Genetic characterization and clinical implications of human papillomavirus type 16 (HPV16) variants from northeastern Argentina

BackgroundHuman papillomavirus type 16 (HPV16) plays a central role in the development of cervical cancer. Worldwide studies indicate the existence of HPV16 variants that show different geographic distributions and oncogenic potential.ObjectiveOur goal was to describe the genetic variation of HPV16 isolates identified in urban women with different grades of cervical lesions living in northeastern Argentina.Study designWe analyzed 116 HPV16-positive cervical samples (16 NLIM, 62 L-SIL, 16 H-SIL and 22 cervical cancer) from patients attending health centers in Misiones (Argentina) during 2006–13. HPV16 isolates were genetically characterized through PCR amplification and direct sequencing of 364 bp within the long control region, and the resulting sequences classified into variants based on phylogenetic analysis (lineages A, B, C and D). A potential association between HPV16 variants and lesion grade was evaluated through an odds ratio (OR) test. A temporal framework for the origin of HPV16 variants was assessed through coalescence analysis (BEAST v 1.7.5).ResultsPhylogenetic analysis of HPV16 sequences showed that 92.1% of the samples clustered with lineage A, and 6.9% to lineage D. HPV16 variants from lineage D were more frequently associated with high-grade lesions and cancer (HSIL+) than lineage A variants at an OR of 13.8 (1.6–117.0). The time to most common recent ancestor (t_MCRA) of all variants was 119,103 years before present (HPD 95% = 48,486–197,239), a date consistent with the time frame for modern human evolution.ConclusionOur results suggest that HPV16 variants from lineage D may represent an additional risk factor for the development of cervical cancer in women living in northeastern Argentina. This study provides new information about viral isolates present in Argentina that will contribute to the monitoring of HPV16 infection in the vaccine era.     

Unexpected inverse correlation between Native American ancestry and Asian American variants of HPV16 in admixed Colombian cervical cancer cases

BackgroundEuropean (E) variants of HPV 16 are evenly distributed among world regions, meanwhile Non-European variants such as European-Asian (EAs), Asian American (AA) and African (Af) are mostly confined to Eastern Asia, The Americas and African regions respectively. Several studies have shown that genetic variation of HPV 16 is associated with the risk of cervical cancer, which also seems to be dependent on the population. This relationship between ethnicity and variants have led to the suggestion that there is co-evolution of variants with humankind. Our aim was to evaluate the relationship between the individual ancestry proportion and infection with HPV 16 variants in cervical cancer.MethodsWe examined the association between ancestry and HPV 16 variants in samples of 82 cervical cancer cases from different regions of Colombia. Individual ancestry proportions (European, African and Native American) were estimated by genotyping 106 ancestry informative markers. Variants were identified by PCR amplification of the E6 gene, followed by reverse line blot hybridization (RLB) with variants specific probes.ResultsOverall European (E) and Asian American (AA) variants frequency was 66.5% and 33.5% respectively. Similar distribution was observed in cases with higher proportions of European or African ancestry. A higher Native American ancestry was significantly associated with higher frequency of E variants (median ancestry > 23.6%, Age and place of birth adjusted OR: 3.55, 95% CI: 1.26–10.03, p = 0.01). Even further, an inverse geographic correlation between Native American ancestry and frequency of infections with AA variants was observed (ρ = −0.825, p = 0.008). Regions with higher proportion of Native American ancestry had a lower frequency of AA variants of HPV 16.ConclusionsThis study suggests replacement of AA variants by E variants of human papillomavirus 16 in cervical cancer cases with high Native American ancestry.     

Human papillomavirus type 16 lineage analysis based on E6 region in cervical samples of Iranian women

It is suggested that distinct HPV 16 variants differ in oncogenic potential and geographic distribution. As such, understanding the regional variants of HPV 16 would be of great importance for evolutionary, epidemiological and biological analysis. In this regard, the sequence variations of E6 gene were investigated to characterize more common variants of HPV 16 in normal cells, premalignant and malignant lesions of the cervix. In total, 106 isolates of HPV 16 were analyzed by PCR and sequencing. Overall, two different lineages (A and D) were identified. Lineage D comprised 70.7% of samples and the remaining 29.3% belonged to lineage A. Regarding to cytology/histology, lineage D was dominant in both normal + CIN I-II and CIN III + ICC groups as it was detected in 80% and 66.2% of cases, respectively. The comparison of the lineages between different groups (35 normal + CIN I-II samples and 71 CIN III + ICC samples) revealed that lineage A is more prevalent in cervical cancer cases (7 (20%) vs. 24 (33.8%)) although the difference observed did not reach statistical significance (p = 0.07). In conclusion, our findings confirm that HPV lineages A and D are more prevalent in Iran, with the lineage D as the most dominant in all studied groups.     

Differential presence of Papillomavirus variants in cervical cancer: An analysis for HPV33, HPV45 and HPV58

BackgroundCertain human papillomaviruses (HPVs) are the causative agents of cervical carcinomas in humans. The identification of the link between infection and cancer has resulted in the successful establishment of clinical strategies such as screening or vaccination programs, aiming to prevent this pathology. More than 150 different HPVs have been described and classified and the large majority of them are not related to cancer. The genus Alphapapillomavirus encompasses many PVs, some of which are identified in humans as oncogenic, according to the epidemiological connection between infection and cervical cancer. Variants of some of these “high-risk” HPVs may have an increased involvement in cervical cancer, although definitive data are still wanting. The aim of the present work was to analyze the presence of HPV33, HPV45 and HPV58 variants in cases of cervical cancer.MethodsSamples from cervical lesions in the context of different cervical cancer surveys were analyzed for presence of HPV DNA. Samples positive for HPV33, HPV45 or HPV58 DNA were selected and the E6/E7 genes were amplified and sequenced. The phylogenetic relationships of these sequences were inferred using an evolutionary placement algorithm and accordingly classified at the variant level.ResultsAll viral E6/E7 sequences were successfully placed in the classification schemes of the corresponding viruses. For HPV33 (n = 23), 45 (n = 61) or 58 (n = 29), the distribution of variants found in cases of cervical cancer is not a random sample of the corresponding diversity. In all three HPVs, the respective A variants were more prevalent in the viral DNA-positive cases of cervical cancer analyzed. This is the first study trying to discern the phylogenetic connection between variants of the oncogenic HPV33, 45 and 58, and squamous cell carcinoma of the cervix.     

The effect of methylenetetrahydrofolate reductase polymorphisms on susceptibility to human papilloma virus infection and cervical cancer

Cervical cancer is the third most common cancer among women worldwide. Several factors lead to cervical cancer, among which human papilloma virus (HPV) infection has a prominent role. Methylenetetrahydrofolate reductase (MTHFR) is crucial in folate metabolic pathway and plays an important role in DNA synthesis and DNA methylation. MTHFR gene polymorphisms, including C677T and A1298C, lead to reduced enzyme activity. This case-control study aims to illustrate the association between MTHFR gene polymorphisms and the risk of cervical cancer.This study was conducted on 196 samples, which included 96 cervical biopsy samples compared to 100 Pap smear samples of normal healthy women without HPV infection. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used for the MTHFR polymorphism detection, followed by fluorescent amplification-based specific hybridization PCR method to detect HPV16 and HPV18.The results show that the MTHFR 677TT genotype plays a protective role in cervical cancer (P = 0.0030) (OR = 0.21, 95% confidence interval [CI]: 0.07–0.59). Furthermore, there was a strong significant association between MTHFR 1298CC genotype and the risk of cervical cancer (OR = 10.69; 95% CI: 4.28–26.71, P = 0.0001).It can be concluded that A1298C polymorphism is a genetic risk factor for cervical cancer in the assessed Iranian population group. It seems that MTHFR 1298CC genotype is more susceptible to HPV 16 infection. Combination analysis of MTHFR C677T and A1298C polymorphisms revealed that combined MTHFR 677CC and 1298CC are strongly associated with a risk of cervical cancer.     

Distribution of human papillomavirus genotypes in invasive cervical cancer in Italy: A representative,single institution case series

Despite worldwide human papillomavirus (HPV) types distribution showed constant rates of HPV 16/18 in cervical cancers, regional variations have been consistently documented. Very little data is available on HPV genotype prevalence among Italian women with invasive cervical cancer. This study aims to determine the HPV type distribution in cervical specimens obtained from Italian women diagnosed with invasive cervical cancer and referred to the European Institute of Oncology (IEO).Two hundred-sixty eight cervical specimens were obtained from patients diagnosed with invasive cervical cancer referred to the European Institute of Oncology between 1996 and 2006.Following preparation, all cervical samples were sent to laboratories at the International Agency for Research on Cancer (IARC, Lyon, France) for DNA extraction and HPV typing by the multiplex PCR/APEX assay. The study population was divided into four groups from different macro regions: (i) Milan and surrounding area (n = 57, 21.3%), (ii) northern Italy (n = 81, 30.2%), (iii) central Italy (n = 64, 23.9%) and (iv) southern Italy (n = 66, 24.6%).The present study is the first at our knowledge that examines a fair number of Italian cervical cancers, about one tenth of all estimated cervical cancer cases occurring yearly, distributed across the whole country. Two-hundred and fifty-one patients (93.7%) resulted HPV DNA positive; of these 201 patients (80.1%) presented a single infection, whereas 50 women (19.9%) presented multiple infection. One hundred and eighty-nine specimens (75.3%) tested positive for either HPV 16 or HPV 18, whereas 62 (24.7%) resulted positive for other high-risk HPV genotypes only. The proportion of HPV 16/18 positive invasive cervical cancers was similar for all the four geographical Italian areas considered. A statistically significant association with younger age and earlier stage was observed for HPV 16/18 related invasive cervical cancers.The results demonstrate that the proportion of HPV 16/18 cervical cancers is fairly constant in all the areas and covers more than 70% of Italian cervical cancer cases. This observation strengthens the decision to start the vaccination programme in all the Italian regions. In addition, the present study provides new and original data on the genotype related differences of the disease that are worth of further investigation.     

Reduction in HPV 16/18-associated high grade cervical lesions following HPV vaccine introduction in the United States – 2008–2012

BackgroundPrevention of pre-invasive cervical lesions is an important benefit of HPV vaccines, but demonstrating impact on these lesions is impeded by changes in cervical cancer screening. Monitoring vaccine-types associated with lesions can help distinguish vaccine impact from screening effects. We examined trends in prevalence of HPV 16/18 types detected in cervical intraepithelial neoplasia 2, 3, and adenocarcinoma in situ (CIN2+) among women diagnosed with CIN2+ from 2008 to 2012 by vaccination status. We estimated vaccine effectiveness against HPV 16/18-attributable CIN2+ among women who received ≥1 dose by increasing time intervals between date of first vaccination and the screening test that led to detection of CIN2+ lesion.MethodsData are from a population-based sentinel surveillance system to monitor HPV vaccine impact on type-specific CIN2+ among adult female residents of five catchment areas in California, Connecticut, New York, Oregon, and Tennessee. Vaccination and cervical cancer screening information was retrieved. Archived diagnostic specimens were obtained from reporting laboratories for HPV DNA typing.ResultsFrom 2008 to 2012, prevalence of HPV 16/18 in CIN2+ lesions statistically significantly decreased from 53.6% to 28.4% among women who received at least one dose (P_trend < .001) but not among unvaccinated women (57.1% vs 52.5%; P_trend = .08) or women with unknown vaccination status (55.0% vs 50.5%; P_trend = .71). Estimated vaccine effectiveness for prevention of HPV 16/18-attributable CIN2+ was 21% (95% CI: 1–37), 49% (95% CI: 28–64), and 72% (95% CI: 45–86) in women who initiated vaccination 25–36 months, 37–48 months, and >48 months prior to the screening test that led to CIN2+ diagnosis.ConclusionsPopulation-based data from the United States indicate significant reductions in CIN2+ lesions attributable to types targeted by the vaccines and increasing HPV vaccine effectiveness with increasing interval between first vaccination and earliest detection of cervical disease.     

Perceived effectiveness of HPV test as a primary screening modality among US providers

BackgroundThe human papillomavirus (HPV) test, administered alone without the Papanicolaou (Pap) test, was recently recognized as a cervical cancer screening option in the United States by the Society of Gynecologic Oncology and the American Society for Colposcopy and Cervical Pathology, and the Food and Drug Administration has approved an HPV test for primary screening.MethodsSurveys of US internists, family practitioners, nurse practitioners, and obstetrician–gynecologists were conducted in 2009 and 2012 to investigate providers' perceptions of the effectiveness of the HPV test administered alone as a population-based screening modality (2009: N = 1040, 141–494 per provider group; 2012: N = 1039, 155–435 per provider group).ResultsThe majority in each provider group agreed that the HPV test administered alone is an effective screening modality in 2009 (75.3%–86.1%) and 2012 (79.5%–91.8%), and agreement rose significantly during this time period among family practitioners (χ² = 15.26, df = 1, p < 0.001) and nurse practitioners (χ² = 4.53, df = 1, p = 0.033).ConclusionsAgreement that the HPV test administered alone is an effective cervical cancer screening modality was widespread among providers in both 2009 and 2012, however implementation of guidelines for screening with the HPV test may be influenced by many other factors including reimbursement and patient preferences.     

HPV vaccine acceptance among adolescent males and their parents in two suburban pediatric practices

PurposeTo measure HPV vaccine acceptance among unvaccinated adolescent males and parents and correlate acceptance with knowledge, awareness, and personal experience.MethodsAdolescent males ages 11–21 years old and their parents completed questionnaires measuring attitudes and knowledge about HPV vaccination and personal experience. Acceptance was defined as wanting the vaccine and conditional acceptance as wanting the vaccine if it would protect against genital warts or cervical cancer.ResultsAdolescent (n = 154) and parent (n = 121) vaccine acceptance was low (16% and 34%, respectively); however, conditional acceptance was higher. While adolescents had similar conditional acceptance for a vaccine against genital warts and cervical cancer, parents reported higher conditional acceptance for protection against genital warts. Independent predictors of acceptance included personal experience and demographic variables.ConclusionsHPV vaccine acceptance among adolescents and parents was low. Conditional acceptance levels highlight the importance of education about a few important benefits of HPV vaccination, which may increase vaccination rates.     

Immunogenicity and safety of an E. coli-produced bivalent human papillomavirus (type 16 and 18) vaccine: A randomized controlled phase 2 clinical trial

BackgroundThis study aimed to investigate the dosage, immunogenicity and safety profile of a novel human papillomavirus (HPV) types 16 and 18 bivalent vaccine produced by E. coli.MethodsThis randomized, double-blinded, controlled phase 2 trial enrolled women aged 18–25 years in China. Totally 1600 eligible participants were randomized to receive 90 μg, 60 μg, or 30 μg of the recombinant HPV 16/18 bivalent vaccine or the control hepatitis B vaccine on a 0, 1 and 6 month schedule. The designated doses are the combined micrograms of HPV16 and 18 VLPs with dose ratio of 2:1. The immunogenicity of the vaccines was assessed by measuring anti-HPV 16 and 18 neutralizing antibodies and total IgG antibodies. Safety of the vaccine was assessed.ResultsAll but one of the seronegative participants who received 3 doses of the HPV vaccines seroconverted at month 7 for anti-HPV 16/18 neutralizing antibodies and IgG antibodies. For HPV 16, the geometric mean titers (GMTs) of the neutralizing antibodies were similar between the 60 μg (GMT = 10,548) and 90 μg (GMT = 12,505) HPV vaccine groups and were significantly higher than those in the 30 μg (GMT = 7596) group. For HPV 18, the GMTs of the neutralizing antibodies were similar among the 3 groups. The HPV vaccine was well tolerated. No vaccine-associated serious adverse events were identified.ConclusionThe prokaryotic-expressed HPV vaccine is safe and immunogenic in women aged 18–25 years. The 60 μg dosage formulation was selected for further investigation for efficacy.Clinical trials registration: NCT01356823.     

Factors related to vaccine uptake by young adult women in the catch-up phase of the National HPV Vaccination Program in Australia: Results from an observational study

BackgroundAustralia commenced a publically-funded, National Human Papillomavirus (HPV) Vaccination Program in 2007 with a two year catch-up phase for females aged 12–26 years.ObjectiveTo identify the factors associated with the uptake of the HPV vaccine (which has a recommended 3-dose schedule in Australia) by young adult women vaccinated by general practitioners and community-based programs within the catch-up phase.Methods1139 women who were eligible to receive the free HPV vaccine during the catch-up period were recruited in 2008–2009 (age 20–29 years at recruitment), in New South Wales, after having a normal (negative) cervical smear result recorded on the NSW Pap Test Register. Participants completed a self-administered questionnaire providing information on vaccination status, and sociodemographic and other factors.ResultsOverall, 880 (77%) women reported receiving ≥1 dose of the vaccine and 777 women (68%) reported receiving ≥2 doses. In multivariable analysis (adjusting for the period for which each woman was eligible for free HPV vaccination), uptake of ≥1 dose of the vaccine was significantly associated with being born in Australia (p < 0.01), being single (p = 0.02), being nulliparous (p < 0.01), living in a higher socioeconomic status area (p-trend = 0.03), living in more remote areas (p = 0.03), drinking alcohol (p < 0.01) and using hormonal contraceptives (p < 0.01). Although vaccinated women were more likely to have fewer sexual partners than unvaccinated women (p-trend = 0.02), they were also more likely to report a prior sexually transmitted infection (STI) (p = 0.03). Similar factors were associated with receiving ≥2 doses.ConclusionsIn this group, women living in higher socioeconomic status areas were more likely to be vaccinated against HPV in the catch-up phase of the national program. Although vaccinated women tended to have fewer sexual partners, they also reported prior STIs, which may be a marker of increased risk of prior exposure to HPV. The findings of this study reinforce the continuing need to prioritise equitable delivery of vaccination to various population subgroups.     

A phase III clinical study to compare the immunogenicity and safety of the 9-valent and quadrivalent HPV vaccines in men

BackgroundA nine-valent human papilloma virus (9vHPV) vaccine has been developed to prevent infections and diseases related to HPV 6/11/16/18 (as per the licensed quadrivalent HPV (qHPV) vaccine) as well as to five additional oncogenic HPV types (HPV 31/33/45/52/58). The 9vHPV vaccine has the potential to prevent 90% of cervical cancers, HPV-related anal, vaginal and vulval cancers and anogenital warts. We compared the immunogenicity and safety of the 9vHPV vaccine versus the qHPV vaccine in 16–26-year-old men.MethodsParticipants (N = 500) were randomised to receive 9vHPV or qHPV vaccines on day 1, month 2 and month 6. Serology testing was performed on day 1 and month 7. HPV type-specific antibody titres (anti-HPV 6/11/16/18/31/33/45/52/58) were determined by competitive Luminex immunoassay and expressed as geometric mean titres and seroconversion rates. Vaccine safety was also assessed.ResultsThe HPV 6/11/16/18 immune responses elicited by the 9vHPV vaccine were comparable with those elicited by the qHPV vaccine. All participants receiving the 9vHPV vaccine seroconverted for HPV 31/33/45/52/58. The 9vHPV and qHPV vaccines showed comparable safety profiles.ConclusionsIn addition to immune responses to HPV 31/33/45/52/58, a three-dose regimen of the 9vHPV vaccine elicited a similar immune response to HPV 6/11/16/18 when compared with the qHPV vaccine in men aged 16–26 years. The safety profile was also similar for the two vaccines. The results from this study support extending the efficacy findings with qHPV vaccine to 9vHPV vaccine in men aged 16–26 years.NCT02114385     

Safety and immunogenicity of a 9-valent HPV vaccine in females 12–26 years of age who previously received the quadrivalent HPV vaccine

ObjectivesTo assess the safety and immunogenicity of the investigational 9-valent (6/11/16/18/31/33/45/52/58) HPV (9vHPV) vaccine in prior recipients of a 3-dose regimen of quadrivalent (6/11/16/18) HPV (qHPV) vaccine.MethodsV503-006 was a randomized, double-blinded, safety/tolerability and immunogenicity study of the 9vHPV vaccine in females 12–26 years of age who were previously vaccinated with qHPV vaccine. Subjects were randomized in a 2:1 ratio to receive 3 doses of 9vHPV vaccine (n = 618) or saline placebo (n = 306) at day 1, month 2, and month 6. Systemic, injection-site and serious adverse experiences (AEs) were monitored. Serum samples were collected at day 1, month 2, and month 7. Anti-HPV 6/11/16/18/31/33/45/52/58 titers were measured using the 9-valent HPV competitive Luminex Immunoassay (cLIA).ResultsThe frequency of injection-site AEs (days 1–5 following any vaccination) was higher in the 9vHPV vaccine group than in the placebo group (91.1% and 43.9%, respectively). The frequencies of vaccine-related systemic AEs (days 1–15 following any vaccination) were generally comparable between the 2 groups (30.6% in the 9vHPV vaccine group, and 25.9% in the placebo group). One vaccine-related serious AE was reported in each of the 9vHPV vaccine and placebo groups. Few subjects (9vHPV = 0.5%; placebo = 0%) discontinued due to an AE. At 4 weeks post-dose 3, over 98% of subjects in the 9vHPV vaccine group were seropositive for HPV types 31/33/45/52/58, with marked elevations in cLIA geometric mean titers (GMTs) to these HPV types. Anti-HPV 31/33/45/52/58 GMTs were lower than in subjects administered 9vHPV vaccine who had not previously received qHPV vaccine (based on cross-study analyses); the clinical significance of this difference is unknown.ConclusionsAdministration of a 3-dose regimen of 9vHPV vaccine to adolescent girls and young women 12–26 years of age who are prior qHPV vaccine recipients is highly immunogenic with respect to HPV types 31/33/45/52/58 and generally well tolerated.     

Allopatric tuberculosis host–pathogen relationships are associated with greater pulmonary impairment

BackgroundHost pathogen relationships can be classified as allopatric, when the pathogens originated from separate, non-overlapping geographic areas from the host; or sympatric, when host and pathogen shared a common ancestral geographic location. It remains unclear if host–pathogen relationships, as defined by phylogenetic lineage, influence clinical outcome. We sought to examine the association between allopatric and sympatric phylogenetic Mycobacterium tuberculosis lineages and pulmonary impairment after tuberculosis (PIAT).MethodsPulmonary function tests were performed on patients 16 years of age and older who had received ⩾20 weeks of treatment for culture-confirmed M. tuberculosis complex. Forced Expiratory Volume in 1 min (FEV1) ⩾80%, Forced Vital Capacity (FVC) ⩾80% and FEV1/FVC >70% of predicted were considered normal. Other results defined pulmonary impairment. Spoligotype and 12-locus mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU-VNTR) were used to assign phylogenetic lineage. PIAT severity was compared between host–pathogen relationships which were defined by geography and ethnic population. We used multivariate logistic regression modeling to calculate adjusted odds ratios (aOR) between phylogenetic lineage and PIAT.ResultsSelf-reported continental ancestry was correlated with Mycobacterium. tuberculosis lineage (p < 0.001). In multivariate analyses adjusting for phylogenetic lineage, age and smoking, the overall aOR for subjects with allopatric host–pathogen relationships and PIAT was 1.8 (95% confidence interval [CI]: 1.1, 2.9) compared to sympatric relationships. Smoking >30 pack-years was also associated with PIAT (aOR: 3.2; 95% CI: 1.5, 7.2) relative to smoking <1 pack-years.ConclusionsPIAT frequency and severity varies by host–pathogen relationship and heavy cigarette consumption, but not phylogenetic lineage alone. Patients who had disease resulting from allopatric–host–pathogen relationship were more likely to have PIAT than patients with disease from sympatric–host–pathogen relationship infection. Further study of this association may identify ways that treatment and preventive efforts can be tailored to specific lineages and racial/ethnic populations.     

Antibody persistence and evidence of immune memory at 5 years following administration of the 9-valent HPV vaccine

BackgroundThe 9-valent HPV (9vHPV) vaccine was developed to prevent infection and disease related to 9 HPV types (HPV6/11/16/18/31/33/45/52/58) which cause approximately 90% of cervical cancers, HPV-related vulvar, vaginal and anal cancers, and genital warts worldwide. In a pivotal efficacy study, the 9vHPV vaccine prevented infection and disease due to the 9 vaccine types. Duration of protection remains to be determined. Vaccines that induce long-term protection are generally characterized by the generation of immune memory. The purpose of this report is to assess the persistence of HPV antibody response and existence of immune memory at 5 years post-vaccination.MethodsA subset of subjects (N = 150) who received 3 doses of 9vHPV vaccine at day 1, month 2 and month 6 in the pivotal efficacy study continued in a study extension and received a fourth dose of 9vHPV vaccine at month 60. Serum HPV antibody levels were measured pre-dose 4 and at 7 and 28 days post-dose 4 by competitive Luminex immunoassay. Adverse events were assessed using a vaccination report card.ResultsHPV antibodies induced following the 3-dose series of 9vHPV vaccine in the base study persisted through month 60 with seropositivity rates ranging from 77.5% to 100%. Geometric mean titers at 1 week and 1 month post-dose 4 were 1.25–4.10 and 1.65–4.88-fold higher, respectively, than levels observed 1 month following the completion of the three-dose primary series. Seropositivity rates were >99% and 100% at 1 week and 1 month post-dose 4, respectively. The fourth dose of 9vHPV vaccine was generally well tolerated.ConclusionsA three-dose regimen of the 9vHPV vaccine induced persistent HPV antibody response through 5 years post-vaccination. Administration of a fourth dose resulted in a strong anamnestic response to all 9 vaccine types. These findings suggest that the efficacy of the 9vHPV vaccine will be long lasting.Clinical Trials.gov Identifier: NCT00543543.     

Knowledge and attitude of students studying at health department towards HPV and HPV vaccination

The human papillomavirus (HPV) is the most common diagnosed sexually transmitted infection in the world. The most frequent disease linked to HPV is cervical cancer as well as other cancers including those of the vulva, vagina, penis, anus, and oropharynx.Our research sought to evaluate the knowledge and attitudes concerning human papillomaviruses and their vaccine among students enrolled in Alt?nba? University's faculties of health sciences.MethodA cross-sectional study was carried out using a survey containing 41 questions about demographic variables, knowledge, and attitudes toward HPV and HPV vaccines. The questions were distributed to students via Google form using social media applications such as WhatsApp.ResultsThe study involved 144 students, 71.5 % of whom were female. 37.5 % of the participants learned about HPV from social media. Knowledge of HPV is present in 82 % of females and 25 % of males. Most of the questions had more accurate replies from female than from male students p < 0.05. As a result, 88 %, 46 % of female respondents and 27 %, 14 % of male respondents, respectively, correctly answered the questions about who should receive HPV vaccinations p < 0.001 and how many doses are necessary.ConclusionParticipants' awareness of HPV, HPV vaccination, and cervical cancer was rather high when compared to other research. However, there are knowledge gaps that need to be corrected and provided through educational programs.     

Improving adolescent HPV vaccination in a randomized controlled cluster trial using the 4 Pillars™ practice Transformation Program

ObjectiveUptake of meningococcal vaccine (MCV) and tetanus, diphtheria and pertussis (Tdap) vaccine among adolescents has approached Healthy People 2020 goals, but human papillomavirus (HPV) vaccination has not. This study evaluated an intervention using the 4 Pillars™ Practice Transformation Program to increase HPV, MCV and Tdap uptake among adolescents in primary care practices.MethodsPractices with at least 50 patients 11–17 years old with estimated vaccination rates less than national goals, were assigned to intervention (n = 11) and control (n = 11) groups in a randomized controlled cluster trial; 9 intervention and 11 control sites completed the study. The baseline and active study periods were 7/1/2013–6/30/2014 and 7/1/2014–3/31/2015, respectively. Vaccination and demographic data for patients who had a visit in both study periods were derived from de-identified EMR extractions. Primary outcomes were vaccination rates and percentage point (PP) changes. Data were analyzed in 2015–16.ResultsAmong the cohort of 10,861 adolescent patients, 38% were 11–13 years old; 50% were female; 18% were non-white; and 64% were commercially insured. Average baseline HPV initiation rates were 52.5% for intervention and 61.8% for control groups. After 9 months, the intervention sites increased HPV initiation 10.2 PP compared with 7.3 PP in control sites (P < 0.001); HPV series completion rates did not differ between groups. Implementation of >10 strategies to improve rates significantly increased the likelihood of HPV series initiation (OR = 2.06, 95% CI = 1.43, 2.96).ConclusionsUsing >10 strategies from the 4 Pillars™ Practice Transformation Program is effective for increasing HPV series initiation among adolescents.Clinical trial registry number: NCT02165722.     

Modification and validation of the Treatment Self Regulation Questionnaire to assess parental motivation for HPV vaccination of adolescents

BackgroundAccording to Self-Determination Theory, the extent to which the motivation underlying behavior is self-determined or controlled influences its sustainability. This is particularly relevant for behaviors that must be repeated, such as completion of the human papillomavirus (HPV) vaccine series. To date, no measures of motivation for HPV vaccination have been developed.MethodsAs part of a larger study, parents (N = 223) whose adolescents receive care at safety-net clinics completed a telephone questionnaire about HPV and the vaccine. We modified the Treatment Self-Regulation Questionnaire to assess parents’ motivation for HPV vaccination in both Spanish and English. We used confirmatory factor analysis to test a three-factor measurement model.ResultsThe three-factor model fit the data well (RMSEA = 0.04, CFI = 0.98, TLI = 0.96), and the scales’ reliabilities were adequate (autonomous: α = 0.87; introjected: α = 0.72; external: α = 0.72). The factor loading strength for one item was stronger for Spanish- than English-speaking participants (p < 0.05); all others were equivalent. The intercorrelations among the scales ranged from −0.17 to 0.32, suggesting discriminant factors. The scales displayed the expected pattern of correlations with other psychosocial determinants of behavior. Vaccination intentions showed a strong correlation with autonomous motivation (r = 0.52), but no correlation with external motivation (r = 0.02), suggesting autonomous motivation may be particularly important in vaccine decision-making.ConclusionFindings support the use of three subscales to measure motivation in HPV vaccination and suggest possible cultural differences in motivation.     

HPV vaccine for teen boys: Dyadic analysis of parents' and sons' beliefs and willingness

ObjectiveParents and adolescents often decide together whether the child should receive human papillomavirus (HPV) vaccine. However, few studies have investigated the dyadic nature of beliefs that affect this process.MethodData came from the 2010 HPV Immunization in Sons (HIS) Study, a national sample of 412 parents and their adolescent sons. We conducted dyadic multivariate logistic regression to examine the relationships between parents' and sons' HPV vaccine beliefs and their willingness to have the son receive the vaccine.ResultsLess than half of parents and sons were willing to have the sons receive HPV vaccine (43% and 29%, respectively). Willing parents and sons anticipated greater regret if the son did not receive HPV vaccine but later contracted an HPV infection (parent odds ratio [OR] = 1.72, 95% confidence interval [CI] = 1.24–2.40; son OR = 1.51, 95% CI = 1.04–2.19) (both p < .05). Lower concerns about side effects, such as pain and fainting, were also associated with willingness.ConclusionParents and sons were more willing to have the son receive HPV vaccine if they had higher anticipated regret about potential HPV infection and lower concerns about side effects. Communication campaigns may be able to target these beliefs to increase parents' and sons' willingness to seek HPV vaccination.