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Journal of Preventive Medicine and... Sep 2018In the literature conflicting opinions are detectable on the onset of adverse events as autoimmune disease post HPV vaccine and often case reports describes the onset of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In the literature conflicting opinions are detectable on the onset of adverse events as autoimmune disease post HPV vaccine and often case reports describes the onset of one of these events, but don't emerge a clear relationship and we don't have data to support it.
METHODS
We carried out a systematic review to identify all scientific publications dealing with the correlation between vaccine anti-papillomavirus and new onset of autoimmune diseases. We searched the main scientific databases (PubMed, Sciverse Scopus, Web of knowledge and Cochrane Central Register of Controlled Clinical Trials) for the following search terms: "vaccine"; "anti-papillomavirus"; "autoimmune"; "disease"; "disorder". To evaluate the safety of HPV vaccines, the dichotomous data on the number of subjects experiencing an autoimmune disorder in the study vaccine group and the placebo group were extracted from each study with subsequent determination of the risk ratios and their 95% confidence intervals. We combined data statistically using a random effects model.
RESULTS
We conduct a meta-analysis on six studies on bivalent and quadrivalent HPV vaccine. The total number of subjects included in the meta-analysis comprised 243,289 in the vaccine group and 248,820 in control groups. Four of the six trials had a Jadad score of 3 or 4 indicating an adequate trial quality. The most frequent autoimmune disease observed across the six studies were musculoskeletal,CNS conditions and endocrinological conditions . The results of the meta-analysis demonstrated no correlation between autoimmune disorders and HPV vaccines (pooled OR 1.038, 95% CI 0.689-1.562).
CONCLUSIONS
No correlation was identified for bivalent and quadrivalent HPV vaccines. It's therefore essential to correctly inform the general population in order to try to increase both Italian and international vaccination coverage.
Topics: Adolescent; Adult; Autoimmune Diseases; Child; Female; Humans; Male; Papillomavirus Infections; Papillomavirus Vaccines; Young Adult
PubMed: 30397675
DOI: 10.15167/2421-4248/jpmh2018.59.3.998 -
PloS One 2017Although cervical cancer is largely preventable through screening, detection and treatment of precancerous abnormalities, it remains one of the top causes of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Although cervical cancer is largely preventable through screening, detection and treatment of precancerous abnormalities, it remains one of the top causes of cancer-related morbidity and mortality globally.
OBJECTIVES
The objective of this systematic review is to understand the evidence of the effect of cervical cancer education compared to control conditions on cervical cancer screening rates in eligible women population at risk of cervical cancer. We also sought to understand the effect of provider recommendations for screening to eligible women on cervical cancer screening (CCS) rates compared to control conditions in eligible women population at risk of cervical cancer.
METHODS
We used the PICO (Problem or Population, Interventions, Comparison and Outcome) framework as described in the Cochrane Collaboration Handbook to develop our search strategy. The details of our search strategy has been described in our systematic review protocol published in the International Prospective Register of systematic reviews (PROSPERO). The protocol registration number is CRD42016045605 available at: http://www.crd.york.ac.uk/prospero/display_record.asp?src=trip&ID=CRD42016045605. The search string was used in Pubmed, Embase, Cochrane Systematic Reviews and Cochrane CENTRAL register of controlled trials to retrieve study reports that were screened for inclusion in this review. Our data synthesis and reporting was guided by the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). We did a qualitative synthesis of evidence and, where appropriate, individual study effects were pooled in meta-analyses using RevMan 5.3 Review Manager. The Higgins I2 was used to assess for heterogeneity in studies pooled together for overall summary effects. We did assessment of risk of bias of individual studies included and assessed risk of publication bias across studies pooled together in meta-analysis by Funnel plot.
RESULTS
Out of 3072 study reports screened, 28 articles were found to be eligible for inclusion in qualitative synthesis (5 of which were included in meta-analysis of educational interventions and 8 combined in meta-analysis of HPV self-sampling interventions), while 45 were excluded for various reasons. The use of theory-based educational interventions significantly increased CCS rates by more than double (OR, 2.46, 95% CI: 1.88, 3.21). Additionally, offering women the option of self-sampling for Human Papillomavirus (HPV) testing increased CCS rates by nearly 2-fold (OR = 1.71, 95% CI: 1.32, 2.22). We also found that invitation letters alone (or with a follow up phone contact), making an appointment, and sending reminders to patients who are due or overdue for screening had a significant effect on improving participation and CCS rates in populations at risk.
CONCLUSION
Our findings supports the implementation of theory-based cervical cancer educational interventions to increase women's participation in cervical cancer screening programs, particularly when targeting communities with low literacy levels. Additionally, cervical cancer screening programs should consider the option of offering women the opportunity for self-sample collection particularly when such women have not responded to previous screening invitation or reminder letters for Pap smear collection as a method of screening.
Topics: Bias; Early Detection of Cancer; Female; Health Education; Humans; Mass Screening; Papillomaviridae; Patient Education as Topic; Prospective Studies; Quality of Life; Treatment Outcome; Uterine Cervical Neoplasms
PubMed: 28873092
DOI: 10.1371/journal.pone.0183924 -
Clinical Microbiology and Infection :... Jan 2019The vaginal microbiota may modulate susceptibility to human papillomavirus (HPV), Chlamydia trachomatis, Neisseria gonorrhoeae and Mycoplasma genitalium infections.... (Meta-Analysis)
Meta-Analysis
The vaginal microbiota and its association with human papillomavirus, Chlamydia trachomatis, Neisseria gonorrhoeae and Mycoplasma genitalium infections: a systematic review and meta-analysis.
BACKGROUND
The vaginal microbiota may modulate susceptibility to human papillomavirus (HPV), Chlamydia trachomatis, Neisseria gonorrhoeae and Mycoplasma genitalium infections. Persistent infection with a carcinogenic HPV is a prerequisite for cervical cancer, and C. trachomatis, N. gonorrheae and M. genitalium genital infections are all associated with pelvic inflammatory disease and subsequent infertility issues.
OBJECTIVES
To evaluate the association between these infections and the vaginal microbiota.
DATA SOURCES
The search was conducted on Medline and the Web of Science for articles published between 2000 and 2016.
STUDY ELIGIBILITY CRITERIA
Inclusion criteria included a measure of association for vaginal microbiota and one of the considered STIs, female population, cohort, cross-sectional and interventional designs, and the use of PCR methods for pathogen detection.
METHODS
The vaginal microbiota was dichotomized into high-Lactobacillus vaginal microbiota (HL-VMB) and low-Lactobacillus vaginal microbiota (LL-VMB), using either Nugent score, Amsel's criteria, presence of clue cells or gene sequencing. A random effects model assuming heterogeneity among the studies was used for each STI considered.
RESULTS
The search yielded 1054 articles, of which 39 met the inclusion criteria. Measures of association with LL-VMB ranged from 0.6 (95% CI 0.3-1.2) to 2.8 (95% CI 0.3-28.0), 0.7 (95% CI 0.4-1.2) to 5.2 (95% CI 1.9-14.8), 0.8 (95% CI 0.5-1.4) to 3.8 (95% CI 0.4-36.2) and 0.4 (95% CI 0.1-1.5) to 6.1 (95% CI 2.0-18.5) for HPV, C. trachomatis, N. gonorrhoeae and M. genitalium infections, respectively.
CONCLUSIONS
Although no clear trend for N. gonorrhoeae and M. genitalium infections could be detected, our results support a protective role of HL-VMB for HPV and C. trachomatis. Overall, these findings advocate for the use of high-resolution characterization methods for the vaginal microbiota and the need for longitudinal studies to lay the foundation for its integration in prevention and treatment strategies.
Topics: Chlamydia Infections; Chlamydia trachomatis; Female; Gonorrhea; Humans; Microbial Interactions; Microbiota; Mycoplasma Infections; Mycoplasma genitalium; Neisseria gonorrhoeae; Papillomaviridae; Pelvic Inflammatory Disease; Sexually Transmitted Diseases; Vagina
PubMed: 29729331
DOI: 10.1016/j.cmi.2018.04.019 -
Human Vaccines & Immunotherapeutics Jun 2016Improving HPV vaccination coverage in the US will require healthcare providers to recommend the vaccine more effectively. To inform quality improvement efforts, we... (Review)
Review
BACKGROUND
Improving HPV vaccination coverage in the US will require healthcare providers to recommend the vaccine more effectively. To inform quality improvement efforts, we systematically reviewed studies of provider communication about HPV vaccination.
METHODS
We searched MEDLINE, CINAHL, EMBASE, and POPLINE in August 2015 to identify studies of provider communication about HPV vaccination.
RESULTS
We identified 101 qualitative and quantitative studies. Providers less often recommended HPV vaccine if they were uncomfortable discussing sex, perceived parents as hesitant, or believed patients to be low risk. Patients less often received recommendations if they were younger, male, or from racial/ethnic minorities. Despite parents' preference for unambiguous recommendations, providers often sent mixed messages by failing to endorse HPV vaccine strongly, differentiating it from other vaccines, and presenting it as an "optional" vaccine that could be delayed.
CONCLUSION
Interventions are needed to help providers deliver effective recommendations in the complex communication environment surrounding HPV vaccination.
Topics: Health Communication; Health Personnel; Humans; Papillomavirus Infections; Papillomavirus Vaccines; United States; Vaccination
PubMed: 26838681
DOI: 10.1080/21645515.2015.1129090 -
Vaccine Mar 2022A WHO global strategy launched in November 2020 sets out an ambitious pathway towards the worldwide elimination of cervical cancer as a public health problem within the... (Review)
Review
A WHO global strategy launched in November 2020 sets out an ambitious pathway towards the worldwide elimination of cervical cancer as a public health problem within the next 100 years. Achieving this goal will require investment in innovative approaches. This review aims to describe integrated approaches that combine human papillomavirus (HPV) vaccination and cervical cancer screening in low- and middle-income countries (LMIC), and their efficacy in increasing uptake of services. A systematic review was conducted analyzing relevant papers from Embase, Medline, CINAHL and CAB Global Health databases, as well as grey literature. Narrative synthesis was performed on the included studies. Meta-analysis was not appropriate due to the heterogeneity and nature of included studies. From 5,278 titles screened, 11 uncontrolled intervention studies from four countries (from Africa and east Asia) were included, all from the past 12 years. Four distinct typologies of integration emerged that either increased awareness of HPV and/or cervical cancer screening, and/or coupled the delivery of HPV vaccination and cervical cancer screening programs. The synthesis of findings suggests that existing HPV vaccination programs can be a useful pathway for educating mothers and other female caregivers about cervical cancer screening; through in person conversations with care providers (preferred) or take-home communications products. Integrated service delivery through outreach and mobile clinics may overcome geographic and economic barriers to access for both HPV vaccination and cervical cancer screening, however these require significant program and system resources. One study promoted HPV vaccination as part of integrated service delivery, but there were no other examples found that examined use of cervical cancer screening platforms to promote or educate on HPV vaccination. This review has demonstrated gaps in published literature on attempts to integrate HPV vaccination and cervical cancer screening. The most promising practices to date seem to relate to integrated health communications for cervical cancer prevention. Future research should further explore the opportunities for integrated health communications to support the efforts towards the new global cervical cancer elimination agenda, and costs and feasibility of integrated service delivery for underserved populations.
Topics: Cervix Uteri; Early Detection of Cancer; Female; Humans; Papillomavirus Infections; Papillomavirus Vaccines; Uterine Cervical Neoplasms; Vaccination
PubMed: 34863615
DOI: 10.1016/j.vaccine.2021.11.013 -
Preventive Medicine Jan 2022An increasing body of evidence supports the validity of self-sampling as an alternative to clinician collection for primary Human Papillomavirus (HPV) screening....
An increasing body of evidence supports the validity of self-sampling as an alternative to clinician collection for primary Human Papillomavirus (HPV) screening. Self-sampling effectively reaches underscreened women and can be a powerful strategy in low- and high-resource settings for all target ages. This work aims to summarize the current use of HPV self-sampling worldwide. It is part of a larger project that describes cervical cancer screening programmes and produces standardized coverage estimates worldwide. A systematic review of the literature and official documents supplemented with a formal World Health Organisation country consultation was conducted. Findings show that the global use of HPV self-sampling is still limited. Only 17 (12%) of countries with identified screening programs recommend its use, nine as the primary collection method, and eight to reach underscreened populations. We identified 10 pilots evaluating the switch to self-sampling in well-established screening programs. The global use of self-sampling is likely to increase in the coming years. COVID-19's pandemic has prompted efforts to accelerate HPV self-sampling introduction globally, and it is now considered a key element in scaling up screening coverage. The information generated by the early experiences can be beneficial for decision-making in both new and existing programs.
Topics: COVID-19; Early Detection of Cancer; Female; Humans; Mass Screening; Papillomaviridae; Papillomavirus Infections; SARS-CoV-2; Self Care; Specimen Handling; Uterine Cervical Neoplasms; Vaginal Smears
PubMed: 34861338
DOI: 10.1016/j.ypmed.2021.106900 -
Clinical Microbiology and Infection :... Aug 2021Only clinically validated HPV assays can be accepted in cervical cancer screening. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Only clinically validated HPV assays can be accepted in cervical cancer screening.
OBJECTIVES
To update the list of high-risk HPV assays that fulfil the 2009 international validation criteria (Meijer-2009).
DATA SOURCES
PubMed/Medline, Embase, Scopus, references from selected studies; published in January 2014 to August 2020.
STUDY ELIGIBILITY CRITERIA
HPV test validation studies and primary screening studies, involving testing with an index HPV test and a comparator HPV test with reporting of disease outcome (occurrence of histologically confirmed cervical precancer; CIN2+).
PARTICIPANTS
Women participating in cervical cancer screening.
INTERVENTIONS
Testing with an index and a comparator HPV test of clinician-collected cervical specimens and assessment of disease outcome (
METHODS
Assessment of relative clinical accuracy (including non-inferiority statistics index vs comparator assay) and test reproducibility in individual studies; random effects meta-analyses of the relative clinical sensitivity and specificity of index vs comparator tests.
RESULTS
Seven hrHPV DNA tests consistently fulfilled all validation criteria in multiple studies using predefined test positivity cut-offs (Abbott RealTime High Risk HPV, Anyplex II HPV HR Detection, BD Onclarity HPV Assay, Cobas 4800 HPV Test, HPV-Risk Assay, PapilloCheck HPV-Screening Test and Xpert HPV). Another assay (Alinity m HR HPV Assay) was fully validated in one validation study. The newer Cobas 6800 HPV Test, was validated in two studies against Cobas 4800. Other tests partially fulfilled the international validation criteria (Cervista HPV HR Test, EUROArray HPV, Hybribio's 14 High-Risk HPV, LMNX Genotyping Kit GP HPV, MALDI-TOF, RIATOL qPCR and a number of other in-house developed assays) since the non-inferior accuracy was reached after a posteriori cut-off optimization, inconsistent accuracy findings in different studies, and/or insufficient reproducibility assessment. The APTIMA HPV Assay targeting E6/E7 mRNA of hrHPV was fully validated in one formal validation study and showed slightly lower pooled sensitivity but higher specificity than the standard comparator tests in seven screening studies. However, the current international validation criteria relate to DNA assays. The additional requirement for longitudinal performance data required for non-DNA based HPV assays was not assessed in this review.
CONCLUSIONS
Eleven hrHPV DNA assays fulfil all requirements for use in cervical cancer screening using clinician-collected specimens.
Topics: Alphapapillomavirus; Early Detection of Cancer; Female; Genotyping Techniques; Humans; Papillomaviridae; Papillomavirus Infections; Reproducibility of Results; Sensitivity and Specificity; Uterine Cervical Neoplasms
PubMed: 33975008
DOI: 10.1016/j.cmi.2021.04.031 -
The Lancet. Global Health Feb 2021HIV enhances human papillomavirus (HPV)-induced carcinogenesis. However, the contribution of HIV to cervical cancer burden at a population level has not been quantified.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
HIV enhances human papillomavirus (HPV)-induced carcinogenesis. However, the contribution of HIV to cervical cancer burden at a population level has not been quantified. We aimed to investigate cervical cancer risk among women living with HIV and to estimate the global cervical cancer burden associated with HIV.
METHODS
We did a systematic literature search and meta-analysis of five databases (PubMed, Embase, Global Health [CABI.org], Web of Science, and Global Index Medicus) to identify studies analysing the association between HIV infection and cervical cancer. We estimated the pooled risk of cervical cancer among women living with HIV across four continents (Africa, Asia, Europe, and North America). The risk ratio (RR) was combined with country-specific UNAIDS estimates of HIV prevalence and GLOBOCAN 2018 estimates of cervical cancer to calculate the proportion of women living with HIV among women with cervical cancer and population attributable fractions and age-standardised incidence rates (ASIRs) of HIV-attributable cervical cancer.
FINDINGS
24 studies met our inclusion criteria, which included 236 127 women living with HIV. The pooled risk of cervical cancer was increased in women living with HIV (RR 6·07, 95% CI 4·40-8·37). Globally, 5·8% (95% CI 4·6-7·3) of new cervical cancer cases in 2018 (33 000 new cases, 95% CI 26 000-42 000) were diagnosed in women living with HIV and 4·9% (95% CI 3·6-6·4) were attributable to HIV infection (28 000 new cases, 20 000-36 000). The most affected regions were southern Africa and eastern Africa. In southern Africa, 63·8% (95% CI 58·9-68·1) of women with cervical cancer (9200 new cases, 95% CI 8500-9800) were living with HIV, as were 27·4% (23·7-31·7) of women in eastern Africa (14 000 new cases, 12 000-17 000). ASIRs of HIV-attributable cervical cancer were more than 20 per 100 000 in six countries, all in southern Africa and eastern Africa.
INTERPRETATION
Women living with HIV have a significantly increased risk of cervical cancer. HPV vaccination and cervical cancer screening for women living with HIV are especially important for countries in southern Africa and eastern Africa, where a substantial HIV-attributable cervical cancer burden has added to the existing cervical cancer burden.
FUNDING
WHO, US Agency for International Development, and US President's Emergency Plan for AIDS Relief.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Alphapapillomavirus; Female; Global Burden of Disease; Global Health; HIV Infections; Humans; Middle Aged; Uterine Cervical Neoplasms; Young Adult
PubMed: 33212031
DOI: 10.1016/S2214-109X(20)30459-9 -
Annals of Oncology : Official Journal... Feb 2020Although local treatments for cervical intraepithelial neoplasia (CIN) are highly effective, it has been reported that treated women remain at increased risk of cervical... (Meta-Analysis)
Meta-Analysis
Incidence and mortality from cervical cancer and other malignancies after treatment of cervical intraepithelial neoplasia: a systematic review and meta-analysis of the literature.
BACKGROUND
Although local treatments for cervical intraepithelial neoplasia (CIN) are highly effective, it has been reported that treated women remain at increased risk of cervical and other cancers. Our aim is to explore the risk of developing or dying from cervical cancer and other human papillomavirus (HPV)- and non-HPV-related malignancies after CIN treatment and infer its magnitude compared with the general population.
MATERIALS AND METHODS
Design: Systematic review and meta-analysis. Eligibility criteria: Studies with registry-based follow-up reporting cancer incidence or mortality after CIN treatment.
DATA SYNTHESIS
Summary effects were estimated using random-effects models.
OUTCOMES
Incidence rate of cervical cancer among women treated for CIN (per 100 000 woman-years). Relative risk (RR) of cervical cancer, other HPV-related anogenital tract cancer (vagina, vulva, anus), any cancer, and mortality, for women treated for CIN versus the general population.
RESULTS
Twenty-seven studies were eligible. The incidence rate for cervical cancer after CIN treatment was 39 per 100 000 woman-years (95% confidence interval 22-69). The RR of cervical cancer was elevated compared with the general population (3.30, 2.57-4.24; P < 0.001). The RR was higher for women more than 50 years old and remained elevated for at least 20 years after treatment. The RR of vaginal (10.84, 5.58-21.10; P < 0.001), vulvar (3.34, 2.39-4.67; P < 0.001), and anal cancer (5.11, 2.73-9.55; P < 0.001) was also higher. Mortality from cervical/vaginal cancer was elevated, but our estimate was more uncertain (RR 5.04, 0.69-36.94; P = 0.073).
CONCLUSIONS
Women treated for CIN have a considerably higher risk to be later diagnosed with cervical and other HPV-related cancers compared with the general population. The higher risk of cervical cancer lasts for at least 20 years after treatment and is higher for women more than 50 years of age. Prolonged follow-up beyond the last screening round may be warranted for previously treated women.
Topics: Alphapapillomavirus; Female; Humans; Incidence; Middle Aged; Papillomavirus Infections; Uterine Cervical Neoplasms; Uterine Cervical Dysplasia
PubMed: 31959338
DOI: 10.1016/j.annonc.2019.11.004 -
The Cochrane Database of Systematic... May 2018Persistent infection with high-risk human papillomaviruses (hrHPV) types is causally linked with the development of cervical precancer and cancer. HPV types 16 and 18... (Review)
Review
BACKGROUND
Persistent infection with high-risk human papillomaviruses (hrHPV) types is causally linked with the development of cervical precancer and cancer. HPV types 16 and 18 cause approximately 70% of cervical cancers worldwide.
OBJECTIVES
To evaluate the harms and protection of prophylactic human papillomaviruses (HPV) vaccines against cervical precancer and HPV16/18 infection in adolescent girls and women.
SEARCH METHODS
We searched MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL) and Embase (June 2017) for reports on effects from trials. We searched trial registries and company results' registers to identify unpublished data for mortality and serious adverse events.
SELECTION CRITERIA
Randomised controlled trials comparing efficacy and safety in females offered HPV vaccines with placebo (vaccine adjuvants or another control vaccine).
DATA COLLECTION AND ANALYSIS
We used Cochrane methodology and GRADE to rate the certainty of evidence for protection against cervical precancer (cervical intraepithelial neoplasia grade 2 and above [CIN2+], CIN grade 3 and above [CIN3+], and adenocarcinoma-in-situ [AIS]), and for harms. We distinguished between the effects of vaccines by participants' baseline HPV DNA status. The outcomes were precancer associated with vaccine HPV types and precancer irrespective of HPV type. Results are presented as risks in control and vaccination groups and risk ratios (RR) with 95% confidence intervals in brackets.
MAIN RESULTS
We included 26 trials (73,428 participants). Ten trials, with follow-up of 1.3 to 8 years, addressed protection against CIN/AIS. Vaccine safety was evaluated over a period of 6 months to 7 years in 23 studies. Studies were not large enough or of sufficient duration to evaluate cervical cancer outcomes. All but one of the trials was funded by the vaccine manufacturers. We judged most included trials to be at low risk of bias. Studies involved monovalent (N = 1), bivalent (N = 18), and quadrivalent vaccines (N = 7). Most women were under 26 years of age. Three trials recruited women aged 25 and over. We summarize the effects of vaccines in participants who had at least one immunisation.Efficacy endpoints by initial HPV DNA statushrHPV negativeHPV vaccines reduce CIN2+, CIN3+, AIS associated with HPV16/18 compared with placebo in adolescent girls and women aged 15 to 26. There is high-certainty evidence that vaccines lower CIN2+ from 164 to 2/10,000 (RR 0.01 (0 to 0.05)) and CIN3+ from 70 to 0/10,000 (RR 0.01 (0.00 to 0.10). There is moderate-certainty evidence that vaccines reduce the risk of AIS from 9 to 0/10,000 (RR 0.10 (0.01 to 0.82).HPV vaccines reduce the risk of any CIN2+ from 287 to 106/10,000 (RR 0.37 (0.25 to 0.55), high certainty) and probably reduce any AIS lesions from 10 to 0/10,000 (RR 0.1 (0.01 to 0.76), moderate certainty). The size of reduction in CIN3+ with vaccines differed between bivalent and quadrivalent vaccines (bivalent: RR 0.08 (0.03 to 0.23), high certainty; quadrivalent: RR 0.54 (0.36 to 0.82), moderate certainty). Data in older women were not available for this comparison.HPV16/18 negativeIn those aged 15 to 26 years, vaccines reduce CIN2+ associated with HPV16/18 from 113 to 6 /10,000 (RR 0.05 (0.03 to 0.10). In women 24 years or older the absolute and relative reduction in the risk of these lesions is smaller (from 45 to 14/10,000, (RR 0.30 (0.11 to 0.81), moderate certainty). HPV vaccines reduce the risk of CIN3+ and AIS associated with HPV16/18 in younger women (RR 0.05 (0.02 to 0.14), high certainty and RR 0.09 (0.01 to 0.72), moderate certainty, respectively). No trials in older women have measured these outcomes.Vaccines reduce any CIN2+ from 231 to 95/10,000, (RR 0.41 (0.32 to 0.52)) in younger women. No data are reported for more severe lesions.Regardless of HPV DNA statusIn younger women HPV vaccines reduce the risk of CIN2+ associated with HPV16/18 from 341 to 157/10,000 (RR 0.46 (0.37 to 0.57), high certainty). Similar reductions in risk were observed for CIN3+ associated with HPV16/18 (high certainty). The number of women with AIS associated with HPV16/18 is reduced from 14 to 5/10,000 with HPV vaccines (high certainty).HPV vaccines reduce any CIN2+ from 559 to 391/10,000 (RR 0.70 (0.58 to 0.85, high certainty) and any AIS from 17 to 5/10,000 (RR 0.32 (0.15 to 0.67), high certainty). The reduction in any CIN3+ differed by vaccine type (bivalent vaccine: RR 0.55 (0.43 to 0.71) and quadrivalent vaccine: RR 0.81 (0.69 to 0.96)).In women vaccinated at 24 to 45 years of age, there is moderate-certainty evidence that the risks of CIN2+ associated with HPV16/18 and any CIN2+ are similar between vaccinated and unvaccinated women (RR 0.74 (0.52 to 1.05) and RR 1.04 (0.83 to 1.30) respectively). No data are reported in this age group for CIN3+ or AIS.Adverse effectsThe risk of serious adverse events is similar between control and HPV vaccines in women of all ages (669 versus 656/10,000, RR 0.98 (0.92 to 1.05), high certainty). Mortality was 11/10,000 in control groups compared with 14/10,000 (9 to 22) with HPV vaccine (RR 1.29 [0.85 to 1.98]; low certainty). The number of deaths was low overall but there is a higher number of deaths in older women. No pattern in the cause or timing of death has been established.Pregnancy outcomesAmong those who became pregnant during the studies, we did not find an increased risk of miscarriage (1618 versus 1424/10,000, RR 0.88 (0.68 to 1.14), high certainty) or termination (931 versus 838/10,000 RR 0.90 (0.80 to 1.02), high certainty). The effects on congenital abnormalities and stillbirths are uncertain (RR 1.22 (0.88 to 1.69), moderate certainty and (RR 1.12 (0.68 to 1.83), moderate certainty, respectively).
AUTHORS' CONCLUSIONS
There is high-certainty evidence that HPV vaccines protect against cervical precancer in adolescent girls and young women aged 15 to 26. The effect is higher for lesions associated with HPV16/18 than for lesions irrespective of HPV type. The effect is greater in those who are negative for hrHPV or HPV16/18 DNA at enrolment than those unselected for HPV DNA status. There is moderate-certainty evidence that HPV vaccines reduce CIN2+ in older women who are HPV16/18 negative, but not when they are unselected by HPV DNA status.We did not find an increased risk of serious adverse effects. Although the number of deaths is low overall, there were more deaths among women older than 25 years who received the vaccine. The deaths reported in the studies have been judged not to be related to the vaccine. Increased risk of adverse pregnancy outcomes after HPV vaccination cannot be excluded, although the risk of miscarriage and termination are similar between trial arms. Long-term of follow-up is needed to monitor the impact on cervical cancer, occurrence of rare harms and pregnancy outcomes.
Topics: Adolescent; Adult; Female; Human papillomavirus 16; Human papillomavirus 18; Humans; Middle Aged; Papillomavirus Infections; Papillomavirus Vaccines; Precancerous Conditions; Pregnancy; Pregnancy Outcome; Randomized Controlled Trials as Topic; Uterine Cervical Neoplasms; Vaccination; Young Adult; Uterine Cervical Dysplasia
PubMed: 29740819
DOI: 10.1002/14651858.CD009069.pub3