Next Article in Journal
Assembly of the Tripartite and RNA Condensates of the Respiratory Syncytial Virus Factory Proteins In Vitro: Role of the Transcription Antiterminator M2-1
Next Article in Special Issue
The High-Risk Human Papillomavirus Type Influences the Tissue Microenvironment in Cervical Intraepithelial Neoplasia Grade 2
Previous Article in Journal
Explainable COVID-19 Detection Based on Chest X-rays Using an End-to-End RegNet Architecture
Previous Article in Special Issue
The Tumor-Specific Immune Landscape in HPV+ Head and Neck Cancer
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Viruses
Volume 15
Issue 6
10.3390/v15061328
viruses-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Diversity of Anal HPV and Non-HPV Sexually Transmitted Infections and Concordance with Genital Infections in HIV-Infected and HIV-Uninfected Women in the Tapajós Region, Amazon, Brazil

by
Luana Lorena Silva Rodrigues
1,2,3,*,
José Henrique Pilotto
2,
Katrini Guidolini Martinelli
4,
Alcina F. Nicol
5,
Vanessa Salete De Paula
6,
Tarik Gheit
7,
Nathália Silva Carlos Oliveira
8,
Carlos Silva-de-Jesus
2,
Vikrant V. Sahasrabuddhe
9,
Diane M. Da Silva
10,11,
W. Martin Kast
10,11,12,
Justin Hardick
13,
Charlotte A. Gaydos
13 and
Mariza Gonçalves Morgado
2,*
1
Programa de Pós-Graduação em Ciências da Saúde, Instituto de Saúde Coletiva, Universidade Federal do Oeste do Pará, Santarém 68135-110, Brazil
2
Laboratório de AIDS e Imunologia Molecular, IOC-FIOCRUZ, Rio de Janeiro 21040-360, Brazil
3
Programa de Pós-Graduação em Medicina Tropical, IOC-FIOCRUZ, Rio de Janeiro 21040-360, Brazil
4
Departamento de Medicina Social, Universidade Federal do Espírito Santo, Vitória 29075-910, Brazil
5
Instituto Nacional de Infectologia Evandro Chagas, INI-FIOCRUZ, Rio de Janeiro 21040-360, Brazil
6
Laboratório de Virologia Molecular e Parasitologia, IOC-FIOCRUZ, Rio de Janeiro 21040-360, Brazil
7
International Agency for Research on Cancer, 69366 Lyon, France
8
Departamento de Patologia, Faculdade de Medicina, Universidade Federal Fluminense, Rio de Janeiro 23033-900, Brazil
9
Division of Cancer Prevention, National Cancer Institute, Bethesda, MD 20892, USA
10
Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA 90033, USA
11
Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA
12
Department of Molecular Microbiology and Immunology, University of Southern California, Los Angeles, CA 90089, USA
13
Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
 
add Show full affiliation list
 
remove Hide full affiliation list
*
Authors to whom correspondence should be addressed.
Viruses 2023, 15(6), 1328; https://doi.org/10.3390/v15061328
Submission received: 1 May 2023 / Revised: 30 May 2023 / Accepted: 2 June 2023 / Published: 6 June 2023
(This article belongs to the Special Issue Immune Responses to Papillomavirus Infections)
Browse Figures
Versions Notes

Abstract

:
The aim of this study was to classify the diversity of anal HPV and non-HPV sexually transmitted infections (STIs) and compare the concordance between anal and genital infections in HIV-infected and uninfected women living in the Tapajós region, Amazon, Brazil. A cross-sectional study was performed with 112 HIV-uninfected and 41 HIV-infected nonindigenous women. Anal and cervical scrapings were collected and analyzed for HPV, Chlamydia trachomatis (CT), Neisseria gonorrheae (NG), Trichomonas vaginalis (TV), Mycoplasma genitalium (MG), and Human alphaherpesvirus 2 (HSV-2). The Kappa test evaluated the concordance between anal and genital infections. The overall prevalence of anal HPV infection was 31.3% in HIV-uninfected and 97.6% in HIV-infected women. The most frequent anal high-risk HPV (hrHPV) types were HPV18 and HPV16 in HIV-uninfected women and HPV51, HPV59, HPV31, and HPV58 in HIV-infected women. Anal HPV75 Betapapillomavirus was also identified. Anal non-HPV STIs were identified in 13.0% of all participants. The concordance analysis was fair for CT, MG, and HSV-2, almost perfect agreement for NG, moderate for HPV, and variable for the most frequent anal hrHPV types. Thus, a high prevalence of anal HPV infection with moderate and fair concordance between anal and genital HPV and non-HPV STIs was observed in our study.

1. Introduction

Data on sexually transmitted infections (STIs) are predominantly related to genital infections. Studies on the anal human papillomavirus (HPV) and non-HPV STIs remain scarce. Cervical cancer screening might contribute to the prevention of anal cancer in women as a secondary prevention measure for anal cancer when stratified to HIV-uninfected women older than 45 years, those with high-risk HPV (hrHPV) cervical infection, or HIV-infected women [1]. Changes in sexual practices and risky behavior trends can increase the prevalence of anal STIs in the developed world [2]. Transmission between the anus and cervix and vice versa are common in women [3,4,5]. This aspect needs to be further investigated because the woman may have HPV infection in both sites, genital and anal, at the same time that it is investigated, but which may be of different HPV types acquired in different exposures in life. The genital site is likely the main source of a concurrent genital–anal HPV infection, which is well mentioned in the scientific literature [4], but it is a hypothesis supported by studies with limitations [6]. Concordance studies between genital and anal infections and the HPV genotypes identified between the two sites can bring clearer answers if they use more robust methodological approaches for HPV detection and genotyping, as well as statistics with better robustness [6]. People living with HIV, men who have sex with men (MSM), and women with cervical cancer are at risk for anal cancer [3]. Recently, age-specific shifts in HPV16 prevalence from the cervix to the anus have been demonstrated, suggesting that HPV infections in the anus persist longer or occur later in life than those in the cervix, particularly in HIV-infected women [7]. Women living in the Tapajós region of the Amazon have a high prevalence of cervical HPV infection and diverse HPV types, along with other STIs [8,9,10]. Therefore, the present study aimed to identify the prevalence and diversity of anal HPV and non-HPV infections and assess the concordance between anal and genital HPV and non-HPV STIs in HIV-uninfected and HIV-infected women. The results obtained in the present study are of relevance when evaluating the utility of cervical screening results in stratifying anal cancer risk.

2. Materials and Methods

2.1. Ethical Issues

Women were invited to participate in the study after signing a written informed consent document in strict compliance with the Brazilian ethical guidelines involving research on human subjects (protocol numbers 2.013.163 and 2.121.697). An epidemiological interview was then conducted.

2.2. Study Design and Population

This study was supported by previous studies in which we evaluated the acceptability of cervico-vaginal self-collection, HPV and other STI testing, and sociodemographic data of 153 nonindigenous women, 112 HIV-uninfected and 41 HIV-infected, living in the Tapajós region, fully described elsewhere [8,9,10]. For the present study, we added the molecular characterization of anal HPV and non-HPV infections in the same study group.

2.3. Anal and Cervical Samples

Anal scraping was performed using a brush introduced approximately 1.95 inches into the anal canal, rotated 680° five times, and later preserved in ThinPrep Solution. Anal and cervical sample collection and processing, as well as the transportation of the biological samples according to international rules (IATA) for laboratory analyses, are described elsewhere [5,6,7].

2.4. DNA Extraction and HPV DNA Detection

DNA extraction from the anal samples was performed with the QIAamp DNA Mini Kit (Qiagen, Valencia, CA, USA) according to the manufacturer’s protocol and was quantified by spectrophotometry on a NanoDrop (ND 1000, Fisher Scientific, Wilmington, DC, USA). Nested PCR was performed to increase the specificity of HPV DNA detection, with PGMY09 and PGMY11 primers for the first round and GP5+ and GP6+ primers for the second round, as previously described [8], in an automatic thermocycler (GeneAmp PCR System 9700—Applied Biosystems).

2.5. HPV Genotyping and Multiple HPV Types

Nested PCR products were purified with a Wizard® SV Gel and PCR Clean-up System (Promega Madison, WI, USA). HPV genotyping and multiple HPV types were performed according to previously published protocols [8,11]. HPV samples were grouped into three groups considering the oncogenic risk classification as follows: high-risk, “probable” or “possible” carcinogenic, and low-risk [12]. The only positive anal scraping sample for Betapapillomavirus was identified through nucleotide sequencing analysis and confirmed at the International Agency for Research on Cancer in Lyon, France, by type-specific multiplex genotyping (TS-MPG) assays combining multiplex polymerase chain reaction (PCR) and bead-based Luminex technology (Luminex Corp., Austin, TX, USA), as described elsewhere [13,14].

2.6. Non-HPV STI Molecular Detection

In this study, the non-HPV STIs assessed were Chlamydia trachomatis (CT), Neisseria gonorrheae (NG), Trichomonas vaginalis (TV), Mycoplasma genitalium (MG), and Human alphaherpesvirus 2 (HSV-2 or herpes simplex virus 2). Duplex real-time PCR was performed for CT and NG, and three real-time PCRs were performed independently to detect TV, MG, and HSV-2. The molecular detection of other non-HPV STIs was performed as previously described [9,10]. All reactions were performed in a QuantStudio 12 K Flex Real-Time PCR System (Applied BioSystems by Life Technologies, Carlsbad, CA, USA).

2.7. Statistical Analysis

Descriptive statistics of the qualitative variables were determined by frequency distribution. The Chi-square test at 95% CI and p-value ≤ 0.05 was used to compare the proportions between the groups. A Mann–Whitney test with 95% CI and p-value ≤ 0.05 was performed to evaluate the associations among median HIV viral load, CD4+ T-cell count, and anal hrHPV infection. Pearson’s correlation test with 95% CI and p-value ≤ 0.05 was performed to evaluate the association of the quantitative proportion of the CD4+ T-cell count and the number of distinct hrHPV types. A Kappa test with 95% CI and p-value ≤ 0.05 was performed to evaluate the concordance between anal and genital HPV and other STIs (non-HPV STIs; CT, NG, TV, MG, and HSV-2) [15] isolated from anal and cervical scraping, respectively [8,9,10]. We categorized the absence and presence of high- and low-risk HPV types, the absence or presence of non-HPV STIs, and the absence and presence of the most frequent anal hrHPV types to perform the proposed Kappa test. Probable and possible carcinogenic HPV types were considered as low-risk HPV for the Kappa test. Statistical analyses were performed using the Statistical Package for Social Sciences (SPSS) software version 19.0 (IBM Corp., Armonk, NY, USA).

3. Results

3.1. Main Sociodemographic Characteristics of the Participants

A total of 153 (N) women agreed to participate in the study, and their anal and cervical scrapings (clinician-collected samples) were collected on the same day. The participants were divided into two groups: HIV-uninfected women (n = 112) and HIV-infected women (n = 41). The mean age of all participants was 36.9 (±12.9) years. Most of the HIV-infected women were single (p = 0.006), had an average of 4.3 gestations (p = 0.050), started sex at the age of 17 years or below (p = 0.052), had more than four sexual partners in life (p = 0.012), and regularly used condoms (p = 0.010) (Table 1). The practice of anal sex (p = 0.457) did not significantly differ between the two groups (Table 1).

3.2. Anal HPV Infection and Diversity

The overall prevalence of anal HPV infection was 31.3% (35/112) among HIV-uninfected women and 97.6% (40/41) among HIV-infected women. A high diversity of anal HPV genotypes was identified in HIV-uninfected and HIV-infected women participating in the study (Figure 1). Anal HPV types of the genus Alphapapillomavirus (97.4%; 38/39) and Betapapillomavirus (2.6%; 1/39) are presented in Figure 1, where we also included the predominant tissue associations and the typical relationships between HPV type and disease, as proposed in [12,16].

3.3. Anal hrHPV and Sociodemographic Characteristics of HIV-Uninfected and HIV-Infected Women in the Tapajós Region, Amazon, Brazil

The groups of HIV-uninfected women (n = 112) and HIV-infected women (n = 41) were further analyzed according to the presence or absence of anal hrHPV, based on sociodemographic characteristics. Among HIV-uninfected women, most of those with anal hrHPV had more than four lifetime sexual partners (p = 0.040) and cervical HPV (p = 0.045), whereas among HIV-infected women, only cervical hrHPV was significantly associated with anal hrHPV (p ≤ 0.001). The practice of anal sex was not significant for the occurrence of anal hrHPV in both groups of women infected and not with HIV (Table 2).

3.4. Single and Multiple Anal HPV Infections and HPV Types in HIV-Uninfected and HIV-Infected Women

Among the HIV-uninfected women, 97.0% (34/35) had single anal HPV infections, and 3.0% (1/35) had multiple anal HPV infections. In HIV-infected women, multiple anal HPV infections were much more prevalent, at 85.0% (34/40), and single anal HPV infections accounted for 15.0% (6/40).
Anal HPV types found in the participants were predominantly of the genus Alphapapillomavirus. Based on the oncogenic risk classification, the HPV samples were grouped into high-risk, “probable” or “possible” carcinogenic, and low-risk groups (Figure 2). Anal hrHPV infections were significantly more prevalent in HIV-infected women than in HIV-uninfected women (Chi-square test p < 0.001).
The overall prevalence of hrHPV was 42.9% (15/35) among HIV-uninfected women and 75.0% (30/40) among HIV-infected women. HPV18 (n = 6) and HPV16 (n = 5) were the most frequent anal hrHPV types in HIV-uninfected women, representing 73.3% (11/15) of the total anal hrHPV types genotyped in this group. The most frequent anal hrHPV types in HIV-infected women were HPV51 (n = 12), HPV59 (n = 10), HPV31 (n = 9), and HPV58 (n = 9).
All HIV-infected women were on combination antiretroviral therapy (cART). There was no significant association between anal hrHPV infection, median HIV viral load (Mann–Whitney test p = 0.110), and median CD4+ counts (Mann–Whitney test p = 0.828). Pearson’s correlation test shows that HIV-infected women with lower CD4+ counts do not carry a significantly higher number of distinct anal hrHPV types (rô = −0.179; p = 0.262).

3.5. Anal Non-HPV STIs in HIV-Uninfected and HIV-Infected Women

Anal non-HPV STIs were identified in 15.2% (17/112) of HIV-uninfected women and 7.3% (3/41) of HIV-infected women (Figure 3). The prevalence of CT, NG, MG, TV, and HSV-2 in the anal compartment of HIV-uninfected and HIV-infected women has already been published elsewhere [7].

3.6. Concordance between Anal and Genital HPV and Non-HPV STIs in HIV-Uninfected and HIV-Infected Women

Genital HPV infection and other STIs observed in the groups of women included in the present study have already been published by our group [8,9,10]. The comparison between the anal and genital microbiota of all women revealed differences between the HPV types and non-HPV STIs isolated from the anal and cervical scrapings collected simultaneously from the same patient (Figure 3). The Kappa test was performed for concordance analysis between anal and genital HPV infection and non-HPV STIs in HIV-uninfected and HIV-infected women. We categorized the absence and presence of high- and low-risk HPV types, the absence or presence of non-HPV STIs, and the absence and presence of the most frequent anal hrHPV types to perform the proposed Kappa test (Table 3). The concordance analysis was fair for CT, MG, and HSV-2, with Kappa values of 0.26, 0.23, and 0.35, respectively; moderate for HPV, considering the oncogenic risk classification, with a Kappa value of 0.44; and in almost perfect agreement for NG, with a Kappa value of 0.85 (Table 3). The Kappa test could not be conducted for TV due to a lack of agreement in the positive results across samples from the same women. Considering the most frequent anal hrHPV types for all women participants, the concordance analysis was poor for HPV16 (Kappa value 0.18), fair for HPV18 (Kappa value 0.34) and HPV31 (Kappa value 0.38), moderate for HPV58 (Kappa value 0.57), and HPV59 (Kappa value 0.41) and substantial for HPV51 (Kappa value 0.78) (Table 3). By group, for HIV-uninfected women, the concordance analysis was no agrément for HPV16 (Kappa value −0.05) and fair for HPV18 (Kappa value 0.37), and for HIV-infected women, fair for HPV31 (Kappa value 0.32) and HPV59 (Kappa value 0.29) and substantial for HPV51 (Kappa value 0.71) and HPV58 (Kappa value 0.69) (Table 3).

4. Discussion

In the present study, a high overall prevalence of anal HPV infection was identified in both HIV-uninfected (31.3%) and HIV-infected (97.6%) women living in the Tapajós region, higher than the national prevalence of anal HPV infection (25.68%) [17]. Moreover, greater diversity and multiplicity of anal HPV genotypes, including the Betapillomavirus genus, were detected (Figure 1).
Our earlier analyses revealed that this cohort of women had a high prevalence of cervical HPV infection, hrHPV, and other STIs [8,9,10]. However, the presence of cervical dysplasias (cervical intraepithelial lesions) did not differ significantly among them [8] and is close to that found in women with abnormal cytology (54.2%) referred to a colposcopy/cervical pathology clinic in Greece [18].
In this study, a high overall prevalence of anal HPV infection was identified in HIV-uninfected and HIV-infected women. However, the prevalence of anal hrHPV infection, despite the practice of anal sex, did not differ significantly among the participants (Table 1). Furthermore, having cervical hrHPV was significantly associated with the presence of anal hrHPV in both HIV-uninfected and HIV-infected groups (Table 2). These findings corroborate the hypothesis that the transmission of HPV between the anus and cervix and vice versa is common in women [3], and there is a high risk of acquiring an anal HPV infection after cervical infection with HPV of the same genotype, which can occur independently of anal sex intercourse [19,20]. Cervical hrHPV infection is a risk factor for acquiring anal hrHPV infection in women with or without cervical intraepithelial lesions, although the prevalence of anal and cervical hrHPV infection identified in this study was very similar, being 42.9% and 47.9% for HIV-uninfected women and 75.0% and 77.5% for HIV-infected women, respectively [21,22].
No significant association was found between anal hrHPV infection and median HIV viral load or median CD4+ count. Although lower CD4+ counts did not lead to a significantly higher number of distinct anal hrHPV types, anal hrHPV infections were significantly more prevalent in HIV-infected women than in HIV-uninfected women (Chi-square test p < 0.001). Persistent hrHPV infection is directly associated with cancer development due to the accumulation of alterations in numerous cellular processes, including DNA repair, angiogenesis, or apoptosis caused by the viral oncogenes E6 and E7 [23,24]. In addition, immunosuppression associated with HIV infection and other STIs makes it difficult to control oncogenic viral processes, increasing the risk of hrHPV-associated anal cancer [25]. High diversity and multiplicity of HPV types in HIV-uninfected and HIV-infected women were identified in anal samples, moderate concordance between anal and genital HPV in the two groups of women was identified (Kappa value 0.44) and variable concordance between anal and genital HPV in the most frequent anal hrHPV types among all participants and by group of women (Table 3). The high diversity and multiplicity of HPV types in anal samples and moderate concordance between anal and genital HPV observed in this study are important because these women were screened simultaneously with a molecular test to detect HPV DNA by conventional PCR, multiplex assays and nucleotide sequencing of the anal and genital samples, which suggests that at different times in life, these women may have contracted different HPV genotypes. Thus, the results do not simply reflect the concomitant or consecutive transmission between the anus and cervix. A fair concordance between anal and genital non-HPV STIs in HIV-uninfected and HIV-infected women was also identified. This result aligns with previous findings because CT, MG, and HSV-2 (Kappa values of 0.26, 0.23, and 0.35, respectively) have higher tropism for cervical epithelial cells, considering the natural history of the disease [26,27].
Our study has some limitations. The cross-sectional epidemiological design does not allow the temporal relationship between exposure and effect to be established, making it difficult to establish a causal relationship. The impediment to performing the Kappa test for concordance analysis for TV and the difficulty in interpreting the results of non-HPV STIs may have occurred due to the low prevalence of other STIs, potentially influenced by the sample size. In addition, as a limitation for performing the Kappa test for concordance analyses, we categorized HPV types as high- and low-risk and the most frequent anal hrHPV types, rather than HPV genotypes, due to the great variability of HPV types observed in both groups, which would reduce the statistical power of the comparative analyses. This is a limitation of this type of comparative study when there is a great diversity of identified HPV genotypes.
This high prevalence of anal HPV and hrHPV infections and the high diversity and multiplicity of HPV types identified in HIV-uninfected and HIV-infected women in the Tapajós region add to the growing body of evidence published in the scientific literature that the high prevalence and long-term persistence of HPV infection is a hereditary characteristic of the prehistoric people of the Amazon [8,28,29]. Those living farther away from the Amazon urban centers are more likely to be infected by hrHPV.
Recent studies have suggested that hrHPV infection is a sufficient cause of anal intraepithelial lesions and anal cancer [23,24,30]. However, others have suggested that HPV high intrahost mutation rates are associated with the anatomical site, HIV coinfection, and the possibility of syndemic interactions [25,30,31]. Further studies on the anogenital microbiome could expand our knowledge about HPV, carcinogenesis, and the role of cofactors in this process, such as non-HPV STIs, including HIV.
The early onset of sexual activity (sex at the age of 17 years or under), a high number of pregnancies (3.4 gestations on average), the number of sexual partners (up to four sexual partners in life), and the nonuse of condoms are possibly the main risk factors related to the high prevalence and diversity of anal HPV types identified in the two groups of women included in the present study. Social factors, such as difficult access to communities and lack of access to basic public health services, have a higher impact on the consequences of long-term persistent anal HPV infection for women. Cultural and behavioral factors, such as low frequency of condom usage and limited hygienic conditions, might explain recurrent infections associated with high HPV prevalence and diversity [32]. In addition, the high prevalence of anal HPV and hrHPV found in this study may be related to the high sensitivity and specificity of the laboratory techniques used for HPV genotyping, as already mentioned in [8].
In agreement with the literature [1,7,33], HPV16 and HPV18 were the most prevalent anal hrHPV types found in HIV-uninfected women. The Ts group of women also had a high prevalence of HPV16 and HPV18 in their cervicovaginal specimens [8]. It may be essential to pay attention to the hypothesis raised by systematic reviews and meta-analyses that HIV-uninfected women with cervical HPV16, especially those older than 45 years, have a similar anal cancer risk profile to that of HIV-infected women [1,7,33]. Therefore, these women are high-risk target groups for secondary anal cancer prevention.
The most frequent anal hrHPV types identified in HIV-infected women included in our study were HPV51, HPV59, HPV31, and HPV58, which are HPV types not covered by the 4-valent or 2-valent HPV vaccines available in Brazil. HPV16, followed by HPV18, are the types most related to anal cancer; however, HPV31, HPV33, HPV45, HPV52, and HPV58 were extracted from the nonHPV16 fraction and are possibly associated with anal cancer [27]. This study reinforces the detection of HPV31 and HPV58 as described in other studies in the anus [27] and described in the literature as a nonHPV16 fraction possibly attributed to anal cancer and further verifies the relationship between HPV51 and HPV59 types that can be attributed to anal cancer. Therefore, these HPV types should be considered for incorporation into a broad-spectrum vaccine for HPV types of clinical importance. To our knowledge, this is the first study on anal HPV infection that compared the concordance between anal and genital infection with HPV and non-HPV STIs on the prevalence and genotyping of anal HPV and the concordance with genital infection in the general population of women in northern Brazil [17]. Compared to HIV-infected women living in other populations [31,34], those living in the Tapajós region have different types of circulating anal hrHPV types with greater diversity and multiplicity of anal HPV types, despite taking cART, being clinically and immunologically well and exhibiting virological suppression. Understanding whether the different types of HPV are acquired independently of one another has implications for the natural history of HPV-related disease and the effectiveness of the prophylactic HPV vaccine. Considering the antagonism or synergism between the viral types in the infection of target tissues would improve the replacement of vaccine types with competing species [20].
The Tapajós region, Amazon, located in northern Brazil, has the highest cervical cancer incidence and mortality rates among women in a national ranking. It is necessary to consider reviewing and updating public health policies on cervical cancer screening and furthering the fight against HIV/AIDS and other STIs. New technologies are warranted for screening and achieving early diagnoses, such as alternative self-collection samples for HPV and non-HPV STIs and DNA testing based on nucleic acid amplification assays (NAATs). Altogether, these approaches might enable a better assessment of cervical screening results to stratify anal cancer risk in high-risk groups, irrespective of HIV status, and to expand cancer screening services to populations in limited-resource settings and remote geographical regions.

5. Conclusions

Overall, the prevalence of anal HPV infection is high in HIV-uninfected and HIV-infected women living in the Tapajós region of the Amazon. We identified a much higher prevalence rate of anal HPV and hrHPV than those reported in the literature for the Brazilian population, with different types of hrHPV not included in the 4-valent HPV vaccine. There was a greater diversity and multiplicity of anal HPV types, particularly in HIV-infected women. Moderate and fair concordance between anal and genital HPV infection and non-HPV STIs were identified, respectively. We encourage public health care officials to consider stratifying anal cancer risk in high-risk groups, irrespective of HIV status, when assessing cervical screening results, particularly in regions where there is a high prevalence of anal HPV and hrHPV infection with high diversity and multiplicity of types.

Author Contributions

Conceptualization, L.L.S.R., J.H., A.F.N., W.M.K., C.A.G. and M.G.M.; methodology, L.L.S.R., K.G.M., N.S.C.O., C.S.-d.-J. and J.H.P.; software, L.L.S.R., K.G.M., N.S.C.O., C.S.-d.-J. and J.H.; validation, L.L.S.R., K.G.M., N.S.C.O., C.S.-d.-J. and J.H.; formal analysis, L.L.S.R., J.H.P., K.G.M., A.F.N., V.S.D.P., N.S.C.O., C.S.-d.-J., V.V.S., D.M.D.S., W.M.K., J.H., C.A.G. and M.G.M.; investigation, L.L.S.R., J.H.P., A.F.N., V.S.D.P., D.M.D.S., W.M.K., J.H. and C.A.G.; resources, J.H.P., A.F.N., V.S.D.P., T.G., W.M.K., J.H., C.A.G. and M.G.M.; data curation, L.L.S.R.; writing—original draft preparation, L.L.S.R., J.H.P., K.G.M., V.S.D.P., D.M.D.S., W.M.K., J.H., C.A.G. and M.G.M.; writing—review and editing, L.L.S.R., J.H.P., A.F.N., K.G.M., V.S.D.P., T.G., N.S.C.O., C.S.-d.-J., V.V.S., D.M.D.S., W.M.K., J.H., C.A.G. and M.G.M.; visualization, L.L.S.R.; supervision, M.G.M.; project administration, L.L.S.R., J.H.P., A.F.N. and M.G.M.; funding acquisition, L.L.S.R., A.F.N., V.S.D.P. and W.M.K. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by the Fundação Amazônia de Amparo a Estudos e Pesquisas (Fapespa)/Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), grant term number/term of grant number 012/2022; Coordination of Personal Improvement of Higher Education (capes) Foundation, Ministry of Education of Brazil, process number 88881.131796/2016-01; Programa Estratégico de Apoio a Pesquisa em Saúde (PAPES VII), Fundação Oswaldo Cruz (FIOCRUZ)/Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), grant number 401810/2015-1; CAPES-PRINT, process number 88887.571326/2020-00; and NIH, US, grant number R01 CA074397.

Institutional Review Board Statement

The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committees of the Universidade do Estado do Pará Campus XII Tapajós (protocol code 2.013.163 and date of approval, 12 April 2017) and the Instituto Oswaldo Cruz, Fundação Oswaldo Cruz (protocol code 2.121.697 and date of approval, 14 June 2017).

Informed Consent Statement

Written informed consent was obtained from the patient(s) to publish this paper.

Data Availability Statement

The data are contained within the article.

Acknowledgments

We thank all the patients participating in this study and the Federal University of Western Pará for granting leave for a doctorate to L.L.S.R. This study was financed in part by the Fundação Amazônia de Amparo a Estudos e Pesquisas (FAPESPA)/Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)—Granting term number 012/2022, and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001 to L.L.S.R. and V.S.P. The Secretaria Municipal de Saúde and Centro de Testagem e Aconselhamento of Santarém, Pará, for authorizing the recruitment of women from the health units. Miguel Moreira, senior researcher at the National Cancer Institute of Brazil for providing training in nucleotide sequencing analysis. Elena Chavez-Juan of the Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA, for technical support in the Flow Cytometry Immune Monitoring core facility, which is supported by NIH grant P30 CA 014089-46.

Conflicts of Interest

The authors declare no conflict of interest. Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy, or views of the International Agency for Research on Cancer/World Health Organization. Opinions expressed by the authors are their own and this material should not be interpreted as representing the official viewpoint of the U.S. Department of Health and Human Services, the National Institutes of Health, or the National Cancer Institute.

References

  1. Lin, C.; Slama, J.; Gonzalez, P.; Goodman, M.T.; Xia, N.; Kreimer, A.R.; Wu, T.; Hessol, N.A.; Shvetsov, Y.; Ortiz, A.P.; et al. Cervical determinants of anal HPV infection and high-grade anal lesions in women: A collaborative pooled analysis. Lancet Infect. Dis. 2019, 19, 880–891. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  2. Assi, R.; Hashim, P.W.; Reddy, V.B.; Einarsdottir, H.; Longo, W.E. Sexually transmitted infections of the anus and rectum. World J. Gastroenterol. 2014, 20, 15262–15268. [Google Scholar] [CrossRef] [PubMed]
  3. Moscicki, A.-B.; Schiffman, M.; Burchell, A.; Albero, G.; Giuliano, A.R.; Goodman, M.T.; Kjaer, S.K.; Palefsky, J. Updating the Natural History of Human Papillomavirus and Anogenital Cancers. Vaccine 2012, 30, F24–F33. [Google Scholar] [CrossRef] [Green Version]
  4. van Eer, K.; Laâbi, I.; van Benthem, B.H.B.; Steenbergen, R.D.M.; King, A.J.; Adema, D.; Buist-Arkema, R.; Beerens, A.; Luijt, D.; Meijer, S.; et al. The association between viral load and concurrent human papillomavirus infection at the genital and anal sites of young women and the impact of vaccination. Tumour Virus Res. 2022, 13, 200233. [Google Scholar] [CrossRef]
  5. Morhason-Bello, I.O.; Baisley, K.; Pavon, M.A.; Adewole, I.F.; Bakare, R.; de Sanjosé, 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. Agents Cancer 2021, 16, 59. [Google Scholar] [CrossRef]
  6. Crawford, R.; Grignon, A.-L.; Kitson, S.; Winder, D.M.; Ball, S.L.R.; Vaughan, K.; Stanley, M.A.; Sterling, J.C.; Goon, P.K.C. High prevalence of HPV in non-cervical sites of women with abnormal cervical cytology. BMC Cancer 2011, 11, 473. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  7. Wei, F.; Xia, N.; Ocampo, R.; Goodman, M.T.; Hessol, N.A.; Grinsztejn, B.; Ortiz, A.P.; Zhao, F.; Kojic, E.M.; Kaul, R.; et al. Age-Specific Prevalence of Anal and Cervical Human Papillomavirus Infection and High-Grade Lesions in 11 177 Women by Human Immunodeficiency Virus Status: A Collaborative Pooled Analysis of 26 Studies. J. Infect. Dis. 2022, 227, 488–497. [Google Scholar] [CrossRef]
  8. Rodrigues, L.L.S.; Morgado, M.G.; Sahasrabuddhe, V.V.; De Paula, V.S.; Oliveira, N.S.; Chavez-Juan, E.; Da Silva, D.M.; Kast, W.M.; Nicol, A.F.; Pilotto, J.H. Cervico-vaginal self-collection in HIV-infected and uninfected women from Tapajós region, Amazon, Brazil: High acceptability, hrHPV diversity and risk factors. Gynecol. Oncol. 2018, 151, 102–110. [Google Scholar] [CrossRef]
  9. Rodrigues, L.L.S.; Pilotto, J.H.; Lima, L.R.P.; Gaydos, C.A.; Hardick, J.; Morgado, M.G.; Martinelli, K.G.; de Paula, V.S.; Nicol, A.F. Self-collected versus clinician-collected samples for HSV-2 and HSV-2/HPV screening in HIV-infected and -uninfected women in the Tapajós region, Amazon, Brazil. Int. J. STD AIDS 2019, 30, 1055–1062. [Google Scholar] [CrossRef]
  10. Rodrigues, L.L.S.; Hardick, J.; Nicol, A.F.; Morgado, M.G.; Martinelli, K.G.; de Paula, V.S.; Pilotto, J.H.; Gaydos, C.A. Sexually transmitted infections among HIV-infected and HIV-uninfected women in the Tapajós region, Amazon, Brazil: Self-collected vs. clinician-collected samples. PLoS ONE 2019, 14, e0215001. [Google Scholar] [CrossRef] [Green Version]
  11. Cornall, A.M.; Poljak, M.; Garland, S.M.; Phillips, S.; Tan, J.H.; Machalek, D.A.; Quinn, M.A.; Tabrizi, S.N. Anyplex II HPV28 detection and Anyplex II HPV HR detection assays are highly concordant with other commercial assays for detection of high-risk HPV genotypes in women with high grade cervical abnormalities. Eur. J. Clin. Microbiol. Infect. Dis. 2017, 36, 545–551. [Google Scholar] [CrossRef]
  12. Doorbar, J.; Quint, W.; Banks, L.; Bravo, I.G.; Stoler, M.; Broker, T.R.; Stanley, M.A. The Biology and Life-Cycle of Human Papillomaviruses. Vaccine 2012, 30 (Suppl. 5), F55–F70. [Google Scholar] [CrossRef] [PubMed]
  13. Schmitt, M.; Dondog, B.; Waterboer, T.; Pawlita, M.; Tommasino, M.; Gheit, T. Abundance of Multiple High-Risk Human Papillomavirus (HPV) Infections Found in Cervical Cells Analyzed by Use of an Ultrasensitive HPV Genotyping Assay. J. Clin. Microbiol. 2010, 48, 143–149. [Google Scholar] [CrossRef] [Green Version]
  14. Gheit, T.; Billoud, G.; de Koning, M.N.C.; Gemignani, F.; Forslund, O.; Sylla, B.S.; Vaccarella, S.; Franceschi, S.; Landi, S.; Quint, W.G.V.; et al. Development of a Sensitive and Specific Multiplex PCR Method Combined with DNA Microarray Primer Extension to Detect Betapapillomavirus Types. J. Clin. Microbiol. 2007, 45, 2537–2544. [Google Scholar] [CrossRef] [Green Version]
  15. Landis, J.R.; Koch, G.G. The Measurement of Observer Agreement for Categorical Data. Biometrics 1977, 33, 159–174. [Google Scholar] [CrossRef] [Green Version]
  16. Egawa, N.; Doorbar, J. The low-risk papillomaviruses. Virus Res. 2017, 231, 119–127. [Google Scholar] [CrossRef]
  17. Colpani, V.; Falcetta, F.S.; Bidinotto, A.B.; Kops, N.L.; Falavigna, M.; Hammes, L.S.; Benzaken, A.S.; Maranhão, A.G.K.; Domingues, C.M.A.S.; Wendland, E.M. Prevalence of human papillomavirus (HPV) in Brazil: A systematic review and meta-analysis. PLoS ONE 2020, 15, e0229154. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  18. 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, 22–29. [Google Scholar] [CrossRef]
  19. Goodman, M.T.; Shvetsov, Y.B.; McDuffie, K.; Wilkens, L.R.; Zhu, X.; Thompson, P.J.; Ning, L.; Killeen, J.; Kamemoto, L.; Hernandez, B.Y. Sequential Acquisition of Human Papillomavirus (HPV) Infection of the Anus and Cervix: The Hawaii HPV Cohort Study. J. Infect. Dis. 2010, 201, 1331–1339. [Google Scholar] [CrossRef]
  20. Goodman, M.T.; McDuffie, K.; Hernandez, B.Y.; Wilkens, L.R.; Zhu, X.; Thompson, P.J.; Killeen, J.; Kamemoto, L.; Shvetsov, Y.B. The Influence of Multiple Human Papillomavirus Types on the Risk of Genotype-Concordant Incident Infections of the Anus and Cervix: The Hawaii HPV Cohort Study. J. Infect. Dis. 2011, 203, 335–340. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  21. Melo, K.M.R.L.; Eleutério Junior, J.; Peixoto, R.A.C.; Rebouças, K.C.F.; Eleutério, R.M.N. Anal High-risk HPV and Liquid-based Cytology of Immunocompetent Brazilian Women with Genital High-risk HPV. Rev. Bras. De Ginecol. E Obstet. 2022, 44, 280–286. [Google Scholar] [CrossRef]
  22. Bregar, A.J.; Cronin, B.; Luis, C.; DiSilvestro, P.; Schechter, S.; Pisharodi, L.; Raker, C.; Clark, M.; Robison, K. Anal and Cervical High-Risk Human Papillomavirus Genotyping in Women with and without Genital Neoplasia. J. Low. Genit. Tract Dis. 2018, 22, 115–119. [Google Scholar] [CrossRef]
  23. Burger, E.A.; De Kok, I.M.C.M.; Groene, E.; Killen, J.; Canfell, K.; Kulasingam, S.; Kuntz, K.M.; Matthijsse, S.; Regan, C.; Simms, K.T.; et al. Estimating the Natural History of Cervical Carcinogenesis Using Simulation Models: A CISNET Comparative Analysis. J. Natl. Cancer Inst. 2020, 112, 955–963. [Google Scholar] [CrossRef] [PubMed]
  24. Szymonowicz, E.A.K.A.; Chen, J. Biological and clinical aspects of HPV-related cancers. Cancer Biol. Med. 2020, 17, 864–878. [Google Scholar] [CrossRef] [PubMed]
  25. Wang, C.C.J.; Palefsky, J.M. HPV-Associated Anal Cancer in the HIV/AIDS Patient. Cancer Treat. Res. 2019, 177, 183–209. [Google Scholar] [CrossRef]
  26. Abdelsamed, H.; Peters, J.; Byrne, G.I. Genetic variation in Chlamydia trachomatis and their hosts: Impact on disease severity and tissue tropism. Future Microbiol. 2013, 8, 1129–1146. [Google Scholar] [CrossRef] [Green Version]
  27. Juliana, N.C.A.; Omar, A.M.; Pleijster, J.; Aftab, F.; Uijldert, N.B.; Ali, S.M.; Ouburg, S.; Sazawal, S.; Morré, S.A.; Deb, S.; et al. The Natural Course of Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, and Mycoplasma genitalium in Pregnant and Post-Delivery Women in Pemba Island, Tanzania. Microorganisms 2021, 9, 1180. [Google Scholar] [CrossRef]
  28. Fonseca, A.J.; Taeko, D.; Chaves, T.A.; Amorim, L.D.D.C.; Murari, R.S.W.; Miranda, A.E.; Chen, Z.; Burk, R.D.; Ferreira, L.C.L. HPV Infection and Cervical Screening in Socially Isolated Indigenous Women Inhabitants of the Amazonian Rainforest. PLoS ONE 2015, 10, e0133635. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  29. Duarte, D.V.; Vieira, R.C.; de Brito, E.B.; Pinheiro, M.D.C.N.; Monteiro, J.D.S.V.; Valente, M.D.R.; Ishikawa, E.A.Y.; Fuzii, H.T.; de Sousa, M.S. Prevalence of Human Papillomavirus Infection and Cervical Cancer Screening among Riverside Women of the Brazilian Amazon. Rev. Bras. De Ginecol. E Obs. RBGO Gynecol. Obstet. 2017, 39, 350–357. [Google Scholar] [CrossRef] [Green Version]
  30. McCloskey, J.C.; Martin Kast, W.; Flexman, J.P.; McCallum, D.; French, M.A.; Phillips, M. Syndemic synergy of HPV and other sexually transmitted pathogens in the development of high-grade anal squamous intraepithelial lesions. Papillomavirus Res. 2017, 4, 90–98. [Google Scholar] [CrossRef]
  31. Dube Mandishora, R.S.; Gjøtterud, K.S.; Lagström, S.; Stray-Pedersen, B.; Duri, K.; Chin’Ombe, N.; Nygård, M.; Christiansen, I.K.; Ambur, O.H.; Chirenje, M.Z.; et al. Intra-host sequence variability in human papillomavirus. Papillomavirus Res. 2018, 5, 180–191. [Google Scholar] [CrossRef]
  32. Ranjeva, S.L.; Baskerville, E.B.; Dukic, V.; Villa, L.L.; Lazcano-Ponce, E.; Giuliano, A.R.; Dwyer, G.; Cobey, S. Recurring infection with ecologically distinct HPV types can explain high prevalence and diversity. Proc. Natl. Acad. Sci. USA 2017, 114, 13573–13578. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  33. Lin, C.; Franceschi, S.; Clifford, G.M. Human papillomavirus types from infection to cancer in the anus, according to sex and HIV status: A systematic review and meta-analysis. Lancet Infect. Dis. 2018, 18, 198–206. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  34. Jalil, E.M.; Wilson, E.C.; Monteiro, L.; de Velasque, L.S.; Cristina Ferreira, A.G.; Nazer, S.C.; Friedman, R.K.; Veloso, V.G.; Eduardo Levi, J.; Grinsztejn, B. High prevalence of anal high-risk HPV infection among transwomen: Estimates from a Brazilian RDS study. J. Int. AIDS Soc. 2021, 24, e25691. [Google Scholar] [CrossRef] [PubMed]
Viruses 15 01328 g001 550
Figure 1. Representative diversity of anal HPV genotypes by genus, with Alphapapillomavirus and Betapapillomavirus identified in HIV-uninfected and HIV-infected women, and the predominant tissue associations and typical relationships between HPV type and disease caused as proposed in [12,16].
Figure 1. Representative diversity of anal HPV genotypes by genus, with Alphapapillomavirus and Betapapillomavirus identified in HIV-uninfected and HIV-infected women, and the predominant tissue associations and typical relationships between HPV type and disease caused as proposed in [12,16].
Viruses 15 01328 g001
Viruses 15 01328 g002 550
Figure 2. Diversity of anal HPV types isolated from HIV-uninfected and HIV-infected women. The columns are not organized by paired samples from the same women but according to the oncogenic risk classification of Alphapapillomavirus. The high-risk HPV types are shown in red, “probable” or “possible” carcinogenic in yellow, and low-risk in blue. Betapapillomavirus is shown in green.
Figure 2. Diversity of anal HPV types isolated from HIV-uninfected and HIV-infected women. The columns are not organized by paired samples from the same women but according to the oncogenic risk classification of Alphapapillomavirus. The high-risk HPV types are shown in red, “probable” or “possible” carcinogenic in yellow, and low-risk in blue. Betapapillomavirus is shown in green.
Viruses 15 01328 g002
Viruses 15 01328 g003 550
Figure 3. Comparison between the anal and genital HPV types and non-HPV STIs isolated from anal and cervical scrapings collected simultaneously from the same patient. The columns are organized by paired samples from the same women.
Figure 3. Comparison between the anal and genital HPV types and non-HPV STIs isolated from anal and cervical scrapings collected simultaneously from the same patient. The columns are organized by paired samples from the same women.
Viruses 15 01328 g003
Table
Table 1. Main sociodemographic characteristics of HIV-uninfected and HIV-infected women in the Tapajós region, Amazon, Brazil.
Table 1. Main sociodemographic characteristics of HIV-uninfected and HIV-infected women in the Tapajós region, Amazon, Brazil.
VariablesHIV-Uninfected n = 112 (%)HIV-Infected n = 41 (%)Total N = 153 (%)p-Value *
Age range (years) 0.242
  ≤2008 (7.1)05 (12.2)13 (8.5)
  21–3036 (32.1)08 (19.5)44 (28.8)
  ≥3168 (60.7)28 (68.3)96 (62.7)
Marital status 0.006
  Single36 (32.7)23 (57.5)59 (39.3)
  Married/living together74 (67.3)17 (42.5)91 (60.7)
Number of pregnancies3.0 (±2.3)4.3 (± 5.7)3.4 (± 3.5)0.050 #
Age at first sexual intercourse (years) 0.052
  ≤1771 (64.0)33 (80.5)104 (68.4)
  ≥18 40 (36.0)08 (19.5)48 (31.6)
Number of sexual partners 0.012
  1–357 (51.4)11 (28.2)68 (45.3)
  ≥454 (48.6)28 (71.8)82 (54.7)
Regular use of condoms 0.010
  Yes 13 (11.7)12 (29.3)25 (16.4)
  No 98 (88.3)29 (70.7)127 (83.6)
Anal sex practice 0.457
  Yes 67 (60.4)22 (53.7)89 (58.6)
  No 44 (39.6)19 (46.3)63 (41.4)
* Chi-square test result. # T-student test result.
Table
Table 2. Anal high-risk HPV according to sociodemographic characteristics of HIV-uninfected and HIV-infected women in the Tapajós region, Amazon, Brazil.
Table 2. Anal high-risk HPV according to sociodemographic characteristics of HIV-uninfected and HIV-infected women in the Tapajós region, Amazon, Brazil.
VariablesAnal hrHPV
Yes
N (%)		No
N (%)		Total (%)p-Value *
HIV-uninfected (n = 112)
Age range (years) 0.510
  ≤200 (0.0)08 (8.2)08 (7.1)
  21–3005 (33.3)31 (32.0)36 (32.1)
  ≥3110 (66.7)58 (59.8)68 (60.7)
Marital status 0.560
  Single06 (40.0)30 (31.6)36 (32.7)
  Married/ living together09 (60.0)65 (68.4)74 (67.3)
Age of first sexual intercourse (years) 0.164
  ≤1712 (80.0)59 (61.5)71 (64.0)
  ≥18 03 (20.0)37 (38.5)40 (36.0)
Number of sexual partners 0.040
  1–304 (26.7)53 (55.2)57 (51.4)
  ≥411 (73.3)43 (44.8)54 (48.6)
Regular use of condoms 0.050
  Yes 04 (26.7)09 (9.4)13 (11.7)
  No 11 (73.3)87 (90.6)98 (88.3)
Anal sex practice 0.591
  Yes 10 (66.7)57 (59.4)67 (60.4)
  No 05 (33.3)39 (40.6)44 (39.6)
Cervical hrHPV 0.045
  Yes 06 (40.0)17 (17.5)23 (20.5)
  No 09 (60.0)80 (82.5)89 (79.5)
HIV-infected (n = 41)
Age range (years) 0.916
  ≤2004 (13.3)01 (9.1)05 (12.2)
  21–3006 (20.0)02 (18.2)08 (19.5)
  ≥3120 (66.7)08 (72.7)28 (68.3)
Marital status 0.730
  Single16 (55.2)07 (63.6)23 (57.5)
  Married/ living together13 (44.8)04 (36.4)17 (42.5)
Age of first sexual intercourse (years) 0.412
  ≤1723 (76.7)10 (90.9)33 (80.5)
  ≥18 07 (23.3)01 (9.1)08 (19.5)
Number of sexual partners 0.935
  1–308 (28.6)03 (27.3)68 (45.3)
  ≥420 (71.4)08 (72.7)82 (54.7)
Regular use of condoms 0.701
  Yes 08 (26.7)04 (36.4)12 (29.3)
  No 22 (73.3)07 (63.6)29 (70.7)
Anal sex practice 0.524
  Yes 17 (56.7)05 (45.5)22 (53.7)
  No 13 (43.3)06 (54.5)19 (46.3)
Cervical hrHPV 0.001
  Yes 27 (90.0)04 (36.4)31 (75.6)
  No 03 (10.0)07 (63.6)10 (24.4)
* Chi-square test result.
Table
Table 3. Concordance of anal and genital HPV, non-HPV STIs, and the most frequent anal high-risk HPV types isolated from HIV-uninfected and HIV-infected women using the Kappa test.
Table 3. Concordance of anal and genital HPV, non-HPV STIs, and the most frequent anal high-risk HPV types isolated from HIV-uninfected and HIV-infected women using the Kappa test.
STIsHPVCTNGMGHSV-2TV
All participants (N = 153)
Agreement 66.01%84.96%99.34%96.07%95.42%- *
Positive101/153130/153152/153147/153146/153- *
Kappa
(95% CI)		0.44
(0.33–0.56)		0.26
(0.05–0.47)		0.85
(0.45–1.00)		0.23
(−0.03–0.66)		0.35
(0.00–0.72)		- *
p-value<0.0010.001<0.0010.003<0.001- *
HIV-uninfected (n = 112) - *
Agreement 61.61%84.82%99.10%95.53%94.64%- *
Positive69/11295/112111/112107/112106/112- *
Kappa
(95% CI)		0.22
(0.07–0.37)		0.29
(0.02–0.51)		0.66
(0.04–1.00)		0.26
(−0.04–0.66)		0.24
(0.00–0.66)		- *
p-value0.0020.002<0.0010.005<0.001- *
HIV-infected (n = 41) - *
Agreement 78.05%85.36%100%- *97.56%- *
Positive32/4135/4141/41- *40/41- *
Kappa
(95% CI)		0.45
(0.16–0.72)		0.22
(0.0–0.64)		1.00 - *0.65
(0.00–1.00)		- *
p-value0.0010.026<0.001- *<0.001- *
The most frequent anal hrHPV typesHPV16HPV18HPV31HPV51HPV58HPV59
All participants (N = 153)
Agreement 88.23%93.46%92.81%96.73%94.77%93.46%
Positive135/153143/153142/153148/153145/153143/153
Kappa
(95% CI)		0.18
(−0.57–0.44)		0.34
(−0.03–0.61)		0.38
(0.06–0.65)		0.78
(0.56–0.94)		0.57
(0.25–0.81)		0.41
(0.07–0.68)
p-value0.018<0.001<0.001<0.001<0.001<0.001
HIV-uninfected (n = 112)
Agreement 89.28%94,64%
Positive100/112106/112
Kappa
(95% CI)		−0.05
(−0.08–0.16)		0.37
(−0.03–0.78)
p-value0.555<0.001
HIV-infected (n = 41)
Agreement 80.48%87.80%90.24%75.60%
Positive 33/4136/4137/4131/41
Kappa
(95% CI)		 0.32
(−0.84–0.66) 		0.71
(0.43–0.93)		0.69
(0.32–0.93)		0.29
(−0.09–0.62)
p-value 0.028<0.001<0.0010.06
* It was not possible to perform the Kappa test because there was no agreement between the positive test and the molecular detection results from samples from the same woman. CT = Chlamydia trachomatis, NG = Neisseria gonorrheae, MG = Mycoplasma genitalium, HSV-2 = herpes simplex virus 2, and TV = Trichomonas vaginalis.
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.

Share and Cite

MDPI and ACS Style

Rodrigues, L.L.S.; Pilotto, J.H.; Martinelli, K.G.; Nicol, A.F.; De Paula, V.S.; Gheit, T.; Oliveira, N.S.C.; Silva-de-Jesus, C.; Sahasrabuddhe, V.V.; Da Silva, D.M.; et al. Diversity of Anal HPV and Non-HPV Sexually Transmitted Infections and Concordance with Genital Infections in HIV-Infected and HIV-Uninfected Women in the Tapajós Region, Amazon, Brazil. Viruses 2023, 15, 1328. https://doi.org/10.3390/v15061328

AMA Style

Rodrigues LLS, Pilotto JH, Martinelli KG, Nicol AF, De Paula VS, Gheit T, Oliveira NSC, Silva-de-Jesus C, Sahasrabuddhe VV, Da Silva DM, et al. Diversity of Anal HPV and Non-HPV Sexually Transmitted Infections and Concordance with Genital Infections in HIV-Infected and HIV-Uninfected Women in the Tapajós Region, Amazon, Brazil. Viruses. 2023; 15(6):1328. https://doi.org/10.3390/v15061328

Chicago/Turabian Style

Rodrigues, Luana Lorena Silva, José Henrique Pilotto, Katrini Guidolini Martinelli, Alcina F. Nicol, Vanessa Salete De Paula, Tarik Gheit, Nathália Silva Carlos Oliveira, Carlos Silva-de-Jesus, Vikrant V. Sahasrabuddhe, Diane M. Da Silva, and et al. 2023. "Diversity of Anal HPV and Non-HPV Sexually Transmitted Infections and Concordance with Genital Infections in HIV-Infected and HIV-Uninfected Women in the Tapajós Region, Amazon, Brazil" Viruses 15, no. 6: 1328. https://doi.org/10.3390/v15061328

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop