Human Papillomavirus 16 Lineage A Variants Associated With Persistent Genital Infections in Men: The HPV Infection in Men (HIM) Study.

BACKGROUND: Human papillomavirus (HPV) 16 non-A lineage variants have higher carcinogenic potential for cervical cancer. HPV-16 variants natural history among males is not established. We evaluated HPV-16 variants prevalence and persistence in the external genitalia of men enrolled in the prospective HPV Infection in Men (HIM) Study. METHODS: The HIM Study included men from the United States, Brazil, and Mexico. HPV-16 variants were distinguished using polymerase chain reaction sequencing. The prevalence of HPV-16 variants was assessed, and associations with infection persistence were estimated. RESULTS: We characterized the HPV-16 variants for 1700 genital swab samples from 753 men and 22 external genital lesions in 17 men. The prevalence of HPV-16 lineages differed by country and marital status (P < .001). Overall, 90.9% of participants harbored lineage A variants. The prevalence of non-A lineages was heterogenous among countries. HPV-16 lineage A variants were associated with a 2.69-fold increased risk of long-term persistent infections compared with non-A lineages. All high-grade penile intraepithelial neoplasia harbored lineage A variants and occurred in the context of long-term persistent infections with the same variants. CONCLUSIONS: The prevalence and persistence of HPV-16 variants observed at the male external genitalia suggest differences in the natural history of these variants between men and women, which may be associated with intrinsic differences in the infected genital epithelia.

The Role of External Genital Lesions in Human Immunodeficiency Virus Seroconversion Among Men Participating in a Multinational Study.

BACKGROUND: Studies in women have shown an increased risk of human immunodeficiency virus (HIV) acquisition with prior human papilloma virus (HPV) infection; however, few studies have been conducted among men. Our objective was to assess whether HPV-related external genital lesions (EGLs) increase risk of HIV seroconversion among men. METHODS: A total of 1379 HIV-negative men aged 18 to 70 years from the United States, Mexico, and Brazil were followed for up to 7 years and underwent clinical examination for EGLs and blood draws every 6 months. Human immunodeficiency virus seroconversion was assessed in archived serum. Cox proportional hazards and marginal structural models assessed the association between EGL status and time to HIV seroconversion. RESULTS: Twenty-nine participants HIV seroconverted during follow-up. Older age was associated with a lower hazard of HIV seroconversion. We found no significant difference in the risk of HIV seroconversion between men with and without EGLs (adjusted hazard ratio, 0.94; 95% confidence interval, 0.32-2.74). Stratified analyses focusing on men that have sex with men found no association between EGLs and HIV seroconversion risk (hazards ratio, 0.63; 95% confidence interval, 0.00-1.86). CONCLUSIONS: External genital lesions were not associated with higher risk for HIV seroconversion in this multinational population, although statistical power was limited as there were few HIV seroconversions. Results may differ in populations at higher risk for HIV.

Differences in Factors Associated With High- and Low-Risk Oral Human Papillomavirus Genotypes in Men.

BACKGROUND: Human papillomavirus (HPV) causes oral warts and oropharyngeal cancer (OPC). Human papillomavirus-attributable OPC incidence among men is significantly increasing worldwide, yet few studies have reported oral HPV across multiple countries or examined factors associated with low- and high-risk HPV separately. METHODS: Oral gargles from 3095 men in the multinational HPV Infection in Men (HIM) Study were HPV genotyped. Multivariable models assessed factors independently associated with high-risk and low-risk HPV prevalence. RESULTS: The prevalence of high-risk and low-risk HPV was 6.0% and 2.8%, respectively. Greater number of sexual partners was only associated with high-risk HPV (1.88; 95% confidence interval [CI], 1.22-2.90) prevalence. In multivariable models, residing in Mexico (1.66; 95% CI, 1.15-2.40) and smoking (1.66; 95% CI, 1.13-2.44) were significantly associated with high-risk HPV, and history of consistent gum bleeding (2.16; 95% CI, 1.35-3.45) was significantly associated with low-risk HPV. Gender of the sexual partner did not alter the results for either high- or low-risk HPV endpoints. CONCLUSIONS: Different factors were independently associated with high- and low-risk oral HPV. Oral sexual behaviors were associated with high-risk HPV, and oral health was associated with low-risk HPV. High-risk HPV prevalence differed by country of residence, highlighting the need for additional studies in multiple countries.

Sequential acquisition of human papillomavirus infection between genital and oral anatomic sites in males.

Oral human papillomavirus (HPV) is associated with increasing rates of HPV-associated oropharyngeal cancer (OPC) in men. Sequential infection from one site to another has been demonstrated at the cervix and anus. Thus, risk of an oral HPV infection after a genital infection of the same type in the HPV infection in men study was investigated. Samples from 3140 men enrolled in a longitudinal cohort were assessed for sequential genital to oral infection with one of nine HPV types (HPV 6, 11, 16, 18, 31, 33, 45, 52 and 58); and then also sequential, same-type oral to genital infection. Incidence rate ratios (IRRs) compared rates of oral HPV among men with and without prior genital infection of the same type. Risk of sequential HPV infections were assessed using Cox proportional hazards model. Incidence of an oral HPV infection was significantly higher among men with a prior genital infection of the same type for any of the 9 HPV types (IRR: 2.3; 95% CI: 1.7-3.0). Hazard ratio of a sequential genital to oral HPV infection was 2.3 (95% CI: 1.7-3.1) and 3.5 (95% CI: 1.9-6.4) for oral to genital infection. Both changed minimally after adjustment for age, country, circumcision, alcohol use, lifetime sexual partners and recent oral sex partners. HPV infections at one site could elevate risk of a subsequent genital or oral HPV infection of the same type in men, emphasizing the importance of vaccination to prevent all HPV infections.

Genital Wart Recurrence Among Men Residing in Brazil, Mexico, and the United States.

BACKGROUND: Genital wart (GW) incidence is high among men. The percentage and rate at which subsequent GW events occur are understudied. The purpose of this study was to describe the rate of subsequent GWs, associated human papillomavirus (HPV) types, and time to subsequent GW event among unvaccinated men. METHODS: The study was nested within a multinational prospective HPV natural history study of men aged 18-70 years in the United States, Mexico, and Brazil, examined every 6 months for a median follow-up of 50.4 months. Subsequent GW events were defined as GWs detected after ≥16 weeks of the prior event. RESULTS: Forty-four percent of men experienced ≥1 GW following the initial episode. Men with ≥2 subsequent events were at highest risk of continued GW experiences, with as high as 10 postinitial GW events. The incidence rate of each subsequent GW increased with increasing events (incidence of first subsequent event was 13.1 vs 36.6/1000 person-months for the fourth event). The proportion of GWs among HPV-6 and/or -11-positive patients remained constant across events. Approximately 63%-69% were positive for ≥1 of the 9-valent HPV vaccine types. CONCLUSIONS: These data highlight the high burden of GWs among men across the lifespan and the need for vaccination to prevent multiple GW episodes.

HPV-6 Molecular Variants Association With the Development of Genital Warts in Men: The HIM Study.

Background: Human papillomavirus type 6 (HPV-6) and HPV-11 are the etiological agents of approximately 90% of genital warts (GWs). The impact of HPV-6 genetic heterogeneity on persistence and progression to GWs remains undetermined. Methods: HPV Infection in Men (HIM) Study participants who had HPV-6 genital swabs and/or GWs preceded by a viable normal genital swab were analyzed. Variants characterization was performed by polymerase chain reaction sequencing and samples classified within lineages (A, B) and sublineages (B1, B2, B3, B4, B5). Country- and age-specific analyses were conducted for individual variants; odds ratios and 95% confidence intervals for the risk of GWs according to HPV-6 variants were calculated. Results: B3 variants were most prevalent. HPV-6 variants distribution differed between countries and case status. HPV-6 B1 variants prevalence was increased in GWs and genital swabs of cases compared to controls. There was difference in B1 and B3 variants detection in GW and the preceding genital swab. We observed significant association of HPV-6 B1 variants detection with GW development. Conclusions: HPV-6 B1 variants are more prevalent in genital swabs that precede GW development, and confer an increased risk for GW. Further research is warranted to understand the possible involvement of B1 variants in the progression to clinically relevant lesions.

Dietary intake of selected nutrients and persistence of HPV infection in men.

Human papillomavirus (HPV) infection is a common sexually transmitted disease. Although often transitory, persistent oncogenic HPV infection may progress to a precursor lesion and, if not treated, can further increase the risk of cancer. The purpose of this study was to investigate the relation between dietary intake and HPV persistent infection in men of a Brazilian cohort. The study population consisted of 1,248 men from the Brazilian cohort of the HIM (HPV in Men) Study, ages 18 to 70 years, who completed a quantitative food frequency questionnaire. U Mann-Whitney test was used to assess differences in median nutrient intake of selected nutrients. The association of dietary intake and persistent HPV infection was assessed in multivariate logistic models. The prevalence of any HPV infection at baseline was 66.6%. Of 1,248 participants analyzed, 1,211 (97.0%) were HPV positive at one or more times during the 4 years of follow-up and 781 (62.6%) were persistently HPV positive. Men with nonpersistent oncogenic HPV infections had higher median intake of retinol (p = 0.008), vitamin A (p < 0.001) and folate (DFE; p = 0.003) and lower median intake of energy (p = 0.005) and lycopene (p = 0.008) in comparison to men with persistent oncogenic infections. No significant association was found between selected nutrients and persistent oncogenic HPV infection. For nononcogenic persistent infections, only vitamin B12 intake was significantly associated (p = 0.003, test for trend). No association was observed between dietary intake and persistent oncogenic-type HPV infection; however, vitamin B12 intake was inversely associated with nononcogenic HPV persistence.

Country-specific HPV-related genital disease among men residing in Brazil, Mexico and The United States: The HIM study.

The purpose of this study was to assess whether the incidence of histopathologically confirmed condyloma and penile intraepithelial neoplasia (PeIN) and rates of genital HPV infection progression to these lesions differs by country (Brazil, Mexico and the U.S.). At each visit, lesions were biopsied and were categorized by pathologic diagnoses. The Linear Array genotyping method was used to identify HPV genotypes from genital swabs, while the INNO-LiPA HPV Genotyping Extra method was used for tissue specimens. Age-specific analyses were conducted for lesion incidence by country, with Kaplan-Meier estimation of cumulative incidence. The proportion of HPV infections that progressed to condyloma and PeIN, the median time to lesion development and the incidence rates were estimated by country. When comparing demographic and sexual characteristics across the three countries, sexual orientation (p = 0.008) and lifetime number of female sexual partners (p < 0.0001) were differentially associated with lesion incidence in the three countries. Condyloma incidence in Brazil and the U.S. decreased with age, while incidence remained constant across the lifespan in Mexico. There were no differences by country and age for PeIN incidence. HPV types 6 and 11 were the most common types to progress to condyloma and HPV types 16, 6 and 11 were the most common types to progress to PeIN in all three countries. The continuous risk of condyloma and PeIN across all age groups and countries in this study emphasizes the need to ensure that strong HPV immunity, such as that obtained through vaccination, is maintained across the lifespan of men.

HPV-11 variability, persistence and progression to genital warts in men: the HIM study.

HPV-11 and HPV-6 are the etiological agents of about 90 % of genital warts (GWs). The intra-typic variability of HPV-11 and its association with infection persistence and GW development remains undetermined. Here, HPV infection in men (HIM) participants who had an HPV-11 genital swab and/or GW, preceded or not by a normal skin genital swab were analysed. Genomic variants were characterized by PCR-sequencing and classified within lineages (A, B) and sublineages (A1, A2, A3, A4). HPV-11 A2 variants were the most frequently detected in the genital swab samples from controls and in both genital swabs and GW samples from cases. The same HPV-11 variant was detected in the GW sample and its preceding genital swab. There was a lack of association between any particular HPV-11 variant and the increased risk for GW development.

Human Papillomavirus Prevalence Among 88 Male Virgins Residing in Brazil, Mexico, and the United States.

This study determined the prevalence and risk factors for genital human papillomavirus (HPV) detection among men who deny ever engaging in penetrative sex. A questionnaire was administered to 4123 men from a cohort study of HPV natural history. Genital exfoliated cells were collected and genotyped for 36 HPV types. Eighty-eight men were classified as virgins. Log-binomial regression models identified factors associated with genital HPV detection. The prevalence of any and high-risk HPV types among 88 male virgins was 25.0% and 18.2%, respectively. Age and smoking status were associated with HPV detection. Further studies are needed to better understand the risk for HPV infection among male virgins.

Incidence, Duration, Persistence, and Factors Associated With High-risk Anal Human Papillomavirus Persistence Among HIV-negative Men Who Have Sex With Men: A Multinational Study.

BACKGROUND: Given high rates of anal disease, we investigated the natural history of high-risk anal human papillomavirus (HPV) among a multinational group of men who have sex with men (MSM) aged 18-64 years. METHODS: Anal specimens from human immunodeficiency virus-negative men from Brazil, Mexico, and the United States were genotyped. Over 2 years, 406 MSM provided evaluable specimens every 6 months for ≥2 visits. These men were stratified into men who have sex only with men (MSOM, n = 70) and men who have sex with women and men (MSWM, n = 336). Persistence was defined as ≥12 months' type-specific duration and could begin with either a prevalent or incident infection. Prevalence ratios and 95% confidence intervals were calculated by Poisson regression. RESULTS: Median follow-up time was 2.1 years. Retention was 82%. Annual cumulative incidence of 9-valent vaccine types was 19% and 8% among MSOM and MSWM, respectively (log-rank P = .02). Duration of anal HPV did not differ for MSOM and MSWM and was a median of 6.9 months for HPV-16 after combining men from the 2 groups. Among men with prevalent high-risk infection (n = 106), a total of 36.8%, retained the infection for at least 24 months. For those with prevalent HPV-16 (n = 27), 29.6% were persistent for at least 24 months. Persistence of high-risk HPV was associated with number of male anal sex partners and inversely associated with number of female sex partners. CONCLUSIONS: MSM with prevalent high-risk HPV infection should be considered at increased risk for nontransient infection.

Reproductive and genital health and risk of cervical human papillomavirus infection: results from the Ludwig-McGill cohort study.

BACKGROUND: There are inconsistencies in the literature on reproductive and genital health determinants of human papillomavirus (HPV) infection, the primary cause of cervical cancer. We examined these factors in the Ludwig-McGill Cohort Study, a longitudinal, repeated-measurements investigation on the natural history of HPV infection. METHODS: We analyzed a cohort subset of 1867 women with one complete year of follow-up. We calculated odds ratios (OR) and 95% confidence intervals (CI) for reproductive and genital health characteristics from questionnaire and laboratory data in relation to 1-year period prevalence of HPV infection. Two outcomes were measured; the first based on phylogenetic grouping of HPV types based on tissue tropism and oncogenicity (Alphapapillomavirus Subgenus 1: species 1, 8, 10 and 13; Subgenus 2: species 5, 6, 7, 9, 11; Subgenus 3: species 3, 4 and 14) and the second based on transient or persistent HPV infections. RESULTS: Lifetime (Subgenus 3 OR = 2.00, CI: 1.23-3.24) and current (Subgenus 3 OR =2.00, CI: 1.15-3.47) condom use and use of contraceptive injections (Subgenus 1 OR = 1.96, CI: 1.22-3.16, Subgenus 2 OR = 1.34, CI: 1.00-1.79) were associated with increased risk of HPV infection. Intrauterine device use was protective (Subgenus 1 OR = 0.48, CI: 0.30-0.75, Subgenus 2 OR = 0.78, CI: 0.62-0.98). These factors were not associated with persistence of HPV infection. Tampon use, previous gynecologic infections and cervical inflammation were associated with an overall increased risk of HPV infection. CONCLUSIONS: Cervical HPV infection was associated with reproductive and genital health factors. Further studies are necessary to confirm the low to moderate associations observed.

The natural history of genital human papillomavirus among HIV-negative men having sex with men and men having sex with women.

BACKGROUND: Although human immunodeficiency virus (HIV)-negative men having sex with men (MSM) bear a substantial burden of human papillomavirus (HPV)-associated disease, prospective studies of genital HPV infection in this population are scarce. METHODS: HPV genotyping was conducted on genital samples from men (aged 18-70 years) from Brazil, Mexico, or the United States who provided specimens at 6-month intervals for up to 4 years. Eligibility criteria included no history of genital warts or HIV infection. Evaluable specimens were collected from 564 MSM and 3029 men having sex with women (MSW). Incidence and clearance estimates with 95% confidence intervals were calculated. RESULTS: The 12-month cumulative incidence of genital HPV was high in both MSM (25%; 95% confidence interval, 21%-30%) and MSW (21%; 20%-23%). After stratifying by city, MSM and MSW incidence rates were comparable, with 3 exceptions where MSM had higher incidence in ≥1 city: the group of quadrivalent vaccine types, HPV-45, and HPV-11. Median times to HPV-16 clearance were also comparable, with point estimates of >6 months for both MSM and MSW. CONCLUSIONS: Unlike with many other sexually transmitted infections, genital HPV natural history may be similar in HIV-negative MSM and MSW. Study periods of ≤6 months, however, may not be long enough to accurately measure the persistence of these infections in men.

Risk of Human Papillomavirus (HPV) Infection and Cervical Neoplasia after Pregnancy.

BACKGROUND: Parity is well established as a risk factor for cervical cancer. It is not clear, however, how pregnancy influences the natural history of HPV infection and cervical neoplasia. Our objective was to study the risk of HPV infection and cervical squamous intraepithelial lesions (SIL) after pregnancy. METHODS: We used the Ludwig-McGill cohort study which includes 2462 women recruited in Sao Paulo, Brazil in 1993-97 and followed for up to 10 years. Cellular specimens were collected every 4-6 months for Pap cytology and HPV detection and genotyping by a polymerase chain reaction protocol. Study nurses recorded pregnancy occurrence during follow-up. HPV and Pap results from pregnant women were available before and after, but not during pregnancy. The associations between pregnancy and post-partum HPV infection/SIL were studied using generalized estimating equation models with logistic link. Adjusted odds ratios (OR) were estimated with empirical adjustment for confounding. RESULTS: We recorded 122 women with a history of pregnancy during follow-up. Of these, 29 reintegrated the cohort study after delivery. No association between HPV and pregnancy was found. A single SIL case (high grade SIL) occurred post-partum. Likewise, there was no association between pregnancy and risk of low grade SIL or any-grade SIL at the next visit (adjusted OR = 0.84, 95 % CI: 0.46-15.33) after controlling for confounders. CONCLUSIONS: No associations were found between pregnancy and HPV or LSIL. The single observed case of HSIL post-partum was more than would be expected based on the rate of these abnormalities among non-pregnant women. As this association was found with only one case, caution is required in the interpretation of these results.

Paving pathways: Brazil's implementation of a national human papillomavirus immunization campaign.

In 2014, Brazil introduced an HPV immunization program for girls 9-13 years of age as part of the Unified Health System's (SUS) National Immunization Program. The first doses were administered in March 2014; the second ones, in September 2014. In less than 3 months more than 3 million girls received the first dose of quadrivalent HPV vaccine, surpassing the target rate of 80%. This paper examines three elements that may influence the program's long-term success in Brazil: sustaining effective outreach, managing a large technology-transfer collaboration, and developing an electronic immunization registry, with a focus on the State of São Paulo. If these three factors are managed, the Government of Brazil is primed to serve as a model of success for other countries interested in implementing a national HPV vaccination program to decrease HPV-related morbidity and mortality.

High genital prevalence of cutaneous human papillomavirus DNA on male genital skin: the HPV Infection in Men Study.

BACKGROUND: The genital skin of males hosts a diversity of HPV genotypes and uncharacterized HPV genotypes. Previously we demonstrated that a specific viral genotype was not identified in 14% of all genital specimens (i.e., HPV unclassified specimens) using the Roche Linear Array method. Our goal was to identify and assess the prevalence of individual HPV types among genital HPV unclassified specimens collected in the HIM Study population, at enrollment, and examine associations with socio-demographic and behavioral characteristics. METHODS: Genital skin specimens of men that were considered unclassified (HPV PCR positive, no genotype specified) at enrollment were typed by sequencing amplified PGMY09/11 products or cloning of PGMY/GP+ nested amplicons followed by sequencing. PGMY/GP+ negative specimens were further analyzed using FAP primers. HPV type classification was conducted through comparisons with sequences in the GenBank database. RESULTS: Readable nucleotide sequences were generated for the majority of previously unclassified specimens (66%), including both characterized (77%) and yet uncharacterized (23%) HPV types. Of the characterized HPV types, most (73%) were Beta [ß]-HPVs, primarily from ß-1 and ß-2 species, followed by Alpha [α]-HPVs (20%). Smokers (current and former) were significantly more likely to have an α-HPV infection, compared with any other genus; no other factors were associated with specific HPV genera or specific ß-HPV species. CONCLUSIONS: Male genital skin harbor a large number of ß-HPV types. Knowledge concerning the prevalence of the diverse HPV types in the men genital is important to better understand the transmission of these viruses.

Cross-cultural nursing care for immigrant women during pregnancy and childbirth: experiences and vulnerabilities.

OBJECTIVE: To understand the experiences and vulnerabilities for cross-cultural nursing care for immigrant women during pregnancy and delivery. METHOD: Exploratory, qualitative research, in the light of the Theory of Diversity and Universality of Cultural Care, in Foz do Iguaçu, Brazil, through interviews with eight postpartum woman and 18 nurses, between February and September 2022. The interpretation of meanings was adopted for analysis. RESULTS: The categories of analysis emerged: Experiences, vulnerabilities and acculturation of immigrant women during pregnancy and delivery; Cross-cultural care and vulnerabilities experienced by immigrants in Brazilian health services. Vulnerabilities were identified in Cultural and Social Structure Dimensions expressed in access to work, low socioeconomic conditions, lack of family and social support and specific services for this population. The potentialities experienced included good care provided by health services, quality of the multidisciplinary team and appreciation of professional knowledge, however, the understanding of expectations and cultural aspects needs to be deepened. FINAL CONSIDERATIONS: Understand that immigrant women experience situations of vulnerability in pregnancy and childbirth, in the Brazilian context, mainly related to social and programmatic dimensions. However, potentialities were also experienced, evidenced by positive aspects in cross-cultural nursing care in Brazil.

Concordance of human papillomavirus types detected on the surface and in the tissue of genital lesions in men.

Swabbing the surface of a genital lesion to obtain a sample for HPV DNA testing is less invasive than a biopsy, but may not represent HPV types present in the lesion tissue. The objective of this study was to examine the concordance of HPV types detected in swab and biopsy samples from 165 genital lesions from men ages 18-70. Lesions included 90 condyloma, 10 penile intraepithelial neoplasia (PeIN), 23 non-condyloma with a known histology, and 42 lesions with an undetermined histology. All lesions were sampled by swabbing the surface of the lesion with a pre-wetted Dacron swab and taking a shave biopsy. HPV genotyping was performed using Linear Array for swab samples and INNO-LiPA for biopsy samples. The kappa and McNemar statistics were used to compare the concordance of detecting HPV types in swab and biopsy samples. Both sampling methods had high agreement for detection of HPV DNA in condyloma (87.8% agreement) and PeIN (100% agreement). There was also high concordance for detection of HPV16 (kappa = 1.00) and HPV18 (kappa = 1.00) in PeIN, however, agreement was low to moderate for detecting HPV6 (kappa = 0.31) and HPV11 (kappa = 0.56) in condyloma. Low to moderate agreement was also observed between sampling methods for detecting individual HPV types in the non-condyloma and lesions with an indefinite histology. The results suggest that obtaining a biopsy in addition to swabbing the surface of a lesion may provide additional information about specific HVP types associated with male genital lesions.

Risk factors for incident condyloma in a multinational cohort of men: the HIM study.

Identifying factors associated with condyloma are necessary for prevention efforts. Risk factors for incident condyloma were examined in a cohort of 2487 men from the United States, Brazil, and Mexico and were followed up every 6 months (median, 17.9 months). Factors strongly associated with condyloma were incident infection with human papillomavirus (HPV) types 6 and 11 (hazard ratio [HR], 12.42 [95% confidence interval {CI}, 3.78-40.77]), age (HR, 0.43 [95% CI, .26-.77]; 45-70 vs 18-30 years), high lifetime number of female partners (HR, 5.69 [95% CI, 1.80-17.97]; ≥21 vs 0 partners), and number of male partners (HR, 4.53 [95% CI, 1.68-12.20]; ≥3 vs 0 partners). The results suggest that HPV types 6 and 11 and recent sexual behavior are strongly associated with incident condyloma.

Translation, cross-cultural adaptation and validity study of the "Play Nicely Program: The Healthy Discipline Handbook" for use in Brazil.

OBJECTIVE: to describe the translation, cross-cultural adaptation and validity process of the "Play Nicely Program: The Healthy Discipline Handbook" for use in Brazil. METHODS: a methodological study that followed the translation, back-translation, expert committee assessment, and pre-test steps. The Content Validity Index (CVI) was calculated for both the judge population and the pre-test population. Four translators, seven expert judges in the field of child health and thirty participants in the pre-test, including parents, teachers and healthcare professionals, participated in the study. RESULTS: in experts' analysis (98.4%), a value of 100% of adequate assessments was obtained, and in the target population's analysis (89.5%), there were 100% of adequate assessments. In both analyses, suggested adaptations were made. CONCLUSIOS: cross-cultural adaptation and content validity into Brazilian Portuguese of the "Play Nicely Program: The Healthy Discipline Handbook" were considered adequate for application in the target population.