Cisplatin overcomes radiotherapy resistance in OCT4-expressing head and neck squamous cell carcinoma.

OBJECTIVES: Cisplatin is combined with radiotherapy for advanced head and neck squamous cell carcinoma (HNSCC). While providing a beneficial effect on survival, it also causes side effects and thus is an important target when considering treatment de-escalation. Currently, there are no biomarkers to predict its patient-selective therapeutic utility. In this study, we examined the role of the stem cell factor OCT4 as a potential biomarker to help clinicians stratify HNSCC patients between radiotherapy and chemoradiotherapy. MATERIALS AND METHODS: OCT4 immunohistochemical staining of a population-validated tissue microarray (PV-TMA) (n = 166) representative of a standard HNSCC patients was carried out, and 5-year survival was analyzed. The results were validated using ex vivo drug sensitivity analysis of HNSCC tumor samples, and further cross-validated in independent oropharyngeal (n = 118), nasopharyngeal (n = 170), and vulvar carcinoma (n = 95) clinical datasets. In vitro, genetically modified, patient-derived HNSCC cells were used. RESULTS: OCT4 expression in HNSCC tumors was associated with radioresistance. However, combination therapy with cisplatin was found to overcome thisradioresistance in OCT4-expressing HNSCC tumors. The results were validated by using several independent patient cohorts. Furthermore, CRISPRa-based OCT4 overexpression in the HNSCC cell line resulted in apoptosis resistance, and cisplatin was found to downregulate OCT4 protein expression in vitro. Ex vivo drug sensitivity analysis of HNSCC tumors confirmed the association between OCT4 expression and cisplatin sensitivity. CONCLUSION: This study introduces OCT4 immunohistochemistry as a simple and cost-effective diagnostic approach for clinical practice to identify HNSCC patients benefitting from radiosensitization by cisplatin using either full or reduced dosing.

Maternal HPV-antibodies and seroconversion to HPV in children during the first 3 years of life.

To assess the dynamics of human papillomavirus (HPV) serology, we analyzed HPV6-,11-,16-,18-, and 45 antibodies in infants during the first 36 months of their life. Serial serum samples of 276/327 mother-child pairs were collected at baseline (mothers) and at months 1, 2, 6, 12, 24 and 36 (offspring), and tested for HPVL1-antibodies using the GST-L1 assay. Concordance between maternal and infant HPV-antibody levels remained high until month-6 (p < = 0.001), indicating maternal antibody transfer. At 1 month, 40-62% of the infants tested seropositive to any of the 5 HPV-types. Between 1-3 years of age, 53% (58/109) of the children born to HPV-seronegative mothers tested HPV-seropositive. Times to positive seroconversion varied between13.4 and 18.7 months, and times to negative seroconversion (decay) between 8.5 and 9.9 months. Significant independent predictors of infants' seroconversion to LR-HPV were hand warts and mother's history of oral warts and seroconversion to LR-HPV. No predictors of seroconversion to HR-HPV were identified. Maternal HPV-IgG-antibodies are transferred to her offspring and remain detectable for 6 months, corroborating the IgG molecule's half-life. Seroconversion to HPV-genotypes 6, 11, 16 and 18 was confirmed among children born to HPV-seronegative mothers, implicating an immune response to these HPV-genotypes during early infancy.

Oral Human Papillomavirus Infection in Children during the First 6 Years of Life, Finland.

Human papillomavirus (HPV) infections are found in children, but transmission modes and outcomes are incompletely understood. We evaluated oral samples from 331 children in Finland who participated in the Finnish Family HPV Study from birth during 9 follow-up visits (mean time 51.9 months). We tested samples for 24 HPV genotypes. Oral HPV prevalence for children varied from 8.7% (at a 36-month visit) to 22.8% (at birth), and 18 HPV genotypes were identified. HPV16 was the most prevalent type to persist, followed by HPV18, HPV33, and HPV6. Persistent, oral, high-risk HPV infection for children was associated with oral HPV carriage of the mother at birth and seroconversion of the mother to high-risk HPV during follow-up (odds ratio 1.60-1.92, 95% CI 1.02-2.74). Children acquire their first oral HPV infection at an early age. The HPV status of the mother has a major impact on the outcome of oral HPV persistence for her offspring.

Breast Milk Is a Potential Vehicle for Human Papillomavirus Transmission to Oral Mucosa of the Spouse.

BACKGROUND: Human papillomavirus (HPV) DNA has been detected in breast milk, but its origin has remained obscure. The aim of the study was to analyze the prevalence and persistence of HPV in breast milk in the Finnish Family HPV cohort study. The association of breast milk HPV positivity with the family members' oral HPV status was evaluated. METHODS: We included 308 families to the study where the mother was breast feeding her offspring. Mothers collected the milk samples manually at day 3, and at months 2, 6 and 12. Cervical and/or oral samples were collected from all family members. HPV testing was performed using nested polymerase chain reaction and Luminex-based Multimetrix kit. RESULTS: Breast milk HPV DNA was found in 10.1% (31/308), 20.1% (39/194) and 28.8% (17/59) of samples at day 3, months 2 and 6, respectively. The following HPV genotypes were detected: 6, 16, 18, 33, 45, 53, 56, 59, 66 and 82. Breast milk HPV persisted among 5.5% (9/164) of the lactating mothers. No significant associations were detected between the persistent breast milk HPV and the offspring's oral incident HPV infection. Breast milk HPV positivity showed a strong association with the fathers' oral HPV positivity at baseline, as well as at 6- and 12-month follow-up visits, with odds ratio (OR) = 3.24 [95% confidence interval (CI): 1.04-10.12], OR = 6.34 (95% CI: 1.84-21.89) and OR = 14.25 (95% CI: 1.16-174.80), respectively. CONCLUSIONS: HPV in breast milk is prevalent among the lactating mothers and HPV can also persist in breast milk. The breast milk is a potential vehicle for HPV transmission to oral mucosa of the spouse but not of the offspring.

High-risk human papillomavirus associated with incident cervical intraepithelial neoplasia developing in mothers in the Finnish Family HPV Study cohort.

BACKGROUND: Cofactors of high-risk (HR) human papillomavirus (HPV) in the progression of cervical intraepithelial neoplasia (CIN) are incompletely characterized. In this study these cofactors were investigated in a longitudinal setting. METHODS: A cohort of 329 women (mean age 25.5 y) were enrolled in the Finnish Family HPV Study, and followed-up for 6 y with serial cervical samples for HPV genotyping, virus integration status, and HPV serology. Hospital records were reviewed until March 2010 and linked with HPV detection data. All incident CIN lesions were subjected to HPV genotyping. HPV covariates were studied in an age- and HPV-matched nested case-control (1:4) setting. RESULTS: Twelve of the 329 women developed an incident CIN: 2 CIN1, 3 CIN2, and 7 CIN3. HPV16 was detected most frequently (7/12), followed by HPV58 (2/12), HPV18, HPV31, and HPV42. HPV integration was present in 4/12 cases. Long-lasting persistence of HPV31 and HPV16 preceded incident CIN2 and CIN3. In multivariate conditional logistic regression, the risk for incident CIN increased up to 4-fold with increasing number of deliveries (p = 0.024) and decreased with history of genital warts (p = 0.036). CONCLUSION: Baseline HR-HPV infections and their persistence precede incident CIN by several years. The 2 independent covariates of HR-HPV were (1) number of deliveries (increasing the risk), and (2) history of genital warts (protective effect).

Incident cervical infections with high- and low-risk human papillomavirus (HPV) infections among mothers in the prospective Finnish Family HPV Study.

BACKGROUND: The knowledge on type specificity and factors that increase or decrease the risk of incident HPV-infections is important to better understand the dynamics of HPV-infections. METHODS: A series of 329 pregnant women were enrolled in Finnish Family HPV Study at 3rd trimester of pregnancy and followed-up for 6 years, during which 203 baseline HPV-negative women acquired incident HPV infection. Incidence times and incidence rates (IR) were calculated for 24 low-and high-risk HPV-types detected by Multiplex-HPV-genotyping at each visit. Poison regression was used to estimate predictors of incident HPV infections of species 7 and 9 HPV-genotypes. RESULTS: HPV16 was the most frequent (47.8%) incident genotype followed by multiple-type infections (25.1%), and single infection with HPV18, 70, 6 and 45. Actuarial mean times to incident event were longest for HPV31 (34.5 months) and HPV45 (32.8 months), while crude mean times were longest for HPV56 (42.4 months) and HPV16 (23.1 months). Actuarial IR was highest for HPV16 and multiple-type infections. Independent protective factors against incident infections were 1) > 2 life-time sexual partners (p = 0.014), 2) later initiation of oral contraceptives (age > 20 years) (p = 0.017) and 3) pregnancy at FU visit (p = 0.0001). CONCLUSIONS: Among newly delivered mothers, higher number of life-time sexual partners, initiation of OC use after age 20 and becoming pregnant during FU decreased the risk for incident species 7/9 HPV infections.

Human papillomavirus and predictors of cervical intraepithelial neoplasia among young mothers in a prospective follow-up study.

OBJECTIVE: To study the incidence times and rates for cervical intraepithelial neoplasia (CIN) and its predictors. MATERIAL AND METHODS: This is a prospective follow-up study at Turku University Hospital, Finland. The Finnish Family human papillomavirus (HPV) study comprised 329 pregnant women followed up for 3 years. In an extension of the follow-up period, 171 women participated in an additional 3 years follow-up. Cervical scrapings for HPV testing and cervical smears were collected at each follow-up visit (2, 12, 24 and 36 months and 6 years). Following two abnormal cervical smears, colposcopy with biopsies was done. The main outcome measures were actuarial and crude incidence times, incidence rates and predictors of incident CIN. RESULTS: During the follow-up period, 10 women (3.2%) developed biopsy-confirmed CIN, and four presented with incident atypical squamous cells suggesting high-grade squamous intraepithelial lesion cytology. The CIN/squamous intraepithelial lesion developed in 74.5 and 66.3 months, with crude incidence rates of 13.4/1,000 and 15.1/1,000 women months at risk, respectively. In multivariate Poisson regression, independent predictors of incident CIN were as follows: high-risk HPV positive at baseline (incidence rate ratio = 5.54; 95% confidence interval 1.02-30.14, p= 0.048); type-specific high-risk HPV persistence during follow-up (incidence rate ratio = 5.84; 95% confidence interval 2.28-17.93, p= 0.0001); cervical smear cytologically diagnosed for atypical squamous cells of undetermined significance or worse at any follow-up visit (incidence rate ratio = 4.56; 95% confidence interval 2.37-8.78, p= 0.0001); and new sexual partner during follow-up (incidence rate ratio = 9.45; 95% confidence interval 1.90-46.97, p= 0.006). CONCLUSION: The results indicate that combined use of cervical smear and HPV testing, with prompt referral to colposcopy, enables accurate detection of incident CIN well before progression to invasive cancer. In addition to baseline and persistent high-risk HPV, abnormal cervical smear and new sexual partner are key predictors of incident CIN.

[Update on current care guidelines. Diagnosis, treatment and follow-up of cytological changes in the cervix, vagina and vulva]. / Kohdunkaulan, emättimen ja ulkosynnytinten solumuutokset--diagnostiikka, hoito ja seuranta.

Approximately 150 cervical cancer cases are diagnosed in Finland annually. Both incidence and mortality have decreased by 80% since organised screening began. Recently, screening based on primary HPV-testing with Pap-smear triage has been shown to be more sensitive and more specific among women over 35 years old in randomised studies and thus may be implemented in routine. Abnormal findings in Pap smears indicate management. Confirmed CIN1 lesions are followed up and CIN2 and worse lesions treated. Follow-up after treatment should be reliably arranged, because elevated risk of cancer remains over 20 years after treatment. Quality control is of utmost importance.

Genotype-specific persistence of genital human papillomavirus (HPV) infections in women followed for 6 years in the Finnish Family HPV Study.

BACKGROUND: Persistent human papillomavirus (HPV) infection is the most important risk factor for cervical cancer, and understanding genotype-specific HPV persistence is essential for elucidating the natural history of HPV infections. METHODS: In the Finnish Family HPV Study, 329 pregnant women (mean age, 25.5 years) were recruited during the third trimester of pregnancy and were followed up for 6 years. Multiplex HPV genotyping for 27 low- and high-risk HPV types was used to define genotype-specific prevalence at each visit. Generalized estimating equation models were constructed to estimate predictors of type-specific persistence (positive results at 2 consecutive visits) of species 7 and 9 HPV genotypes. RESULTS: HPV16 was the most common type, followed by HPV types 18, 31, 35, 45, 58, 70, and 6. Prevalence of multiple infections ranged from 21% to 45%. Persistence was most prolonged for HPV types 35, 58, and 52, with durations of 38.7, 32.1, and 24.2 months, respectively, and was equal for multiple-type infections and HPV16, with durations of 21 and 24 months, respectively. Independent predictors of type-specific persistence of species 7 and 9 HPV genotypes were age (odds ratio, 1.13 [95% confidence interval, 1.02-1.25]; P=.017), oral sex (odds ratio, 0.37 [95% confidence interval, 0.17-0.81]; P=.013), and young age (<13 years) at initiation of smoking (odds ratio, 0.51 [95% confidence interval, 0.27-0.98]; P=.046). CONCLUSION: HPV16 was the most frequent persisting HPV genotype followed by multiple infections. Early initiation of smoking, practicing oral sex and older age increase the risk for persistence of species 7 and 9 HPV genotypes.

Genotype-specific clearance of genital human papillomavirus (HPV) infections among mothers in the Finnish family HPV study.

The majority of cervical human papillomavirus (HPV) infections in young women are transient, but whether the clearance differs among different HPV genotypes and the different factors predicting genotype-specific clearance are partly unknown. In the Finnish Family HPV Study, 131 of 252 women (mean age, 25.5 years) cleared their infection during the prospective follow-up of 6 years (median, 62.4 months; range, 1.6 to 94.5 months). Cervical scrapings collected at each visit were tested for 24 low-risk and high-risk (HR) HPV types with multiplex HPV genotyping. Poison regression (panel data) was used to estimate predictors for the clearance of species 7 and 9 HPV genotypes. Of all HPV genotypes detected in these women, multiple-type and HPV type 16 (HPV16) infections showed clearance least frequently (46.1% and 50.5%, respectively). The actuarial and crude mean times to first clearance were variable among different genotypes. The actuarial clearance rate (events/person-time at risk) was highest for HPV16 and multiple-type infections, while HPV66 and -82 had the highest crude clearance rate. Independent predictors increasing type-specific clearance of species 7/9 HPV genotypes were older age (incidence rate ratio [IRR] = 1.1; 95% confidence interval [95% CI], 1.03 to 1.18; P = 0.002) and baseline oral HR HPV DNA-negative status (IRR = 2.94; 95% CI, 1.03 to 8.36; P = 0.042), while a higher number of sexual partners during the follow-up decreased the probability of clearance (IIR = 0.35; 95% CI, 0.15 to 0.83; P = 0.018). To conclude, HPV16 and multiple-type infections showed the lowest clearance among young mothers. Increasing age and negative oral HR HPV DNA status at baseline were associated with increased clearance, whereas a higher number of current sexual partners decreased the probability of species 7/9 HPV genotype clearance.

Dynamics of human papillomavirus serology in women followed up for 36 months after pregnancy.

We determined L1 antibodies for human papillomavirus (HPV) types 6, 11, 16, 18 and 45 by multiplex serology in our prospective HPV family study. We report seroprevalence, seroconversion and antibody decay in 290 women (mean age, 25.5 years) sampled before delivery and at 12, 24 and 36 months of follow-up. Multiplex HPV genotyping of the baseline oral and genital scrapings was performed. At baseline, seroprevalence of HPV 6, 11, 16, 18 and 45 was 53.3, 21.5, 34.9, 21.5 and 9.0%, respectively. Seropositivity for low-risk HPV (LR-HPV) was associated significantly with age at onset of sexual activity (P=0.001), number of sexual partners until age 20 (P=0.018), lifetime number of sexual partners (P=0.0001), history of genital warts (P=0.0001) and being seropositive for high-risk (HR) HPV (P=0.0001). The same covariates also predicted seropositivity for HR-HPV. During follow-up, 26.7, 13.9, 17.0, 16.8 and 6.6% of the women seroconverted to L1 antigen of HPV 6, 11, 16, 18 and 45, respectively, between 18.2 and 23.8 months. Independent predictors of seroconversion to LR-HPV were unemployment (P=0.019) and absence of anal sex practice (P=0.031), and to HR-HPV, absence of smoking history and lifetime number of sexual partners. Decay of HPV 6, 11, 16, 18 and 45 antibodies was observed in 2.3, 4.0, 5.3, 4.5 and 1.5 % of the women, respectively, with decay time varying from 27.2 to 35.8 months. These data imply that (i) a substantial proportion of young women are seropositive for both LR- and HR-HPV types, (ii) they frequently undergo seroconversion within 18-24 months, predicted by common covariates, and (iii) antibody decay over 3 years is rare.

Effect of second pregnancy on maternal carriage and outcome of high-risk human papillomavirus (HPV). Experience from the prospective finnish family HPV study.

OBJECTIVES: The effect of second pregnancy on human papillomavirus (HPV) carriage and outcome is modelled in longitudinal setting covering two subsequent pregnancies. STUDY DESIGN: Among 329 (baseline pregnant) women prospectively followed up in the Finnish Family HPV Study, two subcohorts were compiled: (i) 78 women (Group B) who became pregnant for the second time during the follow-up, and (ii) 100 women (Group A) who did not develop 2nd pregnancy. The effect of pregnancy on high-risk HPV (HR-HPV) carriage and outcome was analysed using Kaplan-Meier and Cox survival analyses and generalized estimating equation (GEE) modelling of the longitudinal data. RESULTS: Women in the two groups were similar in their baseline HR-HPV status but significantly different in several known risk factors of HR-HPV infection. Group A women showed higher point prevalence of cervical and oral HR-HPV at the 36-month (p = 0.015) and 6-month (p = 0.024) follow-up visit, respectively. Among Group B women, prevalence of both cervical and oral HR-HPV significantly decreased during 2nd pregnancy (p = 0.005 and p = 0.002) as compared with inter-pregnancy period, but increased again after 2nd pregnancy. There was no difference in acquisition or clearance of cervical or oral HR-HPV between the two groups in univariate (Kaplan-Meier) or multivariate (Cox) survival analysis. In the GEE approach, 2nd pregnancy was not significantly associated with cervical or oral HR-HPV carriage or persistence when adjusted for all other covariates. CONCLUSIONS: Second pregnancy is of little impact on carriage and persistence of oral and cervical HR-HPV infections in a longitudinal setting over time.

Human papillomavirus in the placenta and umbilical cord blood.

OBJECTIVE: To analyze human papillomavirus (HPV) DNA in umbilical cord blood and in placenta, including its cellular localization. DESIGN: Longitudinal prospective study. SETTING: Maternity Unit of Turku University Hospital, and MediCity, University of Turku. SAMPLES: Placental and cord blood samples obtained at delivery from 315 mothers and 311 neonates included in the Finnish HPV Family Study. METHODS: HPV testing by nested PCR and sequencing. Tyramide amplified in situ hybridization (ISH) for viral DNA localization in placenta. Correlation to mother's and neonate's oral and genital HPV status and maternal demographic data. MAIN OUTCOME MEASURES: Detection and cellular localization of HPV DNA. RESULTS: HPV DNA was detected in 4.2 and 3.5% of placenta and cord blood samples, respectively, including HPV types 16, 6, 83 and 39. In placenta, HPV6 and 16 DNA was localized in syncytiotrophoblasts. Abnormal cytology increased the risk of HPV+ placenta and cord blood. History of genital warts was the only independent predictor of cord blood HPV in multivariate analysis (adjusted OR=4.0, 95% CI: 1.09-14.54, p=0.036). HPV DNA in cord blood increased the risk of genital (OR=4.0, 95% CI: 1.08-14.83, p=0.048) and oral (OR=4.4, 95% CI: 1.17-16.14, p=0.039) HPV DNA carriage of the neonate. HPV+ placenta increased the risk of oral HPV of the neonate (OR=8.6, 95% CI: 2.73-27.13, p=0.0001). Delivery mode did not predict HPV status of the neonate. CONCLUSIONS: HPV DNA is detected in placental trophoblasts and umbilical cord blood. The presence of HPV DNA at these sites increases the risk of a neonate testing HPV-positive at birth.

Human papillomavirus DNA detected in breast milk.

Human papillomavirus (HPV) testing of 223 breast milk samples 3 days postpartum was performed with polymerase chain reaction, hybridization, and sequencing. HPV-16-DNA was detected in 4.0% of the samples. HPV carriage in the breast milk was not correlated with mother's oral or cervical HPV-status or the demographic data. Oral HPV-infection of the spouse at month 6 and 12 postpartum was statistically significantly associated with HPV carriage in the breast milk.

Natural history of oral papillomavirus infections in spouses: a prospective Finnish HPV Family Study.

BACKGROUND: The natural history of genital human papillomavirus infection is well known, but nearly nothing is known about the outcome of oral HPV-infection. OBJECTIVES AND STUDY DESIGN: To study natural history of oral HPV in spouses during the follow-up 331 women (mean 25.5+/-3.4 years) and 131 men (mean 28.8+/-5.0 years) were recruited from maternity unit. Scrapings from healthy oral mucosa of spouses at baseline, 2, 6, 12 and 24 months and genital samples were taken for HPV testing. HPV DNA was detected by nested PCR and confirmed by hybridization using a cocktail of 12 high-risk (HR) oligoprobes. RESULTS: The detection rate of HR HPVs varied from 15% to 27%. Baseline oral HPV status between the spouses was closely related (odds ratio 4.3; 95% confidence interval 1.6-12.0; P=0.006). Persistent oral infection in one spouse was a significant risk factor (odds ratio 10.0; 95% confidence interval 1.5-68.7; P=0.005) for oral HR HPV persistence in the other partner. Cumulative incidence of new HR HPV infections was identical in both spouses, while men seemed to clear their infection more rapidly. In univariate survival analysis, the partner's oral or genital HPV status, oral sex habits or age did not predict clearance or acquisition of oral HR HPV. CONCLUSION: Natural history of HPV infection in oral mucosa mimics that of genital HPV infection. Oral sex had no association to oral HPV infection, but a persistent oral HPV infection of the spouse increased the risk of persistent oral HPV infection 10-fold in the other spouse.

High-risk types of human papillomavirus (HPV) DNA in oral and genital mucosa of infants during their first 3 years of life: experience from the Finnish HPV Family Study.

BACKGROUND: This study is aimed to clarify data on the acquisition, persistence, and clearance of high-risk types of human papillomavirus (HPV) DNA from the mucosa and the determinants of persistent mucosal HPV infection in infants. METHODS: Oral and genital scrapings from 324 infants were collected at birth, 3 days after delivery, and 1, 2, 6, 12, 24, and 36 months after delivery and tested for the presence of HPV DNA by nested polymerase chain reaction and hybridization with 12 high-risk HPV oligoprobes. HPV status and demographic data for parents were analyzed. RESULTS: During the follow-up period (median duration, 26.2 months), HPV DNA was found to be present in 12%-21% of oral scrape samples and in 4%-15% of genital scrape samples obtained from the infants. Oral HPV infection was acquired by 42% of children, cleared by 11%, and persisted in 10% of the infants, whereas 37% were never infected. The corresponding figures for genital HPV infection were 36%, 14%, 1.5%, and 47%. Kaplan-Meier analysis revealed that both the cumulative incidence of infection and clearance of HPV were parallel in oral and genital sites. Persistent oral HPV infection in the child was significantly associated with persistent oral HPV infection in the mother at month 36 of follow-up, hand warts in the mother, young age at onset of sexual activity for the mother, and the mother's use of oral contraception, as well as with the father's oral HPV status at 24 months. Persistent genital HPV infection in the infant was predicted by if the mother had started smoking at 18-21 years of age and by a history of genital warts. CONCLUSIONS: Persistent carriage of high-risk HPV types was detected in oral and genital mucosa specimens obtained from 10% and 1.5% of the infants during their first 26 months of life. The rates of acquisition and clearance of HPV were similar in oral and genital mucosa.

Transmission of high-risk human papillomavirus (HPV) between parents and infant: a prospective study of HPV in families in Finland.

The Finnish HPV Family Study is a prospective cohort study assessing the dynamics of human papillomavirus (HPV) transmission between parents and infant. Serial genital and oral scrapings from 76 families, including mother, father, and infant, and semen samples were collected over 2 years of follow-up, analyzed by nested PCR, and confirmed by hybridization with 12 high-risk (HR) HPV types. The most common HPV profile was HR HPV in all family members (29%), followed by HPV-positive mother-infant pairs (26%). HPV-positive father-infant pairs were less frequent (11%), and in six (8%) families, only the infant was HR HPV positive. The prevalence of genital HR HPV in the parents ranged from 13 to 25%, and that of oral HPV ranged from 8 to 34%. In the infants, HPV DNA was detected in 15% of the genital and 10% of the oral samples at birth, reaching peaks of 18 and 21%, respectively, at 6 months, and declining to 10% at 24 months. Persistent HPV in the mother was a risk factor for oral HPV in the infant (odds ratio [OR], 5.69; 95% confidence interval [95% CI], 1.5 to 21.3), while oral HPV in the mother at 6 months was a risk factor for genital HR HPV (OR, 6.38; 95% CI, 1.15 to 35.32). No such independent risk could be attributed to subclinical HPV in the father. Persistent maternal cervical HPV and subclinical oral HPV affect the risk of infant HPV. The age of 6 months is a critical point for the infant to acquire or be free of HR HPV DNA.