Prophylactic human papillomavirus (HPV) vaccination programs constitute major public health initiatives worldwide. We assessed the global effect of quadrivalent HPV (4vHPV) vaccination on HPV ...infection and disease. PubMed and Embase were systematically searched for peer-reviewed articles from January 2007 through February 2016 to identify observational studies reporting the impact or effectiveness of 4vHPV vaccination on infection, anogenital warts, and cervical cancer or precancerous lesions. Over the last decade, the impact of HPV vaccination in real-world settings has become increasingly evident, especially among girls vaccinated before HPV exposure in countries with high vaccine uptake. Maximal reductions of approximately 90% for HPV 6/11/16/18 infection, approximately 90% for genital warts, approximately 45% for low-grade cytological cervical abnormalities, and approximately 85% for high-grade histologically proven cervical abnormalities have been reported. The full public health potential of HPV vaccination is not yet realized. HPV-related disease remains a significant source of morbidity and mortality in developing and developed nations, underscoring the need for HPV vaccination programs with high population coverage.
Cervical cancer is caused by oncogenic human papillomaviruses (HR-HPV) and is common among Kenyan women. Identification of factors that increase HR-HPV persistence is critically important. Kenyan ...women exposed to aflatoxin have an increased risk of HR-HPV detection in cervical specimens. This analysis was performed to examine associations between aflatoxin and HR-HPV persistence.
Kenyan women were enrolled in a prospective study. The analytical cohort for this analysis included 67 HIV-uninfected women (mean age 34 years) who completed at least two of three annual study visits and had an available blood sample. Plasma aflatoxin was detected using ultra-high pressure liquid chromatography (UHPLC)-isotope dilution mass spectrometry. Annual cervical swabs were tested for HPV (Roche Linear Array). Ordinal logistic regression models were fitted to examine associations of aflatoxin and HPV persistence.
Aflatoxin was detected in 59.7% of women and was associated with higher risk of persistent detection of any HPV type (OR = 3.03, 95%CI = 1.08-8.55, P = 0.036), HR-HPV types (OR = 3.63, 95%CI = 1.30-10.13, P = 0.014), and HR-HPV types not included in the 9-valent HPV vaccine (OR = 4.46, 95%CI = 1.13-17.58, P = 0.032).
Aflatoxin detection was associated with increased risk of HR-HPV persistence in Kenyan women. Further studies, including mechanistic studies are needed to determine if aflatoxin synergistically interacts with HR-HPV to increase cervical cancer risk.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background We performed a study to better characterize the natural history of genital human papillomavirus (HPV) infection in a cohort of closely followed adolescent women. Methods A cohort of 60 ...adolescent women was followed over a 2.2-year period, on average. A median of 41.5 self-collected vaginal and clinician-obtained cervical swabs were obtained from each subject Results HPV was detected in 45.3% of all adequate specimens, by use of a polymerase chain reaction/reverse blot strip assay. Oncogenic—or high-risk (HR)—HPV types were detected in 38.6% of specimens, and nononcogenic—or low-risk (LR)—types were detected in 19.6% of specimens. During the entire study period, 49 of 60 subjects tested positive for HPV (cumulative prevalence, 81.7%). The most frequently detected HR types were HPV types 52, 16, and 59. Infections with multiple HPV types were common. The median duration of persistence of a specific HPV type was 168 days, and HR types were more persistent than LR types. Abnormal cervical cytological results occurred in 37% of the adolescent women and were significantly associated with HR HPV infection. Conclusions The cumulative prevalence of HPV infection in sexually active adolescent women is extremely high, involves numerous HPV types, and frequently results in cervical dysplasia.
Clinical trials of the 4-valent human papillomavirus (HPV) vaccine demonstrate high efficacy, but surveillance studies are essential to examine the long-term impact of vaccine introduction on HPV ...prevalence in community settings. The aims of this study were to determine during the 11 years after vaccine introduction the prevalence of (1) vaccine-type HPV in adolescent and young adult women who were vaccinated (to assess vaccine effectiveness) and (2) vaccine-type HPV in women who were unvaccinated (to assess herd protection).
Young women 13 to 26 years of age were recruited from hospital-based and community health clinics for 4 surveillance studies from 2006 to 2017. We determined the proportion of vaccinated and unvaccinated women who were positive for vaccine-type HPV across the studies, and the odds of positivity for vaccine-type HPV using logistic regression; all analyses were propensity score-adjusted to control for between-wave differences in participant characteristics.
Vaccination rates increased from 0% to 84.3% (97% of study participants received the 4-valent vaccine). Among women who were vaccinated, 4-valent vaccine-type HPV detection decreased from 35% to 6.7% (80.9% decline; odds ratio 0.13, 95% confidence interval 0.08 to 0.22). Among women who were unvaccinated, 4-valent vaccine-type HPV detection decreased from 32.4% to 19.4% (40% decline; odds ratio 0.50, 95% confidence interval 0.26 to 0.97). Estimated vaccine effectiveness was 90.6% in wave 3 and 80.1% in wave 4.
In this study in which trends in HPV in a US community >10 years after 4-valent HPV vaccine introduction and after 9-valent vaccine introduction were examined, we found evidence of vaccine effectiveness and herd protection. Further research is needed to examine trends in 9-valent vaccine-type HPV after higher rates of vaccination are achieved.
The aims of this study were to compare prevalence rates of human papillomavirus (HPV) in young women before and after HPV vaccine introduction to determine the following: (1) whether vaccine-type HPV ...infection decreased, (2) whether there was evidence of herd protection, and (3) whether there was evidence for type-replacement (increased prevalence of nonvaccine-type HPV).
Young women 13 to 26 years of age who had had sexual contact were recruited from 2 primary care clinics in 2006-2007 for a prevaccination surveillance study (N = 368, none were vaccinated) and 2009-2010 for a postvaccination surveillance study (N = 409, 59% were vaccinated). Participants completed a questionnaire and were tested for cervicovaginal HPV DNA. HPV prevalence rates were compared in the pre- versus postsurveillance studies by using χ(2) tests. Propensity score weighting was used to balance differences in covariates between the 2 surveillance studies.
The mean age was ∼19 years for both groups of participants and most were African American and non-Hispanic. After propensity score weighting, the prevalence rate for vaccine-type HPV decreased substantially (31.7%-13.4%, P < .0001). The decrease in vaccine-type HPV not only occurred among vaccinated (31.8%-9.9%, P < .0001) but also among unvaccinated (30.2%-15.4%, P < .0001) postsurveillance study participants. Nonvaccine-type HPV increased (60.7%-75.9%, P < .0001) for vaccinated postsurveillance study participants.
Four years after licensing of the quadrivalent HPV vaccine, there was a substantial decrease in vaccine-type HPV prevalence and evidence of herd protection in this community. The increase in nonvaccine-type HPV in vaccinated participants should be interpreted with caution but warrants further study.
•Cross-protective effect of HPV vaccines against non-vaccine types is inconsistent.•Cross-protection does not cover all HPV types included by the nonavalent vaccine.•Bivalent and quadrivalent ...vaccines’ cross-protection is partial and wanes over time.•Direct protection afforded by HPV types included in HPV vaccines is complete and durable.
The extent of cross-protection provided by currently licensed bivalent and quadrivalent HPV vaccines versus direct protection against HPV 31-, 33-, 45-, 52-, and 58-related disease is debated. A systematic literature review was conducted to establish the duration and magnitude of cross-protection in interventional and observational studies.
PubMed and Embase databases were searched to identify randomized controlled trials (RCT) and observational studies published between 2008 and 2019 reporting on efficacy and effectiveness of HPV vaccines in women against non-vaccine types 31, 33, 45, 52, 58, and 6 and 11 (non-bivalent types). Key outcomes of interest were vaccine efficacy against 6- and 12-month persistent infection or genital lesions, and type-specific genital HPV prevalence or incidence. RCT data were analyzed for the according-to-protocol (bivalent vaccine) or negative-for-14-HPV-types (quadrivalent vaccine) efficacy cohorts.
Data from 23 RCTs and 33 observational studies evaluating cross-protection were extracted. RCTs assessed cross-protection in post-hoc analyses of small size subgroups. Among fully vaccinated, baseline HPV-naïve women, the bivalent vaccine showed statistically significant cross-protective efficacy, although with wide confidence intervals, against 6-month and 12-month persistent cervical infections and CIN2+ only consistently for HPV 31 and 45, with the highest effect observed for HPV 31 (range 64.6% 95% CI: 27.6 to 83.9 to 79.1% 97.7% CI: 27.6 to 95.9 for 6-month persistent infection; maximal follow-up 4.7 years). No cross-protection was shown in extended follow-up. The quadrivalent vaccine efficacy reached statistical significance for HPV 31 (46.2% 15.3–66.4; follow-up: 3.6 years). Similarly, observational studies found consistently significant effectiveness only against HPV 31 and 45 with both vaccines.
RCTs and observational studies show that cross-protection is inconsistent across non-vaccine HPV types and is largely driven by HPV 31 and 45. Furthermore, existing data suggest that it wanes over time; its long-term durability has not been established.
Human papillomavirus type 16 (HPV-16) is sexually transmitted and is present in 50 percent of cervical cancers. This randomized, double-blind trial assessed the effectiveness of a vaccine that ...consists of HPV-16 L1 virus-like particles in women who were seronegative for HPV-16. The vaccine was highly effective in preventing HPV-16 infection.
The vaccine prevents HPV-16 infection, which is present in half of cervical cancers.
Human papillomavirus (HPV) infection is a common sexually transmitted disease.
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Although most infections are benign, persistent infection (repeated detection of an oncogenic type of HPV) is associated with the development of cervical and other anogenital cancers.
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Of the more than 30 types of HPV known to infect human genitalia, HPV type 16 (HPV-16) is most commonly linked with cancer, since it is present in 50 percent of cervical cancers and high-grade cervical intraepithelial neoplasias
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and in 25 percent of low-grade cervical intraepithelial neoplasias.
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A vaccine that prevents persistent HPV-16 infection could substantially reduce the incidence . . .
Background. Human papillomavirus (HPV) vaccine effectiveness and herd protection are not well established in community settings. Our objective was to determine trends in vaccine-type HPV in young ...women during the 8 years after vaccine introduction, to assess changes in HPV prevalence and characterize herd protection in a community. Methods. We recruited 3 samples of sexually experienced, 13–26-year-old adolescent girls and young women (hereafter women; N = 1180) from 2006–2014: before widespread vaccine introduction (wave 1) and 3 (wave 2) and 7 (wave 3) years after vaccine introduction. We determined the prevalence of vaccine-type HPV (HPV-6, -11, -16, and -18) among all, vaccinated, and unvaccinated women at waves 1, 2, and 3, adjusted for differences in participant characteristics, then examined whether changes in HPV prevalence were significant using inverse propensity score-weighted logistic regression. Results. Vaccination rates increased from 0% to 71.3% across the 3 waves. Adjusted vaccine-type HPV prevalence changed from 34.8% to 8.7% (75.0% decline) in all women, from 34.9% to 3.2% (90.8% decline) in vaccinated women, and from 32.5% to 22.0% (32.3% decline) in unvaccinated women. Among vaccinated participants, vaccine-type HPV prevalence decreased significantly from wave 1 to wave 2 (adjusted odds ratio, 0.21; 95% confidence interval, .13–.34) and from wave 1 to wave 3 (0.06; .03–.13). The same decreases were also significant among unvaccinated participants (adjusted odds ratios, 0.44; 95% confidence interval, .27–.71 and 0.59; .35–.98, respectively). Conclusions. The prevalence of vaccine-type HPV decreased >90% in vaccinated women, demonstrating high effectiveness in a community setting, and >30% in unvaccinated women, providing evidence of herd protection.
•Cross-protection antibody response to non-vaccine HPV types varies widely.•Antibody response is mostly detected for HPV 31 six months after third vaccine dose.•Cross-protection antibody response is ...lower than that with direct protection.•Data on duration of immune response to non-vaccine HPV beyond two years is limited.
Studies on the cross-protective effect of HPV bivalent and quadrivalent vaccines demonstrated inconsistent findings against additional HPV types covered by the nonavalent vaccine. The objective of this study was to conduct a systematic literature review to assess the consistency and durability of the cross-protective neutralizing antibody immune responses of the currently licensed bivalent and quadrivalent vaccines to non-vaccine HPV types targeted by the nonavalent vaccine (HPV 6, 11, 31, 33, 45, 52, and 58).
PubMed and EMBASE databases were searched from 2008 to 2019 to identify studies reporting antibody/immune response after vaccination with either the bivalent, quadrivalent, or nonavalent vaccine. Key outcomes were seroconversion, seropositivity or geometric mean titers against HPV types 6, 11, 31, 33, 45, 52, and 58.
Eighteen publications met inclusion criteria, reporting on 14 interventional and five observational studies. Across all studies, immune responses to non-vaccine high-risk HPV types after bivalent vaccination were higher than baseline or quadrivalent vaccine. Nonavalent vaccine elicited near total seroconversion to HPV types 31, 33, 45, 52, and 58, with seropositivity remaining near 100% up to 24 months post-dose 1. In contrast, bivalent and quadrivalent vaccination resulted in lower seroconversion levels for non-vaccine types, which waned over time.
The cross-protection antibody/immune response among participants having received all three doses of bivalent or quadrivalent vaccine is not comparable to the specific response elicited by HPV vaccine types. Even in cases where a statistically significant cross-reactive immunological response is reported, long-term data on the duration of the response beyond two years are very limited. Further, the lack of a standard for assays limits comparability of results between studies.
BackgroundHuman papillomavirus (HPV)–6/11/16/18 vaccine reduces the risk of HPV-6/11/16/18–related cervical intraepithelial neoplasia (CIN) 1–3 or adenocarcinoma in situ (AIS). Here, its impact on ...CIN1–3/AIS associated with nonvaccine oncogenic HPV types was evaluated MethodsWe enrolled 17,622 women aged 16–26 years. All underwent cervicovaginal sampling and Pap testing at regular intervals for up to 4 years. HPV genotying was performed for biopsy samples, and histological diagnoses were determined by a pathology panel. Analyses were conducted among subjects who were negative for 14 HPV types on day 1. Prespecified analyses included infection of ⩾6 months’ duration and CIN1–3/AIS due to the 2 and 5 most common HPV types in cervical cancer after HPV types 16 and 18, as well as all tested nonvaccine types ResultsVaccination reduced the incidence of HPV-31/45 infection by 40.3% (95% confidence interval CI, 13.9% to 59.0%) and of CIN1–3/AIS by 43.6% (95% CI, 12.9% to 64.1%), respectively. The reduction in HPV-31/33/45/52/58 infection and CIN1–3/AIS was 25.0% (95% CI, 5.0% to 40.9%) and 29.2% (95% CI, 8.3% to 45.5%), respectively. Efficacy for CIN2–3/AIS associated with the 10 nonvaccine HPV types was 32.5% (95% CI, 6.0% to 51.9%). Reductions were most notable for HPV-31 ConclusionsHPV-6/11/16/18 vaccine reduced the risk of CIN2–3/AIS associated with nonvaccine types responsible for ∼20% of cervical cancers. The clinical benefit of cross-protection is not expected to be fully additive to the efficacy already observed against HPV-6/11/16/18–related disease, because women may have >1 CIN lesion, each associated with a different HPV type Trial registrationClinicalTrials.gov identifiers: NCT00092521, NCT00092534, and NCT00092482
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