The quality of life of frequently vs. infrequently screened HPV vaccinated women.

PURPOSE: Cervical lesions caused by human papillomavirus (HPV) are related to decreased quality of life (QoL) of women. Also, cervical cancer (CC) screening can cause psychological adverse effects. It has been assumed that by decreasing the HPV-related disease burden, HPV vaccinations would increase the QoL. This study compares the effect of CC screening on QoL of HPV vaccinated women in two different screening protocols. METHODS: A total of 753 HPV16/18 vaccinated women were randomized to frequent (22/25/28 years of age) and infrequent (28 years of age) CC screening arms. QoL questionnaires (EQ VAS, RAND 36, amended CECA 10) were sent at the age of 28. RESULTS: Median EQ VAS scores were 80 (Q1-Q3 75-90) in both screening arms. Mean RAND 36 scores of frequently and infrequently screened women were 78.13/81.64 in Physical role functioning domain and, respectively, 77.93/80.18 in Pain, 69.10/69.12 in General Health, 54.67/53.61 in Energy, 83.72/85.11 in Social functioning, 69.53/69.68 in Emotional role functioning, and 68.16/69.29 in Emotional well-being domain. Among women with a self-reported history of Pap cytology abnormalities, overall mean scores of amended CECA 10 were 69.52/72.07, and among women with a self-reported history of genital warts, 60.09/66.73, respectively. CONCLUSION: There was no significant difference in the QoL of HPV vaccinated women between the two CC screening arms. Women were mostly satisfied with the screening experience despite the screening frequency. This information is important for the future screening program planning as we need to reach the best possible balance with screening benefits and harms. TRIAL REGISTRATION NUMBER: NCT02149030, date of registration 29/5/2014.

Scientific approaches toward improving cervical cancer elimination strategies.

At the 2023 EUROGIN workshop scientific basis for strategies to accelerate the elimination of cervical cancer and its causative agent, human papillomavirus (HPV) were reviewed. Although some countries have reached key performance indicators toward elimination (>90% of girls HPV vaccinated and >70% of women HPV screened), most are yet to reach these targets, implying a need for improved strategies. Gender-neutral vaccination, even with moderate vaccination coverage was highlighted as a strategy to achieve elimination more rapidly. It is more resilient against major disturbances in vaccination delivery, such as what happened during the coronavirus pandemic. Further, an analysis of ethical/legal issues indicated that female-restricted vaccination is problematic. Extended catch-up of vaccination with concomitant screening, and outreach to vulnerable groups were highlighted. Although birth cohorts with high coverage of HPV vaccination at school are protected against HPV, and HPVs have a very low reproductive rate in women above age 35, adult women below age 30 have inadequate direct protection. In addition to herd protection from gender-neutral vaccination, this group can be protected by offering concomitant catch-up HPV vaccination and HPV screening. Furthermore, hepatitis B vaccination experiences indicate that elimination cannot be achieved without prioritizing vulnerable/migrant populations. The long-lasting durability of vaccination-induced antibody responses suggests prolonged protection with HPV vaccines when adequately administrated. Finally, cost-effectiveness modelling suggests that high-coverage HPV vaccination in multiple population segments will be resource-saving due to reduced need for screening. In summary, the workshop found that strategically optimal deployment of vaccination will accelerate elimination of HPV and cervical cancer.

Ecological diversity profiles of non-vaccine-targeted HPVs after gender-based community vaccination efforts.

The long-term effect of population-level human papillomavirus (HPV) vaccination on the viral ecology of the untargeted HPVs is poorly understood. We performed an 8-year follow-up of 33 communities randomized to gender-neutral HPV16/18 vaccination, girls-only HPV16/18 vaccination, and control communities without HPV vaccination. The 1992/93 and 1994 birth cohorts were invited in school years 2007/8 and 2008/9. Follow-up cervico-vaginal sampling at 18 and 22 years of age, 4 and 8 years post-vaccination, respectively, were attended by 11,396 and 5,602 participants. HPV types 6/11/16/18/31/33/35/39/45/51/52/56/58/59/66/68 were genotyped and used for the community-level ecological diversity estimations. Gender-neutral vaccination communities with a stronger herd immunity than girls-only vaccination communities show a significantly increased HPV α-diversity (p = 1.1 × 10-8) from 4 to 8 years post-vaccination, despite the clearance of the vaccine-targeted HPVs in these communities. This likely sign of niche occupation by the non-vaccine-targeted HPVs will potentially affect the future cervical cancer screening programs but should not interfere with the WHO mission to eliminate cervical cancer.

Assessing the risk of cervical neoplasia in the post-HPV vaccination era.

This review is based on the recent EUROGIN scientific session: "Assessing risk of cervical cancer in the post-vaccination era," which addressed the demands of cervical intraepithelial neoplasia (CIN)/squamous intraepithelial lesion (SIL) triage now that the prevalence of vaccine-targeted oncogenic high-risk (hr) human papillomaviruses (HPVs) is decreasing. Change in the prevalence distribution of oncogenic HPV types that follows national HPV vaccination programs is setting the stage for loss of positive predictive value of conventional but possibly also new triage modalities. Understanding the contribution of the latter, most notably hypermethylation of cellular and viral genes in a new setting where most oncogenic HPV types are no longer present, requires studies on their performance in vaccinated women with CIN/SIL that are associated with nonvaccine HPV types. Lessons learned from this research may highlight the potential of cervical cells for risk prediction of all women's cancers.

Association of Chlamydia trachomatis infection with cervical atypia in adolescent women with short-term or long-term use of oral contraceptives: a longitudinal study in HPV vaccinated women.

OBJECTIVE: We assessed the relationship between Chlamydia trachomatis infection, duration of oral contraceptive (OC) use and cervical atypia among young adult Finnish women. DESIGN: A longitudinal study. SETTING AND PARTICIPANTS: Women who were included in this study participated in a community-randomised trial on the effectiveness of human papillomavirus (HPV) vaccination and C. trachomatis screening at ages 18.5 and 22 years in Finland. They completed questionnaires on both visits about sexual behaviours. The cytology test results at age 18.5 and 22 years were also available for those women. The total number of participants in this study at 18.5 years of age were 11 701 and at 22 years of age were 6618. MAIN OUTCOME MEASURE: ORs with 95% CIs using univariable and multivariable logistic regression were used to assess the association between C. trachomatis infection, duration of OC and squamous intraepithelial lesions (SIL). RESULTS: There were 940 cytological SIL cases at the first screening visit and 129 cytological SIL cases at the second screening visit. Among the 22 years old, more than fourfold adjusted risk of SIL was associated with C. trachomatis positivity. The HPV16/18, condom use, smoking and number of sexual partners adjusted joint effect of prolonged OC use and C. trachomatis was significantly increased (OR 4.7, 95% CI 1.7 to 12.8) in the 22-year-old women. This observed joint effect was 1.6 times higher than expected on a multiplicative scale. On additive scale, the observed relative excess risk from interaction was 1.8. CONCLUSION: The risk of SIL in HPV vaccinated women is significantly increased if they are C. trachomatis positive and have used OC for 5 or more years. The biological basis may be lack of condom facilitated protection against sexually transmitted diseases. TRIAL REGISTRATION NUMBER: NCT00534638.

Head-to-Head Comparison of Bi- and Nonavalent Human Papillomavirus Vaccine-Induced Antibody Responses.

For head-to-head comparison of human papillomavirus (HPV) antibody levels induced by different vaccines, 25-year-old vaccine-naive women were given either the bivalent (n = 188) or the nonavalent HPV vaccine (n = 184). Six months after vaccination antibodies against pseudovirions from 17 different HPV types (HPV6/11/16/18/31/33/35/39/45/51/52/56/58/59/66/68/73) were measured. Antibodies against HPV16/18 were higher after bivalent HPV vaccination (mean international units [IU] 1140.1 and 170.5 for HPV16 and 18, respectively) than after nonavalent vaccination (265.1 and 22.3 IUs, respectively). The bivalent vaccine commonly induced antibodies against the nonvaccine HPV types 31/33/35/45 or 58. The nonavalent vaccine induced higher antibodies against HPV6/11/31/33/45/52/58 and 35.

Human exposome assessment platform.

The Human Exposome Assessment Platform (HEAP) is a research resource for the integrated and efficient management and analysis of human exposome data. The project will provide the complete workflow for obtaining exposome actionable knowledge from population-based cohorts. HEAP is a state-of-the-science service composed of computational resources from partner institutions, accessed through a software framework that provides the world's fastest Hadoop platform for data warehousing and applied artificial intelligence (AI). The software, will provide a decision support system for researchers and policymakers. All the data managed and processed by HEAP, together with the analysis pipelines, will be available for future research. In addition, the platform enables adding new data and analysis pipelines. HEAP's final product can be deployed in multiple instances to create a network of shareable and reusable knowledge on the impact of exposures on public health.

Effectiveness of various human papillomavirus vaccination strategies: A community randomized trial in Finland.

INTRODUCTION: We conducted a community-randomized trial (NCTBLINDED) in Finland to assess gender-neutral and girls-only vaccination strategies with the AS04-adjuvanted human papillomavirus (HPV)-16/18 (AS04-HPV-16/18)vaccine. METHODS: Girls and boys (12-15 years) were invited. We randomized 33 communities (1:1:1 ratio): Arm A: 90% of randomly selected girls and boys received AS04-HPV-16/18 vaccine and 10% received hepatitis B vaccine (HBV); Arm B: 90% of randomly selected girls received AS04-HPV-16/18 vaccine, 10% of girls received HBV, and all boys received HBV; Arm C: all participants received HBV. Effectiveness measurements against prevalence of HPV-16/18 cervical infection were estimated in girls at 18.5 years. The main measures were: (1) overall effectiveness comparing Arms A or B, regardless of vaccination status, vs Arm C; (2) total effectiveness comparing AS04-HPV-16/18 vaccinated girls in pooled Arms A/B vs Arm C; (3) indirect effectiveness (herd effect) comparing girls receiving HBV or unvaccinated in Arm A vs Arm C. Co-primary objectives were overall effectiveness following gender-neutral or girls-only vaccination. RESULTS: Of 80,272 adolescents invited, 34,412 were enrolled. Overall effectiveness was 23.8% (95% confidence interval: -19.0, 51.1; P = 0.232) with gender-neutral vaccination. Following girls-only vaccination, overall effectiveness was 49.6% (20.1, 68.2; P = 0.004). Total effectiveness was over 90% regardless of vaccination strategy. No herd effect was found. Immunogenicity of the AS04-HPV-16/18 vaccine was high in both sexes. CONCLUSIONS: This study illustrates the difficulty in conducting community randomized trials. It is not plausible that vaccinating boys would reduce overall effectiveness, and the apparent lack of herd effect was unexpected given findings from other studies. This analysis was likely confounded by several factors but confirms the vaccine's high total effectiveness as in clinical trials.

Chlamydia trachomatis, Pelvic Inflammatory Disease, and Epithelial Ovarian Cancer.

Epidemiologic, clinical, molecular and translational research findings support an interrelationship between Chlamydia trachomatis, pelvic inflammatory disease (PID), and epithelial ovarian cancer (EOC). Overall, the link between C. trachomatis, PID, and EOC seems to be relatively weak, although nondifferential misclassification bias may have attenuated the results. The predominant tubal origin of EOC and the role of chronic inflammation in tumorigenesis suggest that the association is biologically plausible. Thus, C. trachomatis and PID may represent potential risk factors or risk markers for EOC. However, many steps in this chain of events are still poorly understood and need to be addressed in future studies. Research gaps include time of exposure in relation to the long-term consequences and lag time to EOC. Data of differential risk for EOC between chlamydial and nonchlamydial PID is also needed. Another major research gap has been the absence of high-performance biomarkers for C. trachomatis, PID, and EOC, as well as EOC precursors. Biomarkers for C. trachomatis and PID leading to increased risk of EOC should be developed. If the association is confirmed, C. trachomatis and PID prevention efforts may play a role in reducing the burden of EOC.

Human papillomavirus seroprevalence in pregnant women following gender-neutral and girls-only vaccination programs in Finland: A cross-sectional cohort analysis following a cluster randomized trial.

BACKGROUND: Cervical cancer elimination through human papillomavirus (HPV) vaccination programs requires the attainment of herd effect. Due to its uniquely high basic reproduction number, the vaccination coverage required to achieve herd effect against HPV type 16 exceeds what is attainable in most populations. We have compared how gender-neutral and girls-only vaccination strategies create herd effect against HPV16 under moderate vaccination coverage achieved in a population-based, community-randomized trial. METHODS AND FINDINGS: In 2007-2010, the 1992-1995 birth cohorts of 33 Finnish communities were randomized to receive gender-neutral HPV vaccination (Arm A), girls-only HPV vaccination (Arm B), or no HPV vaccination (Arm C) (11 communities per trial arm). HPV16/18/31/33/35/45 seroprevalence differences between the pre-vaccination era (2005-2010) and post-vaccination era (2011-2016) were compared between all 8,022 unvaccinated women <23 years old and resident in the 33 communities during 2005-2016 (2,657, 2,691, and 2,674 in Arms A, B, and C, respectively). Post- versus pre-vaccination-era HPV seroprevalence ratios (PRs) were compared by arm. Possible outcome misclassification was quantified via probabilistic bias analysis. An HPV16 and HPV18 seroprevalence reduction was observed post-vaccination in the gender-neutral vaccination arm in the entire study population (PR16 = 0.64, 95% CI 0.10-0.85; PR18 = 0.72, 95% CI 0.22-0.96) and for HPV16 also in the herpes simplex virus type 2 seropositive core group (PR16 = 0.64, 95% CI 0.50-0.81). Observed reductions in HPV31/33/35/45 seroprevalence (PR31/33/35/45 = 0.88, 95% CI 0.81-0.97) were replicated in Arm C (PR31/33/35/45 = 0.79, 95% CI 0.69-0.90). CONCLUSIONS: In this study we only observed herd effect against HPV16/18 after gender-neutral vaccination with moderate vaccination coverage. With only moderate vaccination coverage, a gender-neutral vaccination strategy can facilitate the control of even HPV16. Our findings may have limited transportability to other vaccination coverage levels. TRIAL REGISTRATION: ClinicalTrials.gov number NCT00534638, https://clinicaltrials.gov/ct2/show/NCT00534638.

Sustainability of neutralising antibodies induced by bivalent or quadrivalent HPV vaccines and correlation with efficacy: a combined follow-up analysis of data from two randomised, double-blind, multicentre, phase 3 trials.

BACKGROUND: Quadrivalent and bivalent vaccines against oncogenic human papillomavirus (HPV) are used worldwide with different reported overall efficacies against HPV infections. Although protective concentrations of vaccine-induced antibodies are still not formally defined, we evaluated the sustainability of neutralising antibodies in vaccine trial participants 2-12 years after vaccination and the correlation with reported vaccine efficacy. METHODS: We did a follow-up analysis of data from the Finnish cohorts of two international, randomised, double-blind, phase 3 trials of HPV vaccines, PATRICIA (bivalent, HPV16 and 18) and FUTURE II (quadrivalent, HPV6, 11, 16, and 18). In 2002 and 2004-05, respectively, Finnish girls aged 16-17 years participated in one of these two trials and consented to health registry follow-up with the Finnish Cancer Registry. The cohorts were also linked with the Finnish Maternity Cohort (FMC) that collects first-trimester serum samples from nearly all pregnant Finnish women, resulting in 2046 post-vaccination serum samples obtained during up to 12 years of follow-up. We obtained serum samples from the FMC-based follow-up of the FUTURE II trial (from the quadrivalent vaccine recipients) and the PATRICIA trial (from corresponding bivalent vaccine recipients who were aligned by follow-up time, and matched by the number of pregnancies). We assessed neutralising antibody concentrations (type-specific seroprevalence) to HPV6, 16, and 18, and cross-neutralising antibody responses to non-vaccine HPV types 31, 33, 45, 52, and 58 from 2 to 12 years after vaccination. FINDINGS: Up to Dec 31, 2016, we obtained and analysed 577 serum samples from the quadrivalent vaccine recipients and 568 from the bivalent vaccine recipients. In 681 first-pregnancy serum samples, neutralising antibodies to HPV6, 16, and 18 were generally found up to 12 years after vaccination. However, 51 (15%) of 339 quadrivalent vaccine recipients had no detectable HPV18 neutralising antibodies 2-12 years after vaccination, whereas all 342 corresponding bivalent vaccine recipients had HPV18 neutralising antibodies.. In seropositive quadrivalent vaccine recipients, HPV16 geometric mean titres (GMT) halved by years 5-7 (GMT 3679, 95% CI 2377 to 4708) compared with years 2-4 (6642, 2371 to 13 717). Between 5 and 12 years after vaccination, GMT of neutralising antibodies to HPV16 and 18 were 5·7 times and 12·4 times higher, respectively, in seropositive bivalent vaccine recipients than in the quadrivalent vaccine recipients. Cross-neutralising antibodies to HPV31, 33, 45, 52, and 58 were more prevalent in the bivalent vaccine recipients but, when measurable, sustainable up to 12 years after vaccination with similar GMTs in both vaccine cohorts. Seroprevalence for HPV16, 31, 33, 52, and 58 significantly correlated with vaccine efficacy against persistent HPV infections in the bivalent vaccine recipients only (rs=0·90, 95% CI 0·09 to 0·99, p=0·037, compared with rs=0·62, 95% CI -0·58 to 0·97, p=0·27 for the quadrivalent vaccine recipients). Correlation of protection with prevalence of neutralising or cross-neutralising HPV antibodies was not significant in the quadrivalent vaccine recipients. INTERPRETATION: The observed significant differences in the immunogenicity of the two vaccines are in line with the differences in their cross-protective efficacy. Protective HPV vaccine-induced antibody titres can be detected up to 12 years after vaccination. FUNDING: Academy of Finland and Finnish Cancer Foundation.

Elimination of HPV-associated oropharyngeal cancers in Nordic countries.

Incidence of human papillomavirus (HPV, most notably HPV type 16) associated oropharyngeal squamous cell carcinoma (OPSCC) among middle-aged (50-69 year-old) males has tripled in four high income Nordic countries (Denmark, Finland, Norway and Sweden) over the last 30 years. In Finland and Sweden, this increase was preceded by an HPV16 epidemic in fertile-aged populations in the 1980's. The recent implementation of school-based prophylactic HPV vaccination in early adolescent boys and girls will gradually decrease the incidence, and eventually eliminate the HPV-associated OPSCCs (especially tonsillar and base of tongue carcinomas) in the Nordic countries. However, beyond the adolescent and young adult birth cohorts vaccinated, there are approximately 50 birth cohorts (born in 1995 or before) that would benefit from screening for HPV-associated OPSCC. This article reviews the need, prerequisites, proof-of-concept trial and prospects of preventing HPV-associated OPSCC in the Nordic countries.

Preterm birth rate after bivalent HPV vaccination: Registry-based follow-up of a randomized clinical trial.

A registry-based follow-up of pregnancy data until the end of 2014 was conducted based on a community-randomized trial to assess human papillomavirus (HPV) vaccination strategies and a reference cohort from the same community with no intervention. Our objective was to determine whether prophylactic HPV vaccination (three doses of Cervarix® (AS04-HPV-16/18)-vaccine) affects preterm birth (PTB) rates. All identified 80,272 residents in 1992-95 birth cohorts in Finland were eligible for the trial and 20,513 of 39,420 (51.9%) females consented to participate. The final study population consisted of age-aligned 6226 HPV16/18 vaccinated females and 1770 HBV vaccinated (Engerix® B, hepatitis B-virus vaccine) females that did not receive HPV vaccine at the age of 18 from the 1992-93 birth cohorts, and 19,849 females from the 1990-91 non-vaccinated reference birth cohorts. We compared the rates of preterm (22 + 0-36 + 6 pregnancy weeks) and early preterm (22 + 0-31 + 6) per term (at least 37 + 0) singleton births among the HPV- and non-HPV-vaccinated women, using nationwide Medical Birth Registry data. We observed 409 singleton first pregnancies lasting at least 22 + 0 weeks among 6226 HPV-vaccinated and 1923 among 21,619 non-HPV-vaccinated women. In the first pregnancy the PTB rate was 13/409 (3.2%) among the HPV-vaccinated and 98/1923 (5.1%) among the non-HPV-vaccinated (OR 0.61, 95% CI 0.34-1.09). Early preterm birth rate was 0/409 (0%) in the HPV-vaccinated women and 20/1923 (1.0%) in the non-HPV-vaccinated women (p = 0.04). PTB rate, especially early PTB rate, was lower among the HPV-vaccinated women. Reduction of PTB incidence after prophylactic HPV vaccination would lead to public health benefits globally. Trial Registration:NCT00534638.

Human papillomavirus vaccine efficacy against invasive, HPV-positive cancers: population-based follow-up of a cluster-randomised trial.

BACKGROUND: Human papillomavirus (HPV) vaccination protects against HPV, a necessary risk factor for cervical cancer. We now report results from population-based follow-up of randomised cohorts that vaccination provides HPV-type-specific protection against invasive cancer. METHODS: Individually and/or cluster randomised cohorts of HPV-vaccinated and non-vaccinated women were enrolled in 2002-2005. HPV vaccine cohorts comprised originally 16-17 year-old HPV 16/18-vaccinated PATRICIA (NCT00122681) and 012 trial (NCT00169494) participants (2465) and HPV6/11/16/18-vaccinated FUTURE II (NCT00092534) participants (866). Altogether, 3341 vaccines were followed by the Finnish Cancer Registry in the same way as 16 526 non-HPV-vaccinated controls. The control cohort stemmed from 15 665 originally 18-19 years-old women enrolled in 2003 (6499) or 2005 (9166) and 861 placebo recipients of the FUTURE II trial. The follow-up started 6 months after the clinical trials in 2007 and 2009 and ended in 2019. It was age aligned for the cohorts. FINDINGS: During a follow-up time of up to 11 years, we identified 17 HPV-positive invasive cancer cases (14 cervical cancers, 1 vaginal cancer, 1 vulvar cancer and 1 tongue cancer) in the non-HPV-vaccinated cohorts and no cases in the HPV-vaccinated cohorts. HPV typing of diagnostic tumour blocks found HPV16 in nine cervical cancer cases, HPV18, HPV33 and HPV52 each in two cases and HPV45 in one cervical cancer case. The vaginal, vulvar and tongue cancer cases were, respectively, positive for HPV16, HPV52/66 and HPV213. Intention-to-treat vaccine efficacy against all HPV-positive cancers was 100% (95% CI 2 to 100, p<0.05). INTERPRETATION: Vaccination is effective against invasive HPV-positive cancer. TRIAL REGISTRATION NUMBER: NCT00122681, Post-results; NCT00169494, Post-results; NCT00092534, Post-results.

Differing Age-Specific Cervical Cancer Incidence Between Different Types of Human Papillomavirus: Implications for Predicting the Impact of Elimination Programs.

The elimination of cervical cancer rests on high efficacy of human papillomavirus (HPV) vaccines. The HPV type distribution among cases of invasive cervical cancer (ICC) is used to make predictions about the impact of eliminating different types of HPV, but accumulating evidence of differences in age-specific cancer incidence by HPV type exists. We used one of the largest population-based series of HPV genotyping of ICCs (n = 2,850; Sweden, 2002-2011) to estimate age-specific ICC incidence by HPV type and obtain estimates of the cancer-protective impact of the removal of different HPV types. In the base case, the age-specific ICC incidence had 2 peaks, and the standardized lifetime risk (SLTR, the lifetime number of cases per birth cohort of 100,000 females) for HPV-positive ICC was 651 per 100,000 female births. In the absence of vaccine types HPV 16 and HPV 18, the SLTR for ICC was reduced to 157 per 100,000 female births (24% of HPV-positive SLTR). Elimination of all 9 types that can currently be vaccinated against reduced the remaining SLTR to 47 per 100,000 female births (7%), the remaining ICC incidence only slowly increasing with age. In conclusion, after elimination of vaccine-protected HPV types, very few cases of ICC will be left, especially among fertile, reproductive-age women.

Efficacy of AS04-Adjuvanted Vaccine Against Human Papillomavirus (HPV) Types 16 and 18 in Clearing Incident HPV Infections: Pooled Analysis of Data From the Costa Rica Vaccine Trial and the PATRICIA Study.

Clinical trial data and real-world evidence suggest that the AS04-adjuvanted vaccine targeting human papillomavirus types 16 and 18 (AS04-HPV-16/18) vaccine provides nearly 90% protection against cervical intraepithelial neoplasia grade 3 or higher irrespective of type, among women vaccinated before sexual debut. This high efficacy is not fully explained by cross-protection. Although AS04-HPV-16/18 vaccination does not affect clearance of prevalent infections, it may accelerate clearance of newly acquired infections. We pooled data from 2 large-scale randomized controlled trials to evaluate efficacy of the AS04-HPV-16/18 vaccine against clearance of nontargeted incident infections. Results of our analysis do not suggest an effect in expediting clearance of incident infections.