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Changes in HPV Seroprevalence from an Unvaccinated toward a Girls-Only Vaccinated Population in the Netherlands
Hella Pasmans, Joske Hoes, Liza Tymchenko, Hester E. de Melker and Fiona R.M. van der Klis
Hella Pasmans
Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
For correspondence: hella.pasmans@rivm.nl
Joske Hoes
Liza Tymchenko
Hester E. de Melker
Fiona R.M. van der Klis
DOI: 10.1158/1055-9965.EPI-20-0596 Published November 2020
Background: In the Netherlands, bivalent human papillomavirus (HPV) vaccination was included in the National Immunization Program for 12-year-old girls in 2010 (vaccination coverage, 45%–60%). We examined possible changes in HPV seroprevalence in the HPV-unvaccinated Dutch population aged 0–89 years, comparing prevaccination data with data of approximately 6 years after implementation of national vaccination.
Methods: Serum samples of men and women were used from two cross-sectional population-based serosurveillance studies performed before (2006–07, n = 6,384) and after (2016–17, n = 5,645) implementation of HPV vaccination in the Netherlands. Seven high-risk HPV-specific antibodies (HPV16, 18, 31, 33, 45, 52, and 58) were tested in a virus-like particle-based multiplex immunoassay.
Results: Type-specific HPV seroprevalence increased in women between 2006–07 and 2016–17. Also, a higher seroprevalence for at least one type in women >15 years was found in 2016–17 (31.7%) compared with 2006–07 (25.2%). In men, overall HPV seroprevalence remained similar; however, a lower seroprevalence was found for HPV16 in 2016–17 (7.5%) compared with 2006–07 (10.6%).
Conclusions: Our results indicate an increase in high-risk HPV types in women and a rather stable exposure in men. No clear effects of the strategy of girls-only vaccination were observed in men, probably because of the short time after introduction combined with suboptimal coverage.
Impact: No herd immunity has been observed yet in a population with suboptimal HPV vaccination coverage.
Human papillomavirus (HPV), a virus capable of infecting the epithelial cells of the mucosa, is the cause of anogenital warts and cervical cancer (1). Besides cervical cancer, HPV is also linked to various other cancers in the anogenital tract and oral cavity (2). By routine HPV vaccination and effective cervical cancer screening programs, countries can reduce the burden of HPV-related disease.
All current globally available vaccines provide protection against HPV types 16 and 18, for example, and are included in the current bivalent vaccine. HPV types 6 and 11 are added in the quadrivalent vaccine and the nonavalent vaccine included additional HPV types 31, 33, 45, 52, and 58. Vaccination against HPV has been implemented in many countries, with the primary aim to protect women against cervical cancer. In the Netherlands, the bivalent HPV vaccine was implemented in the Dutch National Immunization Program as a girls-only vaccine for 12-year olds in a three-dose schedule in 2010, and is currently still being used, protecting them against HPV types 16 and 18. In addition, a catch-up campaign was initiated for girls from the birth cohorts 1993–1996 (i.e., 13–16 year olds) in 2009. From 2014 onward, the Netherlands shifted to a two-dose schedule (starting from birth cohort 2001 onward). The HPV vaccination coverage in girls in the Netherlands varied from 2009–2017 from 45% to 62% (3).
To gain information about previous HPV exposure, HPV serology is established as an important tool for population-based studies (4). This provides a view on type-specific cumulative lifetime exposure to HPV. Antibodies against HPV L1 virus-like particles (VLP) remain stable over time, and therefore reflect past infection and cumulative exposure. However, not everyone who contracted HPV will seroconvert, and the rate of seroconversion is known to be sex dependent (5). After HPV vaccination, HPV-specific antibodies are 10–100 times higher than (natural) infection-induced antibodies in serum (6), and therefore could be used to monitor vaccine uptake.
We assessed the (natural) infection-induced HPV seroprevalence for seven high-risk (hr) HPV types in the Dutch population in 2006/2007 (i.e., 4 years before the introduction of HPV) and 2016/2017 (i.e., 6 years postvaccination implementation). In addition, we investigated the effects of the introduction of the HPV vaccination on the seroprevalence of HPV types in our population.
Serum samples from two cross-sectional population-based serosurveillance studies performed from February 2006 to June 2007 and from September 2016 to October 2017 in the Netherlands were used for this study. Participants were 0–79 years of age in the 2006–2007 survey (n = 6,384), and 0–89 years of age for the 2016–17 cohort (n = 5,645). Study designs have been previously described in detail (7, 8). Briefly, the randomly invited participants were asked to fill in a questionnaire and to provide a blood sample. Questionnaires of both surveys included data on demographic characteristics, ethnicity (first- and second-generation migrants), vaccination history, and sexual behavior. Vaccination history was determined via the individuals' registration booklet and the Dutch vaccination registration Praeventis (9). The questionnaire used in 2006–7 was extended in the 2016–17 survey with more questions regarding sexual behavior. Information related to sexual behavior was only available from participants older than 14 years of age in both the 2006–07 study and the 2016–17 study.
We obtained written informed consent from all participants or their guardians before participation. The studies were conducted in accordance with recognized ethical guidelines (the Declaration of Helsinki) and were approved by an institutional review board "The Medical Ethics Committee Noord-Holland" in the Netherlands (METC number: ISRCTN 20164309 and M015–022).
Serologic measurement
Serum samples of both surveys were stored at −80°C until analysis, samples were measured at random for age and sex. For the measurement of HPV-specific IgG serum antibodies against L1 VLP of HPV16, 18, 31, 33, 45, 52, and 58, a VLP-based multiplex immunoassay was used as described previously (10). GSK (2006–07 survey) and MSD (Merck Sharp & Dohme; 2016–17 survey) produced the HPV-VLPs in used these studies. Briefly, VLPs were conjugated to seven distinct fluorescent microspheres via amine coupling. Serum samples were 1/50, 1/100, or 1/10,000 diluted and incubated with the VLP-coupled microspheres. HPV-specific IgG serum antibodies were detected using a secondary goat anti-human phycoerythrin-labeled antibody. Four in-house control sera and an in-house standard were used on each plate. The in-house standard (IVIG, lot LE12H227AF, Baxter) was calibrated against reference serum of GSK for all the seven HPV types. HPV-specific IgG antibodies were analyzed using the Bioplex system 200 with Bioplex software (Bio-Rad Laboratories). Samples were assumed to be seropositive above cutoffs according to the 99% Frey method (with 99% one-sided t values, based on concentrations measured in children of 1–10 years old (n = 859; ref. 11) and found to be 9, 13, 27, 11, 19, 14, and 31 Luminex units/mL (LU/mL; ref. 10) for HPV16, 18, 31, 33, 45, 52, and 58, respectively. As samples from 2016–17 were measured using a different batch of VLPs than those used in 2006–07, a correction formula was applied on the data of the 2016–17 survey. This correction formula was based on retesting of a random subset of 160 samples of the 2006–07 samples with the new VLPs. The correction formula was applied to the 2016–17 antibody measurements to align them with the 2006–07 measurements.
Data analyses were conducted using SAS version 9.4 and GraphPad Prism version 8.0.2. Women who were vaccinated against HPV according to the vaccination registry (n = 228) were excluded from analysis. In addition, women under 31 years of age and with arbitrary antibody concentration cutoff of >100 LU/mL for HPV16 and >50 LU/mL for HPV18 were considered to be "highly likely to have been vaccinated" and were excluded from the analyses (n = 18). Characteristics of the study population were compared among the 2006–2007 cohort and the 2016–2017 cohort using χ2 tests. Seroprevalence for "any" or "all" hr-HPV-type(s) refer to the seven hr-serotypes that have been measured in this study. The study design (i.e., a two-stage cluster sampling method including specific regions and municipalities from which participants were invited) was taken into account in the analyses, as well as weights determined proportional to the reference population (Dutch population, January 1, 2007 and January 1, 2017, respectively) taking into account sex, age, ethnic origin, and urbanization degree. Seroprevalences were calculated per age-cohort and as large differences already have been observed between men and women (10), analyses were stratified for men and women. Crude seroprevalences of the different cohorts, age groups, and/or sexes were compared using Monte Carlo simulations. Parameters of the beta distribution for both seroprevalences were estimated and used in the simulations to obtain P values. Geometric mean concentrations (GMC) were calculated among HPV16 and HPV18 seropositive individuals from both cohorts, taking the study design into account. P values of <0.05 were considered statistically significant.
The associations between HPV seropositivity (positive for at least one out of the seven HPV types) in sexually active individuals older than 14 years of age who were not vaccinated and demographic characteristics (age, ethnic origin, degree of urbanization, education level, and socioeconomic status), was examined for the 2016–2017 cohort for men and women separately. In addition, associations with (sexual) behavior characteristics were taken into account, including: body mass index (BMI), alcohol consumption, smoking, having a steady partner, age of sexual debut (being defined as the first time of vaginal and/or penile intercourse), condom use at last sex act, number of partners in the last 6 months, lifetime number of partners, and reported history of STI (note: participants with missing values for a specific variable were allocated to a unknown category). We used generalized estimation equation (GEE) logistic regression models with a log link function and robust error variance. The incorporation of a GEE with exchangeable correlation structure accounted for dependency of multiple HPV types within an individual. First, univariate logistic regression analyses were conducted to study characteristics associated with HPV seropositivity. Variables that had P < 0.1 in univariate analyses were included in the multivariate analysis and backward selection (dropping variables one-by-one) was then applied. Hence, a multivariate model only including independently associated risk factors (P < 0.05) remained.
To study the differences in seroprevalence between the 2006–2007 and 2016–2017 cohort more closely, a pooled dataset was created including all HPV-unvaccinated participants from both cohorts. Again, the association between HPV seropositivity in sexually active individuals older than 14 years of age and demographics and sexual behavior characteristics was studied, in addition to the variable defining the cohort. Only characteristics available from both surveys were considered for inclusion in the model. Using a Poisson regression with robust error variance, we first calculated the crude prevalence ratio (PR). Next, we included the variables of interest to adjust for differences between the two surveys resulting in an adjusted PR (aPR). The analyses were performed for seroprevalence of any HPV type as well as type-specific. In addition, we stratified the analyses for men and women; we assumed that if herd effects on seroprevalence were to be observed this short after HPV vaccine introduction, this would be among men (first-order effect), in particular, younger males. Therefore, we looked also into the aPR for younger males (15–39 years of age).
Study and participant characteristics
We tested 5,645 serum samples, with corresponding response rates of 13.2% for men and 18.4% for women from the 2016–17 survey, and 6,384 serum samples, with corresponding response rates 28.9% for men and 34.7% for women from the 2006–07, which were tested previously (10, 12). Study characteristics were stratified for sex. In the 2016–17 survey, for both men and women, participants of 15 years and older were higher educated and had a higher net monthly income in comparison with both men and women in the 2006–07 survey. The mean age of sexual debut for people under 25 years of age was similar between the different surveys and sexes. However, age of sexual debut across all ages was lower in the 2016–17 survey compared with 2006–07 survey, for both men and women. In addition, the percentage of participants reporting to have a current steady partner was lower in 2016–2017, while "the number of sex partners in the last 6 months" and "ever having been diagnosed with a sexually transmitted disease (STD)" were higher in the 2016–17 survey compared with 2006–07 (Table 1).
Sociodemographic and sexual behavior characteristics of participants aged 15 years and older without vaccination, with a blood sample for HPV IgG antibody determination in the Netherlands, by sex and survey.
HPV Seroprevalence
Age-specific seroprevalence and GMC in an unvaccinated population, by sex and survey
An increase in seroprevalence for any hr-HPV type was observed in women in the age cohort from 15–19 years old, which reflects the median age of sexual debut. In the 2016–17 survey, seroprevalence for any type increased from 3.0% (10–14 years old) to 30.5% (20–24 years old) and 33.7% (25–29 years old) and peaked at 37.0% in the 30–39 year old. The greatest rise was seen for HPV16 and HPV18. This increase in seroprevalence was much more gradual for men, and mainly in the 2006–07 survey was most pronounced for any hr-HPV type and HPV16 (Fig. 1). Samples sizes of age cohorts can be found in Table 1 and Supplementary Table S1.
Age-specific seroprevalence (%; with 95% CIs) of any high-risk type HPV IgG antibodies for men (A) and women (B), HPV 16 for men (C) and women (D), and HPV18 for men (E) and women (F) in the unvaccinated general population of the Netherlands.
Low seroprevalences were observed in children 0–14 years of age in both sexes and surveys. In the 2016–17 survey, the highest seroprevalences in children (0–14) were detected for HPV16 and HPV18 (Fig. 1).
In the older female age groups, overall seroprevalence decreased from the age of 49 years onward in the 2006–07 survey and from 60–69 years onward in the 2016–17 survey. Age-specific higher seroprevalence for any hr-HPV type was observed in 2016–17 compared with 2006–07, being significant in age groups 30–39 (P = 0.0108), 50–59 (P = 0.0406), and 60–69 (P = 0.0056) years of age. A lower seroprevalence for any hr-HPV type was observed in the age group 10–14 (P = 0.0118) in 2016–17 compared with 2006–07. In men, a lower age-specific seroprevalence for any hr-HPV type was observed in 2016–17 compared with 2006–07, being only significant in the age groups 10–14 (P = 0.0056). No significant difference was found for the age-specific seroprevalence for any hr-HPV type excluding 16 and 18 in the age groups 10–14 and 15–19 years of age between the two surveys, P = 0.091 and P = 0.1206, respectively.
Overall HPV seroprevalence from unvaccinated individuals 15 years and onward
Unvaccinated female participants older than 15 years of age showed significantly higher seroprevalence for any hr-HPV type in 2016–17 compared with 2006–07; 31.4% [95% confidence interval (CI), 29.1–33.7] and 25.2% (95% CI, 23.1–2.3), respectively. For men from 15 years of age and older, seroprevalence for any hr-HPV type was similar between the 2006–07 and 2016–17 surveys; 19.7% (95% CI, 17.9–21.6) and 20.3% (95% CI, 18.4–22.1), respectively. In women, also seropositivity for one up to all seven types was significantly higher in 2016–17 and hr-type specific. Type-specific HPV16, HPV18, HPV31, and HPV58 were higher in 2016–17 compared with 2006–07, which was also true for the combinations HPV16 and 18, HPV16 or 18, and HPV16 and/or 18 (Table 2).
Weighted seroprevalence, and corresponding 95% CIs, for seven high-risk HPV types and combinations in the total population of the Netherlands from 15 years of age without vaccination, stratified by sex and survey.
For men, this was true for the combination HPV16 or 18, positivity for more than two hr-HPV types and type-specific HPV18, 31, 33, 45, 52, and 58. For HPV16 a lower seroprevalence was seen in 2016–17 (7.5%; 95% CI, 6.5–8.5) compared with 2006–07 (10.6%; 95% CI, 9.2–12.0). Just as for the combination HPV16 and 18, HPV16 and/or HPV18 and positivity for more than one hr-HPV type (Table 2). HPV16 was also most prevalent in both surveys, followed by HPV18, HPV45, and the rest of the types (Table 2). Only a very small percentage of the males were seropositive for all seven hr-HPV types, 0.6% and 0.3% for 2006–07 and 2016–17, respectively.
HPV type-specific antibody concentrations among seropositive individuals
The age-specific HPV16 GMCs of (natural) infection-induced seropositive women as well as of seropositive men were comparable in all age cohorts between both studies. No differences were found between the GMCs of the HPV16 and HPV18 seropositive individuals between 2006–07 and 2016–17 (Supplementary Fig. S3).
Risk factors for hr-HPV seropositivity
For women, the univariate analysis showed an association for HPV seropositivity for any hr-HPV type with middle educational level, being a first- or second-generation migrant, having a lower income, ever used alcohol, not having a steady partner, lower age of sexual debut, having more than two sexual partners last 6 months, history of reported STD, and having more than two sexual partners during lifetime. In the backward selection model, low and middle educational level, first-generation migrants, more than two sexual partners during lifetime, and history of self-reported STDs remained and were independently associated with seropositivity for any hr-HPV type (Table 3A and B).
Table 3A.
Risk factor analysis for any high-risk type HPV IgG seropositivity among sexually active and unvaccinated participants from 15 years of age in the Netherlands, by sex.
Table 3B.
For men, the univariate analyses showed only an association of seropositivity for any hr-HPV type with history of self-reported STDs (Table 3A and B).
Pooled risk factor analysis associated with HPV seropositivity for the 2006–07 and 2016–17 surveys
HPV seropositivity for any hr-HPV type for women from 15 years onward was 25.2% in 2006–07 and 31.4% in 2016–17. After pooling both surveys, and adjusting for demographic characteristics (age, sex, urbanization, education, income, ethnicity) and sexual risk factors (age of sexual debut, number of partners during the last 6 months, history of STDs), this resulted in a smaller, but still significant, difference between 2006–07 and 2016–17, (aPR 1.16; 95% CI, 1.02–1.32). Before adjustment of any variables, all seven hr-HPV types were significantly higher in 2016–17 compared with 2006–07. However, after adjustment for the demographic characteristics and sexual risk factors, the differences remained only significant for HPV16 (aPR 1.29; 95% CI, 1.07–1.55), HPV18 (aPR 1.31; 95% CI, 1.01–1.70), HPV31 (aPR 1.54; 95% CI, 1.111–2.14), and HPV52 (aPR 1.27; 95% CI, 1.00–1.62; Table 4).
Pooled analysis of the 2006–7 and 2016–17 survey after adjustments for sociodemographic characteristics.
For men from 15 years onward, HPV seropositivity for any hr-HPV type was significantly lower in 2016–17(18.2%) compared with 2006–07 (20.3%). After adjustment for the demographic characteristics and sexual risk factors, this did not remain significant (aPR 0.99; 95% CI, 0.83–1.17). Before adjustment, HPV16, HPV18, and HPV31 were significantly lower in 2016–17 compared with 2006–07 and HPV45 was significantly higher in 2016–17 compared with 2006–07. This difference only remained significant for HPV16 after adjustment (aPR 0.71; 95% CI, 0.55–0.91; Table 4) and HPV45 (aPR 1.47; 95% CI, 1.13–1.92). Zooming in on men in the age cohort of 15–39, a nonsignificant decrease for HPV16 between 2006–07 and 2016–17 was observed (aPR 0.84; 95% CI, 0.52–1.37).
In this study, we assessed the (natural) infection-induced seroprevalence of seven hr-HPV types in the Dutch population before and 6 to 7 years after the introduction of a girls-only bivalent HPV vaccination program, with an uptake varying over the years between 42% and 61%. Surprisingly, HPV seroprevalence in female age cohorts of 15 years and older has increased in a 10-year time period, mainly due to a significant increase in HPV16, 18, 31, and 58. In men, however, seroprevalence for any hr-HPV type remained similar with a decreasing trend found for HPV16 and increasing trend for HPV45.
We restricted the analyses to unvaccinated individuals thereby estimating naturally acquired and cumulative type-specific HPV exposure. The increase in seroprevalence with age for women was in line with the age of sexual debut. The peak in HPV seropositivity was highest in women ages 30–39, which has been reported in other publications (13–15). This peak in seroprevalence around 10 to 20 years after sexual debut might reflect repeated exposures resulting in a subsequent increase of the seroconversion rate to induce a detectable antibody response (16).
In the 2006–07 survey, the seroprevalence in middle-aged and older women declined at an earlier age than in the 2016–17 survey, where levels started to decrease from 70 years and onward. In males, this decline in HPV seropositivity is not seen. The slight decrease of seropositivity observed in older women could be explained by waning of antibodies which was suggested by af Geijersstam and colleagues (4). This would mean that seroprevalence is underestimating lifetime cumulative exposure. Alternatively, it could reflect a cohort effect, which is more likely as this effect is not seen in both sexes. Indeed, although age of sexual debut is similar, the sexual behavior pattern differs in the younger women having more lifetime sexual partners than the older women in this cohort (17).
Hr-HPV antibodies, albeit at very low concentrations, could be detected in children, which confirm other population studies (10, 16). These antibodies might be derived from vertical or horizontal transmission (18).
In both surveys, a lower seroprevalence is observed in males compared with women, which conform other population studies (10, 13, 15, 16, 19). It is unlikely that the overall lower seroprevalence seen in males is due to lower infection rates, because males reported a significantly higher number of lifetime sexual partners compared with females in the 2016–17 cohort. HPV DNA prevalence studies showed similar results among both sexes (20, 21). The fact that women display a higher seroprevalence then men is likely to be explained by the anatomic site of the HPV infection, influencing its immune response. Infections at the epithelium of the cervix and anal tract induce higher immune response in comparison with infections that occur at the keratinized epithelia, such as genital skin (22–25).
Seroprevalence for HPV16 was highest of all HPV types in both surveys, which is in accordance with other population studies (15, 16, 26–29). In a 10-year time period, HPV type-specific seroprevalence for HPV16, 18, 31, and 58 has increased in the female population of 15 years and older in the Netherlands. In addition, being seropositive for one up to all seven types increased over the years. This is possibly explained by the observed change toward a higher number of sexual partners in the last 6 months and history of self-reported STDs in the 2016–17 survey compared with the 2006–07 survey.
The risk factor analysis was restricted to the HPV unvaccinated, sexually active population from 15 years onward and stratified for sex. For women several behavioral factors, such as number of lifetime partners, history of STDs, and ethnicity, were independently associated with HPV seropositivity, which was also found in other studies (10, 15, 30, 31). Alcohol use and smoking were only associated with HPV seropositivity in the univariate model. This is especially interesting with respect to the current increased risk in HPV-associated head and neck cancers (32, 33). In these studies, alcohol use is often allied together with tobacco use; however, in our study, we could not find an association with smoking or alcohol use in the multivariate model. Other studies find varying results, showing a negative association (29), a positive association (14, 34), or no association at all (35). Thereby leaving the relation between smoking and HPV seropositivity unclear.
In the male part of our study, we only found history of self-reported STDs to be significantly associated with HPV seropositivity in the univariate analyses. In the backward selection model, this factor did not remain independently associated with HPV seropositivity anymore. Comparison with other studies is challenging as most population studies combine men and women in their risk factor analysis. Studies including separate male analysis reported a variety of associated factors. Most consistent findings were associations related to age (13, 31, 36–42), number of male anal sexual partners (30, 40, 41, 43), and (self-reported) circumcision (44). Number of male anal sexual partners and (self-reported) circumcision were unfortunately not included in our questionnaire. In addition, some of these studies were performed among men who have sex with men, which is considered a high-risk population with specific behavior, complicating direct comparison.
Also after pooling both surveys and adjusting for demographic and sexual risk factors, the increase in HPV seroprevalence in women in the years after the introduction of the HPV vaccine remained significant.
An interesting finding is the decreased HPV16 seroprevalence between the two surveys for the Dutch male population. Although this might be due to herd immunity of the girls-only vaccination program, among 15–39 year old men, we observed a not statistically significant decline, while they seem likely to be the first age groups benefitting from the girls-only vaccination. In the even younger age group of 10–14 year old boys, we did find a difference between the two surveys for any hr-HPV type, but when excluding the vaccine types this difference was not significant anymore. This indicates that the. Albeit minor, difference in seroprevalence in the 10-year period was mainly attributable to the vaccine types. Please note that in this age group, the seroprevalences could not be adjusted as questionnaires including sexual behavior were only filled in by people above 15 years of age. In Australia, with high vaccine uptake percentages, herd protection impacts on seroprevalence in males (15–39 years of age) from a girls-only vaccination program were clearly shown 5 years after introduction of HPV vaccination (45). Moreover, even a benefit for the nonvaccinated females was observed (46). In contrast, no reduction was found in HPV seropositivity in males followed by a girls-only vaccination program in a study in the United States with comparable vaccination coverage in a girls-only program as in the Netherlands (47). With a vaccination coverage of approximately 50% among vaccine-eligible girls in the Netherlands in 2016–17, herd effects on seroprevalence in the male part of the population might therefore be less pronounced. Nevertheless, in recent analysis among STI clinic visitors in the Netherlands, both first-order herd immunity effects among unvaccinated males as well as second-order herd immunity effects in unvaccinated women were found (48). However, this was measured through infection rates where effects can be detected earlier than by seroprevalence.
A strength of this study is that we compared two surveys with a broad age range, one before and one 6 to 7 years after introduction of the HPV vaccination program, thereby enabling us to evaluate this program at a population level. An additional strength of this study is that an identical methodology and antibody assay is used between the two surveys. It must be kept in mind that the VLP sources have changed over time and could possibly cause some variance, for which we corrected by using QC and bridging. Furthermore, this study used two-stage cluster sampling strategy, including oversampling of minorities (7, 8), therefore being representative of the total Dutch population.
The use of different techniques and associated cutoff levels hinders the comparison with other (population) studies. International standardization for all hr-HPV types, in addition to HPV16 and 18 which are applied in this study, could help to overcome this difficulty in future studies. Besides this, it could be argued that HPV seropositivity is not a conclusive marker for cumulative exposure. HPV has the capability to evade the host immune system and as a consequence, detectable HPV-specific antibodies in serum are only developed in approximately 50%–70% of HPV-infected individuals (22). Thus, seroprevalence will underestimate the actual lifetime HPV exposure and infection rate. Moreover, it should be noted that questions regarding sexual behavior were among the least well completed. Self-reporting of sexual behavior could lead to bias due to social desirability and this was also illustrated by our risk factor analysis for some variables (e.g., a high unknown category).
HPV prophylactic vaccination programs are most effective when offered to nonsexually active preadolescents. In the Netherlands, the age of receiving the HPV vaccine is approximately 12 years old and recently the Health Council has advised to lower the age to 9 years. Our data support this change as HPV seropositivity begins to increase markedly after 10 years of age. In addition, the Health Council also advised to implement a sex-neutral HPV program which will be effective from 2021. On top of that, a catch-up vaccination will be offered to all young adults up to 26 years of age (49).
To conclude, our data showed that HPV infection-specific seroprevalence in women has increased in the Netherlands in a 10-year period. In men, however, seroprevalence for any hr-HPV type remained similar, a decrease was found for HPV16 and an increase for HPV45. Whether the decline in HPV16 is a first sign of a herd effect remains uncertain because a less pronounced effect was observed in men ages 15–39 years of age, where we would have expected that a herd effect would be visible first. Future seroprevalence studies will be interesting to capture the effect of a longer follow-up period after introduction of the girls-only program and possibly effects of the sex-neutral vaccination.
Disclosure of Potential Conflicts of Interest
No potential conflicts of interest were disclosed.
H. Pasmans: Conceptualization, formal analysis, investigation, methodology, writing–original draft. J. Hoes: Formal analysis, writing–review and editing. L. Tymchenko: Data curation, investigation. H.E. de Melker: Conceptualization, supervision, writing–review and editing. F.R.M. van der Klis: Conceptualization, supervision, funding acquisition, project administration, writing–review and editing.
The authors thank GSK (GlaxoSmithKline Bio) for providing at cost part of the VLPs and MSD (Merck Sharp & Dohme) for kindly donating part of the VLPs that we used in our assays. GSK and MSD were provided the opportunity to review a preliminary version of this manuscript in order to ensure the protection of its proprietary information and intellectual property, but the authors are solely responsible for final content and interpretation. The authors also thank Eric Vos, Mirjam Knol, and Liesbeth Mollema for their help with the statistical analyses.
This research was supported by the Dutch Ministry of Health, Welfare and Sport. This study was supported by the Dutch Ministry of Health, Welfare and Sport (VWS). The funding source had no involvement in study design, collection, analysis, and interpretation of data; in writing of the manuscript; and in decision to submit the article for publication.
Note: Supplementary data for this article are available at Cancer Epidemiology, Biomarkers & Prevention Online (http://cebp.aacrjournals.org/).
Cancer Epidemiol Biomarkers Prev 2020;29:2243–54
Received April 21, 2020.
Revision received June 25, 2020.
Accepted August 5, 2020.
Published first August 20, 2020.
©2020 American Association for Cancer Research.
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You are going to email the following Changes in HPV Seroprevalence from an Unvaccinated toward a Girls-Only Vaccinated Population in the Netherlands
Cancer Epidemiol Biomarkers Prev November 1 2020 (29) (11) 2243-2254; DOI: 10.1158/1055-9965.EPI-20-0596


Irrigation company in Kerikeri - represented Kerifresh Limited on Board.
L & F Limited provides the management services for Speris Finance & Yoogo. My role covers full responsibility for Finance, Credit, Compliance, Risk, IT & Asset Management.
The company owns AB Equipment, NZ Trucks, Speirs Finance, and Yoogo. Turnover more than $300m pa and 600 staff approximately. I have overall financial, compliance & risk management responsibility for all entities.
Overall financial and compliance responsibility for a growing finance company, backed by Private equity owners. The company is in a strong growth mode and needs agility to cope with new directions and situations as they arise.
Commercial & Financial Expertise as and when you need it (and not on your payroll when you don't). See my website - www.cfoondemand.co.nz - or download the brochure here. Contact me to discuss how I might add value to your business.
With the sale of the Greenlane Group of companies worldwide to a UK listed company (giving the shareholders the opportunity to realise 8x the value offered 12 months ago), my role at Greenlane becomes redundant. For the period to end of December, I will be tidying up the 11 entities worldwide, while also seeking the next challenge. Available from January 2015.
Overall global responsibility for Finance, Insurance, ICT. Assisting the CEO to eliminate silo behaviour and to align the Group to push for a significant role in the renewable energy space, as well as enhance shareholder value.
Overall financial responsibility, alongside ICT, Legal & Insurance.


I was not mistaken. But the main target of Steven Landsburg's "On My Mind" column in Forbes magazine was the neo-racist ideas he had ferreted out—on John Kerry's website.
Kerry had proposed, "Federal contracts, wherever possible, should be performed by American workers." Landsburg was morally offended that anyone would argue that American workers should be given preference over Asian or African workers.
Now I do not know what parents pay to send their kids to the University of Rochester. But if the philosophical imbecility of Landsburg is representative of the faculty, it is too much.
To be more concerned about the well-being of one's fellow Americans is not "xenophobia," which means a fear or hatred or foreigners. It is patriotism, which entails a special love for one's own country and countrymen, not a hatred of any other country or people. Preferring Americans no more means hating other peoples than preferring one's family means hating all other families. An icy indifference as to whether one's countrymen are winning—be it in a competition for jobs or Olympic medals—is moral treason and the mark of a dead soul.
We are all born into families, clans, tribes, neighborhoods, countries, all of which—as well as the friends we make, the schools that nurture us, the churches at which we worship—have a claim upon our love and loyalty.
The professor's piece testifies to another truth. Free-trade fanatics are running out of statistical proofs so fast they must defend their position on the grounds that, no matter if it fails America, it is a morally superior position. For look at what a soaring dependency on imports is doing to our country.
Last year's trade deficit topped $617 billion. In January, it hit $58.3 billion, portending a deficit in 2005 of $700 billion. U.S. trade and budget deficits combined are 10 percent of GDP. We are borrowing $2 billion a day abroad to subsidize our lifestyle. The American consumer has never been more indebted—in credit cards, auto loans, mortgages.
The dollar has lost a third of its value against the euro in three years. Gold is back close to $450 an ounce, a run-up of 70 percent. Oil is bumping up against $55 a barrel. When South Korea and then Japan's Koizumi hinted their treasuries might diversify reserves and hold a lesser share in dollars, the Dow experienced what pilots call, as you grab the arm rests and hold on for dear life, "a little choppiness." The last fruits of free-trade globalism may be financial collapse.
Under Bush, 2.8 million manufacturing jobs, one in six, have been lost. Real wages of working Americans are stagnant. Two-thirds of a million textile and apparel workers face wipeout from Chinese imports that are now unrestricted. As Paul Craig Roberts writes, the jobs being created pay less and demand less in education and training than the jobs being outsourced. Our workers are being sacrificed on the altar of globalism. Says Landsburg: tough luck!
If economics professors are so fanatic about free trade, why not eliminate their tenure and import English-speaking economics professors from India at half the pay? For as Landsburg instructs us, "It is plain ugly to care more" about him than a total stranger.
Moreover, the stranger might come to love America and even prefer America, which some deracinated academics find so racist a sentiment.


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Governor's Cup Wine Competition shows growing depth in state's wineries
One hundred fifty and growing.
No matter what you're counting, which in this case is the estimated number of wineries in Colorado, 150 is an awfully nice round number.
It's not really round, however, because there likely are another eight or nine additional wineries in the state since the last unofficial census, but you get the idea: Colorado's wine industry is doing quite well, thank you.
There are two major events each year that celebrate the health of grape growing and winemaking in Colorado.
One is the late-summer Colorado Mountain Winefest, deservedly named the "Best Wine Festival in the Nation" by USA Today, and another is the late-summer, almost-winter Colorado Uncorked, perhaps equally well-known as the Colorado Governor's Cup.
The Governor's Cup this year went down Nov. 15 at the History Colorado Center, a magnificent building (opened in 2012) at 12th and Broadway in Denver's Golden Triangle neighborhood.
The Governor's Cup is really that, a handsome silver chalice awarded to the wine voted Best of Show from the 14 finalists in the annual Governor's Cup Wine Competition.
For many of the 600 or so Colorado-wine enthusiasts present, one highlight this year was the range of wineries represented in those 14 wines.
"It was great to see that we had some of the state's oldest wineries and some of the state's newest wineries," remarked Doug Caskey, executive director of the Colorado Wine Industry Development Board. "We also saw some new varieties and hybrids, which is what we want to see as winemakers continue to hone their skills in the search for Colorado's perfect grape."
Among the 14 finalists for the (actual) Governor's Cup were several wineries with more than one wine.
Carlson Winery was pouring its Cherry wine and the 2018 NSFW White, a Vidal Blanc blend; The Storm Cellar (founded in 2017 in the North Fork Valley) poured its 2018 Dry Riesling and 2018 Riesling; and BookCliff Vineyards (Boulder but coming soon to the Grand Valley) served its 2016 Ensemble and its 2016 Graciano, one of the newer (to Colorado) grape varieties on display.
The Best of Show went to Qutori Winery's 2017 Syrah, a double-gold medal winner made from grapes grown by Nancy Janes at Whitewater Hill Vineyards in Grand Junction.
Qutori, located on Colorado Highway 133 north of Paonia at the Root & Vine Market, is another of the fresh-cheeked wineries Caskey mentioned.
The list also included Jayme Henderson and Steve Steese of The Storm Cellar, who had two wines make it to the Governor's Cup case.
In only its second vintage and its first appearance at the Governor's Cup, Qutori received not only the top prize, but also racked up silver medals with its 2017 Estate Pinot Noir, 2017 Reserve Pinot Noir and 2018 Chardonnay.
A fifth entry, a 2017 bourbon barrel-aged Pinot Noir, garnered a bronze.
"We were pretty excited," said an understated Julie Bennett, who does much of the heavy lifting at Qutori, along with her husband, Rich, and son/winemaker, Kyle. "Kyle's 27 and this was his first wine, so he was particularly excited. Winemaking has been a real passion for him."
Julie Bennett kindly added her thanks to the many North Fork winemakers who gave Qutori advice and support, including Rob Kimball from 5680 Winery.
Among the veteran winemakers making a welcome return appearance this year at the Governor's Cup was Sue Phillips of Plum Creek Cellars (founded by Doug and Sue Phillips in 1984), who poured her winery's 2016 Cabernet Franc.
Phillips' presence gave the Governor's Cup finale a reach of 35 years, which in many circles would be considered maturing gracefully.
A complete list of the 2019 Governor's Cup wines can be found at coloradowine.com/uncorked/.
On the subject of new wineries, we may see two more wineries open this year or next in the North Fork Valley, plus Kaibab Sauvage's emergent enterprise, Sauvage Spectrum Estate Winery and Vineyards, in the Grand Valley.
Sauvage has cultivated grapes in the valley for 20 years and after watching winemakers garner awards with his fruit, he recently decided to jump into the fray with his own line of wines.
Grape growers rarely receive accolades for growing excellent fruit, although you can't squeeze a winemaker without him or her uttering some iteration of the timeless phrase, "I let the fruit talk for itself."
Sauvage offers two white sparkling wines, one extra dry and another off-dry under his Sparklet label, and he plans to release a sparkling rosé and a still white wine under the Domaine Sauvage label.
Sauvage Spectrum wines are available at select restaurants and liquor stores in the Grand Valley.

redpajama_set_name: RedPajamaCommonCrawl


Videos, tutorals, diagrams and patterns on the theme of block stitch.
In this case the bullion block doesn`t have the additional side loop.
In this tutorial you will see how to crochet the bullion block stitch around three different height posts: double post, treble post and double treble post.
Also we show you completely different way to work a bullion block when the additional side loop of each block is hidden inside of the next stitch.
Unusual but very beautiful way to work a bullion block stitch.
The bullion block shown is this tutorial takes two stitches on row below.
With this free crochet tutorial for beginners you will learn how to crochet a bullion block stitch.


Staff was lazy and made a rare trip to KFC for dinner.
It turns out that Jeff likes KFC chicken even more than Carl's Jr. french fries.
Staff gave the hovering and meowing Jeff many bites of Original Recipe. But later, an odd sound indicated Jeff had found his way to the table with the chicken bucket.
He was attempting to extract a wing.
In the future Staff will have to get a bigger bucket; or perhaps Jeff would enjoy the Double Down.


Winners at the Ashcroft Arts Club's annual Art Show and Sale.
May. 1, 2013 1:00 p.m.
Another painting year has come to a close for th Ashcroft Arts Club. We welcomed new members, new and exciting art, as well as our long time members.
The Art Show this year (Apr. 20-23) was a resounding success, featuring painting, photography and very funky sculptures.
The first place winner of the Peoples Choice is Wet Spring by Pauline Ogilvie. First place in Students Choice is Leopard by Kobus Kitshoff. Second place pick in both catagories is Bobcat/TotemPole by Doug Tucker of Clinton.
Next up in our art world is the 2nd Annual PleinAir Paint-Out on May 22nd-23rd. Everyone is welcome to sign up for a fun time.
July and August will once again see our annual ArtWalk around Ashcroft. Lots going on this summer in our area.


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bank holidays philippines 2020
Bank Holidays in Kerala 2021 & 2020: Get the list of bank holidays in Kerala observed in Thiruvananthapuram, Kochi, Kozhikode and Trivandrum by Kerala govt with dates & information. For a successful and relaxing vacation, it is a necessity to plan things thoroughly. These are holidays that fall under the Negotiable Instruments Act, 1881. List of Bank Holidays UK 2020 include national and local holidays for England, Wales, Northern Ireland and Scotland. All the information display below is also available via our API as well as downloadable as a csv. Maundy Thursday is part of the Holy Week tradition observed by most Filipinos. Mawlid, or Milad, marks the birth of the Islamic prophet Muhammed, or Mohamed, in the year 570 of the Gregorian calendar. The above is the list of 2020 public holidays declared in Philippines which includes federal, regional government holidays and popular observances. 2020 Public Holidays Philippines Service. Christmas Day is one of the biggest Christian celebrations and falls on December 25 in the Gregorian calendar. UPDATE: May Day (Early May Bank Holiday) has moved to 8 May 2020 (Friday) as part of the 75th anniversary of VE Day commemorations. Provincial Holiday: Guipúzcoa: Jan 22: Wednesday: Feast of Saint Vicente: Provincial Holiday: Huesca: Jan 22: Wednesday: Martyr Vicente's Feast: Provincial Holiday: Valencia: Jan 23: Thursday: Day of … Additional Special Non-Working Day is a special non-working holiday in Philippines, Bonifacio Day is a regular holiday in Philippines. Eid al-Adha Day 2 is a common local holiday in Philippines. We also counting the number of days or weeks until the bank holidays 2020 in uk. These dates may be modified as official changes are announced, so please check back regularly for updates. The Philippine's Independence day is a large celebratory event held across the country on June 12 each year. National and other holidays observed by the Bank 2020 Signup here to get started.. All the information No matter which state you belong to, the holiday page can be used for various purposes. Regular Holiday : Jan 23: Thursday: First Philippine Republic Day: Special Working Public Holiday : Jan 25: Saturday: Chinese Lunar New Year's Day: Special Non-working Holiday : Feb 25: Tuesday: … Philippines has a total of 36 holidays in 2020. This holiday page for the month of November 2020 has been personalised for the people across the country. Make sure your destination has been well-thought of, researched, and decided. Generally, no fixed list of holiday dates in the Philippines can be provided because some holidays are movable. July 31 a regular holiday for Eid'l Adha in the Philippines, Philippines announces Public Holiday dates for 2021. Holy Saturday is the day before Easter Sunday. Public holidays in Manila […] required to start. the requests to a particular state or city. No credit Eid-al-Fitr is a holiday to mark the end of the Islamic month of Ramadan, during which Muslims fast during the hours of daylight. Labor Day, or May Day, is a day off for workers in many countries around the world. Below is a full list of when the main Portuguese holidays occur in 2020; including days off such as bank holidays and Portugal's school holidays. If you are searching for a UK Calendar 2020 including holidays, go to the 2020 calendar page to download. — The Agong's Birthday holiday has been changed from 6 June 2020 (Saturday) to 8 June 2020 (Monday). July 27 Iglesia ni Cristo Day: Araw ng Iglesia ni Cristo: Dia de la Iglesia ni Cristo: Fixed Eid al-Adha (Id ul-Adha) is an Islamic festival falling on the 10th day of the month of Dhul Hijja (Thou al-Hijja) to commemorate the willingness of Ibrahim (Abraham) to sacrifice his son. But most importantly, make sure to … New Year's Eve is the last day of the year, December 31, in the Gregorian calendar. bank holidays and observances API with coverage for all countries and locations of the world. Panama Public Holidays 2020 This page contains a national calendar of all 2020 public holidays for Panama. 2020 Bank of China Holidays; 2020 Belarus Bank Holidays These dates may be modified as official changes are announced, so … … Rizal Day is a regular holiday in Philippines. Signup here to get started. km. In the table below, you will find the details of the holidays and when they are observed. It is a day of alms giving and prayers for the dead. You can get more detailed information on each holiday by clicking on them. UK Bank Holidays 2020. 2020-05-20: Philippines End of Ramadan Public Holiday May 25; 2019-11-16: Philippines … 2024 Holidays - Philippines Below are Public Holidays for Philippines for the calendar year 2024. Ireland Bank Holidays 2020 This page contains a national calendar of all 2020 bank holidays. All Saints' Day Holiday: 30 Nov: Mon: Bonifacio Day: 8 Dec: Tue: Immaculate Conception: 24 Dec: Thu: Christmas Holiday: 25 Dec: Fri: Christmas Day: 30 Dec: Wed: Rizal Day: 31 Dec: Thu: New Year's Eve: Visit gov.ph for the original release. The Feast of the Immaculate Conception is a Christian observance on December 8 each year. These dates may be modified as official changes are announced, so please check back regularly for updates. First Philippine Republic Day is a special working public holiday in Philippines. The Labor Code of the Philippines specifies two types of holidays: the 'regular holiday' and the 'special non-working day'. public and Chinese New Year is not considered an official holiday in the Philippines but it is widely celebrated, particularly in Chinese communities. Ninoy Aquino Day is a special non-working holiday in Philippines, National Heroes Day is a regular holiday in Philippines, Yamashita Surrender Day is a special working public holiday in Philippines, Feast of the Nativity of Mary is a special working public holiday in Philippines, September Equinox in Philippines (Manila). It is located on the island of Luzon and on the eastern shores of the Manila Bay. The list of public holidays 2020 has been announced by the Tamil Nadu government. (UPDATED) President Rodrigo Duterte finally signs the proclamation declaring the regular holidays and special non-working days for 2020. A working holiday which was first observed in 2020. Search for: Recent Posts. added to our API as well. During bank holidays November 2020, all banking institutions shall remain closed. Bank Holidays in Delhi 2021 & 2020: Get the list of bank holidays in Delhi observed in Delhi govt with dates & information. Office Holidays lists when countries across the world have public holidays and bank holidays to help you plan your meetings better. Spain Public Holidays 2020 ; This page contains a national calendar of all 2020 public holidays. below, you will find the details of the holidays and when they are observed. Office Holidays provides calendars with dates and information on public holidays and bank holidays in key countries around the world. ∅ - National Holiday, ∇ - Restricted Holiday New Year's Day on January 1 in the Gregorian calendar is a public holiday in the Philippines. Good Friday is part of the Holy Week holiday in the Philippines. All Souls' Day falls on November 2 each year. Check 2017 Asian Development Bank (ABD) holidays in Manila, Philippines. However, the President is tasked by law under the provisions of Republic Act 9492 to issue a Proclamation prior to their occurrence to finalize the specific date of their observance. Easter Sunday commemorates Jesus Christ's resurrection, according to Christian belief. Philippines Public Holidays 2021 This page contains a national calendar of all 2021 public holidays. 178 of 1948) December 31 to January 3. 1 January (Wednesday): New Year's Day (Ano Novo) 10 April (Friday): Good Friday (Sexta-feira Santa) updates or sign up for our newsletter to receive regular updates. The above is the list of 2020 public holidays declared in USA which includes federal, regional government holidays and popular observances. Christmas Eve is the day before Christmas Day and falls on December 24 in the Gregorian calendar. View the API documentation for a full description of Isra and Mi'raj (Isra Me'raj, Israa and Mi'raaj, Laylat Al-Isra wa Al-Miraj, Lailat al Miraj, Night Journey and Ascension to Heaven) marks the night that the Prophet Mohammad traveled from Mecca to Jerusalem, ascended to heaven and returned. People Power Anniversary in the Philippines commemorates the successful non-violent demonstration in Manila in 1986 that saw a change of government for the nation. 2020 Public Holidays USA Service. Araw ng Kagitingan, also known as the Day of Valor, annually falls on or around April 9 in the Philippines. Honoring the millions of Filipinos who fought and died as a result of the war against the occupation forces of the United States that began on February 4, 1899 and ended in 1902. List of Public Holidays and National Holidays for the Philippines in the year 2020 New Year's Day is on Wednesday, 01 January 2020 Chinese New Year is on Saturday, 25 January 2020 Seven of these holidays fall on a Saturday or a Sunday. In the table These dates may be modified as official changes are announced, so please check back regularly for Observances and Celebrations in UK, 2018 - 2019 - 2020 2018 Portugal Public Holidays 2020 This page contains a national calendar of all 2020 public holidays. Many churches honor all their saints on All Saints' Day, also known as All Hallows' Day. Date Day Holiday December Solstice in Philippines (Manila). The capital of the Philippines, Manila is considered one of the most densely populated cities in the world. 2020-05-20: Philippines End of Ramadan Public Holiday May 25; 2019-11-16: Philippines 2020 Public Holidays Announced; 2019-10-30: Philippines Public Sector Holiday October 31; 2019-10-03: Philippines Mulls Public Holidays Reduction; 2019-09-16: Philippines 2020 SK Public Holiday Postponed Until 2023; 2019-09-10: Philippines Mulls 2020 SK Public Holiday Postponement; 2019-08-14: Philippines … These dates may be modified as official changes are announced, so please check back regularly for updates. Our mission is to make a simple-to-use and developer-friendly worldwide Public and Bank Holidays for Philippines 2020: List of Philippines public holidays, national holiday celebrations, bank holidays, official holiday calendar, legal holidays, religious festivals for the year 2020. Use our Holiday data in your applications programmatically. You can get more detailed information on each holiday by clicking on them. Portuguese public holidays 2020. Scroll down to view the national list or choose your autonomous community's calendar. The new date is set for the third Sunday of every June, beginning in 2020. Here is the Official List of Philippine Holidays and Long Weekends 2020. We also provide USA holiday calendar for 2020 in Word, Excel, PDF and printable online formats. These dates may be modified as official changes are announced, so please check back regularly for updates. Our API allows you to specify the State and Region as part of the API requests, thereby limiting Sign up to receive a weekly email update on forthcoming public holidays around the world in your inbox every Sunday. There is a difference in the pay that employers are required to pay between the two type of holidays. Official List of Philippine National Holidays for 2021. It has a total population of 1.78 million and a land area of 42.88 sq. Muharram is the first month of the Islamic calendar and a time of remembrance or mourning. Philippines : public and bank holidays, closure of banks, stock exchanges, school vacations ... Culture : A working holiday which will be first observed in 2020. 2020; 2021; The Bank's offices in Japan -- Head Office, branches, and local offices -- are closed on Saturdays, Sundays, and the following days: National holidays (as defined in Act No. Philippines has a total of 36 holidays in 2020. All updates are automatically 30 July 2020: July 31 a regular holiday for Eid'l Adha in the Philippines source: Public Holiday News 30 July 2020: Philippines announces Public Holiday dates for 2021 source : Public Holiday News Office Holidays provides calendars with dates and information on public holidays and bank holidays in key countries around the world. This holiday aims to promote, protect, and safeguard the constitutionally guaranteed right to freedom of expression, speech and of the press in the Philippines. You can also make sure you mark them on your calendar. display below is also available via our API as well as downloadable as a csv. card is We also provide Philippines holiday calendar for 2020 in Word, Excel, PDF and printable online formats. Holiday; 1 Jan: Wed: New Year's Day: 25 Jan: Sat: Lunar New Year: 26 Jan: Sun: The Second Day of Lunar New Year: 27 Jan: Mon: The Third Day of Lunar New Year: 28 Jan: Tue: The Fourth Day of Lunar New Year: 4 Apr: Sat: Ching Ming Festival: 10 Apr: Fri: Good Friday: 11 Apr: Sat: The Day Following Good Friday: 13 Apr: Mon: Easter Monday if a bank holiday is on a weekend, a 'substitute' weekday becomes a bank holiday, normally the following Monday. 2020 Holidays - Philippines Below are Public Holidays for Philippines for the calendar year 2020. the supported countries, states and regions. From 2021, Agong's Birthday will be observed on the first Monday of June. Date Day Holiday States; 1 Jan: Wed: LIST: Philippine holidays 2020. People can withdraw and deposit money through ATMs. Holy Week holiday bank holidays philippines 2020 Philippines which includes federal, regional government holidays and Long Weekends.... 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2020 bank holidays philippines 2020


text:
Population of Russia
Population of Kamensk-Shakhtinsky
The population in Kamensk-Shakhtinsky for 2022 is 95 306. Kamensk-Shakhtinsky is one of 1117 cities in Russia and ranks 180 in the Russia population. Kamensk-Shakhtinsky city population data has been obtained from public sources. On the Population HUB website you can find out the number of people in any of the regions of the Earth.
Population - Kamensk-Shakhtinsky
95 306 people
Flag of Russia Data for January 2022
Cities starting with letter K
Cities starting with letter K 19 letters in the name
Cities in Russia starting with letter K
A population count in Kamensk-Shakhtinsky was carried out in 2022.
⚡ What place does Kamensk-Shakhtinsky have in terms of population in Russia?
Kamensk-Shakhtinsky is ranked #180 in the city population ranking in Russia.
List of cities in Russia
Population of Zheleznogorsk
Population of Kansk
Population of Nazran
Population of Pushkin
Population of Gatchina


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Q: EditText Cursor Positioning Inaccuracies I'e been experiencing some odd behavior from the text cursor in the EditTexts of my android application. Essentially, the cursor does not always accurately represent it's position in a word (it's all over the place). As such, typing a character into an edit text can result in the character being placed somewhere different (usually before or after the cursor indicated position). Also, when the cursor is placed inside of or next to a word, that word is often offset slightly.
Here is an example of the phenomenon;

Notice the words moving position from picture to picture, and in the second example the cursor indicates that it is before the i but is in fact before the e two indexes to the right.
Here is the EditText element of this View in the XML;
<EditText
    android:id="@+id/hazard_obs_text"
    android:layout_width="0dp"
    android:layout_height="0dp"
    android:layout_below="@+id/hazard_observation"
    android:layout_alignLeft="@+id/hazard_observation"
    android:layout_alignRight="@+id/hazard_observation"
    android:layout_above="@+id/finalise_hazard"
    android:layout_marginTop="5dp"
    android:background="@drawable/whitebackselector"
    android:hint="Recommendation Text"
    android:textSize="9sp"
    android:gravity="start"
    android:paddingLeft="5dp"
    android:enabled="false"
/>

As you can see, it is inside a RelativeLayout, and has a custom blank white background with some subtle shading around the edge. It is also part of a Fragment layout. Nothing out of the ordinary as far as I can see. No exceptions or errors are being thrown. I am stumped. Does anyone have any ideas what could be causing this odd behavior?
Extra details by request;
The Layout isn't changed programmatically in any way except to be inflated initially (it is in a Fragment after all). Below is any line of code that interacts programmatically with the above example EditText -
obsText = (EditText) fragmentView.findViewById(R.id.hazard_obs_text);
...
obsText.setEnabled(tf); // Where tf is a boolean value.
...
obsText.getText().clear();
...
obsText.setText(observations[0].split("  ", 3)[1]); // Where observations[0] is a string.
...
obsText.setText(currentAssessment.obsDescript); // Setting another string.

Below is the full fragment layout. It is worth noting that I am also having the same issue in a very simple LinearLayout -
<?xml version="1.0" encoding="utf-8"?>
<RelativeLayout xmlns:android="http://schemas.android.com/apk/res/android"
            android:background="#070054"
            android:layout_width="fill_parent"
            android:layout_height="fill_parent"
            >
<AutoCompleteTextView
    android:id="@+id/hazard_code"
    android:layout_width="0dp"
    android:layout_height="20dp"
    android:layout_alignParentTop="true"
    android:layout_alignParentLeft="true"
    android:layout_toLeftOf="@+id/hazard_code_browse_button"
    android:layout_marginTop="10dp"
    android:layout_marginLeft="10dp"
    android:gravity="center_vertical"
    android:hint="Hazard Code"
    android:background="@drawable/whitebackselector"
    android:singleLine="true"
    android:textSize="12sp"
    android:selectAllOnFocus="true"
    android:paddingLeft="5dp"
    android:dropDownWidth="fill_parent"
    android:dropDownHeight="125dp"
    android:dropDownVerticalOffset="1dp"
    android:completionThreshold="1"
/>
<Button
    android:id="@+id/hazard_code_browse_button"
    android:layout_width="30dp"
    android:layout_height="20dp"
    android:layout_toLeftOf="@+id/sfrp_drops"
    android:layout_marginTop="10dp"
    android:layout_marginBottom="5dp"
    android:layout_marginRight="7dp"
    android:background="@drawable/crossselector"
/>
<Spinner
    android:id="@+id/hazard_observation"
    android:layout_width="0dp"
    android:layout_height="20dp"
    android:layout_marginTop="10dp"
    android:layout_toRightOf="@+id/sfrp_drops"
    android:layout_toLeftOf="@+id/pictures"
    android:background="@drawable/whitebackselector"
    android:paddingLeft="5dp"
    android:dropDownWidth="wrap_content"
    android:dropDownHeight="125dp"
    android:dropDownVerticalOffset="1dp"
    android:enabled="false"
/>
<LinearLayout
    android:id="@+id/sfrp_drops"
    android:orientation="horizontal"
    android:layout_centerHorizontal="true"
    android:layout_width="160dp"
    android:layout_height="20dp"
    android:layout_marginTop="10dp"
    android:layout_marginRight="5dp"
>
    <Spinner
        android:id="@+id/hazard_severity"
        android:layout_width="0dp"
        android:layout_height="20dp"
        android:layout_weight="1"
        android:background="@drawable/whitebackselector"
        android:prompt="@string/hazard_severity"
        android:paddingLeft="5dp"
        android:enabled="false"
    />
    <Spinner
        android:id="@+id/hazard_frequency"
        android:layout_width="0dp"
        android:layout_height="20dp"
        android:layout_marginLeft="5dp"
        android:layout_weight="1"
        android:background="@drawable/whitebackselector"
        android:prompt="@string/hazard_frequency"
        android:paddingLeft="5dp"
        android:enabled="false"
    />
    <Spinner
        android:id="@+id/hazard_risk"
        android:layout_width="0dp"
        android:layout_height="20dp"
        android:layout_marginLeft="10dp"
        android:layout_weight="1"
        android:background="@drawable/whitebackselector"
        android:prompt="@string/hazard_risk"
        android:paddingLeft="5dp"
        android:enabled="false"
    />
    <Spinner
        android:id="@+id/hazard_priority"
        android:layout_width="0dp"
        android:layout_height="20dp"
        android:layout_marginLeft="5dp"
        android:layout_weight="1"
        android:background="@drawable/whitebackselector"
        android:prompt="@string/hazard_priority"
        android:paddingLeft="5dp"
        android:enabled="false"
    />
</LinearLayout>
<LinearLayout
    android:id="@+id/pictures"
    android:orientation="vertical"
    android:layout_width="25dp"
    android:layout_height="fill_parent"
    android:layout_alignParentTop="true"
    android:layout_alignParentRight="true"
    android:layout_margin="5dp"
    android:background="@drawable/photoreel"
>
    <ImageView
        android:id="@+id/photo_icon"
        android:src="@drawable/hal"
        android:layout_width="fill_parent"
        android:layout_height="0dp"
        android:layout_weight="1"
    />
    <Button
        android:layout_width="fill_parent"
        android:layout_height="0dp"
        android:layout_weight="1"
    />
    <Button
        android:layout_width="fill_parent"
        android:layout_height="0dp"
        android:layout_weight="1"
    />
    <Button
        android:layout_width="fill_parent"
        android:layout_height="0dp"
        android:layout_weight="1"
    />
    <Button
        android:layout_width="fill_parent"
        android:layout_height="0dp"
        android:layout_weight="1"
    />
</LinearLayout>
<EditText
    android:id="@+id/hazard_obs_text"
    android:layout_width="0dp"
    android:layout_height="0dp"
    android:layout_below="@+id/hazard_observation"
    android:layout_alignLeft="@+id/hazard_observation"
    android:layout_alignRight="@+id/hazard_observation"
    android:layout_above="@+id/finalise_hazard"
    android:layout_marginTop="5dp"
    android:background="@drawable/whitebackselector"
    android:hint="Recommendation Text"
    android:textSize="9sp"
    android:gravity="start"
    android:paddingLeft="5dp"
    android:enabled="false"
/>
<EditText
    android:id="@+id/hazard_act_text"
    android:layout_width="0dp"
    android:layout_height="0dp"
    android:layout_below="@+id/sfrp_drops"
    android:layout_alignLeft="@+id/sfrp_drops"
    android:layout_alignRight="@+id/sfrp_drops"
    android:layout_above="@+id/finalise_hazard"
    android:layout_marginTop="5dp"
    android:background="@drawable/whitebackselector"
    android:hint="Observation Text"
    android:textSize="9sp"
    android:gravity="start"
    android:paddingLeft="5dp"
    android:enabled="false"
/>
<Button
    android:id="@+id/finalise_hazard"
    android:layout_width="0dp"
    android:layout_height="30dp"
    android:layout_alignRight="@+id/hazard_obs_text"
    android:layout_alignLeft="@+id/hazard_act_text"
    android:layout_alignParentBottom="true"
    android:layout_marginTop="5dp"
    android:layout_marginBottom="5dp"
    android:background="@drawable/plainbuttonselector"
    android:padding="0dp"
    android:textColor="#FFFFFF"
    android:text="Finalise Entry"
    android:enabled="false"
/>
<EditText
    android:id="@+id/peoples_at_risk"
    android:layout_width="0dp"
    android:layout_height="20dp"
    android:layout_below="@+id/hazard_location"
    android:layout_alignLeft="@+id/hazard_code"
    android:layout_toLeftOf="@+id/hazard_act_text"
    android:layout_marginTop="5dp"
    android:layout_marginRight="7dp"
    android:background="@drawable/whitebackselector"
    android:textSize="9sp"
    android:singleLine="true"
    android:paddingLeft="5dp"
    android:hint="Peoples at Risk"
    android:enabled="false"
/>
<EditText
    android:id="@+id/hazard_location"
    android:layout_width="0dp"
    android:layout_height="40dp"
    android:layout_below="@+id/hazard_code"
    android:layout_alignLeft="@+id/hazard_code"
    android:layout_toLeftOf="@+id/hazard_act_text"
    android:layout_marginTop="5dp"
    android:layout_marginRight="7dp"
    android:background="@drawable/whitebackselector"
    android:textSize="9sp"
    android:paddingLeft="5dp"
    android:gravity="start"
    android:hint="Hazard Location"
    android:enabled="false"
/>
<EditText
    android:id="@+id/relevant_legistlation"
    android:layout_width="0dp"
    android:layout_height="0dp"
    android:layout_below="@+id/peoples_at_risk"
    android:layout_alignLeft="@+id/hazard_code"
    android:layout_toLeftOf="@+id/hazard_act_text"
    android:layout_alignParentBottom="true"
    android:layout_marginTop="5dp"
    android:layout_marginBottom="5dp"
    android:layout_marginRight="7dp"
    android:background="@drawable/whitebackselector"
    android:textSize="9sp"
    android:paddingLeft="5dp"
    android:gravity="start"
    android:hint="Relevant Legislation"
    android:enabled="false"
/>
</RelativeLayout>

I am experiencing the issue on a Nexus 10, Galaxy Note 10.1, & Xperia Z2 tablets with the latest version of Android installed. I've also tested this on an old Xperia phone as well which is not having the issue, which begs the question of whether it could be related to screen size. Other applications on the same devices aren't having this issue.
Any help would be greatly appreciated. This has been hounding me for some time now. I am willing to manually award a bounty to anyone who can help towards a solution/explanation.

A: I spent a great deal of time trying various bits'n'bobs to solve this issue, but the final change that fixed it entirely was adding a (previously absent) uses-sdk element and it's attributes to the Android Manifest.
<uses-sdk android:minSdkVersion="1" android:targetSdkVersion="4" />

These were the lowest values that could be declared without incurring the problem.

redpajama_set_name: RedPajamaStackExchange


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