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Risk factors for cervical HPV infection and genotypes distribution in HIV-infected South Brazilian women

Risk factors for cervical HPV infection and genotypes distribution in HIV-infected South... Background: Human Papillomavirus (HPV) infection is particularly burdensome for women infected with human immunodeficiency virus (HIV), which increases their risk of developing cervical lesions and cancer (CC). We conducted a molecular study of the distribution of cervical HPV genotypes and the risk factors for this infection in HIV-infected Brazilian women. Findings: Cervical and endocervical samples for Papanicolaou screening and HPV detection were collected from 178 HIV-infected women using highly active antiretroviral therapy (HAART) of Maringá city/Brazil. Risk factors were assessed using a standardized questionnaire, and the data regarding to HIV infection from medical records. HPV was detected by polymerase chain reaction (PCR), and genotyping using PCR-restriction fragment length polymorphism analysis. HIV infection was well controlled, but women with a current CD4+ T lymphocyte count between 200–350 cells/mm (37.6%) had a two-fold greater risk of HPV infection than those with > 350 cells/mm (26.4%). HPV was associated with parity ≥3, hormonal contraceptive use and current smoker. HPV infection occurred with high frequency (46.6%) but a low frequency of cervical abnormalities was detected (7.30%), mainly low-grade squamous intraephitelial cervical lesions (LSIL) (84.6%). A high frequency of multiple HPV infections was detected (23.0%), and the most frequent HPV genotype was HPV-72 (6.7%), followed by −16, -31 and -51 (6.14% each). Conclusions: We showed that HAART use does not protect HIV-infected women from HPV, but appear to exert some protection against cervical lesions development. This study provides other important information about risk factors and cervical HPV in HIV-infected women, which can contribute to planning protocols. Keywords: HIV, HPV, Genotypes, Risk factors, Cervical lesions, Cervical cancer Findings immunodeficiency virus (HIV)-infected women, as they It is estimated that in 2020, cervical cancer (CC) will be are more vulnerable to infection and are less likely to diagnosed in over 665,035 women worldwide, and 357,852 clear the virus, which increases their risk of developing will die as a result [1]. The frequency of CC is much cervical lesions and cancer. Moreover, in HIV-infected higher in underdeveloped or developing countries than it women, CC responds poorly to the recommended ther- is in developed countries [2]. In Brazil, CC is the third apies, is more aggressive, and in cases of recurrence, most common cancer among women, with 17.540 new has a worse prognosis [5]. In Brazil, approximately cases diagnosed in 2012 [3]. 180,000 HIV-positive individuals are undergoing highly The association between persistent high-risk (HR) Human active antiretroviral therapy (HAART) administered by Papillomavirus (HPV) and CC has been well established [4]. thePublicHealth System [6]. Whilethistherapy has HPV infection is particularly burdensome for human been associated with a substantial reduction in AIDS- related mortality, its role in preventing HPV infection and progression to CC is still poorly studied and con- * Correspondence: smpelloso@gmail.com troversial [6,7]. Department of Nursing, State University of Maringá, Paraná, Brazil Full list of author information is available at the end of the article © 2014 Rocha-Brischiliari et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. Rocha-Brischiliari et al. Infectious Agents and Cancer 2014, 9:6 Page 2 of 6 http://www.infectagentscancer.com/content/9/1/6 Studies have unanimously showed that HIV-infected fragment length polymorphism analysis using HpyCH4V women are more commonly infected with non-16 and [12] was performed. Co-amplification of the human β- −18 HR-HPV genotypes, such as 52 and 58 [8,9]. Given globin gene was performed, as an internal control, using that current vaccines target HPV -16/-18, these findings the following primers under the same conditions as those may have important implications for future HPV vac- used for HPV-PCR: GH20 (5’-GAAGAGCCAAGGACA cines that target other types of HPV that are associated GGTAC-3’)/PC04 (5’-CAACTTCATCCACGTTCACC-3′) with disease risk in HIV-infected women [10]. (Figure 1). Considering that epidemiological data from different Statistical analysis was performed using Open Source populations are required for public policies addressing Epidemiologic Statistics for Public Health/OpenEpi, Ver- CC prevention in HIV-infected women and that few sion 2.3.1. All variables were expressed as absolute and studies from Brazil and Latin America have collected relative frequencies. For univariate analysis, categorical these data, we conducted a molecular study of the distri- variables were compared with HPV infection by χ - bution of cervical HPV genotypes and the risk factors as- square and Fisher’s exact test. Some variables of interest sociated with this infection in HIV-infected Brazilian with p < 0.20 were selected for logistic regression ana- women. lysis. A crude odds ratio (OR) and 95% confidence inter- In total, 178 HIV-infected women using HAART, aged val (CI) were calculated. A p-value < 0.05 was considered 18 to 66 years, who attended the Specialized Assistance significant. Service (SAE) for sexually transmitted diseases (STD)/ Most HIV-infected women showed excellent control of AIDS of Maringá city/Southern Brazil, from April 1 to the HIV infection, based on HAART proper use (79.2%), October 30, 2011, were included. The inclusion criterion high current CD4+ T lymphocyte count (37.6% with 200– 3 3 required that the women had been diagnosed twice with 350 cells/mm and 26.4% with > 350 cells/mm )and low HIV/AIDS using different methods and using HAART. current viral load (58.4% < minimum limit and 38.8% be- The exclusion criteria were previous hysterectomy, current tween the minimum limit and 100 copies/ml). or recent pregnancy, age younger than 18 years, and no Univariate analysis revealed an association between history of sexual activity. HPV infection and parity ≥ 3 (p = 0.01), not undergoing Of the 424 HIV-infected women enrolled in the SAE, 100 were excluded, and a total of 324 were eligible for the study. The sample size was calculated with an HPV prevalence of 50%, confidence interval of 95%, error esti- mate of 5%. With an increase of 10% for possible partici- pant losses, the total sample size was fixed at 178 randomly selected women. The women were interviewed using a standardized questionnaire to obtain socio-economic and demographic information, obstetric and gynecologic history and data on their sexual behavior. Data regarding HIV infection were obtained from SAE medical records. A single nursing con- tacted all of the women, administered the questionnaire and collected the cervical samples. This project was ap- proved by the Committee for Ethics in Research Involving Humans at the State University of Maringá (UEM)/ Paraná, Brazil (nº 085/2011). Ecto/endocervical samples were collected with an Ayre’s spatula and cytobrush for cervical cytology (Papanicolaou screening) and polymerase chain reaction (PCR); the sam- Figure 1 Electrophoretic analysis of HPV genotyping by PCR- ples were suspended in 1 ml of 0.9% NaCl solution and restriction fragment length polymorphism analysis (PCR-RFLP) stored at -20°C. The cytological smears were sent to the using HpyCH4V in 8% polyacrylamide gel stained with Clinical Cytology Laboratory of UEM and were graded ac- ethidium bromide. Sample A1, genotype −31 (HR) in single HPV cording to the Bethesda System [11]. Genomic DNA was infection (216, 108, 94 base pairs-pb); A2, genotype −56 (HR) in single extracted using an AxyPrep™ Body Fluid Viral DNA/RNA HPV infection (244, 121 pb); A3, genotypes −13 (LR), -16 and −58 (HR) in multiple HPV infection (244, 216, 191, 103, 99, 91 e 89 pb); A4, Miniprep kit (Axygen, CA, USA). PCR amplification of genotype −51 (HR) in single HPV infection (171, 147, 137 pb); A5, HPV was carried out using the following primers: MY09 genotypes −16 (HR) and −61 (LR) on double HPV infection (216, (5’CGTCCMAARGGAWACTGATC-3’)/MY11(5’-GCMCA 191, 171, 147, 137). M, molecular weight marker (25 base pairs). GGGWCATAAYAATGG-3’). Genotyping by PCR-restriction Rocha-Brischiliari et al. Infectious Agents and Cancer 2014, 9:6 Page 3 of 6 http://www.infectagentscancer.com/content/9/1/6 Table 1 Univariate analysis of epidemiologic and HIV Table 1 Univariate analysis of epidemiologic and HIV infection data in 178 women and association with HPV infection data in 178 women and association with HPV a b (Continued) Variables n (%) HPV OR (95% CI) p value (%) Gynecologic infections Age ranges (years) (number) 18-30 28 (15.7) 60.7 1.93 (0.94-1.99) 0.13 0 55 (30.9) 40.0 1.0 31-40 60 (33.7) 43.3 0.96 (0.47-1.95) 0.89 1-2 93 (52.2) 48.4 1.41 (0.68-2.92) 0.32 > 40 90 (50.6) 44.4 1.0 ≥ 3 30 (16.9) 53.3 1.71 (0.64-4.64) 0.23 Education (years) Cigarette smoking < 8 85 (47.8) 45.9 1.69 (0.93-3.06) 0.84 Yes 35 (19.7) 65.7 2.76 (1.15-6.67) 0.01 ≥ 8 93 (52.2) 47.3 1.0 No 100 (56.2) 41.0 1.0 Marital status Ex-smoker 43 (24.1) 44.2 0.41 (0.15-1.14) 0.05 Married 93 (52.2) 45.2 1.0 Period of HIV infection (years) Unmarried 31 (17.4) 48.4 1.14 (0.46-2.77) 0.75 < 5 76 (42.7) 56.6 1.72 (0.79-3.75) 0.13 Widowed 54 (30.3) 48.1 1.13 (0.55-2.33) 0.72 5-10 51 (28.6) 35.5 0.72 (0.30-1.72) 0.41 Skin color > 10 51 (28.6) 43.1 1.0 White 114 (64.0) 42.1 1.0 HAART correct use Not white 64 (36.0) 54.7 1.66 (0.86-3.22) 0.10 Yes 141 (79.2) 46.8 1.04 (0.47-2.28) 0.92 Menarche (years) No 37 (20.8) 45.9 1.0 < 13 95 (53.4) 43.2 0.74 (0.39-1.40) 0.32 Current CD4+ ≥ 13 83 (46.6) 50.6 1.0 T lymphocyte (cells/mm ) Age of sexual debut (years) < 200 15 (8.4) 66.7 2.76 (0.81-9.92) 0.06 < 18 112 (62.9) 45.5 0.89 (0.46-1.71) 0.70 200-350 67 (37.6) 56.3 1.78 (0.76-4.16) 0.14 ≥ 18 66 (37.1) 48.5 1.0 > 350 47 (26.4) 42.0 1.0 Sexual partners CD4+ T lymphocyte (number) range (cells/mm ) 1 16 (9.0) 56.2 1.0 < 200 64 (35.9) 51.5 1.21 (0.53-2.76) 0.62 2-7 74 (41.6) 44.6 0.63 (0.18-2.10) 0.39 200-350 67 (37.6) 41.8 0.82 (0.36-1.85) 0.59 > 7 88 (49.4) 46.6 0.68 (0.20-2.22) 0.47 > 350 47 (26.4) 46.8 1.0 Parity (number) Recent viral load (copies/ml) 0 20 (11.2) 70.0 1.0 < L min 104 (58.4) 43.3 1.0 1-2 67 (37.7) 49.2 0.42 (0.12-1.35) 0.10 1-100.000 69 (38.8) 49.3 1.27 (0.66-2.46) 0.43 ≥ 3 91 (51.1) 39.6 0.28 (0.09-0.88) 0.01 > 100.000 5 (2.8) 80.0 5.24 (0.52-27.6) 0.17 History of Pap screening in the Viral load range past three years (copies/ml) Yes 143 (80.3) 42.7 1.0 1-100.000 50 (28.1) 50.0 1.0 No 35 (19.7) 62.9 2.27 (1.01-5.23) 0.03 > 100.000 128 (71.9) 45.3 0.83 (0.41-1.68) 0.57 Hormonal a Odds ratio (OR) 95% confidence interval (CI). contraceptive use b A p-value < 0.05 was considered significant. Highly active antiretroviral therapy (HAART). Yes 135 (75.9) 43.7 0.61 (0.29-1.30) 0.16 Papanicolaou secreening (Pap screening). No 43 (24.1) 55.8 1.0 Gynecologic infections Pap screening in the last 3 years (p = 0.03), current smok- Yes 127 (71.3) 48.0 1.22 (0.60-2.47) 0.55 ing (p = 0.01), previous smoking (p = 0.05) and current No 51 (28.7) 43.1 1.0 3 CD4+ T lymphocyte count < 200 cells/mm (p = 0.06) (Table 1). After logistic regression, HPV infection was associated with parity ≥ 3 (p < 0.01; OR = 0.17, 0.05-0.55), hormonal Rocha-Brischiliari et al. Infectious Agents and Cancer 2014, 9:6 Page 4 of 6 http://www.infectagentscancer.com/content/9/1/6 Table 2 Multivariate analysis of epidemiologic and HIV not be excluded a high-grade squamous intraepithelial infection data in 178 women and association with HPV cervical lesion (ASC-H) (Table 3). a b Variables Adjusted OR 95% CI p value The frequency of HPV was 46.6% (n = 83), and in 23.0% of participants (n = 41) multiple HPV genotypes were de- Skin color 1.46 0.71-3.02 0.30 tected. Low-risk (LR)-HPV was detected in 14.6% (n = 26), Parity number = 0 1.45 0.14-1.45 0.18 and HR-HPV was detected in 32.0% (n = 57) of the Parity number ≥ 3 0.17 0.05-0.55 < 0.01 women (p < 0.01). LR and HR-HPV showed similar fre- History of Pap smear in 2.08 0.86-5.00 0.10 quencies in single and multiple infections (p = 0.0727 and the past three years 0.0949, respectively). However, in multiple HPV infec- Hormonal contraceptives use 0.40 0.17-0.92 0.03 tions, HR-HPV was more frequent than LR-HPV in both Smoker 3.04 1.24-7.46 0.01 women with normal cervical cells (NILM) (n = 26, 15.8% Ex-smoker 1.42 0.62-3.24 0.40 and n = 7, 4.2%, respectively) and those with LSIL (n = 31, HIV infection for 5 years 1.93 0.85-4.35 0.11 17.4% and n = 10, 5.6%, respectively) (p = 0.01). HPV in- or less fection occurred most commonly in women with NILM HIV infection between 1.51 0.20-129 0.15 (n = 72, 40.4%) (p = 0.022) (Table 3). 5–10 years A total of 37 different HPV genotypes were detected CD4+ T lymphocyte < 200 3.04 0.86-10.6 0.08 in the 178 women studied. The most frequent HR-HPV (cells/mm ) genotypes were HPV 16, 31 and 51 (6.18% each); HPV CD4+ T lymphocyte < 200–350 1.66 1.05-2.62 0.02 66 and 58 (3.4% each); HPV 59 and 82 (2.8% each); and (cells/mm ) HPV 56 and 69 (2.3% each). The most commonly de- Odds ratio (OR) 95% confidence interval (CI). b tected LR-HPV genotypes were HPV 72 (6.74%); HPV A p-value < 0.05 was considered significant. Papanicolaou secreening (Pap screening). 61 (3.9%); and HPV 11, 70, 74 and 83 (2.3% each) Cells per cubic millimeter (cells/mm ). (Table 4). In the present study, we found that although HIV infec- contraceptive use (p = 0.03; OR = 0.40, 95% CI = 0.17- tion was well controlled, women with a current CD4+ T 0.92), current smoking (p = 0.01; OR = 95% CI = 3.04, lymphocyte count between 200–350 cells/mm (37.6%) 0.24-7.46), and current CD4+ T lymphocyte count < 200 had a two-fold greater risk of HPV infection than those 3 3 cells/mm (p = 0.08; OR = 3.04, 95% CI = 0.86-10.6 ) and with > 350 cells/mm (26.4%). However, our results also between 200–350 cells/mm (p = 0.02; OR = 1.66, 95% showed that although the frequency of HPV was high CI = 1.05-2.62 ) (Table 2). (46.6%), a low frequency of cervical abnormalities was de- A total of 7.3% (n = 13) of the women showed cervical tected (7.30%), mainly LSIL (84.6%). Recently, it was re- abnormalities, of which 84.6% (n = 11) were low-grade ported that HPV frequency was much lower (6.7%) in squamous intraepithelial cervical lesions (LSIL) and 7.7% HIV-uninfected women in the city in which this study was (n = 1) for both atypical squamous cervical cells (ASC) conducted [13]. Therefore, HAART use or/and the com- of undetermined significance (ASC-US) and ASC could prehensive care delivered to these patients through the Table 3 Single and multiple HPV infections in 178 women with HIV Pap Single HPV infections Multiple HPV infections screening LR-HPV HR-HPV Total *LR-HPV **HR-HPV Total findings n% n% n % n % n % n % # ### # NILM (n = 165) 14 8.5 23 13.4 37 88.1 7 4.2 26 15.8 33 20.0 ASC-US (n = 1) - - - - - - - - 1 100 1 100 ASC-H - - - - - - 1 100 - - 1 100 (n = 1) ### LSIL (n = 11) 2 18.2 3 27.3 5 11.9 2 18.2 4 36.4 6 54.6 ## ## ## ## Total (n = 178) 16 9.0 26 14.6 42 100.0 10 5.6 31 17.4 41 23.0 Pap (Papanicolaou) screening with normal cervical cells (NILM). Atypical squamous cervical cells of undetermined significance (ASC-US). Atypical squamous cervical cells could not be excluded a high-grade squamous intraepithelial cervical lesion (ASC-H). Low-grade squamous intraepithelial cervical lesions (LSIL). *Multiple HPV infections without high- risk HPV (HR-HPV) involvement (i.e. low-risk-LR and/or undetermined-risk HPV). **Multiple HPV infections with HR-HPV involvement (i.e. HR and/or undetermined-risk and/or LR-HPV). HPV infection was more prevalent in women with normal cytology (NILM) (p = 0.022). ## LR- and HR-HPV were detected with similar prevalence in single or multiple HPV infections (p = 0.0727 and 0.0949, respectively). ### In multiple HPV infections, HR-HPV was more prevalent than LR in women with NILM and LSIL (p = 0.01). Rocha-Brischiliari et al. Infectious Agents and Cancer 2014, 9:6 Page 5 of 6 http://www.infectagentscancer.com/content/9/1/6 Table 4 Distribution of 37 HPV genotypes detected in SAE appears to exert some protection against cervical le- 178 women with HIV sions development in this population. HPV genotypes Women detected HPV infection was positively associated with parity number ≥ 3, hormonal contraceptive use and smoker. A n% relationship between these risk factors and CC has been High-risk (HR) reported in HIV-uninfected women [14,15]. Our results 16 11 7.9 suggest that they are also associated with HPV infection 31 11 7.9 in HIV-infected women. These data are important for 51 11 7.9 public policies targeting HIV-infected women to prevent 58 6 4.3 HPV infection and CC. 66 6 4.3 Multiple HPV infections were frequently detected, oc- curring in half of the HPV positive women; similar findings 82 5 3.6 have already been widely reported [5,10,14]. Interestingly, 59 5 3.6 the most common HPV genotype was −72 (LR, 8.6%), 18 4 2.9 followed by HPV −16, -31 and −51 (7.9% each). These data 56 4 2.9 differ from those described by others in that HR-HPV was 33 3 2.2 detected more frequently. Nonetheless, they are in part 73 3 2.2 agreement with studies showing that these women are commonly infected with the non-18/-16 HR-HPV geno- 53 3 2.2 types [8,9]. 39 1 0.7 In conclusion, we acknowledge that we did not include 45 1 0.7 HIV-uninfected women for comparison. However, we have 68 1 0.7 provided very important information about the risk factors 26 1 0.7 associated with HPV frequency and genotypes in HIV- Low-risk (LR) infected women, and this information can contribute to planning protocols for CC prevention in these patients. It 72 12 8.6 should be noted that the STD/AIDS program of the Brazil- 61 7 5.1 ian Ministry of Health distributes HAART free of charge 70 4 2.9 and ensures its use. This program also provides compre- 74 4 2.9 hensive care to HIV-positive patients, which certainly con- 83 4 2.9 tributed to the low frequency of cervical lesions (most were 11 4 2.9 LSIL) we observed. This study can serve as a model for the populations of other Latin American countries. 13 3 2.2 62 3 2.2 Abbreviations HPV: Human papillomavirus; HIV: Human immunodeficiency virus; 81 3 2.2 HR-HPV: High-risk HPV; LR-HPV: Low risk HPV; CC: Cervical cancer; 84 3 2.2 SAE: Specialized Assistance Service; STD: Sexually transmitted disease; AIDS: Acquired immunodeficiency syndrome; PCR: Polymerase chain 55 2 1.4 reaction; LSIL: Low-grade squamous intraepithelial cervical lesions; 67 2 1.4 ASC-UUS: Atypical squamous cervical cells of undetermined significance; ASC-H: Atypical squamous cervical cells could not be excluded a high-grade 43 2 1.4 squamous intraepithelial cervical lesion; OpenEpi: Open source Epidemiologic Statistics for Public Health; OR: Odds ratio; CI: Confidence 6 2 1.4 interval; HAART: Highly active antiretroviral therapy. 30 2 1.4 Competing interests 54 1 0.7 The authors declare that they have no competing interests. 44 1 0.7 Authors’ contributions 91 1 0.7 All of the authors contributed to the manuscript. SCR-B, RPS, FG, and ALPA 42 1 0.7 searched the literature and prepared the manuscript. SCR-B, MDBC and SMP collected the biological samples from the women. MELC, ALPA and FG wrote 69 1 0.7 the manuscript. MELC, RPS, FG and ALPA participated in methodology 64 1 0.7 design and execution. MMTI performed the experiments related to cervical cytology. RGS and AAFG performed the statistical analysis. SCR-B, MDBC and SMP contributed to the statistical analysis and design of the study. MDBC, SMP and MELC were involved in revising the manuscript critically for important intellectual content. MELC revised the final version of the manuscript and provided information and suggestions. All of the authors read and approved the final draft of the manuscript. Rocha-Brischiliari et al. Infectious Agents and Cancer 2014, 9:6 Page 6 of 6 http://www.infectagentscancer.com/content/9/1/6 Acknowledgements This work was supported by grants from Fundação Araucária de Apoio ao Desenvolvimento Cientifico e Tecnológico do Paraná/Ministério da Saúde do Brasil/PPSUS (Grant number 20533, 521/2010) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (project 23038.006960/2010-31). Author details Department of Nursing, State University of Maringá, Paraná, Brazil. Department of Clinical Analysis and Biomedicine, State University of Maringá, Paraná, Brazil. Department of Statistics, State University of Maringá, Paraná, Brazil. Department of Medicine, State University of Maringá, Paraná, Brazil. Received: 16 July 2013 Accepted: 3 February 2014 Published: 11 February 2014 References 1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM: GLOBOCAN 2008 v2.0, Cancer Incidence and Mortality Worldwide: IARC Cancer Base No. 10 [Internet]. Lyon, France: International Agency for Research on Cancer; 2010 [http://globocan.iarc.fr] 2. Kling M, Zeichner JA: The role of the Human papilloma-virus (HPV) vaccine in developing countries. Int J Dermatol 2010, 49:377–379. 3. INCA/MS – National Cancer Institute: Cancer Surveillance Data in Brazil. 2012 [http:// www.inca.gov.br/estimativa/2012/] 4. Spangler JM, Munger K: The human Papillomavirus type 16 E6 oncoprotein activates mTORC1 signaling and increases protein synthesis. J Virol 2010, 84:9398–9407. 5. Luque AE, Hitti J, Mwachari C, Lane C, Messing S, Cohn SE, Adler D, Rose R, Coombs R: Prevalence of human Papillomavirus genotypes in HIV-1-infected women in Seattle, USA and Nairobi, Kenya: results from the Women’sHIV Interdisciplinary Network (WHIN). JInfectDis 2010, 14:e810–e814. 6. Brazil MH: Recommendations for antiretroviral therapy for adults living with HIV / AIDS in Brazil – 2012. 2012 [http://www.aids.gov.br/sites/ default/files/anexos/publicacao/2012/52140/ consenso_adulto2012_ principais_mudancas_pdf_11946] 7. Kreitchmann R, Bajotto H, Silva DAR, Fuchs SC: Squamous intraepithelial lesions in HIV-infected women: prevalence, incidence, progression and regression. Arch Gynecol Obstet 2013, 288:1107–1113. 8. Luque AE, Jabeen M, Messing S, Lane CA, Demeter LM, Rose RC, Reichman RC: Prevalence of human papillomavirus genotypes and related abnormalities of cervical cytological results among HIV-1–infected women in Rochester, New York. J Infect Dis 2006, 194:428–434. 9. Blossom DB, Beigi RH, Farrell JJ, Mackay W, Qadadri B, Brown DR, Rwambuya S, Walker CJ, Kambugu FS, Abdul-Karim FW, Whalen CC, Salata RA: Human papil- lomavirus genotypes associated with cervical cytologic abnormalities and HIV infection in Ugandan women. J Med Virol 2007, 79(6):758–765. 10. McKenzie ND, Kobetz EN, Hnatyszyn J, Twiggs LB, Lucci JA 3rd: Women with HIV are more commonly infected with non-16 and −18 high-risk HPV types. Gynecol Oncol 2010, 116(3):572–577. 11. Solomon D, Nayar R: Bethesda System for Cervical–Vaginal Cytology. Rio de Janeiro: Revinter; 2005:67–87. 12. Santiago E, Camacho L, Junquera ML, Vázquez F: Full HPV typing by a single restriction enzyme. J Clin Virol 2006, 37(1):38–46. 13. da Silva MC, Martins HP, de Souza JL, Tognim MC, Svidzinski TI, Teixeira JJ, Consolaro ME: Prevalence of HPV infection and genotypes in women with normal cervical cytology in the state of Paraná, Brazil. Arch Gynecol Obstet 2012, 286(4):1015–1022. 14. Adler DH: The impact of HAART on HPV-related cervical disease. Curr HIV Submit your next manuscript to BioMed Central Res 2010, 8(7):493–497. and take full advantage of: 15. Schuman P, Ohmit SE, Klein RS, Duerr A, Cu-Uvin S, Jamieson DJ, Anderson J, Shah KV: HIV Epidemiology Research Study (HERS) Group: longitudinal study of cervical squamous intraepithelial lesions in • Convenient online submission human immunodeficiency virus (HIV)-seropositive and at-risk HIV- • Thorough peer review seronegative women. JInfectDis 2003, 188:128–136. • No space constraints or color figure charges doi:10.1186/1750-9378-9-6 • Immediate publication on acceptance Cite this article as: Rocha-Brischiliari et al.: Risk factors for cervical HPV • Inclusion in PubMed, CAS, Scopus and Google Scholar infection and genotypes distribution in HIV-infected South Brazilian women. Infectious Agents and Cancer 2014 9:6. • Research which is freely available for redistribution Submit your manuscript at www.biomedcentral.com/submit http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Infectious Agents and Cancer Springer Journals

Risk factors for cervical HPV infection and genotypes distribution in HIV-infected South Brazilian women

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Springer Journals
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Copyright © 2014 by Rocha-Brischiliari et al.; licensee BioMed Central Ltd.
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Biomedicine; Cancer Research; Infectious Diseases; Oncology
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Abstract

Background: Human Papillomavirus (HPV) infection is particularly burdensome for women infected with human immunodeficiency virus (HIV), which increases their risk of developing cervical lesions and cancer (CC). We conducted a molecular study of the distribution of cervical HPV genotypes and the risk factors for this infection in HIV-infected Brazilian women. Findings: Cervical and endocervical samples for Papanicolaou screening and HPV detection were collected from 178 HIV-infected women using highly active antiretroviral therapy (HAART) of Maringá city/Brazil. Risk factors were assessed using a standardized questionnaire, and the data regarding to HIV infection from medical records. HPV was detected by polymerase chain reaction (PCR), and genotyping using PCR-restriction fragment length polymorphism analysis. HIV infection was well controlled, but women with a current CD4+ T lymphocyte count between 200–350 cells/mm (37.6%) had a two-fold greater risk of HPV infection than those with > 350 cells/mm (26.4%). HPV was associated with parity ≥3, hormonal contraceptive use and current smoker. HPV infection occurred with high frequency (46.6%) but a low frequency of cervical abnormalities was detected (7.30%), mainly low-grade squamous intraephitelial cervical lesions (LSIL) (84.6%). A high frequency of multiple HPV infections was detected (23.0%), and the most frequent HPV genotype was HPV-72 (6.7%), followed by −16, -31 and -51 (6.14% each). Conclusions: We showed that HAART use does not protect HIV-infected women from HPV, but appear to exert some protection against cervical lesions development. This study provides other important information about risk factors and cervical HPV in HIV-infected women, which can contribute to planning protocols. Keywords: HIV, HPV, Genotypes, Risk factors, Cervical lesions, Cervical cancer Findings immunodeficiency virus (HIV)-infected women, as they It is estimated that in 2020, cervical cancer (CC) will be are more vulnerable to infection and are less likely to diagnosed in over 665,035 women worldwide, and 357,852 clear the virus, which increases their risk of developing will die as a result [1]. The frequency of CC is much cervical lesions and cancer. Moreover, in HIV-infected higher in underdeveloped or developing countries than it women, CC responds poorly to the recommended ther- is in developed countries [2]. In Brazil, CC is the third apies, is more aggressive, and in cases of recurrence, most common cancer among women, with 17.540 new has a worse prognosis [5]. In Brazil, approximately cases diagnosed in 2012 [3]. 180,000 HIV-positive individuals are undergoing highly The association between persistent high-risk (HR) Human active antiretroviral therapy (HAART) administered by Papillomavirus (HPV) and CC has been well established [4]. thePublicHealth System [6]. Whilethistherapy has HPV infection is particularly burdensome for human been associated with a substantial reduction in AIDS- related mortality, its role in preventing HPV infection and progression to CC is still poorly studied and con- * Correspondence: smpelloso@gmail.com troversial [6,7]. Department of Nursing, State University of Maringá, Paraná, Brazil Full list of author information is available at the end of the article © 2014 Rocha-Brischiliari et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. Rocha-Brischiliari et al. Infectious Agents and Cancer 2014, 9:6 Page 2 of 6 http://www.infectagentscancer.com/content/9/1/6 Studies have unanimously showed that HIV-infected fragment length polymorphism analysis using HpyCH4V women are more commonly infected with non-16 and [12] was performed. Co-amplification of the human β- −18 HR-HPV genotypes, such as 52 and 58 [8,9]. Given globin gene was performed, as an internal control, using that current vaccines target HPV -16/-18, these findings the following primers under the same conditions as those may have important implications for future HPV vac- used for HPV-PCR: GH20 (5’-GAAGAGCCAAGGACA cines that target other types of HPV that are associated GGTAC-3’)/PC04 (5’-CAACTTCATCCACGTTCACC-3′) with disease risk in HIV-infected women [10]. (Figure 1). Considering that epidemiological data from different Statistical analysis was performed using Open Source populations are required for public policies addressing Epidemiologic Statistics for Public Health/OpenEpi, Ver- CC prevention in HIV-infected women and that few sion 2.3.1. All variables were expressed as absolute and studies from Brazil and Latin America have collected relative frequencies. For univariate analysis, categorical these data, we conducted a molecular study of the distri- variables were compared with HPV infection by χ - bution of cervical HPV genotypes and the risk factors as- square and Fisher’s exact test. Some variables of interest sociated with this infection in HIV-infected Brazilian with p < 0.20 were selected for logistic regression ana- women. lysis. A crude odds ratio (OR) and 95% confidence inter- In total, 178 HIV-infected women using HAART, aged val (CI) were calculated. A p-value < 0.05 was considered 18 to 66 years, who attended the Specialized Assistance significant. Service (SAE) for sexually transmitted diseases (STD)/ Most HIV-infected women showed excellent control of AIDS of Maringá city/Southern Brazil, from April 1 to the HIV infection, based on HAART proper use (79.2%), October 30, 2011, were included. The inclusion criterion high current CD4+ T lymphocyte count (37.6% with 200– 3 3 required that the women had been diagnosed twice with 350 cells/mm and 26.4% with > 350 cells/mm )and low HIV/AIDS using different methods and using HAART. current viral load (58.4% < minimum limit and 38.8% be- The exclusion criteria were previous hysterectomy, current tween the minimum limit and 100 copies/ml). or recent pregnancy, age younger than 18 years, and no Univariate analysis revealed an association between history of sexual activity. HPV infection and parity ≥ 3 (p = 0.01), not undergoing Of the 424 HIV-infected women enrolled in the SAE, 100 were excluded, and a total of 324 were eligible for the study. The sample size was calculated with an HPV prevalence of 50%, confidence interval of 95%, error esti- mate of 5%. With an increase of 10% for possible partici- pant losses, the total sample size was fixed at 178 randomly selected women. The women were interviewed using a standardized questionnaire to obtain socio-economic and demographic information, obstetric and gynecologic history and data on their sexual behavior. Data regarding HIV infection were obtained from SAE medical records. A single nursing con- tacted all of the women, administered the questionnaire and collected the cervical samples. This project was ap- proved by the Committee for Ethics in Research Involving Humans at the State University of Maringá (UEM)/ Paraná, Brazil (nº 085/2011). Ecto/endocervical samples were collected with an Ayre’s spatula and cytobrush for cervical cytology (Papanicolaou screening) and polymerase chain reaction (PCR); the sam- Figure 1 Electrophoretic analysis of HPV genotyping by PCR- ples were suspended in 1 ml of 0.9% NaCl solution and restriction fragment length polymorphism analysis (PCR-RFLP) stored at -20°C. The cytological smears were sent to the using HpyCH4V in 8% polyacrylamide gel stained with Clinical Cytology Laboratory of UEM and were graded ac- ethidium bromide. Sample A1, genotype −31 (HR) in single HPV cording to the Bethesda System [11]. Genomic DNA was infection (216, 108, 94 base pairs-pb); A2, genotype −56 (HR) in single extracted using an AxyPrep™ Body Fluid Viral DNA/RNA HPV infection (244, 121 pb); A3, genotypes −13 (LR), -16 and −58 (HR) in multiple HPV infection (244, 216, 191, 103, 99, 91 e 89 pb); A4, Miniprep kit (Axygen, CA, USA). PCR amplification of genotype −51 (HR) in single HPV infection (171, 147, 137 pb); A5, HPV was carried out using the following primers: MY09 genotypes −16 (HR) and −61 (LR) on double HPV infection (216, (5’CGTCCMAARGGAWACTGATC-3’)/MY11(5’-GCMCA 191, 171, 147, 137). M, molecular weight marker (25 base pairs). GGGWCATAAYAATGG-3’). Genotyping by PCR-restriction Rocha-Brischiliari et al. Infectious Agents and Cancer 2014, 9:6 Page 3 of 6 http://www.infectagentscancer.com/content/9/1/6 Table 1 Univariate analysis of epidemiologic and HIV Table 1 Univariate analysis of epidemiologic and HIV infection data in 178 women and association with HPV infection data in 178 women and association with HPV a b (Continued) Variables n (%) HPV OR (95% CI) p value (%) Gynecologic infections Age ranges (years) (number) 18-30 28 (15.7) 60.7 1.93 (0.94-1.99) 0.13 0 55 (30.9) 40.0 1.0 31-40 60 (33.7) 43.3 0.96 (0.47-1.95) 0.89 1-2 93 (52.2) 48.4 1.41 (0.68-2.92) 0.32 > 40 90 (50.6) 44.4 1.0 ≥ 3 30 (16.9) 53.3 1.71 (0.64-4.64) 0.23 Education (years) Cigarette smoking < 8 85 (47.8) 45.9 1.69 (0.93-3.06) 0.84 Yes 35 (19.7) 65.7 2.76 (1.15-6.67) 0.01 ≥ 8 93 (52.2) 47.3 1.0 No 100 (56.2) 41.0 1.0 Marital status Ex-smoker 43 (24.1) 44.2 0.41 (0.15-1.14) 0.05 Married 93 (52.2) 45.2 1.0 Period of HIV infection (years) Unmarried 31 (17.4) 48.4 1.14 (0.46-2.77) 0.75 < 5 76 (42.7) 56.6 1.72 (0.79-3.75) 0.13 Widowed 54 (30.3) 48.1 1.13 (0.55-2.33) 0.72 5-10 51 (28.6) 35.5 0.72 (0.30-1.72) 0.41 Skin color > 10 51 (28.6) 43.1 1.0 White 114 (64.0) 42.1 1.0 HAART correct use Not white 64 (36.0) 54.7 1.66 (0.86-3.22) 0.10 Yes 141 (79.2) 46.8 1.04 (0.47-2.28) 0.92 Menarche (years) No 37 (20.8) 45.9 1.0 < 13 95 (53.4) 43.2 0.74 (0.39-1.40) 0.32 Current CD4+ ≥ 13 83 (46.6) 50.6 1.0 T lymphocyte (cells/mm ) Age of sexual debut (years) < 200 15 (8.4) 66.7 2.76 (0.81-9.92) 0.06 < 18 112 (62.9) 45.5 0.89 (0.46-1.71) 0.70 200-350 67 (37.6) 56.3 1.78 (0.76-4.16) 0.14 ≥ 18 66 (37.1) 48.5 1.0 > 350 47 (26.4) 42.0 1.0 Sexual partners CD4+ T lymphocyte (number) range (cells/mm ) 1 16 (9.0) 56.2 1.0 < 200 64 (35.9) 51.5 1.21 (0.53-2.76) 0.62 2-7 74 (41.6) 44.6 0.63 (0.18-2.10) 0.39 200-350 67 (37.6) 41.8 0.82 (0.36-1.85) 0.59 > 7 88 (49.4) 46.6 0.68 (0.20-2.22) 0.47 > 350 47 (26.4) 46.8 1.0 Parity (number) Recent viral load (copies/ml) 0 20 (11.2) 70.0 1.0 < L min 104 (58.4) 43.3 1.0 1-2 67 (37.7) 49.2 0.42 (0.12-1.35) 0.10 1-100.000 69 (38.8) 49.3 1.27 (0.66-2.46) 0.43 ≥ 3 91 (51.1) 39.6 0.28 (0.09-0.88) 0.01 > 100.000 5 (2.8) 80.0 5.24 (0.52-27.6) 0.17 History of Pap screening in the Viral load range past three years (copies/ml) Yes 143 (80.3) 42.7 1.0 1-100.000 50 (28.1) 50.0 1.0 No 35 (19.7) 62.9 2.27 (1.01-5.23) 0.03 > 100.000 128 (71.9) 45.3 0.83 (0.41-1.68) 0.57 Hormonal a Odds ratio (OR) 95% confidence interval (CI). contraceptive use b A p-value < 0.05 was considered significant. Highly active antiretroviral therapy (HAART). Yes 135 (75.9) 43.7 0.61 (0.29-1.30) 0.16 Papanicolaou secreening (Pap screening). No 43 (24.1) 55.8 1.0 Gynecologic infections Pap screening in the last 3 years (p = 0.03), current smok- Yes 127 (71.3) 48.0 1.22 (0.60-2.47) 0.55 ing (p = 0.01), previous smoking (p = 0.05) and current No 51 (28.7) 43.1 1.0 3 CD4+ T lymphocyte count < 200 cells/mm (p = 0.06) (Table 1). After logistic regression, HPV infection was associated with parity ≥ 3 (p < 0.01; OR = 0.17, 0.05-0.55), hormonal Rocha-Brischiliari et al. Infectious Agents and Cancer 2014, 9:6 Page 4 of 6 http://www.infectagentscancer.com/content/9/1/6 Table 2 Multivariate analysis of epidemiologic and HIV not be excluded a high-grade squamous intraepithelial infection data in 178 women and association with HPV cervical lesion (ASC-H) (Table 3). a b Variables Adjusted OR 95% CI p value The frequency of HPV was 46.6% (n = 83), and in 23.0% of participants (n = 41) multiple HPV genotypes were de- Skin color 1.46 0.71-3.02 0.30 tected. Low-risk (LR)-HPV was detected in 14.6% (n = 26), Parity number = 0 1.45 0.14-1.45 0.18 and HR-HPV was detected in 32.0% (n = 57) of the Parity number ≥ 3 0.17 0.05-0.55 < 0.01 women (p < 0.01). LR and HR-HPV showed similar fre- History of Pap smear in 2.08 0.86-5.00 0.10 quencies in single and multiple infections (p = 0.0727 and the past three years 0.0949, respectively). However, in multiple HPV infec- Hormonal contraceptives use 0.40 0.17-0.92 0.03 tions, HR-HPV was more frequent than LR-HPV in both Smoker 3.04 1.24-7.46 0.01 women with normal cervical cells (NILM) (n = 26, 15.8% Ex-smoker 1.42 0.62-3.24 0.40 and n = 7, 4.2%, respectively) and those with LSIL (n = 31, HIV infection for 5 years 1.93 0.85-4.35 0.11 17.4% and n = 10, 5.6%, respectively) (p = 0.01). HPV in- or less fection occurred most commonly in women with NILM HIV infection between 1.51 0.20-129 0.15 (n = 72, 40.4%) (p = 0.022) (Table 3). 5–10 years A total of 37 different HPV genotypes were detected CD4+ T lymphocyte < 200 3.04 0.86-10.6 0.08 in the 178 women studied. The most frequent HR-HPV (cells/mm ) genotypes were HPV 16, 31 and 51 (6.18% each); HPV CD4+ T lymphocyte < 200–350 1.66 1.05-2.62 0.02 66 and 58 (3.4% each); HPV 59 and 82 (2.8% each); and (cells/mm ) HPV 56 and 69 (2.3% each). The most commonly de- Odds ratio (OR) 95% confidence interval (CI). b tected LR-HPV genotypes were HPV 72 (6.74%); HPV A p-value < 0.05 was considered significant. Papanicolaou secreening (Pap screening). 61 (3.9%); and HPV 11, 70, 74 and 83 (2.3% each) Cells per cubic millimeter (cells/mm ). (Table 4). In the present study, we found that although HIV infec- contraceptive use (p = 0.03; OR = 0.40, 95% CI = 0.17- tion was well controlled, women with a current CD4+ T 0.92), current smoking (p = 0.01; OR = 95% CI = 3.04, lymphocyte count between 200–350 cells/mm (37.6%) 0.24-7.46), and current CD4+ T lymphocyte count < 200 had a two-fold greater risk of HPV infection than those 3 3 cells/mm (p = 0.08; OR = 3.04, 95% CI = 0.86-10.6 ) and with > 350 cells/mm (26.4%). However, our results also between 200–350 cells/mm (p = 0.02; OR = 1.66, 95% showed that although the frequency of HPV was high CI = 1.05-2.62 ) (Table 2). (46.6%), a low frequency of cervical abnormalities was de- A total of 7.3% (n = 13) of the women showed cervical tected (7.30%), mainly LSIL (84.6%). Recently, it was re- abnormalities, of which 84.6% (n = 11) were low-grade ported that HPV frequency was much lower (6.7%) in squamous intraepithelial cervical lesions (LSIL) and 7.7% HIV-uninfected women in the city in which this study was (n = 1) for both atypical squamous cervical cells (ASC) conducted [13]. Therefore, HAART use or/and the com- of undetermined significance (ASC-US) and ASC could prehensive care delivered to these patients through the Table 3 Single and multiple HPV infections in 178 women with HIV Pap Single HPV infections Multiple HPV infections screening LR-HPV HR-HPV Total *LR-HPV **HR-HPV Total findings n% n% n % n % n % n % # ### # NILM (n = 165) 14 8.5 23 13.4 37 88.1 7 4.2 26 15.8 33 20.0 ASC-US (n = 1) - - - - - - - - 1 100 1 100 ASC-H - - - - - - 1 100 - - 1 100 (n = 1) ### LSIL (n = 11) 2 18.2 3 27.3 5 11.9 2 18.2 4 36.4 6 54.6 ## ## ## ## Total (n = 178) 16 9.0 26 14.6 42 100.0 10 5.6 31 17.4 41 23.0 Pap (Papanicolaou) screening with normal cervical cells (NILM). Atypical squamous cervical cells of undetermined significance (ASC-US). Atypical squamous cervical cells could not be excluded a high-grade squamous intraepithelial cervical lesion (ASC-H). Low-grade squamous intraepithelial cervical lesions (LSIL). *Multiple HPV infections without high- risk HPV (HR-HPV) involvement (i.e. low-risk-LR and/or undetermined-risk HPV). **Multiple HPV infections with HR-HPV involvement (i.e. HR and/or undetermined-risk and/or LR-HPV). HPV infection was more prevalent in women with normal cytology (NILM) (p = 0.022). ## LR- and HR-HPV were detected with similar prevalence in single or multiple HPV infections (p = 0.0727 and 0.0949, respectively). ### In multiple HPV infections, HR-HPV was more prevalent than LR in women with NILM and LSIL (p = 0.01). Rocha-Brischiliari et al. Infectious Agents and Cancer 2014, 9:6 Page 5 of 6 http://www.infectagentscancer.com/content/9/1/6 Table 4 Distribution of 37 HPV genotypes detected in SAE appears to exert some protection against cervical le- 178 women with HIV sions development in this population. HPV genotypes Women detected HPV infection was positively associated with parity number ≥ 3, hormonal contraceptive use and smoker. A n% relationship between these risk factors and CC has been High-risk (HR) reported in HIV-uninfected women [14,15]. Our results 16 11 7.9 suggest that they are also associated with HPV infection 31 11 7.9 in HIV-infected women. These data are important for 51 11 7.9 public policies targeting HIV-infected women to prevent 58 6 4.3 HPV infection and CC. 66 6 4.3 Multiple HPV infections were frequently detected, oc- curring in half of the HPV positive women; similar findings 82 5 3.6 have already been widely reported [5,10,14]. Interestingly, 59 5 3.6 the most common HPV genotype was −72 (LR, 8.6%), 18 4 2.9 followed by HPV −16, -31 and −51 (7.9% each). These data 56 4 2.9 differ from those described by others in that HR-HPV was 33 3 2.2 detected more frequently. Nonetheless, they are in part 73 3 2.2 agreement with studies showing that these women are commonly infected with the non-18/-16 HR-HPV geno- 53 3 2.2 types [8,9]. 39 1 0.7 In conclusion, we acknowledge that we did not include 45 1 0.7 HIV-uninfected women for comparison. However, we have 68 1 0.7 provided very important information about the risk factors 26 1 0.7 associated with HPV frequency and genotypes in HIV- Low-risk (LR) infected women, and this information can contribute to planning protocols for CC prevention in these patients. It 72 12 8.6 should be noted that the STD/AIDS program of the Brazil- 61 7 5.1 ian Ministry of Health distributes HAART free of charge 70 4 2.9 and ensures its use. This program also provides compre- 74 4 2.9 hensive care to HIV-positive patients, which certainly con- 83 4 2.9 tributed to the low frequency of cervical lesions (most were 11 4 2.9 LSIL) we observed. This study can serve as a model for the populations of other Latin American countries. 13 3 2.2 62 3 2.2 Abbreviations HPV: Human papillomavirus; HIV: Human immunodeficiency virus; 81 3 2.2 HR-HPV: High-risk HPV; LR-HPV: Low risk HPV; CC: Cervical cancer; 84 3 2.2 SAE: Specialized Assistance Service; STD: Sexually transmitted disease; AIDS: Acquired immunodeficiency syndrome; PCR: Polymerase chain 55 2 1.4 reaction; LSIL: Low-grade squamous intraepithelial cervical lesions; 67 2 1.4 ASC-UUS: Atypical squamous cervical cells of undetermined significance; ASC-H: Atypical squamous cervical cells could not be excluded a high-grade 43 2 1.4 squamous intraepithelial cervical lesion; OpenEpi: Open source Epidemiologic Statistics for Public Health; OR: Odds ratio; CI: Confidence 6 2 1.4 interval; HAART: Highly active antiretroviral therapy. 30 2 1.4 Competing interests 54 1 0.7 The authors declare that they have no competing interests. 44 1 0.7 Authors’ contributions 91 1 0.7 All of the authors contributed to the manuscript. SCR-B, RPS, FG, and ALPA 42 1 0.7 searched the literature and prepared the manuscript. SCR-B, MDBC and SMP collected the biological samples from the women. MELC, ALPA and FG wrote 69 1 0.7 the manuscript. MELC, RPS, FG and ALPA participated in methodology 64 1 0.7 design and execution. MMTI performed the experiments related to cervical cytology. RGS and AAFG performed the statistical analysis. SCR-B, MDBC and SMP contributed to the statistical analysis and design of the study. MDBC, SMP and MELC were involved in revising the manuscript critically for important intellectual content. MELC revised the final version of the manuscript and provided information and suggestions. All of the authors read and approved the final draft of the manuscript. Rocha-Brischiliari et al. Infectious Agents and Cancer 2014, 9:6 Page 6 of 6 http://www.infectagentscancer.com/content/9/1/6 Acknowledgements This work was supported by grants from Fundação Araucária de Apoio ao Desenvolvimento Cientifico e Tecnológico do Paraná/Ministério da Saúde do Brasil/PPSUS (Grant number 20533, 521/2010) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (project 23038.006960/2010-31). Author details Department of Nursing, State University of Maringá, Paraná, Brazil. Department of Clinical Analysis and Biomedicine, State University of Maringá, Paraná, Brazil. Department of Statistics, State University of Maringá, Paraná, Brazil. Department of Medicine, State University of Maringá, Paraná, Brazil. Received: 16 July 2013 Accepted: 3 February 2014 Published: 11 February 2014 References 1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM: GLOBOCAN 2008 v2.0, Cancer Incidence and Mortality Worldwide: IARC Cancer Base No. 10 [Internet]. Lyon, France: International Agency for Research on Cancer; 2010 [http://globocan.iarc.fr] 2. Kling M, Zeichner JA: The role of the Human papilloma-virus (HPV) vaccine in developing countries. Int J Dermatol 2010, 49:377–379. 3. INCA/MS – National Cancer Institute: Cancer Surveillance Data in Brazil. 2012 [http:// www.inca.gov.br/estimativa/2012/] 4. Spangler JM, Munger K: The human Papillomavirus type 16 E6 oncoprotein activates mTORC1 signaling and increases protein synthesis. J Virol 2010, 84:9398–9407. 5. Luque AE, Hitti J, Mwachari C, Lane C, Messing S, Cohn SE, Adler D, Rose R, Coombs R: Prevalence of human Papillomavirus genotypes in HIV-1-infected women in Seattle, USA and Nairobi, Kenya: results from the Women’sHIV Interdisciplinary Network (WHIN). JInfectDis 2010, 14:e810–e814. 6. Brazil MH: Recommendations for antiretroviral therapy for adults living with HIV / AIDS in Brazil – 2012. 2012 [http://www.aids.gov.br/sites/ default/files/anexos/publicacao/2012/52140/ consenso_adulto2012_ principais_mudancas_pdf_11946] 7. Kreitchmann R, Bajotto H, Silva DAR, Fuchs SC: Squamous intraepithelial lesions in HIV-infected women: prevalence, incidence, progression and regression. Arch Gynecol Obstet 2013, 288:1107–1113. 8. Luque AE, Jabeen M, Messing S, Lane CA, Demeter LM, Rose RC, Reichman RC: Prevalence of human papillomavirus genotypes and related abnormalities of cervical cytological results among HIV-1–infected women in Rochester, New York. J Infect Dis 2006, 194:428–434. 9. Blossom DB, Beigi RH, Farrell JJ, Mackay W, Qadadri B, Brown DR, Rwambuya S, Walker CJ, Kambugu FS, Abdul-Karim FW, Whalen CC, Salata RA: Human papil- lomavirus genotypes associated with cervical cytologic abnormalities and HIV infection in Ugandan women. J Med Virol 2007, 79(6):758–765. 10. McKenzie ND, Kobetz EN, Hnatyszyn J, Twiggs LB, Lucci JA 3rd: Women with HIV are more commonly infected with non-16 and −18 high-risk HPV types. Gynecol Oncol 2010, 116(3):572–577. 11. Solomon D, Nayar R: Bethesda System for Cervical–Vaginal Cytology. Rio de Janeiro: Revinter; 2005:67–87. 12. Santiago E, Camacho L, Junquera ML, Vázquez F: Full HPV typing by a single restriction enzyme. J Clin Virol 2006, 37(1):38–46. 13. da Silva MC, Martins HP, de Souza JL, Tognim MC, Svidzinski TI, Teixeira JJ, Consolaro ME: Prevalence of HPV infection and genotypes in women with normal cervical cytology in the state of Paraná, Brazil. Arch Gynecol Obstet 2012, 286(4):1015–1022. 14. Adler DH: The impact of HAART on HPV-related cervical disease. Curr HIV Submit your next manuscript to BioMed Central Res 2010, 8(7):493–497. and take full advantage of: 15. Schuman P, Ohmit SE, Klein RS, Duerr A, Cu-Uvin S, Jamieson DJ, Anderson J, Shah KV: HIV Epidemiology Research Study (HERS) Group: longitudinal study of cervical squamous intraepithelial lesions in • Convenient online submission human immunodeficiency virus (HIV)-seropositive and at-risk HIV- • Thorough peer review seronegative women. JInfectDis 2003, 188:128–136. • No space constraints or color figure charges doi:10.1186/1750-9378-9-6 • Immediate publication on acceptance Cite this article as: Rocha-Brischiliari et al.: Risk factors for cervical HPV • Inclusion in PubMed, CAS, Scopus and Google Scholar infection and genotypes distribution in HIV-infected South Brazilian women. Infectious Agents and Cancer 2014 9:6. • Research which is freely available for redistribution Submit your manuscript at www.biomedcentral.com/submit

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