Abstract
Background: The prevalence of human papillomavirus (HPV) infections in other anatomical sites besides the uterine cervix is unknown in East Africa. Here, we assessed the prevalence and concordance of HPVs in different anatomical sites in HIV concordant couples in Rwanda. Methods: Fifty HIV-positive concordant male-female couples at the HIV clinic at the University Teaching Hospital of Kigali in Rwanda were interviewed, swabbed from the oral cavity (OC), oropharynx (OP), anal canal (AC), vagina (V), uterine cervix (UC) and penis. A pap smear test and a self-collected vaginal swab (Vself) were taken. Twelve high-risk (HR)-HPVs were analyzed. Results: HR-HPVs occurred in 10%/12% in OC, 10%/0% in OP and 2%/24% in AC (p = 0.002) in men and women, respectively. HR-HPVs occurred in 24% of UC, 32% of Vself, 30% of V and 24% of P samples. Only 22.2% of all HR-HPV infections were shared by both partners (κ −0.34 ± 0.11; p = 0.004). The type-specific HR-HPV concordance was significant between male to female OC-OC (κ 0.56 ± 0.17), V-VSelf (κ 0.70 ± 0.10), UC-V (κ 0.54 ± 0.13), UC-Vself (κ 0.51 ± 0.13) and UC-female AC (κ 0.42 ± 0.15). Conclusions: HPV infections are prevalent in HIV-positive couples in Rwanda but concordance within couples is low. Vaginal self-sampling for HPV is representative of cervical HPV status.
Keywords: human papillomavirus, HIV, mucous membrane, cervical cancer, Rwanda
1. Introduction
Chronic infection by high-risk human papillomaviruses (HR-HPVs) of the uterine cervix is the most important risk factor associated with the development of high-grade squamous intraepithelial lesions (HSIL) and cervical cancer where HPV16 and HPV18 stand for most cervical cancer cases [1]. Only a minority of HPV infections, however, become chronic, i.e., persisting for more than two years, since the immune system clears most HPV infections within a few months in immunocompetent individuals [2,3]. Co-infection with human immunodeficiency virus (HIV) may increase the risk of developing persistent HR-HPV infections and increases the risk of developing HPV-associated cancers [2,4,5]. HR-HPV infection is an important risk factor for the development of vaginal, penile, anal and head and neck cancer (HNC) [6]. In Western countries, there has been a dramatic increase in the incidence of HPV-associated oropharyngeal cancer squamous cell carcinoma (OPSCC), e.g., from before 2000 to 2009 the prevalence of HPV+ OPSCC increased from 40.5% to 72.2% [7]. The prevalence is particularly high in Sweden where it was reported that 85% of OPSCC in 2016 were HPV-positive [8]. The prevalence of HPV-positive OPSCC, however, varies significantly between countries. While developed countries report high prevalence figures for HPV+ OPSCC, HPV+ OPSCC seems to constitute less than 20% of all OPSCC in developing countries where prevalence figures also are uncertain for many countries [9].
In our previous study, we showed that 56% of all HR-HPV infections are chronic in Rwandan women living with HIV (WLWH) [2]. While cervical HPV infections and cervical cancer have been studied in most sub-Saharan countries, there is a lack of knowledge regarding the prevalence of HPV infections in other mucous membranes besides the uterine cervix. There is also a scarcity of knowledge on HPV co-infections between different anatomical sites among WLWH in East Africa. In this study, our primary aim was to assess the prevalence of HPV infections in different anatomical sites and to assess the concordance of HPV infections between HIV-positive concordant couples and co-infections between mucous membranes. Moreover, we examined the concordance between self-collected and physician-collected vaginal HPV screening.
2. Materials and Methods
In this cross-sectional study, 50 HIV-positive concordant opposite-sex couples attending the HIV clinic at the University Teaching Hospital of Kigali (CHUK) in Kigali, Rwanda were recruited after informed consent. The couples lived together, and all participants were treated with antiretroviral therapy (ART). Inclusion criteria were literate individuals who were diagnosed with HIV and were 21 years old or older. Exclusion criteria were previous HPV vaccination, cervical lesions, women and men who have not had sexual intercourse or sexual activity with other individuals, and men and women for any reason considered not able to comply with the study protocol.
The participants were given a structured questionnaire including questions covering medical history, sexual and obstetric history, previous sexually transmitted infections (STIs), and questions covering risk factors for contraction of HPV infection. This was followed by taking a swab sample for HPV using the Aptima Multitest Swab (Hologic Inc., Marlborough, MA, USA) from the buccal mucosa, tonsillar area, and anal canal. In men, swab samples were taken from the glans penis/opening of the urethra. In women, swab samples for HPV were taken from the vagina by the woman herself and another vaginal sample was taken by the physician. This was followed by an HPV swab sample and a pap smear sample taken with a wood spatula from the uterine cervix taken by the physician.
2.1. Real-Time PCR for Detection of HPVs
A real-time PCR assay targeting type-specific segments of the E6/E7 region for 12 high-risk (HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59), two low-risk (HPV6 and 11) HPV types and beta-globin was used [10]. Nucleic acid from the 200 µL specimen was extracted by a MagNA Pure LC instrument (Roche Molecular, Mannheim, Germany) using the DNA Isolation I kit. The nucleic acids were eluted in 100 µL volume, and 5 µL of this were used for each real-time PCR reaction. Multiplex real-time PCR was performed in 8 parallel 20 µL-reactions containing oligonucleotides described in Table S1, and Universal Mastermix (Applied Biosystems, Foster City, CA, USA). After 10 min of denaturation at 95 °C, the PCR was run for 45 cycles (15 s at 95 °C, 60 s at 58 °C) in a QuantStudio 6 384-well system (Applied Biosystems). The performance for each multiplex reagent mixture was evaluated using pUC57 plasmids with inserts of the targeted HPV sequences, synthesized by GenScript Corp. (Piscataway, NJ, USA). Combinations were only accepted if the cycle threshold (Ct) value in multiplex was no more than 1 cycle higher than detection carried out in separate reactions. The same plasmids were used in each run parallel with patient specimens to verify the performance of each target PCR. Only patient specimens with Ct values < 40 were considered positive.
2.2. Cytology
Cytology of pap smears was classified according to the 2014 Bethesda System and the following cytological diagnosis: Negative for squamous intraepithelial lesion or malignancy (NILM), atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL), atypical squamous cells cannot exclude HSIL (ASC-H), atypical glandular cells (AGC), endocervical adenocarcinoma in situ (AIS), high-grade squamous intraepithelial lesion (HSIL) and squamous cell carcinoma (SCC).
2.3. Statistics
The SPSS version 24 (IBM) was used to assess the significance of differences detected in different main outcomes between and within groups. The chi-square test was used to compare categories. To compare the concordance of HR-HPV infections between different mucous membranes and between couples, Cohen’s kappa statistics were used. The Cohen’s kappa coefficient (κ) was estimated where κ < 0 = poor, 0–0.20 = slight, 0.21–0.40 = fair, 0.41–0.60 = moderate, 0.61–0.80 = substantial and 0.81–1.00 = almost perfect agreement. Bivariate logistic regression analysis was performed, and crude odds ratios (COR) and adjusted odds ratios (AOR) were calculated for explanatory variables correlating with being HR-HPV positive in any mucous membrane. Statistical significance was set to p < 0.05.
3. Results
3.1. Demographic Characteristics
Demographic data are displayed in Table 1. The median age of the 100 HIV-positive participants was 51.5 years (mean age 53.1 ± 9.1 years). Only 22% of men and women had passed secondary school. More women than men were unemployed (40% vs. 16%, respectively). The proportion of men who had or currently smoked and drank alcohol was significantly higher than that of women (p < 0.0001 and p = 0.017, respectively). Male participants reported a higher number of previous sex partners and orogenital sex partners than their female partners (p = 0.015 and p = 0.009, respectively). No participant reported same-sex sexual activity. Previous STIs were common among the participants, i.e., gonorrhea infection had occurred in 44% and 34%, syphilis in 18% and 24% and chlamydia in 12% and 12% of men and women, respectively. The proportion of men with CD4 counts lower than 200 cells/mL was significantly higher compared with women (p = 0.01), however, no difference was observed in HIV viral load between men and women. Ninety percent of men and women were in the agreement with the kind of contraceptive method used with their partner or in the agreement with not using a contraceptive method. Among 30 men reporting using contraceptive methods, 17% reported a different contraceptive method than their female partner or reported using a contraceptive method while their partner reported not using a contraceptive method.
Table 1.
Characteristics of patients (N = 100).
| Sex, n (%) | |||
|---|---|---|---|
| Characteristics | Male 50 (50) |
Female 50 (50) |
p-Value |
| Age | 0.008 | ||
| 30–39 | 2 (4) | 5 (10) | |
| 40–49 | 7 (14) | 20 (40) | |
| 50–59 | 23 (46) | 19 (38) | |
| 60–69 | 15 (30) | 5 (10) | |
| 70–79 | 3 (6) | 1 (2) | |
| Level of Education | 0.663 | ||
| None | 3 (6) | 5 (10) | |
| Incomplete primary school | 4 (8) | 7 (14) | |
| Complete Primary school | 13 (26) | 15 (30) | |
| Incomplete Secondary school | 19 (38) | 12 (24) | |
| Complete secondary school | 8 (16) | 9 (18) | |
| Incomplete University | 0 (0) | 0 (0) | |
| Complete University | 2 (4) | 2 (4) | |
| Occupation | 0.001 | ||
| Farming | 3 (6) | 8 (16) | |
| Civil servant | 1 (2) | 0 (0) | |
| Business | 10 (20) | 13 (26) | |
| Community health worker | 1 (2) | 3 (6) | |
| Driver | 4 (8) | 0 (0) | |
| Tourism | 3 (6) | 4 (8) | |
| Security guard | 4 (8) | 0 (0) | |
| Technical worker | 7 (14) | 0 (0) | |
| Pastor | 1 (2) | 1 (2) | |
| Private sector | 1 (2) | 0 (0) | |
| Retired | 7 (14) | 1 (2) | |
| Unemployed | 8 (16) | 20 (40) | |
| CD4 (cells/mL) | 0.01 | ||
| <200 | 10 (20) | 4 (8) | |
| 200–500 | 29 (58) | 21 (42) | |
| >500 | 11 (22) | 25 (50) | |
| Viral load (Virus/mL) | 0.459 | ||
| <400 | 47 (94) | 48 (96) | |
| 400–5000 | 3 (6) | 2 (4) | |
| >5000 | 0 (0) | 0 (0) | |
| Serious diseases | 0.221 | ||
| No | 27 (54) | 33 (66) | |
| Yes | 23 (46) | 17 (34) | |
| Specified | |||
| Cancer | 3 (6) | 2 (4) | |
| Cardiovascular | 6 (12) | 4 (8) | |
| Rheumatic disease | 2 (4) | 1 (2) | |
| Diabetes | 5 (10) | 4 (8) | |
| Respiratory tract disease | 2 (4) | 3 (6) | |
| Hepatitis B | 1 (2) | 1 (2) | |
| Other diseases | 4 (8) | 2 (4) | |
| Smoking | <0.0001 | ||
| No | 25 (50) | 45 (90) | |
| Yes | 2 (4) | 0 (0) | |
| Ex-smoker | 23 (46) | 5 (10) | |
| Use of alcohol | 0.010 | ||
| Never | 29 (58) | 40 (80) | |
| Once a month | 2 (4) | 3 (6) | |
| Once a week | 7 (14) | 6 (12) | |
| Several times a week | 12 (24) | 1 (2) | |
| Live births * | |||
| 0 | - | 2 (4) | |
| 1–2 | - | 16 (32) | |
| 3–4 | - | 17 (34) | |
| 5–6 | - | 9 (18) | |
| More than 6 | - | 6 (12) | |
| Abortions * | |||
| 0 | - | 27 (54) | |
| 1 | - | 10 (20) | |
| 2 | - | 9 (18) | |
| More than 2 | - | 4 (8) | |
| First sexual intercourse | 0.425 | ||
| 10–14 | 2 (4) | 0 (0) | |
| 15–19 | 13 (26) | 18 (36) | |
| 20–24 | 23 (46) | 23 (46) | |
| 25–29 | 9 (18) | 8 (16) | |
| 30–35 | 3 (6) | 1 (2) | |
| Number of sex partners | 0.012 | ||
| 1–2 | 17 (34) | 27 (54) | |
| 3–4 | 10 (20) | 15 (30) | |
| 5–6 | 7 (14) | 5 (10) | |
| 7–8 | 3 (6) | 0 (0) | |
| >8 | 13 (26) | 3 (6) | |
| Number of orogenital sex partners of the opposite sex | 0.007 | ||
| 0 partners | 9 (18) | 8 (16) | |
| 1–2 partners | 14 (28) | 29 (58) | |
| 3–4 partners | 10 (20) | 10 (20) | |
| 5–6 partners | 5 (10) | 2 (4) | |
| 7–8 partners | 2 (4) | 0 (0) | |
| >8 partners | 10 (20) | 1 (2) | |
| Number of orogenital sex partners of the same sex | 1.00 | ||
| 0 partners | 50 (100) | 50 (100) | |
| 1 partner and above | 0 (0) | 0 (0) | |
| Number of anal sex partners of the opposite sex | 0.315 | ||
| 0 partners | 49 (98) | 50 (100) | |
| 1–2 partners | 1 (2) | 0 (0) | |
| Number of anal sex partners of the same sex | 1.00 | ||
| 0 partners | 50 (100) | 50 (100) | |
| 1 partner and above | 0 (0) | 0 (0) | |
| Previous gonorrhoea infection | 0.385 | ||
| Yes | 22 (44) | 17 (34) | |
| No | 28 (56) | 32 (64) | |
| I do not know | 0 (0) | 1 (2) | |
| Previous syphilis infection | 0.461 | ||
| Yes | 9 (18) | 12 (24) | |
| No | 41 (82) | 38 (76) | |
| I do not know | 0 (0) | 0 (0) | |
| Previous chlamydia infection | 0.697 | ||
| Yes | 6 (12) | 6 (12) | |
| No | 35 (70) | 38 (76) | |
| I do not know | 9 (18) | 6 (12) | |
| Previous other STI | N/A | ||
| No | 42 (84) | 42 (84) | |
| Yes-specified | |||
| Urinary tract infection | 6 (12) | 4 (8) | |
| Bacterial vaginosis | - | 2 (4) | |
| Trichomonas vaginalis | - | 2 (4) | |
| Not specified | 2 (4) | - | |
| Contraceptive methods | N/A | ||
| Female sterilization | 3 (6) | 3 (6) | |
| Male sterilization | 1 (2) | 1 (2) | |
| Contraceptive implant | 6 (12) | 6 (12) | |
| Contraceptive injectable | 3 (6) | 4 (8) | |
| Contraceptive pills | 1 (2) | 2 (4) | |
| Male condom | 12 (24) | 8 (16) | |
| Rhythm method monitoring fertility | 3 (6) | 4 (8) | |
| Withdrawal of penis before ejaculation | 1 (2) | 0 (0) | |
| Other method | 0 (0) | 1 (2) | |
| None of them | 20 (40) | 21 (42) | |
| Pap smear test | N/A | ||
| Yes | - | 29 (58) | |
| No | - | 20 (40) | |
| I do not know | - | 1 (2) | |
Data are presented as number of individuals (%). p-values were calculated between males and females using the chi-square test. N/A = not applicable. * = Not-applicable to men.
3.2. Prevalence of HPV in Different Mucous Membranes and Cytology
The prevalence of different HPV types in different mucous membranes in men and women is displayed in Table 2. All analysed HPV types were detected in the cohort where HPV16, HPV52 and HPV35 were the most prevalent HR-HPV infections constituting 30%, 10% and 8%, respectively, of all HR-HPV infections in all assessed mucous membranes. HPV16 constituted 77%, 21%, 19%, 46%, 28–35% and 11% of all oral, oropharyngeal, anal, cervical, vaginal and penile HR-HPV infections, respectively.
Table 2.
HR- and LR-HPV infections in different mucous membranes; n (%).
| Oral | Oropharynx | Anus | Cervix | Vagina -sc |
Vagina -pc |
Penis | Sum (% of All Infections) |
|
|---|---|---|---|---|---|---|---|---|
| HPV6 | 1 (1) | 2 (4) | 2 (4) | 2 (4) | 1 (2) | 8 (7) | ||
| HPV11 | 1 (1) | 1 (2) | 1 (2) | 3 (3) | ||||
| HPV16 | 10 (10) | 2 (2) | 3 (3) | 6 (12) | 5 (10) | 6 (12) | 2 (4) | 34 (30) |
| HPV18 | 1 (1) | 1 (2) | 4 (8) | 6 (5) | ||||
| HPV31 | 1 (1) | 2 (2) | 2 (4) | 5 (4) | ||||
| HPV33 | 1 (1) | 1 (1) | ||||||
| HPV35 | 3 (3) | 2 (4) | 2 (4) | 2 (4) | 9 (8) | |||
| HPV39 | 1 (1) | 1 (2) | 2 (4) | 1 (2) | 1 (2) | 6 (5) | ||
| HPV45 | 1 (1) | 3 (6) | 4 (4) | |||||
| HPV51 | 1 (1) | 1 (1) | 1 (2) | 2 (4) | 5 (4) | |||
| HPV52 | 2 (1) | 1 (1) | 1 (2) | 3 (6) | 2 (4) | 2 (4) | 11 (10) | |
| HPV56 | 1 (1) | 1 (2) | 2 (4) | 2 (4) | 1 (2) | 7 (6) | ||
| HPV58 | 1 (1) | 1 (2) | 1 (2) | 1 (2) | 2 (4) | 6 (5) | ||
| HPV59 | 2 (2) | 1 (1) | 1 (2) | 1 (2) | 1 (2) | 2 (4) | 8 (7) |
Sc = self-collected; pc = physician-collected.
The prevalence of LR- and HR-HPV infection-positivity in different mucous membranes in men and women are displayed in Table 3 and in Table S2. Of the studied 100 participants, 45% were HR-HPV-positive in one or more mucous membranes. HR-HPV infections occurred in 10% of the oral cavity and oropharynx in men compared with 12% and 0% in women, respectively (p = 1.00 and p = 0.06, respectively). Oral and oropharyngeal LR-HPV infections were not detected in any of the study participants. Anal HR-HPV infections were significantly more common in women than men (24% vs. 2%, respectively, p = 0.002). In contrast, anal LR-HPV infections were rare in women and occurred to a similar degree in men (2% and 2%, respectively). Cervical HR-HPV and LR-HPV infections occurred in 24% and 6% of women, respectively. Vaginal HR-HPV and LR-HPV infections were detected with self-sampling in 32% and 4% of women, respectively, and with physician-taken sampling in 30% and 4% of women, respectively. A similar degree of genital HPV-positivity occurred also in men, i.e., penile HR-HPV and LR-HPV infections occurred in 24% and 4%, respectively. Co-infections of more than one HR-HPV type occurred in 1/5 male oral sample, 0/6 female oral sample, 2/5 male oropharyngeal sample, 0/1 male anal sample, 0/12 female anal sample, 1/12 cervical sample, 2/15 physician-taken vaginal sample, 2/16 vaginal self-sample and 5/12 penile sample. Low-grade and high-grade squamous intraepithelial lesions (LSIL and HSIL) in pap smears occurred in 8.7% and 4.3% of female genital HR-HPV-positive cases and in 11.1% and 0% of female genital HR-HPV-negative cases (Table S3).
Table 3.
Prevalence of HPVs in different mucous membranes.
| Anatomical Site of HPV Infection | Yes/No | Males (n = 50) | Females (n = 50) | p-Value |
|---|---|---|---|---|
| Oral LR-HPV | Yes | 0 (0) | 0 (0) | 1.00 |
| No | 50 (100) | 50 (100) | ||
| Oral HR-HPV | Yes | 5 (10) | 6 (12) | 1.00 |
| No | 45 (90) | 44 (88) | ||
| Oropharynx LR-HPV | Yes | 0 (0) | 0 (0) | 1.00 |
| No | 50 (100) | 50 (100) | ||
| Oropharynx HR-HPV | Yes | 5 (10) | 0 (0) | 0.06 |
| No | 45 (90) | 50 (100) | ||
| Anus LR-HPV | Yes | 1 (2) | 1 (2) | 1.00 |
| No | 49 (98) | 49 (98) | ||
| Anus HR-HPV | Yes | 1 (2) | 12 (24) | 0.002 |
| No | 49 (98) | 38 (76) | ||
| Penis LR-HPV | Yes | 2 (4) | ||
| No | 48 (96) | |||
| Penis HR-HPV | Yes | 12 (24) | ||
| No | 38 (76) | |||
| Vagina LR-HPV (physician sampling) | Yes | 2 (4) | ||
| No | 48 (96) | |||
| Vagina HR-HPV (physician sampling) | Yes | 15 (30) | ||
| No | 35 (70) | |||
| Vagina LR-HPV (self-sampling) | Yes | 2 (4) | ||
| No | 48 (96) | |||
| Vagina HR-HPV (self-sampling) | Yes | 16 (32) | ||
| No | 34 (68) | |||
| Cervix LR-HPV | Yes | 3 (6) | ||
| No | 47 (94) | |||
| Cervix HR-HPV | Yes | 12 (24) | ||
| No | 38 (76) |
Data are presented as number of individuals (%). p-values were calculated between males and females using the Fisher’s exact test. HPV = human papillomavirus; HR-HPV = high-risk human papillomavirus; LR-HPV = low-risk human papillomavirus.
3.3. Concordance of HR-HPV Infections
HR-HPV type-specific concordances between mucous membranes and between couples are displayed in Table 4. Male oral to oropharyngeal HPV concordance was 87% (κ 0.46 ± 0.17; p < 0.001). Male-to-female oral HPV concordance was 90% (κ 0.56 ± 0.17; p < 0.001). The concordance of type-specific HR-HPVs in vaginal samples taken by the physician and by the participant herself was 87% (κ 0.70 ± 0.10; p < 0.001). The type-specific HR-HPV concordance between cervical samples and vaginal samples taken by the physician and the participant herself was 81% (κ 0.54 ± 0.13; p < 0.001) and 80% (κ 0.51 ± 0.13; p < 0.001), respectively. The type-specific HR-HPV concordance between cervical and female anal samples was 79% (κ 0.42 ± 0.15; p = 0.002). The type-specific HR-HPV concordance between vaginal self-sample and physician-sample vs. female anal samples was 74% and 72% (κ 0.36 ± 0.14; p = 0.005 and κ 0.30 ± 0.14; p = 0.02, respectively). Only 22.2% of HR-HPVs infections were shared by the couples and concordance was 35% (−0.34 ± 0.11; p = 0.004; Table S4). Of the six couple-concordant HR-HPV infections, five were HPV16 and one was HPV39.
Table 4.
Concordances (κ) between mucous membranes and couples.
| M Oral |
M Oropharynx |
M Anus |
Penis | F Oral |
F Oropharynx |
F Anus |
Cervix | Vagina-sc | Vagina-pc | |
|---|---|---|---|---|---|---|---|---|---|---|
| M Oral | 1 |
0.46
±0.17 *** |
−0.03 ±0.03 |
−0.03 ±0.11 |
0.56
±0.17 *** |
No cases | −0.20 ±0.05 |
−0.08 ±0.11 |
−0.12 ±0.09 |
−0.13 ±0.09 |
| M Oropharynx | 1 | −0.03±0.03 | 0.04 ±0.12 |
0.02 ±0.14 |
No cases | −0.22 ±0.05 |
−0.21 ±0.05 |
−0.25
±0.07 * |
−0.24
±0.06 * |
|
| M Anus | 1 | 0.07 ±0.07 |
−0.03 ±0.03 |
No cases | −0.04 ±0.04 |
0.11 ±0.10 |
−0.04 ±0.04 |
0.08 ±0.07 |
||
| Penis | 1 | −0.19 ±0.06 |
No cases |
−0.25
±0.09 * |
−0.18 ±0.11 |
−0.36 ±0.09 ** |
−0.24
±0.10 # |
|||
| F Oral | 1 | No cases | 0.07 ±0.14 |
−0.07 ±0.11 |
−0.004 ±0.11 |
−0.10 ±0.10 |
||||
| F Oropharynx | No cases | No cases | No cases | No cases | No cases | |||||
| F Anus | 1 |
0.42
±0.15 ** |
0.36
±0.13 ** |
0.30
±0.14 * |
||||||
| Cervix | 1 |
0.54
±0.13 *** |
0.51
±0.13 *** |
|||||||
| Vagina-sc | 1 |
0.70
±0.10 *** |
||||||||
| Vagina-pc | 1 |
M = male; F = female; SC = self-collected; PC = physician-collected; Statistical significance is indicated with * for p < 0.05, ** for p < 0.01, *** for p < 0.001 and # p = 0.054.
3.4. Risk Factors Contracting HR-HPV Infections
Having more than two previous sex partners was associated with the risk of contracting HR-HPV infections in any mucous membrane in men in univariate analysis (p = 0.03) but not in multivariate analysis (p = 0.67; Table 5). Having more than one abortion and more than two previous sex partners, being previously infected by gonorrhea and not knowing if being infected by chlamydia were factors associated with the risk of contracting HR-HPV infections in any mucous membrane in women (Table 5).
Table 5.
Risk of HR-HPV infections in any mucous membrane in men and women.
| Men | Women | |||||||
|---|---|---|---|---|---|---|---|---|
| COR (95% CI) | Sign. | AOR (95% CI) | Sign. | COR (95% CI) | Sign. | AOR (95% CI) | Sign. | |
| Age | ||||||||
| ≤51 | Reference | Reference | Reference | Reference | ||||
| >51 | 0.52 (0.15–1.81) | 0.31 | 0.38 (0.05-3.13) | 0.37 | 2.12 (0.60–7.48) | 0.25 | 9.80 (0.21–461.39) | 0.25 |
| Level of Education | ||||||||
| Less than complete secondary school | Reference | Reference | Reference | Reference | ||||
| Complete secondary school and beyond | 1.67 (0.43–6.50) | 0.46 | 2.18 (0.22–21.68) | 0.51 | 1.03 (0.27–3.94) | 0.97 | 3.01 (0.17–54.01) | 0.45 |
| CD4 (cells/mL) | 0.65 | 0.20 | 0.31 | 0.09 | ||||
| >500 | Reference | Reference | Reference | Reference | ||||
| 200–500 | 1.14 (0.17–7.60) | 0.89 | 0.51 (0.01–21.17) | 0.72 | 1.27 (0.15–10.53) | 0.82 | 0.02 (0–2.33) | 0.08 |
| <200 | 1.88 (0.41–8.60) | 0.41 | 5.09 (0.34–76.07) | 0.24 | 2.55 (0.76–8.48) | 0.13 | 70.80 (0.45–11,134) | 0.10 |
| Viral load (Virus/mL) | ||||||||
| <400 | Reference | Reference | Reference | Reference | ||||
| 400–5000 | 3,446,346,331 (0-) | 1.00 | 21,944,977,929, (0-) | 1.00 | 0.85 (0.05–14.33) | 0.91 | 18.30 (0–8,605,648) | 0.66 |
| Smoking | ||||||||
| Never | Reference | Reference | Reference | Reference | ||||
| Ever | 1.00 (0.32–3.17) | 1.00 | 1.44 (0.18–11.68) | 0.73 | 1.31 (0.20–8.62) | 0.78 | 1.89 (0.01–639.98) | 0.83 |
| Use of alcohol | ||||||||
| Never/seldom | Reference | Reference | Reference | Reference | ||||
| Once a month and more | 2.39 (0.73–7.78) | 0.15 | 4.98 (0.63–39.50) | 0.13 | 0.49 (0.12–2.02) | 0.33 | 2.16 (0.10–46.36) | 0.62 |
| Live births | 0.36 | 0.22 | ||||||
| 0–2 | Reference | Reference | ||||||
| 3–4 | 0.56 (0.15–2.14) | 0.40 | 0.17 (0.06–4.92) | 0.30 | ||||
| >4 | 1.60 (0.39–6.62) | 0.52 | 6.46 (0.11–386.53) | 0.37 | ||||
| Abortions | ||||||||
| 0–1 | Reference | Reference | ||||||
| >1 | 7.22 (1.40–37.25) | 0.02 | 276.39 (1.18–64,873) | 0.04 | ||||
| First sexual intercourse | ||||||||
| <21 | Reference | Reference | Reference | Reference | ||||
| ≥21 | 0.71 (0.22–2.25) | 0.56 | 0.82 (0.12–5.85) | 0.84 | 1.21 (0.39–3.69) | 0.74 | 0.43 (0.03–6.18) | 0.53 |
| Number of sex partners | ||||||||
| 0–2 | Reference | Reference | Reference | Reference | ||||
| >2 | 3.82 (1.13–12.95) | 0.03 | 1.77 (0.13–23.67) | 0.67 | 3.00 (0.54–16.60) | 0.21 | 1478.09 (1.53–1,430,837) | 0.04 |
| Number of orogenital sex partners | ||||||||
| 0–2 | Reference | Reference | Reference | Reference | ||||
| >2 | 3.34 (0.96–11.62) | 0.06 | 2.72 (0.22–33.95) | 0.44 | 0.99 (0.28–3.52) | 0.99 | 0.19 (0.01–5.93) | 0.34 |
| Previous gonorrhoea infection | 0.21 | 0.10 | ||||||
| No | Reference | Reference | Reference | Reference | ||||
| Yes | 2.08 (0.64–6.73) | 0.22 | 1.63 (0.19–14.19) | 0.66 | 3.09 (0.88–10.83) | 0.08 | 1042.63 (1.88–577,026) | 0.03 |
| I do not know | 2,077,039,084 (0-) | 1.00 | 89,632,519 (0-) | 1.00 | ||||
| Previous syphilis infection | 0.21 | |||||||
| No | Reference | Reference | Reference | Reference | ||||
| Yes | 1.54 (0.36–6.67) | 0.56 | 0.77 (0.03–18.51) | 0.87 | 2.00 (0.51–7.78) | 0.32 | 0.01 (0.00–2.42) | 0.10 |
| Previous chlamydia infection | 0.25 | 0.71 | 0.25 | 0.10 | ||||
| No | Reference | Reference | Reference | Reference | ||||
| Yes | 2.50 (0.43–14.54) | 0.31 | 0.28 (0.00–18.95) | 0.55 | 2.22 (0.36–13.62) | 0.39 | 0.06 (0–20.71) | 0.35 |
| I do not know | 3.13 (0.69–14.08) | 0.14 | 1.54 (0.08–30.84) | 0.78 | 5.56 (0.59–52.16) | 0.13 | 23,199 (2.30–233,872,654) | 0.03 |
| Contraceptive methods | ||||||||
| Other method than condom/none | Reference | Reference | Reference | Reference | ||||
| Male condom | 0.32 (0.06–1.68) | 0.18 | 0.26 (0.02–3.57) | 0.31 | 0.45 (0.09–2.13) | 0.31 | 1.55 (0.03–72.71) | 0.82 |
| Pap smear test | 0.84 | 0.92 | ||||||
| No | Reference | Reference | ||||||
| Yes | 0.71 (0.22–2.22) | 0.55 | 0.57 (0.04–8.97) | 0.69 | ||||
| I do not know | 0 (0-) | 1.00 | 0 (0-) | 1.00 | ||||
| Partner HR-HPV positive | ||||||||
| No | Reference | Reference | Reference | Reference | ||||
| Yes | 1.57 (0.49–5.08) | 0.45 | 0.82 (0.12–5.55) | 0.84 | 1.57 (0.49–5.08) | 0.45 | 17.93 (0.24–1320) | 0.19 |
COR (crude odds ratio) and AOR (adjusted odds ratio) with 95% CI (confidence intervals) are indicated.
4. Discussion
In the present study, we show that the prevalence of HPV infections was high in men living with HIV (MLWH) and WLWH, but HR-HPV infections were discordant within couples. While couples displayed concordant oral to oral HR-HPV infections, oral to genital HR-HPV infections were discordant. A high concordance between vaginal self-collected, vaginal physician-collected and cervical HR-HPV samples was observed. Previous exposure to STIs, the number of sex partners and undergoing abortions were factors correlating with the risk of being infected by HR-HPV.
Our study and previous studies have shown a high prevalence of HPV infections in Rwandan men and women, especially in MLWH and WLWH [2,5,11,12,13]. The prevalence of HR-HPVs in the vagina/uterine cervix of 24–32% of WLWH was similar to the degree of positivity we previously observed at the same HIV clinic but in another cohort of women [11]. In the present study, we found that HPV16 was the most prevalent type followed by HPV-52 and HPV35, which is in accordance with our previous study analysing HPV in the uterine cervix in WLWH and HIV-negative women in Rwanda [11]. Few previous studies have been conducted analysing the prevalence of HPVs in the oral cavity and oropharynx in Africa. We show that 10–12% of our studied cohort were positive for oral group 1 HR-HPVs (IARC), which is in accordance with a cross-sectional study in Nigerian women but significantly higher than the prevalence in HIV cohorts from South Africa [14,15,16,17]. Oral to oral concordance was also high in couples, and HPV16 dominated among HPVs present in the oral cavity. Similarly, few studies have assessed the prevalence of penile HPV infections in sub-Saharan Africa. In a cross-sectional study conducted on Tanzanian men, one in five men were positive for HPV, and HIV constituted a risk factor for penile HPV [18]. In another study from Tanzania, the prevalence of penile HR-HPVs in MLWH was 25.7%, which was higher than the 15.8% observed in HIV-negative men [19]. We found similar rates (24%) for HR-HPV positivity in our cohort of MLWH. While HR-HPVs were rarely detected in male anal samples, HR-HPVs were commonly detected in female anal samples but detected to a less degree than in vaginal and cervical samples. Type-specific HR-HPV concordance between the three sites was high. A high concordance between anal and cervical HR-HPVs has been demonstrated in several previous studies [20,21,22,23].
In agreement with previous studies in sub-Saharan Africa [24,25,26], we demonstrate a high concordance between HR-HPVs detected in cervical and vaginal samples independent of whether the sample was collected by the patient herself or by the physician. The concordance between self- and physician-collected vaginal HR-HPV samplings was also high. The degree of concordance is in accordance with previous studies conducted in WLWH in Ethiopia and in other low-income countries [27,28]. Studies from Uganda have shown that self-administrated HPV testing is suitable and feasible in low-resource settings [29].
Besides a positive concordance between male and female oral HR-HPV strains, we observed a high discordance of type-specific sharing of HR-HPV infections between men and women. Our findings contrast with a larger study conducted in South Africa where HIV-concordant male-female partners shared HR-HPV strains [30]. In our questionnaire we did not cover extramarital sexual activity, however, men reported having more sexual partners, reported different contraceptive methods than their female partners and had more often than women multiple genital HR-HPV infections.
We confirm again the relationship between gonorrhea infection and not knowing if being previously infected with chlamydia with HR-HPV infections in women [11]. To have had multiple sexual partners was correlated in women with the degree of HR-HPV-positivity in accordance with previous studies [31,32]. Voluntary/spontaneous abortion was found to be correlated with HR-HPV positivity in line with a meta-analysis showing a correlation between HPV infections and the risk of spontaneous abortion [33]. Taken together, exposure to unprotected sex correlates to the acquisition of HPV, however, we could not find a correlation between the use of condoms and protection against HPV.
Rwanda is at the top in Africa when it comes to the vaccination of schoolgirls, reaching 89% of the target population [34]. Still, the majority of Rwandan women are unvaccinated and have never been screened for cervical cancer [11]. Moreover, the vaccination of boys has not been implemented in Africa and was only recently implemented in some but not all European countries and in the USA [35,36]. To further reduce the number of HPV-related cancers in East Africa we suggest that the focus should also be set to vaccinating boys in the future.
The likelihood of being cervical cancer screened is higher in WLWH than in HIV-negative women in East Africa [37]. To note, in our included cohort of WLWH in 2021, 58% had undergone a pap smear test, which is an increase compared to the 27% who had undergone a pap smear in our previously studied cohort at the HIV clinic in 2015 [11]. The current percentage of women living with HIV who had been screened is higher than the one estimated for Rwanda in previous reports [37]. It is currently unknown whether the increase in cervical cancer screening in Rwanda also includes other women than risk patients for cervical cancer.
The strength of our study is that we were able to analyse the concordance of HPV infections in multiple mucous membranes and analyse concordance of HPVs among HIV-positive couples. As far as we know, no previous study in East Africa has studied HPV co-infections in mucous membranes among risk patients. The present study has, however, also limitations. First, the cohort assessed was small and this may explain why no variable was related to HPV-positivity in men. Secondly, in our questionnaire, we did not cover extramarital sexual behaviour so we can only present indirect evidence for extramarital sexual activity contributing to the high degree of HR-HPV-positivity in men. Thirdly, we had a high average age of the participants, which most likely led to a lower degree of HPV positivity than in a younger cohort of individuals.
5. Conclusions
HPV infection is prevalent in mucous membranes among HIV-positive concordant couples in Rwanda. While oral to oral transmission was common in HIV-positive couples, genital infections were discordant. Vaginal HPV self-screening has, moreover, a high sensitivity to detect cervical HPVs. Our findings highlight the need for additional studies on HPV transmission in other mucous membranes than the uterine cervix in sub-Saharan Africa. In addition, the high prevalence of HPV concordance among HIV-positive concordant couples suggests that to further lower the HPV burden of disease in Africa, the focus should also be set on the vaccination of boys.
Acknowledgments
The authors are thankful to the clinical staff at the HIV clinic at CHUK for help with the project and to Emile Bienvenu, Rwanda Food and Drug Agency, Kigali, Rwanda, for valuable inputs on the project.
Supplementary Materials
The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/v15041005/s1, Table S1. Primers and probes for real-time PCR; Table S2. HPV infections in mucous membranes of HIV+ couples; Table S3. Vaginal and cervical HR-HPV infections and correlation to cervical cytology; Table S4. Type-specific HR-HPV concordance in any mucous membrane in couples.
Author Contributions
Conceptualization, S.U., C.M.M., B.H., M.A. and D.G.; methodology, S.U., B.N., M.A. and D.G.; validation, S.U., B.N., B.H., M.A. and D.G.; formal analysis, S.U., B.N., B.H., M.A. and D.G.; investigation, S.U., B.N., B.H., M.A. and D.G.; resources, M.A. and D.G.; data curation, S.U., M.A. and D.G.; writing—original draft preparation, S.U. and D.G.; writing—S.U., B.N., C.M.M., B.H., M.A. and D.G.; supervision, B.H., C.M.M., M.A. and D.G. All authors have read and agreed to the published version of the manuscript.
Institutional Review Board Statement
The present study was approved by the Rwanda National Ethics committee (registration number 43/RNEC/2021) and the Swedish Ethical Review Authority (registration number 2021-02464).
Informed Consent Statement
Informed consent was obtained from all subjects involved in the study.
Data Availability Statement
Additional data can be obtained after written request to the Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Medicinaregatan 3A SE-413 90 Göteborg, Sweden. Email: klinvet@gu.se.
Conflicts of Interest
The authors declare no conflict of interest.
Funding Statement
This study was funded by the Swedish International Development Cooperation Agency (Sida; 2019/37:9), the Assar Gabrielsson Foundation (FB21-49) and the Wilhelm and Martina Lundgren Foundation (2019-2833).
Footnotes
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.
References
- 1.De Vuyst H., Alemany L., Lacey C., Chibwesha C.J., Sahasrabuddhe V., Banura C., Denny L., Parham G.P. The Burden of Human Papillomavirus Infections and Related Diseases in Sub-Saharan Africa. Vaccine. 2013;31:F32–F46. doi: 10.1016/j.vaccine.2012.07.092. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Mukanyangezi M., Rugwizangoga B., Manzi O., Rulisa S., Hellstrand K., Tobin G., Martner A., Bienvenu E., Giglio D. Persistence rate of cervical human papillomavirus infections and abnormal cytology in Rwanda. HIV Med. 2019;20:485–495. doi: 10.1111/hiv.12782. [DOI] [PubMed] [Google Scholar]
- 3.Franco E.L., Villa L.L., Sobrinho J.P., Prado J.M., Rousseau M., Désy M., Rohan T.E. Epidemiology of Acquisition and Clearance of Cervical Human Papillomavirus Infection in Women from a High-Risk Area for Cervical Cancer. J. Infect. Dis. 1999;180:1415–1423. doi: 10.1086/315086. [DOI] [PubMed] [Google Scholar]
- 4.Giuliano A.R., Tortolero-Luna G., Ferrer E., Burchell A.N., de Sanjose S., Kjaer S.K., Munoz N., Schiffman M., Bosch F.X. Epidemiology of human papillomavirus infection in men, cancers other than cervical and benign conditions. Vaccine. 2008;26((Suppl. S10)):K17–K28. doi: 10.1016/j.vaccine.2008.06.021. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Murenzi G., Kim H.Y., Munyaneza A., Tuyisenge P., Zawadi T.M., Buteera A.M., Adedimeji A., Mutesa L., Castle P.E., Anastos K., et al. Anogenital Human Papillomavirus and HIV Infection in Rwandan Men Who Have Sex with Men. J. Acquir. Immune. Defic. Syndr. 2020;84:463–469. doi: 10.1097/QAI.0000000000002376. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Lekoane K.M.B., Kuupiel D., Mashamba-Thompson T.P., Ginindza T.G. The interplay of HIV and human papillomavirus-related cancers in sub-Saharan Africa: Scoping review. Syst. Rev. 2020;9:1–13. doi: 10.1186/s13643-020-01354-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Mehanna H., Beech T., Nicholson T., El-Hariry I., McConkey C., Paleri V., Roberts S. Prevalence of human papillomavirus in oropharyngeal and nonoropharyngeal head and neck cancer--systematic review and meta-analysis of trends by time and region. Head Neck. 2013;35:747–755. doi: 10.1002/hed.22015. [DOI] [PubMed] [Google Scholar]
- 8.Huvud-Och Halscancer Nationellt Vårdprogram. 2022. [(accessed on 20 March 2022)]. Available online: https://cancercentrum.se/samverkan/cancerdiagnoser/huvud-och-hals/vardprogram/
- 9.de Martel C., Plummer M., Vignat J., Franceschi S. Worldwide burden of cancer attributable to HPV by site, country and HPV type. Int. J. Cancer. 2017;141:664–670. doi: 10.1002/ijc.30716. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Lindh M., Gorander S., Andersson E., Horal P., Mattsby-Balzer I., Ryd W. Real-time Taqman PCR targeting 14 human papilloma virus types. J. Clin. Virol. 2007;40:321–324. doi: 10.1016/j.jcv.2007.09.009. [DOI] [PubMed] [Google Scholar]
- 11.Mukanyangezi M.F., Sengpiel V., Manzi O., Tobin G., Rulisa S., Bienvenu E., Giglio D. Screening for human papillomavirus, cervical cytological abnormalities and associated risk factors in HIV-positive and HIV-negative women in Rwanda. HIV Med. 2018;19:152–166. doi: 10.1111/hiv.12564. [DOI] [PubMed] [Google Scholar]
- 12.Mpunga T., Chantal Umulisa M., Tenet V., Rugwizangoga B., Milner D.A., Jr., Munyanshongore C., Heideman D.A.M., Bleeker M.C.G., Tommasino M., Franceschi S., et al. Human papillomavirus genotypes in cervical and other HPV-related anogenital cancer in Rwanda, according to HIV status. Int. J. Cancer. 2020;146:1514–1522. doi: 10.1002/ijc.32491. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Veldhuijzen N.J., Dhont N., Vyankandondera J., Gasarabwe A., Busasa R., Crucitti T., van de Wijgert J.H.H.M. Prevalence and Concordance of HPV, HIV, and HSV-2 in Heterosexual Couples in Kigali, Rwanda. Sex. Transm. Dis. 2012;39:128–135. doi: 10.1097/OLQ.0b013e3182367c4c. [DOI] [PubMed] [Google Scholar]
- 14.Mistry H.B., Lebelo R.L., Matshonyonge F., Nchabeleng M., Mathebula M., Bogers J.P., Wood N.H. Oral and oropharyngeal high-risk HPV prevalence, HIV status, and risk behaviours in a cohort of South African men who have sex with men. AIMS Public Health. 2022;9:129–141. doi: 10.3934/publichealth.2022010. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Wood N.H., Makua K.S., Lebelo R.L., Redzic N., Benoy I., Vanderveken O.M., Bogers J. Human Papillomavirus Prevalence in Oral and Oropharyngeal Rinse and Gargle Specimens of Dental Patients and of an HIV-Positive Cohort from Pretoria, South Africa. Adv. Virol. 2020;2020:2395219. doi: 10.1155/2020/2395219. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Chikandiwa A., Pisa P.T., Chersich M.F., Muller E.E., Mayaud P., Delany-Moretlwe S. Oropharyngeal HPV infection: Prevalence and sampling methods among HIV-infected men in South Africa. Int. J. STD AIDS. 2018;29:776–780. doi: 10.1177/0956462418755882. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Morhason-Bello I.O., Baisley K., Pavon M.A., Adewole I.F., Bakare R., de Sanjose S., Francis S.C., Watson-Jones D. Prevalence and genotype specific concordance of oro-genital and anal human papillomavirus infections among sexually active Nigerian women. Infect. Agent Cancer. 2021;16:59. doi: 10.1186/s13027-021-00398-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Olesen T.B., Mwaiselage J., Iftner T., Kahesa C., Rasch V., Frederiksen K., Munk C., Kjaer S.K. Risk factors for genital human papillomavirus among men in Tanzania. J. Med. Virol. 2017;89:345–351. doi: 10.1002/jmv.24627. [DOI] [PubMed] [Google Scholar]
- 19.Olesen T.B., Iftner T., Mwaiselage J., Kahesa C., Rasch V., Ngoma T., Munk C., Kjaer S.K. Prevalence and type distribution of human papillomavirus among 1813 men in Tanzania and the relationship to HIV status. Sex. Transm. Dis. 2013;40:592–598. doi: 10.1097/OLQ.0b013e31828fcf57. [DOI] [PubMed] [Google Scholar]
- 20.Duan R., Zhang H., Wu A., Li C., Li L., Xu X., Qiao Y., Zhao F., Clifford G. Prevalence and risk factors for anogenital HPV infection and neoplasia among women living with HIV in China. Sex. Transm. Infect. 2022;98:247–254. doi: 10.1136/sextrans-2021-055019. [DOI] [PubMed] [Google Scholar]
- 21.Nasioutziki M., Chatzistamatiou K., Loufopoulos P.D., Vavoulidis E., Tsampazis N., Pratilas G.C., Liberis A., Karpa V., Parcharidis E., Daniilidis A., et al. Cervical, anal and oral HPV detection and HPV type concordance among women referred for colposcopy. Infect. Agents Cancer. 2020;15:22. doi: 10.1186/s13027-020-00287-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Thorsteinsson K., Storgaard M., Katzenstein T.L., Ladelund S., Ronsholt F.F., Johansen I.S., Pedersen G., Gaardsting A., Nielsen L.N., Bonde J., et al. Prevalence of cervical, oral, and anal human papillomavirus infection in women living with HIV in Denmark—The SHADE cohort study. J. Clin. Virol. 2018;105:64–71. doi: 10.1016/j.jcv.2018.05.010. [DOI] [PubMed] [Google Scholar]
- 23.D’Hauwers K.W., Cornelissen T., Depuydt C.E., Bogers J., Donders A.R., Leuridan E., Van Damme P., Tjalma W.A. Anal human papillomavirus DNA in women at a colposcopy clinic. Eur. J. Obstet. Gynecol. Reprod. Biol. 2012;164:69–73. doi: 10.1016/j.ejogrb.2012.05.014. [DOI] [PubMed] [Google Scholar]
- 24.Senkomago V., Ting J., Kwatampora J., Gukare H., Mugo N., Kimani J., Smith J.S. High-risk HPV-RNA screening of physician- and self-collected specimens for detection of cervical lesions among female sex workers in Nairobi, Kenya. Int. J. Gynaecol. Obstet. 2018;143:217–224. doi: 10.1002/ijgo.12628. [DOI] [PubMed] [Google Scholar]
- 25.Untiet S., Vassilakos P., McCarey C., Tebeu P.M., Kengne-Fosso G., Menoud P.A., Boulvain M., Navarria I., Petignat P. HPV self-sampling as primary screening test in sub-Saharan Africa: Implication for a triaging strategy. Int. J. Cancer. 2014;135:1911–1917. doi: 10.1002/ijc.28834. [DOI] [PubMed] [Google Scholar]
- 26.Safaeian M., Kiddugavu M., Gravitt P.E., Ssekasanvu J., Murokora D., Sklar M., Serwadda D., Wawer M.J., Shah K.V., Gray R. Comparability of self-collected vaginal swabs and physician-collected cervical swabs for detection of human papillomavirus infections in Rakai, Uganda. Sex. Transm. Dis. 2007;34:429–436. doi: 10.1097/01.olq.0000243623.67673.22. [DOI] [PubMed] [Google Scholar]
- 27.Bogale A.L., Teklehaymanot T., Ali J.H., Kassie G.M., Medhin G., Baye A.Y., Shiferaw A.Y. Comparison of self-collected versus clinician collected cervicovaginal specimens for detection of high risk human papillomavirus among HIV infected women in Ethiopia. BMC Women’s Health. 2022;22:360. doi: 10.1186/s12905-022-01944-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Mulki A.K., Withers M. Human Papilloma Virus self-sampling performance in low- and middle-income countries. BMC Women’s Health. 2021;21:1–11. doi: 10.1186/s12905-020-01158-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Kamath MulkiNakalembe M., Makanga P., Kambugu A., Laker-Oketta M., Huchko M.J., Martin J. A public health approach to cervical cancer screening in Africa through community-based self-administered HPV testing and mobile treatment provision. Cancer Med. 2020;9:8701–8712. doi: 10.1002/cam4.3468. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Mbulawa Z.Z., Coetzee D., Marais D.J., Kamupira M., Zwane E., Allan B., Constant D., Moodley J.R., Hoffman M., Williamson A.L. Genital human papillomavirus prevalence and human papillomavirus concordance in heterosexual couples are positively associated with human immunodeficiency virus coinfection. J. Infect. Dis. 2009;199:1514–1524. doi: 10.1086/598220. [DOI] [PubMed] [Google Scholar]
- 31.McClung N., Mathoma A., Gargano J.W., Nyepetsi N.G., Querec T.D., Onyekwuluje J., Mine M., Morroni C., Luckett R., Markowitz L.E., et al. HPV prevalence among young adult women living with and without HIV in Botswana for future HPV vaccine impact monitoring. BMC Infect. Dis. 2022;22:176. doi: 10.1186/s12879-022-07130-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Dartell M., Rasch V., Munk C., Kahesa C., Mwaiselage J., Iftner T., Kjaer S.K. Risk factors for high-risk human papillomavirus detection among HIV-negative and HIV-positive women from Tanzania. Sex. Transm. Dis. 2013;40:737–743. doi: 10.1097/OLQ.0000000000000005. [DOI] [PubMed] [Google Scholar]
- 33.Xiong Y.Q., Mo Y., Luo Q.M., Huo S.T., He W.Q., Chen Q. The Risk of Human Papillomavirus Infection for Spontaneous Abortion, Spontaneous Preterm Birth, and Pregnancy Rate of Assisted Reproductive Technologies: A Systematic Review and Meta-Analysis. Gynecol. Obstet. Investig. 2018;83:417–427. doi: 10.1159/000482008. [DOI] [PubMed] [Google Scholar]
- 34.Stefan D.C., Dangou J.M., Barango P., Mahamadou I.D., Kapambwe S. Targeting elimination of cervical cancer by 2030: A baseline assessment in six African countries-part II. Ecancermedicalscience. 2022;16:1454. doi: 10.3332/ecancer.2022.1454. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35.Nguyen-Huu N.H., Thilly N., Derrough T., Sdona E., Claudot F., Pulcini C., Agrinier N., group H.P.V.P.W. Human papillomavirus vaccination coverage, policies, and practical implementation across Europe. Vaccine. 2020;38:1315–1331. doi: 10.1016/j.vaccine.2019.11.081. [DOI] [PubMed] [Google Scholar]
- 36.Chido-Amajuoyi O.G., Talluri R., Wonodi C., Shete S. Trends in HPV Vaccination Initiation and Completion within Ages 9–12 Years: 2008–2018. Pediatrics. 2021;147:e2020012765. doi: 10.1542/peds.2020-012765. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37.Yang L., Boily M.C., Ronn M.M., Obiri-Yeboah D., Morhason-Bello I., Meda N., Lompo O., Mayaud P., Pickles M., Brisson M., et al. Regional and country-level trends in cervical cancer screening coverage in sub-Saharan Africa: A systematic analysis of population-based surveys (2000–2020) PLoS Med. 2023;20:e1004143. doi: 10.1371/journal.pmed.1004143. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
Additional data can be obtained after written request to the Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Medicinaregatan 3A SE-413 90 Göteborg, Sweden. Email: klinvet@gu.se.