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Human Reproduction Update Nov 2022To provide the optimal milieu for implantation and fetal development, the female reproductive system must orchestrate uterine dynamics with the appropriate hormones...
BACKGROUND
To provide the optimal milieu for implantation and fetal development, the female reproductive system must orchestrate uterine dynamics with the appropriate hormones produced by the ovaries. Mature oocytes may be fertilized in the fallopian tubes, and the resulting zygote is transported toward the uterus, where it can implant and continue developing. The cervix acts as a physical barrier to protect the fetus throughout pregnancy, and the vagina acts as a birth canal (involving uterine and cervix mechanisms) and facilitates copulation. Fertility can be compromised by pathologies that affect any of these organs or processes, and therefore, being able to accurately model them or restore their function is of paramount importance in applied and translational research. However, innate differences in human and animal model reproductive tracts, and the static nature of 2D cell/tissue culture techniques, necessitate continued research and development of dynamic and more complex in vitro platforms, ex vivo approaches and in vivo therapies to study and support reproductive biology. To meet this need, bioengineering is propelling the research on female reproduction into a new dimension through a wide range of potential applications and preclinical models, and the burgeoning number and variety of studies makes for a rapidly changing state of the field.
OBJECTIVE AND RATIONALE
This review aims to summarize the mounting evidence on bioengineering strategies, platforms and therapies currently available and under development in the context of female reproductive medicine, in order to further understand female reproductive biology and provide new options for fertility restoration. Specifically, techniques used in, or for, the uterus (endometrium and myometrium), ovary, fallopian tubes, cervix and vagina will be discussed.
SEARCH METHODS
A systematic search of full-text articles available in PubMed and Embase databases was conducted to identify relevant studies published between January 2000 and September 2021. The search terms included: bioengineering, reproduction, artificial, biomaterial, microfluidic, bioprinting, organoid, hydrogel, scaffold, uterus, endometrium, ovary, fallopian tubes, oviduct, cervix, vagina, endometriosis, adenomyosis, uterine fibroids, chlamydia, Asherman's syndrome, intrauterine adhesions, uterine polyps, polycystic ovary syndrome and primary ovarian insufficiency. Additional studies were identified by manually searching the references of the selected articles and of complementary reviews. Eligibility criteria included original, rigorous and accessible peer-reviewed work, published in English, on female reproductive bioengineering techniques in preclinical (in vitro/in vivo/ex vivo) and/or clinical testing phases.
OUTCOMES
Out of the 10 390 records identified, 312 studies were included for systematic review. Owing to inconsistencies in the study measurements and designs, the findings were assessed qualitatively rather than by meta-analysis. Hydrogels and scaffolds were commonly applied in various bioengineering-related studies of the female reproductive tract. Emerging technologies, such as organoids and bioprinting, offered personalized diagnoses and alternative treatment options, respectively. Promising microfluidic systems combining various bioengineering approaches have also shown translational value.
WIDER IMPLICATIONS
The complexity of the molecular, endocrine and tissue-level interactions regulating female reproduction present challenges for bioengineering approaches to replace female reproductive organs. However, interdisciplinary work is providing valuable insight into the physicochemical properties necessary for reproductive biological processes to occur. Defining the landscape of reproductive bioengineering technologies currently available and under development for women can provide alternative models for toxicology/drug testing, ex vivo fertility options, clinical therapies and a basis for future organ regeneration studies.
Topics: Animals; Female; Humans; Pregnancy; Bioengineering; Embryo Implantation; Genitalia, Female; Reproduction; Uterus
PubMed: 35652272
DOI: 10.1093/humupd/dmac025 -
American Journal of Obstetrics and... Sep 2022To assess the efficacy and safety of vaginal progesterone to prevent recurrent preterm birth and adverse perinatal outcomes in singleton gestations with a history of... (Meta-Analysis)
Meta-Analysis Review
Does vaginal progesterone prevent recurrent preterm birth in women with a singleton gestation and a history of spontaneous preterm birth? Evidence from a systematic review and meta-analysis.
OBJECTIVE
To assess the efficacy and safety of vaginal progesterone to prevent recurrent preterm birth and adverse perinatal outcomes in singleton gestations with a history of spontaneous preterm birth.
DATA SOURCES
MEDLINE, Embase, LILACS, and CINAHL (from their inception to February 28, 2022), Cochrane databases, Google Scholar, bibliographies, and conference proceedings.
STUDY ELIGIBILITY CRITERIA
Randomized controlled trials that compared vaginal progesterone to placebo or no treatment in asymptomatic women with a singleton gestation and a history of spontaneous preterm birth.
METHODS
The primary outcomes were preterm birth <37 and <34 weeks of gestation. The secondary outcomes included adverse maternal and perinatal outcomes. Pooled relative risks with 95% confidence intervals were calculated. We assessed the risk of bias in the included studies, heterogeneity (I test), small-study effects, publication bias, and quality of evidence; performed subgroup and sensitivity analyses; and calculated 95% prediction intervals and adjusted relative risks.
RESULTS
Ten studies (2958 women) met the inclusion criteria: 7 with a sample size <150 (small studies) and 3 with a sample size >600 (large studies). Among the 7 small studies, 4 were at high risk of bias, 2 were at some concerns of bias, and only 1 was at low risk of bias. All the large studies were at low risk of bias. Vaginal progesterone significantly decreased the risk of preterm birth <37 weeks (relative risk, 0.64; 95% confidence interval, 0.50-0.81; I=75%; 95% prediction interval, 0.31-1.32; very low-quality evidence) and <34 weeks (relative risk, 0.62; 95% confidence interval, 0.42-0.92; I=66%; 95% prediction interval, 0.23-1.68; very low-quality evidence), and the risk of admission to the neonatal intensive care unit (relative risk, 0.53; 95% confidence interval, 0.33-0.85; I=67%; 95% prediction interval, 0.16-1.79; low-quality evidence). There were no significant differences between the vaginal progesterone and the placebo or no treatment groups in other adverse perinatal and maternal outcomes. Subgroup analyses revealed that vaginal progesterone decreased the risk of preterm birth <37 weeks (relative risk, 0.43; 95% confidence interval, 0.33-0.55; I=0%) and <34 weeks (relative risk, 0.27; 95% confidence interval, 0.15-0.49; I=0%) in the small but not in the large studies (relative risk, 0.98; 95% confidence interval, 0.88-1.09; I=0% for preterm birth <37 weeks; and relative risk, 0.94; 95% confidence interval, 0.78-1.13; I=0% for preterm birth <34 weeks). Sensitivity analyses restricted to studies at low risk of bias indicated that vaginal progesterone did not reduce the risk of preterm birth <37 weeks (relative risk, 0.96; 95% confidence interval, 0.84-1.09) and <34 weeks (relative risk, 0.90; 95% confidence interval, 0.71-1.15). There was clear evidence of substantial small-study effects in the meta-analyses of preterm birth <37 and <34 weeks of gestation because of funnel plot asymmetry and the marked differences in the pooled relative risks obtained from fixed-effect and random-effects models. The adjustment for small-study effects resulted in a markedly reduced and nonsignificant effect of vaginal progesterone on preterm birth <37 weeks (relative risk, 0.86; 95% confidence interval, 0.68-1.10) and <34 weeks (relative risk, 0.92; 95% confidence interval, 0.60-1.42).
CONCLUSION
There is no convincing evidence supporting the use of vaginal progesterone to prevent recurrent preterm birth or to improve perinatal outcomes in singleton gestations with a history of spontaneous preterm birth.
Topics: Female; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Pregnancy; Premature Birth; Progesterone; Vagina
PubMed: 35460628
DOI: 10.1016/j.ajog.2022.04.023 -
The Journal of Sexual Medicine Mar 2022Genitourinary syndrome of menopause (GSM) is a widespread condition with a great impact on quality of life and self-image. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Genitourinary syndrome of menopause (GSM) is a widespread condition with a great impact on quality of life and self-image.
AIM
We aimed to systematically review the current literature on CO2-Laser therapy efficacy for the treatment of GSM.
METHODS
MEDLINE and Embase databases were systematically queried in December 2020 Studies included women with a diagnosis of Vulvo-Vaginal Atrophy (VVA) or GSM without an history of gynaecological and/or breast cancer, pelvic organ prolapse staged higher than 2, pelvic radiotherapy or Sjogren's Syndrome. The quality of the evidence was assessed with the Cochrane risk of bias tool. This study is registered on PROSPERO, number CRD42021238121.
OUTCOMES
Effects of CO2-Laser therapy on GSM symptoms assessed through subjective or objective efficacy measurement methods.
RESULTS
A total of 803 articles were identified. Of these, 25 studies were included in this review for a total of 1,152 patients. All studies showed a significant reduction in VVA and/or GSM symptoms (dryness, dyspareunia, itching, burning, dysuria). The pooled mean differences for the symptoms were: dryness -5.15 (95% CI:-5.72,-4.58; P < .001; I:62%; n = 296), dyspareunia -5.27 (95% CI:-5.93,-4.62; P < .001; I:68%; n = 296), itching -2.75 (95% CI:-4.0,-1.51; P < .001; I:93%; n = 281), burning -2.66 (95% CI:-3.75, -1.57; P < .001; I:86%; n = 296) and dysuria -2.14 (95% CI:-3.41,-0.87; P < .001; I:95%; n = 281). FSFI, WHIS and VMV scores also improved significantly. The pooled mean differences for these scores were: FSFI 10.8 (95% CI:8.41,13.37; P < .001; I:84%; n = 273), WHIS 8.29 (95% CI:6.16,10.42; P < .001; I:95%; n = 262) and VMV 30.4 (95% CI:22.38,38.55; P < .001; I:24%; n = 68). CO2-Laser application showed a beneficial safety profile and no major adverse events were reported.
CLINICAL IMPLICATIONS
Vaginal laser treatment resulted in both a statistically and clinically significant improvement in GSM symptoms. FSFI improved significantly in all 8 included studies but it reached a clinically relevant level only in 2 of them.
STRENGTHS & LIMITATIONS
The strength of the current meta-analysis is the comprehensive literature search. We reported data from a high number of patients (1,152) and high number of laser applications (more than 3,800). The main limitations are related to the high heterogeneity of the included studies investigating laser effects. Moreover, most of them are single center and nonrandomized studies.
CONCLUSION
The data suggest that CO2-Laser is a safe energy-based therapeutic option for the management of VVA and/or GSM symptoms in postmenopausal women; however, the quality of the body of evidence is "very low" or "low". Filippini M, Porcari I, Ruffolo AF, et al., CO2-Laser therapy and Genitourinary Syndrome of Menopause: A Systematic Review and Meta-Analysis. J Sex Med 2022;19:452-470.
Topics: Atrophy; Carbon Dioxide; Female; Humans; Laser Therapy; Lasers, Gas; Menopause; Quality of Life; Treatment Outcome; Vagina; Vaginal Diseases
PubMed: 35101378
DOI: 10.1016/j.jsxm.2021.12.010 -
Journal of Obstetrics and Gynaecology... Apr 2021To compare success and complication rates of apical suspension procedures for the surgical management of symptomatic uterine or vaginal vault prolapse. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To compare success and complication rates of apical suspension procedures for the surgical management of symptomatic uterine or vaginal vault prolapse.
TARGET POPULATION
Women with symptomatic uterine or vaginal vault prolapse seeking surgical correction.
OPTIONS
Interventions included abdominal apical reconstructive repairs (sacrocolpopexy, sacrohysteropexy, or uterosacral hysteropexy) via open, laparoscopic, or robotic approaches; vaginal apical reconstructive repairs (vault suspensions or hysteropexy, sacrospinous, uterosacral, iliococcygeus, McCall's, or Manchester types); and vaginal obliterative procedures (with or without uterus in situ). Individual procedures or broad categories of procedures were compared: (1) vaginal versus abdominal routes for reconstruction, (2) abdominal procedures for reconstruction, (3) vaginal procedures for reconstruction, (4) hysterectomy and suspension versus hysteropexy for reconstruction, and (5) reconstructive versus obliterative options.
OUTCOMES
The Urogynaecology Committee selected outcomes of interest: objective failure (obtained via validated pelvic organ prolapse [POP] quantification systems and defined as overall objective failure as well as failure rate by compartment); subjective failure (recurrence of bulge symptoms determined subjectively, with or without use of a validated questionnaire); reoperation for POP recurrence; complications of postoperative lower urinary tract symptoms (de novo or postoperative stress urinary incontinence; reoperation for persistent, recurrent, or de novo stress urinary incontinence; urge urinary incontinence; and voiding dysfunction); perioperatively recognized urinary tract injury (bladder or ureter); other complications (mesh exposure, defined as mesh being visible and exposed in the vagina, and non-sexual pelvic pain); and sexual function (de novo dyspareunia and sexual function score according to a validated questionnaire).
BENEFITS, HARMS, AND COSTS
This guideline will benefit patients seeking surgical correction of apical POP by improving counselling on surgical treatment options and possible outcomes. It will also benefit surgical providers by improving their knowledge of various surgical approaches. Data presented could be used to develop frameworks and tools for shared decision-making.
EVIDENCE
We searched Medline, the Cochrane Central Register of Controlled Trials (CENTRAL), and Embase from 2002 to 2019. The search included multiple terms for apical POP surgical procedures, approaches, and complications. We excluded POP repairs using transvaginal mesh and studies that compared procedures without apical suspension. We included randomized controlled trials and prospective or retrospective comparative studies. We limited language of publication to English and French and accessibility to full text. A systematic review and meta-analysis was performed.
VALIDATION METHODS
The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and weak recommendations).
INTENDED USERS
Gynaecologists, urologists, urogynaecologists, and other health care providers who assess, counsel, and care for women with POP.
SUMMARY STATEMENTS
All statements refer to correction of apical vaginal prolapse in the short and medium term (up to 5 years), except when otherwise specified.
Topics: Decision Making, Shared; Female; Gynecologic Surgical Procedures; Humans; Pelvic Organ Prolapse; Societies, Medical; Surgical Mesh; Treatment Outcome; Uterine Prolapse
PubMed: 33548503
DOI: 10.1016/j.jogc.2021.02.001 -
The vaginal microbiome and the risk of preterm birth: a systematic review and network meta-analysis.Scientific Reports May 2022Preterm birth is a major cause of neonatal morbidity and mortality worldwide. Increasing evidence links the vaginal microbiome to the risk of spontaneous preterm labour... (Meta-Analysis)
Meta-Analysis
Preterm birth is a major cause of neonatal morbidity and mortality worldwide. Increasing evidence links the vaginal microbiome to the risk of spontaneous preterm labour that leads to preterm birth. The aim of this systematic review and network meta-analysis was to investigate the association between the vaginal microbiome, defined as community state types (CSTs, i.e. dominance of specific lactobacilli spp, or not (low-lactobacilli)), and the risk of preterm birth. Systematic review using PubMed, Web of Science, Embase and Cochrane library was performed. Longitudinal studies using culture-independent methods categorizing the vaginal microbiome in at least three different CSTs to assess the risk of preterm birth were included. A (network) meta-analysis was conducted, presenting pooled odds ratios (OR) and 95% confidence intervals (CI); and weighted proportions and 95% CI. All 17 studies were published between 2014 and 2021 and included 38-539 pregnancies and 8-107 preterm births. Women presenting with "low-lactobacilli" vaginal microbiome were at increased risk (OR 1.69, 95% CI 1.15-2.49) for delivering preterm compared to Lactobacillus crispatus dominant women. Our network meta-analysis supports the microbiome being predictive of preterm birth, where low abundance of lactobacilli is associated with the highest risk, and L. crispatus dominance the lowest.
Topics: Female; Humans; Infant, Newborn; Lactobacillus; Lactobacillus crispatus; Microbiota; Network Meta-Analysis; Pregnancy; Premature Birth; Vagina
PubMed: 35562576
DOI: 10.1038/s41598-022-12007-9 -
Revista Brasileira de Ginecologia E... Oct 2022To evaluate the efficacy of the hormonal and nonhormonal approaches to symptoms of sexual dysfunction and vaginal atrophy in postmenopausal women. (Review)
Review
OBJECTIVE
To evaluate the efficacy of the hormonal and nonhormonal approaches to symptoms of sexual dysfunction and vaginal atrophy in postmenopausal women.
DATA SOURCES
We conducted a search on the PubMed, Embase, Scopus, Web of Science, SciELO, the Cochrane Central Register of Controlled Trials (CENTRAL), and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases, as well as on clinical trial databases. We analyzed studies published between 1996 and May 30, 2020. No language restrictions were applied.
SELECTION OF STUDIES
We selected randomized clinical trials that evaluated the treatment of sexual dysfunction in postmenopausal women.
DATA COLLECTION
Three authors (ACAS, APFC, and JL) reviewed each article based on its title and abstract. Relevant data were subsequently taken from the full-text article. Any discrepancies during the review were resolved by consensus between all the listed authors.
DATA SYNTHESIS
A total of 55 studies were included in the systematic review. The approaches tested to treat sexual dysfunction were as follows: lubricants and moisturizers (18 studies); phytoestrogens (14 studies); dehydroepiandrosterone (DHEA; 8 studies); ospemifene (5 studies); vaginal testosterone (4 studies); pelvic floor muscle exercises (2 studies); oxytocin (2 studies); vaginal CO laser (2 studies); lidocaine (1 study); and vitamin E vaginal suppository (1 study).
CONCLUSION
We identified literature that lacks coherence in terms of the proposed treatments and selected outcome measures. Despite the great diversity in treatment modalities and outcome measures, the present systematic review can shed light on potential targets for the treatment, which is deemed necessary for sexual dysfunction, assuming that most randomized trials were evaluated with a low risk of bias according to the Cochrane Collaboration risk of bias tool. The present review is registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD42018100488).
Topics: Female; Humans; Postmenopause; Vagina; Exercise Therapy; Atrophy
PubMed: 36446564
DOI: 10.1055/s-0042-1756148 -
Frontiers in Cellular and Infection... 2021, first described in 1999, is a prevalent bacterial species of the vaginal microbiome. As does not easily grow on de Man-Rogosa-Sharpe agar, but can grow anaerobically... (Review)
Review
, first described in 1999, is a prevalent bacterial species of the vaginal microbiome. As does not easily grow on de Man-Rogosa-Sharpe agar, but can grow anaerobically on blood agar, it has been initially overlooked by traditional culture methods. It was not until the wide application of molecular biology techniques that the function of in the vaginal microbiome was carefully explored. has the smallest genome among known and it has many probiotic characteristics, but is partly different from other major vaginal species, such as , in contributing to the maintenance of a healthy vaginal microbiome. It is not only commonly present in the healthy vagina but quite often recovered in high numbers in bacterial vaginosis (BV). Increasing evidence suggests that is a transitional species that colonizes after the vaginal environment is disturbed and offers overall less protection against vaginal dysbiosis and, subsequently, leads to BV, sexually transmitted infections, and adverse pregnancy outcomes. Accordingly, under certain conditions, is a genuine vaginal symbiont, but it also seems to be an opportunistic pathogen. Further studies are necessary to identify the exact role of this intriguing species in vaginal health and diseases.
Topics: Dysbiosis; Female; Humans; Lactobacillus; Pregnancy; Vagina; Vaginosis, Bacterial
PubMed: 34881196
DOI: 10.3389/fcimb.2021.792787 -
BJOG : An International Journal of... Jan 2020Persistent infection with high-risk human papillomavirus can lead to cervical dysplasia and cancer. Recent studies have suggested associations between the composition of...
BACKGROUND
Persistent infection with high-risk human papillomavirus can lead to cervical dysplasia and cancer. Recent studies have suggested associations between the composition of the vaginal microbiota, infection with human papillomavirus (HPV) and progression to cervical dysplasia and cancer.
OBJECTIVE
To assess how specific cervico-vaginal microbiota compositions are associated with HPV infection, cervical dysplasia and cancer, we conducted a systematic review and network meta-analysis (registered in PROSPERO: CRD42018112862).
SEARCH STRATEGY
PubMed, Web of science, Embase and Cochrane database.
SELECTION CRITERIA
All original studies describing at least two community state types of bacteria (CST), based on molecular techniques enabling identification of bacteria, and reporting the association with HPV infection, cervical dysplasia and/or cervical cancer.
DATA COLLECTION AND ANALYSIS
For the meta-analysis, a network map was constructed to provide an overview of the network relationships and to assess how many studies provided direct evidence for the different vaginal microbiota compositions and HPV, cervical dysplasia or cancer. Thereafter, the consistency of the model was assessed, and forest plots were constructed to pool and summarise the available evidence, presenting odds ratios and 95% confidence intervals.
MAIN RESULTS
Vaginal microbiota dominated by non-Lactobacilli species or Lactobacillus iners were associated with three to five times higher odds of any prevalent HPV and two to three times higher for high-risk HPV and dysplasia/cervical cancer compared with Lactobacillus crispatus.
CONCLUSIONS
These findings suggest an association between certain bacterial community types of the vaginal microbiota and HPV infection and HPV-related disease. This may be useful for guiding treatment options or serve as biomarkers for HPV-related disease.
TWEETABLE ABSTRACT
This network meta-analysis suggests an association between different vaginal bacterial community types and the risk of HPV.
Topics: Female; Humans; Lactobacillus; Microbiota; Network Meta-Analysis; Papillomaviridae; Papillomavirus Infections; RNA, Ribosomal, 16S; Uterine Cervical Neoplasms; Vagina; Uterine Cervical Dysplasia
PubMed: 31237400
DOI: 10.1111/1471-0528.15854 -
Nutrients Oct 2022This systematic review and meta-analysis aimed to determine if probiotic supplementation in pregnancy reduced maternal Group B streptococcus (GBS) recto-vaginal... (Meta-Analysis)
Meta-Analysis Review
This systematic review and meta-analysis aimed to determine if probiotic supplementation in pregnancy reduced maternal Group B streptococcus (GBS) recto-vaginal colonization in pregnant women at 35-37 weeks of gestation. Electronic databases (i.e., PubMed, MEDLINE, ClinicalTrials.gov, ScienceDirect, and the Cochrane Library) were searched from inception up to February 2022. We included RCTs assessing the effects of probiotic supplementation in pregnancy on GBS recto-vaginal colonization. The primary outcome was GBS-positive recto-vaginal cultures performed at 35-37 weeks of gestation. Secondarily, we evaluated obstetric and short-term neonatal outcomes. A total of 132 publications were identified; 9 full-length articles were reviewed to finally include 5 studies. Probiotic supplementation reduced vaginal GBS colonization: the GBS positive culture rate was estimated at 31.9% (96/301) in the intervention group compared to 38.6% (109/282) in the control group (OR = 0.62, 95% CI 0.40-0.94, I2 4.8%, = 0.38). The treatment started after 30 weeks of gestation and was more effective in reducing GBS colonization (OR 0.41, 95% CI 0.21-0.78, I2 0%, = 0.55). Probiotic administration during pregnancy, namely in the third trimester, was associated with a reduced GBS recto-vaginal colonization at 35-37 weeks and a safe perinatal profile. Whether this new strategy could reduce the exposition of pregnant women to significant doses of antibiotics in labor needs to be evaluated in other trials.
Topics: Infant, Newborn; Female; Pregnancy; Humans; Pregnant Women; Streptococcal Infections; Streptococcus agalactiae; Vagina; Probiotics; Pregnancy Complications, Infectious
PubMed: 36364782
DOI: 10.3390/nu14214520 -
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