomodulatory medication use and poor oral health/hygiene.
[6–8]
These
factors reduce oral HPV clearance by the immune system.
[6–8]
Despite the decline in global incidence of HIV infection and HIV/AIDs-
related deaths, Sub-Saharan Africa still has unacceptably high incidence
CONTACT O.F Adebayo wendyfunmi@gmail.com Department of Oral Medicine and Oral Pathology,
Obafemi Awolowo University, Ile-Ife, Osun State, 220005Nigeria
JOURNAL OF IMMUNOASSAY AND IMMUNOCHEMISTRY
https://doi.org/10.1080/15321819.2024.2441778
© 2024 Taylor & Francis Group, LLC

rates with Nigeria ranking fourth in terms of the number of HIV cases on
the continent.
[9,10]
According to UNAIDS 2024, HIV infection affects about
40 million people globally with an average of 5.1 million persons affected in
Western and Central Africa.
[11]
Many people living with HIV in Nigeria are
unaware of their status due to inadequate number of testing and counseling
sites.
[10]
Although sex workers are the main key populations living with
HIV in Nigeria, there is a rising prevalence of HIV infection among men
having sex with men.
[10]
Furthermore, punitive laws against homosexuality
in Nigeria make it difficult for men having sex with men (MSM) to seek
HIV services.
HIV infection reduces the host defense mechanism and increases the
susceptibility to opportunistic infections and co-infections by viruses.
[12,13]
In addition, HIV infection is also a risk factor for oral HPV infection and
a probable factor for persistent oral HPV infection, thus increasing HPV
virulence.
[13]
The increased virulence might be the cause of an increase in
the incidence of head and neck squamous cell carcinoma in this subset of
patients.
[14]
Several studies have revealed a higher prevalence of oral HPV
infection in HIV-infected individuals compared to healthy individuals with
determinants such as time since HIV diagnosis, time with Antiretroviral
therapy (ART), ART regimen, CD4 count and viral suppression being
identified.
[13,15,16]
Considering the paucity of studies assessing the relationship between HIV
infection and oral HPV infection in terms of prevalence and quantification in
Nigeria as well as the potential increase in incidence of oropharyngeal squa-
mous cell carcinoma (OPSCC) in the coming decades, there is need to conduct
this cross-sectional study on the relationship of oral HPV and HIV.
[7]
In
addition, this study will document the oral HPV experience among HIV-
positive individuals which will help in assessment of the need for oral HPV
vaccine and development of other preventive protocols for oral HPV infection
in them. This study is aimed at determining the prevalence and genotyping of
oral HPV in HIV positive subjects.
Methods
A cross-sectional study conducted among HIV-positive patients at the
Institute of Human Virology in Nigeria, Obafemi Awolowo University
Teaching Hospital Ile-Ife, Osun State, Nigeria. All molecular analysis of the
samples obtained was carried out at the African Centre of Excellence for
Genomics of Infectious Diseases (ACEGID), Redeemer’s University, Ede,
Osun State, Nigeria. The study was conducted within 12 months from
July 2021 to June 2022 following the ethical and proposal approval from the
Obafemi Awolowo University Teaching Hospitals Complex Ile-Ife Ethics and
Research committee.
2O. F. ADEBAYO ET AL.

The inclusion criteria were patients 18 years and older with laboratory
diagnosis of HIV infection without any history of HPV-related cancers such
as head and neck squamous cell carcinoma (HNSCC)or genital cancers and
patients with no history of other immunosuppression states besides HIV/
AIDS. Exclusion criteria included patients with history of other immunosup-
pressed states; patients on immunosuppressant medications; patients with
history of HPV-related cancers; and patients with clinically suspicious lesions
for HNSCC or genital cancers.
Using STATA 13.0 statistical software when comparing two propor-
tions with alpha as 0.05, power of 80%, prevalence of oral HPV infection
in HIV positive individuals with CD4 count less than or equal to 200/uL
being 55% and CD4 count greater than 200/uLbeing19.5%, a total sample
size of 56 was obtained. An attrition rate of 10% (rounded off to 6) was
added to the calculated sample size giving a total of 62. Relevant clinical,
virological and immunological data of the HIV-positive subjects were
retrieved from their medical records. Written informed consent was
obtained from the participants. Oral mucosal examination using mouth
mirror and dental probe was done under natural daylight and observed
findings were noted in the UCSF Oral epidemiology project lesion report
form. Each study participant was given a questionnaire and saliva collec-
tion kit labeled with the same unique identification number. Participants
who could not read or write were assisted in filling the questionnaire by
the investigator. Those who could not comprehend the questions were
guided in filling the questionnaire by the instructor. There was
a minimum interval of 10 minutes between eating, drinking or brushing
and oral rinse collection. Oral rinses were obtained by asking each
participant to rinse the mouth with 15 ml of 0.9% normal saline for 30
seconds and spitting into a Falcon tube stored at −20°C until ready for
screening and subsequent DNA extraction.
Elisa antigen tests for HPV
All samples collected were subjected to a serological test using Melsin® HPV
Antigen ELISA test kit according to the manufacturer’s instructions.
HPV DNA extraction/isolation
Samples positive for HPV Antigen ELISA kit and few that were negative for
HPV Antigen ELISA kit were selected for DNA extraction. The Zymo®
research quick viral DNA extraction kit was used for the extraction of
HPV DNA according to the manufacturer’s instruction with slight mod-
ification. DNA samples obtained were stored for PCR and whole-genome
sequencing.
JOURNAL OF IMMUNOASSAY AND IMMUNOCHEMISTRY 3

Nested PCR and genotyping
Nested PCR using two general consensus PCR primers (PGMY09/11 and
GP5+/6+) was employed to validate the presence of HPV in the samples.
[17]
Sanger sequencing and whole-genome sequencing were used for genotyping.
HPV DNA positive samples were purified and isolated, then the purified PCR
products were submitted for automated DNA sequencing for forward and
reverse sequencing. Whole-genome sequencing was also done on the HPV
DNA positive samples. The sequences obtained were compared with HPV
genomes deposited in the NCBI-Gen Bank using the BLAST program
(NCBI).
[18]
Statistical analysis
STATA 13 software package (StataCorp LP, College Station, TX) was used for
sample size estimation and data analysis. Using STATA statistical software
used for calculating sample size when comparing two proportions with alpha
= 0.05, power = 80%, prevalence of oral HPV infection in HIV positive indi-
viduals with CD4 count less than or equal to 200/uL and CD4 count greater
than 200/uL being 55% and 19.5%, respectively, a total sample size of 56 was
obtained. Attrition rate of 10% (rounded off to 6) was added to the calculated
sample size giving a total of 62.
Descriptive statistics was used to summarize the participant’s demographic
characteristics and risk factors. (Sexual behavior and practices, smoking status
and alcohol use) for oral HPV infection in HIV positive individuals. Simple
frequency and percentage of HPV positives among HIV positive individuals
with relative 95% CI was calculated to determine prevalence. Chi-square
statistics was used for the risk indicators that were categorical variables and
t-test for the continuous variables to explore their relationship with oral HPV
carriage in HIV patients. Risk indicators were fitted into a logistic regression
model to explore their relationship with oral HPV carriage in HIV positive
individuals. Predictor selection was done using the “best fit” approach and
regression models were checked for fit using the Hosmer–Lemeshow good-
ness-of-fit test.
Results
Sociodemographic characteristics of participants
Sixty-six HIV positive patients who fulfilled the inclusion criteria were
enrolled. The sociodemographic characteristics of the participants are shown
in Table 1. The median age of the study participants was 43.0 years (IQR =
38.0 years, 51.0 years) with a range of 18 years to 67 years. There were 51 (77%)
females of all the participants.
4O. F. ADEBAYO ET AL.

Sexual behavioural and lifestyle characteristics of the participants
The median age at first sex was 20.0 years (IQR = 18.0 years, 22.0 years)
with a range of 13 years to 35 years. All the study participants were
heterosexual except for one lesbian. Majority of the participants who
reported to have ever practiced anal sex (5/6, 83.3%) and oral sex (10/
14, 71.4%) are females. Forty-five (68.2%) participants had only one
sexual partner in the last 12 months. Only one male reported having up
to three sexual partners in the last 12 months. The percentage of parti-
cipants reported to have ever taken alcohol (29/66, 43.9%) is higher than
those reported to have ever smoked tobacco (5/66, 7.6%). The sexual
behavior, practices as well as the lifestyle characteristics of the partici-
pants are shown in Table 2.
HIV parameters of the participants
The HIV parameters of the patients are described in Table 3.
Oral HPV prevalence
The methods of oral HPV detection and the prevalence obtained with each
method are illustrated in Table 4. The summary of the process of sorting
samples and different methods of detection applied is shown in Figure 1. With
the HPV ELISA antigen detection method, 18 out of 6 samples showed oral
HPV positivity giving a prevalence of 27.2%. Only 28 samples were subjected
to nested PCR including 18 samples that showed HPV positivity with ELISA
antigen test, while the remaining 10 were chosen randomly from those that
were negative with HPV ELISA antigen test.
Table 1. Sociodemographic characteristics of the
participants.
N = 66
Median(IQR)
Age (years) 43.0 (38.0, 51.0)
n (%)
Gender
Male 15 (22.7)
Female 51 (77.3)
Marital Status
Single 4 (6.0)
Married 43 (65.2)
Divorced 6 (9.1)
Widowed 13 (19.7)
Highest Educational attainment
None 2 (3.0)
Primary school 18 (27.3)
Secondary school 30 (45.5)
Tertiary 16 (24.2)
JOURNAL OF IMMUNOASSAY AND IMMUNOCHEMISTRY 5

Four out of 18 (22.2%) HPV ELISA antigen positives came out
positive with nested PCR and sequencing. Ten out of the 28 samples
showed positivity for oral HPV resulting in a prevalence of 35.7% using
nested PCR with sequencing. In addition, 8 of the 10 hPVpositive
samples were detected in the female patients enrolled into the study.
There was however no association between gender and presence of oral
HPV infection.
Oral HPV genotyping
Only four out of the 12 samples sequenced gave enough reads for genotyping.
These four samples were samples 31, 39, 41, and 65. Samples 31 and 39 did not
show positivity with PCR but gave HPV genotypes with sequencing, hence the
Table 2. Sexual behavior and lifestyle characteristics of the participants.
Total P value
Median (IQR)
Age at first sex (years) 20.0 (18.0, 22.0)
n (%)
Who do you have sex with? Male Female
Male 0 (0.0) 15(100) 15 (100)
Female 50 (98.0) 1 (2.0) 51(100)
Ever practiced anal sex?
Yes 1(16.7) 5 (83.3) 6 (100)
No 14 (23.3) 46 (76.7) 61 (100)
Ever practiced oral sex? 0.452
Yes 4 (28.6) 10 (71.4) 14 (100)
No 11(20.8) 41 (78.8) 52(100)
Last practiced anal sex 0.226
<6 months 0 (0.0) 2 (100.0) 2 (100)
6 months-1 year 0 (0.0) 1(100.0) 1 (100)
≤5 years 0 (0.0) 1 (100.0) 1 (100)
>5 years 1 (50.0) 1 (50.0) 2 (100)
Not applicable 14 (23.3) 46 (76.7) 60 (100)
Last practiced oral sex 0.293
<6 months 1(25.0) 3 (75.0) 4 (100)
6 months-1 year 1(33.3) 2 (66.7) 3 (100)
≤5 years 2 (66.7) 1 (33.3) 3 (100)
>5 years 0 (0.0) 4 (100.0) 4 (100)
Not applicable 11(21.2) 41(78.8) 52 (100)
Ever smoked 0.06
Yes 3 (60.0) 2 (40.0) 5 (100)
No 12 (19.7) 49 (80.3) 61(100)
Currently smoke 0.082
Yes 1(100) 0 (0.0) 1 (100)
No 14 (21.5) 51 (78.5) 65 (100)
Ever drunk alcohol 0.0009
Yes 11(37.9) 18 (62.1) 29 (100)
No 4 (10.8) 33 (89.2) 37 (100)
Still drink N = 16 %
Spirit 3 18.8
Beer 7 43.7
Red wine 6 37.5
6O. F. ADEBAYO ET AL.

increase in HPV positive samples from 8 to 10, giving a prevalence of 35.7%.
The genotypes and samples from which they are obtained are expressed below:
●HPV16 for sample 39 with 99% similarity with sequence from Nepal with
accession number KX947270.1
●HPV JEB2 for sample 31 with 96% similarity with accession number
AB706258.1 from Vietnam.
●HPV 6 for Sample 65 with 97% similarity with accession number
KR674057.1 from Kenya.
●HPV 72 for sample 41 with 94% similarity with accession number
JQ902133.1 from China
HPV16 L1 gene sequences were downloaded from NCBI and aligned to our
sequence using MAFFT. Phylogenetic tree constructed using Geneious (CITE)
is Figure 1. Our sequence clustered in the same clade with KX947270.1 from
Nepal.
Risk indicators for oral HPV carriage
The result of this bivariate analysis is shown in Table 5. Age at first sex was the
only sexual behavior variable associated with oral HPV positivity by PCR test
Table 3. HIV parameters of the participants.
N = 66
Mean (SD) RANGE (MIN-MAX)
Time Since HIV diagnosis (months) 93.2 (54.5) 1–216
Time with cART (months) 87.6 (51.8) 1–204
Current CD4 count (cells/ul) 609.7 (273.4) 88–1264
Viral load (copies/ml) 114.8 (645.8) 1–5251
N (%)
cART regimen
TLD 61 (92.4)
AL 1 (1.5)
AR 1 (1.5)
AAL 1 (1.5)
LZD 1 (1.5)
LTAR 1 (1.5)
TLD =Tenofovir + Lamivudine +Dolutegravir; AL = Abacavir + Lamivudine AAL= Abacavir +
Atazanavir + Lamivudine; AR = Atazanavir +Ritonavir; LZD= Lamivudine + Zidovudine +
Dolutegravir.
Table 4. Oral HPV detection methods and prevalence.
Method of HPV detection
N = 66 Prevalence (%)
HPV positive HPV negative
ELISA-Ag test 18 48 27.2
N = 28
Nested PCR 8 20 28.6
Nested PCR with sequencing 10 18 35.7
ELISA = Enzyme-linked Immunosorbent assay, Ag = Antigen, PCR = Polymerase Chain Reaction.
JOURNAL OF IMMUNOASSAY AND IMMUNOCHEMISTRY 7

(Mean (SD): 22.6 years (5.9) in oral HPV positive, 19.7 years (3.1) in oral HPV
negative individuals, p = 0.036).
CD4 count levels did not show any significant association with oral HPV
positivity by PCR test on bivariate analysis. Likewise, other HIV parameters
did not show any association with oral HPV positivity PCR test.
The result of the multivariate analysis is shown in Table 6. Following
adjustment for CD4 count, oral sex practice, and age, the odds of oral HPV
infection increases with increase in age at first sexual intercourse (OR 150.49,
95% CI: 1.40–16155.47, p = 0.036). The Hosmer-Lemeshow goodness of fit test
was not significant, hence a good fit (p = 0.076).
Discussion
This cross-sectional study gave information on the prevalence of oral HPV in
a cohort of HIV individuals. It also provided data on the oral HPV genotypes
Figure 1. Phylogenetic tree of the HPV 16 genotype.
8O. F. ADEBAYO ET AL.

as well as the risk indicators for oral HPV infection in this cohort. Till date, no
data exists on oral HPV in Nigeria on the Global HPV database.
[19]
This is also
one of the few studies in West Africa region, especially Nigeria to explore the
relationship between oral HPV infection and HIV infection.
The oral HPV prevalence of 35.7% in our HIV positive cohort is higher than
the prevalence reported in most previous studies with the same cohort.
Vacharotayangul et al, reported a lower oral HPV prevalence of 17.2% in
Bangkok
[20]
and Riddell et al., 23%
[21]
in the US among similar study popula-
tions using the same detection method of PCR and sequencing. Similarly, studies
carried out among HIV MSM cohort by Rollo et al. ,
[14]
Mistry et al. ,
[22]
Vergori
et al, ,
[23]
and Hernandez et al.
[24]
revealed lower oral HPV prevalence than in
this study using the same detection method.
However, few past studies reported prevalence estimates similar to that
obtained in this study. For instance, in a study conducted among HIV positive
and negative individuals in an Italian population,Visalliet al reported oral
HPV prevalence of 33.3% in the HIV positive group.
[25]
Another study by
Muller et al. among HIV positive dental patients in the US observed
a prevalence of 32% which is similar to this study’s prevalence.
[26]
Oral HPV
Table 5. Association between potential risk indicators and oral HPV infection.
Variable
MEAN(SD) t statistic P value
HPV positive HPV negative
Age at first sex (years) 22.6 (5.9) 19.7 (3.1) −2.1467 0.036*
Age (years) 46.0 (3.3) 42.9 (1.3) −0.9272 0.3578
CD4 count (cells/ul) 561.0 (178.7) 612.8(248.9) 0.5946 0.5545
Viral load (copies/ml) 19.1 (0.7) 138.1(0.7) 0.4744 0.6371
Time since HIV diagnosis (months) 123.3(55.7) 91.1(53.4) −1.6537 0.1038
Time with cART (months) 119.8(52.8) 84.7(49.9) 0.0597
n (%) n (%) X
2
value
HPV positive HPV negative
Oral sex practice
Yes 1(8.3) 11(91.7) 0.6715 0.413
No 8(18.6) 38(72.4)
Anal sex practice
Yes 1 (25.0) 3 (75.0) 0.2601 0.610
No 8 (14.8) 46 (85.2)
Number of sexual partners in the last 12 months
None 2 8 3.3469 0.341
One 7(17.9) 32(82.1)
Two 0 (0.0) 8(100.0)
Three 0 (0.0) 1 (100.0)
cART = combination Anti-Retroviral Therapy; *statistical significance.
Table 6. Multivariate logistic regression of the potential risk indicators of oral
HPV infection.
Variable Odds ratio 95% CI P value
CD4 count (Square root) 0.93 0.78, 1.11 0.433
Age at first sex (Log) 150.49 1.40, 16155.47 0.036*
Oral sex practice 0.69 0.07, 7.24 0.756
Age (years) 1.02 0.92, 1.13 0.748
Time with cART (months) 1.02 0.99, 1.04 0.084
JOURNAL OF IMMUNOASSAY AND IMMUNOCHEMISTRY 9

prevalence higher than that observed in this study was not found in similar
previous studies as revealed by the 2021 World Human Papilloma Virus and
Related Diseases Report.
[19]
The discrepancy in this study’s prevalence and lower prevalence observed in
previous similar studies could be due to the difference in scope, location, and
period of study as well as higher cART uptake in the countries where the
previous studies were done. Probably, the lower prevalence obtained in studies
done among HIV positive MSM is due to the difference in the sampling frame,
although HIV positivity is common to both.
The median age of this study’s participants (median age (IQR): 43.0 years
(38.0 years, 51.0 years) fall within the young and middle-aged groups. This is
in consistent with the age group of people living with HIV/AIDS as reflected in
UNAIDS 2022 fact sheet.
[27]
Furthermore, the female sex forms a larger
percentage of PLWH.
[27]
Factors contributing to a higher female prevalence
include gender inequality linked to sociocultural norms, increased suscept-
ibility to violence, less comprehensive education, poor awareness, denial of
access to health services, and poverty among others.
[28,29]
The most prevalent genotype could not be determined from this study due
to the very few genotypes obtained which carry an equal prevalence of 25%
each. The detection of HPV 16 which is a high-risk HPV type is consistent
with the finding of most studies conducted among HIV positive individuals.
HPV 16 type, which is the most common genotype in oral infections, asides
from being the most frequent type in HPV-associated oral and oropharyngeal
cancers is the only high-risk HPV type observed in this study.
In addition, HPV 16 and 18 genotypes have been consistently implicated in
70% of all cervical cancer cases globally.
[30]
Also, HIV infection increases
women susceptibility to developing cervical cancer by six-fold and shortens
the process of carcinogenesis in the setting of a co-infection with high-risk
HPV types.
[30]
The presence of HPV genotype 16 among the PCR positive samples in the
study cohort is not surprising as it is one of the popular and high-risk
genotypes. Although the patient has a good viral profile but the presence of
this HPV genotype may be a marker for cancer.
The question of whether oncogenic/high-risk HPV type or non-oncogenic
/low-risk HPV type is more prevalent in HIV positive cohort remains unan-
swered. Despite the ongoing debate, most studies reported HPV 16 as the most
prevalent oral HPV genotype in HIV cohorts while few studies observed the
presence of only high-risk HPV types including HPV 16 in HIV positive
individuals.
[14,16,21,22,26,31]
The finding of HPV 16 genotype in this study
supports the increased predisposition of HIV cohorts to HPV-induced oral
and oropharyngeal cancer as suggested in previous studies. Other high-risk
oral HPV types in previous studies among HIV positive individuals which
were not detected in this study include 18, 39, 52, 66, and 51.
[13,14,16,21,26]
10 O. F. ADEBAYO ET AL.

Although the HPV genotype 16 was detected in only one sample, the
maximum likelihood phylogenetic analysis revealed that the sequence is clo-
sely related to sequences from Nepal among the sequences available in the
databases. This study may not be able to conclude that the sample does not
descend directly from Nigeria because it is only found in one sample however
it may reflect a broader diversity and dynamics of the virus. Studies have
revealed a high diversity of the HPV 16 genotype,
[32]
hence the need for
further studies to elucidate the molecular epidemiology of HPV 16 genotype
and variants among HIV and non-HIV cohorts.
HPV 6 and 72 are the low-risk HPV types detected in this study. HPV 6 is
one of the commonly found low-risk HPV types in oral infection. It is also
a commonly reported low-risk HPV type observed in oral infection in HIV
positive individuals by most studies.
[13,14,26]
Together with HPV11, it has been
implicated in the development of oral and anogenital warts. This finding
suggests an increased predisposition of HIV-infected individuals to oral warts.
Another commonly isolated low-risk HPV genotype in the oral samples of
HIV positive cohorts is HPV 72 which was also detected in this
study.
[13,14,16,23,24,26]
Gheitet al in 2020
[33]
observed HPV 72 as one of the
most common HPV types in oral HPV infection of HIV-infected individuals.
Davidson et al. in 2014
[34]
also found this low-risk type in healthy individuals
with oral HPV infection. Data from the Global Human Papilloma Virus and
related disease Report in October 2021 showed HPV 72 as one of the low-risk
types isolated from the oral cavity of patients with oral and oropharyngeal
cancers. This does not mean these cancers are HPV 72 driven as this is a low-
risk type with low/no oncogenic potential and also in these cancer cases, high-
risk HPV types and other low-risk types were identified. However, this con-
firms the possibility of HPV 72 in oral infection and not just in anogenital
infection where it causes external warts.
[35]
The fourth genotype identified in this study is HPV JEB2. This is
a taxonomically unclassified type with partial L1 reference sequence.
[36]
This
genotype has been noted in studies on genital HPV infection in both males and
females but more commonly in cervical HPV infection.
[36–38]
So far, none of
the studies on oral HPV infection has observed this type. The observation of
this type in this study can be explained by oral sex performance which can
cause infection of the oral cavity with a type usually found on the genitals.
Findings from this study show a higher prevalence of low-risk HPV type in
HIV positive individuals. Although few studies had a similar report,
[16,39]
most
studies gave a contrary report.
[14,23,24]
This may be due to the large sample size
in those studies compared to the modest sample size used in this study.
However, the presence of four different variants among the four samples
sequenced demonstrates the presence of different genotypes of the virus in
circulation in the country. More studies are therefore recommended in order
to elucidate the spectrum of HPV genotype in the country.
JOURNAL OF IMMUNOASSAY AND IMMUNOCHEMISTRY 11

Interestingly, a positive association with age at first sex was noted on
bivariate analysis and logistic regression following adjustments for age, CD4
count, oral sex performance and time with cART. The odds for oral HPV
increased about 150 folds for every year increase in age at first sexual inter-
course with the opposite sex. Similarly, Rollo et al. reported a fourfold
increased odds of oral HPV infection for every year increase in age at first
sex of HIV-infected MSM.
[14]
This observation can be attributed to the older
age of the participants in this study reflecting a measurable age cohort effect on
age at first sex. More so, the older age at first sex may be preceded by oral sex
performance at a younger age. No other sexual behavior or practice such as
oral sex performance, anal sex performance and number of sexual partners in
the last 12 months was associated with oral HPV infection in this study. This
contrasts with other studies which reported at least one or two of these
variables as risk indicator(s). Previous studies have consistently observed
increased number of sexual partners as a risk indicator.
[16,40,41]
while the
question of oral sex performance as a risk indicator remains unanswered in
the literature.
[16,40,41]
In addition, none of the lifestyle characteristics such as
tobacco smoking and alcohol use showed an association with oral HPV
infection in this study. This also contrasts with previous findings of tobacco
smoking or alcohol use as determinants of oral HPV infection in this
population.
[13,39]
This observation of no association with previously reported
risk indicators may be due to the modest sample size, shorter duration of this
study and also a factor of the relatively lower consumption of tobacco in our
study population compared with others.
None of the HIV parameters was significantly associated with oral HPV
infection. CD4 count level, an important indicator of HIV suppression and
immunosuppression level is one of the HIV parameters assessed in this study.
Although the mean CD4 count was lower in HPV positive individuals, this
assessment did not show any significant association of this parameter with oral
HPV infection. This is in contrast with other studies that observed association
between lower CD4 count levels (>200/ul) and oral HPV infection.
[13,42,43]
even though there is no consensus regarding the role of CD4 count level as
a determinant of oral HPV infection in HIV infection.
[26,44,45]
This can be
attributed to the mean CD4 counts as well as the undetectable HIV viral load
of this study’s participants. The majority had CD4 count levels greater than
500/ul and HIV RNA load less than 20 copies per ml which implies good viral
suppression with mild/no immunosuppression in the participants.
Also, time with cART did not show a significant association with oral
HPV infection in this study. This agrees with the observation in pre-
vious studies although there are conflicting reports in the literature. The
relationship of oral HPV infection and time with cART is usually
determined by the timing of the HPV infection and initiation of
cART.
[46]
If HPV infection was acquired before initiation of cART,
12 O. F. ADEBAYO ET AL.

HPV will expand and will not be controlled in the 24 weeks of cART
initiation, because immune reconstitution does not occur by 24 weeks,
hence an increase in the rate of detection of oral HPV between 12 and
24 weeks.
[47,48]
This can be the explanation for reduced rate of detection of oral HPV in our
study cohort as reflected by the mean time with cART (SD) (87.6 (51.8)) which
is greater than the 24 weeks required for immune reconstitution irrespective of
the timing of HPV infection. Other HIV parameters such as HIV viral load
and time since HIV diagnosis did not reveal any association with oral HPV
infection which is consistent with other studies that observed no
association.
[23,49]
Despite the lack of evidence-based preventive measures against oral HPV
infection, some methods of prevention have been proposed by some research-
ers. An example is the use of dental dams and condoms which do not offer full
protection due to the possibility of HPV transmission through skin
contact.
[50,51]
Another proposed method is HPV vaccination which is a valid
preventive measure against cervical HPV infection but with unclear role in the
prevention of oral HPV infection.
[50,51]
Consequently, this study serves as a foundation for future studies on the
topic in this region of the world. Additionally, the multiple detection methods
and techniques, including molecular methods employed in this study makes
the findings valid and dependable as it confirms to the global best practices in
molecular detection of oral pathogens
Conclusion
The prevalence of HPV in the oral cavity is 35.7%, confirming the higher
prevalence of oral HPV infection with both non-oncogenic HPV types (HPV 6
and 72) and oncogenic HPV type 16 in HIV positive individuals. HPV JEB2,
a taxonomically unclassified type which requires further investigation was also
isolated in one of the samples. In addition, age at first sexual intercourse had
positive association with oral HPV infection on adjusting for age, CD4 count
levels, oral sex performance and time with cART.
Limitations
First, a large percentage of the study participants had good viral suppression
evidenced by high CD4 count and low viral load. Although this is desirable,
this may have masked the effect of CD4 count and viral load and oral HPV
infection since most of them had adequate control of the HIV infection.
Additionally, the cultural values and beliefs on sexual behavior and practices
could have modified the participants’ responses to the questions on sexual
behavior and practices in the questionnaire
JOURNAL OF IMMUNOASSAY AND IMMUNOCHEMISTRY 13

Recommendations
The data presented here showed the prevalence of oral HPV among HIV,
however, more studies need to be done in order to determine the circulating
genotype for proper management and prevention of HPV-induced oral
cancer.
Acknowledgments
Special thanks to the African Centre of Excellence for Genomics of Infectious Diseases
(ACEGID) laboratory, Redeemers University, Ede, Osun state, Nigeria for the allowance to
run the laboratory aspects of the work.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Funding
The project was fully funded out of pocket.
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