Beneficial effects of natural products on female sexual dysfunction: A systematic review and meta-analysis

BackgroundFemale sexual dysfunction (FSD) includes female orgasmic disorder, female sexual interest or arousal disorder, and genito-pelvic pain or penetration disorder. FSD affects 40% of women worldwide, but it is understudied and likely undertreated. Natural products are frequently used by women to treat FSD, but scientific evidence of their efficacy is lacking.ObjectiveThis systematic review and meta-analysis focused on the study of the efficacy of natural products on FSD.Study designSystematic review and meta-analysis of existing studies on natural products in the treatment of FSD.MethodsThe literature search included MEDLINE, EMBASE, PsycINFO, and the Cochrane Central Register of Controlled Trial databases for studies published from January 2000 to February 2020. The quality and the level of evidence of the studies were assessed. The association between natural products and FSD was summarized using standardized mean differences (SMD) with a 95% confidence interval (CI).ResultsA total of 536 studies were identified, with 20 of them meeting the criteria. According to this meta-analysis, Tribulus terrestris showed a significant positive effect in improving overall female sexual function (SMD = 1.12, 95% CI = 0.46 - 1.79, p = 0.001) and individual sexual arousal (SMD = 1.03, 95% CI = 0.22 - 1.84, p = 0.013), sexual desire (SMD = 1.08, 95% CI = 0.52 - 1.63, p ≤ 0.001) and sexual orgasm (SMD = 0.51, 95% CI = 0.02 - 1.00, p = 0.040) domains compared to placebo. Panax ginseng was found to be effective in treating sexual arousal (SMD = 0.54, 95% CI = 0.11 - 0.97, p = 0.014) and sexual desire (SMD = 0.59, 95% CI = 0.27 - 0.90, p < 0.001) compared to placebo. Meanwhile, other natural products reviewed in this study, such as Trifolium pretense, did not differ significantly from placebo in terms of improving FSD.ConclusionPreliminary evidence suggests that Tribulus terrestris and Panax ginseng may be effective as alternative treatments for FSD in a clinical setting.     

Obesity and the likelihood of sexual behavioral risk factors for HPV and cervical cancer

Obesity is associated with higher cervical cancer mortality, but its relationship with sexual behavioral risk factors that predispose women to human papilloma virus (HPV) and cervical cancer is unclear. We used data from 3,329 women participants, aged 20-59 years, of the 1999-2004 National Health and Nutrition Examination Survey, to analyze the relationship between BMI and age at first intercourse, number of sexual partners, condom use during sexual activity, history of sexually transmitted disease (STD), herpes simplex virus 2 (HSV-2) seropositivity, and HPV prevalence. BMI was not associated with the prevalence of HPV. Mildly obese women (BMI 30.0-34.9 kg/m(2)) were least likely to report a STD history (9% vs. 13% in normal weight) and >or=2 sexual partners in the previous year (8% vs. 13%) while overweight women (BMI 25.0-29.9 kg/m(2)) were least likely to report >or=10 lifetime partners; among those with multiple partners, BMI was not associated with sexual activity without condoms in the past month. After adjustment for age, race/ethnicity, and education, women with higher BMI were less likely to report sexual behavioral risk factors than normal-weight women; however, odds ratios were only significant for mildly obese women for reporting a STD history (0.74, 95% confidence interval 0.55-0.99) and having >or=2 sexual partners in the last year (0.57, 0.39-0.85). Higher BMI was not associated with HSV-2 seropositivity after adjustment. HPV and sexual behavioral risk factors for HPV and cervical cancer are not more prevalent in obese than normal-weight women and unlikely to account for higher-observed cervical cancer mortality in obese women.     

553 例女性宫颈高危型HPV 感染与宫颈病变的相关性研究

目的:研究女性生殖道高危型人乳头瘤病毒(high risk human papilloma virus,hrHPV)感染现状及子宫颈上皮内瘤样病变(cervical intraepithelial neoplasia,CI N)的现患率,并分析该人群年龄与HPV感染及宫颈癌前病变的相关性以及hrHPV病毒载量与宫颈病变之间剂量-效应关系。方法:对553例30岁-78岁有性生活史的女性进行以人群为基础的横断面调查。对所有接受筛查的妇女均行宫颈HPV检测及电子阴道镜下病理活检,并以病理结果作为诊断子宫颈病变的金标准。资料采用EXCEL整理,利用x2检验和非条件Logistic回归分析危险因素和CI N的关系。结果:553例受检对象总体阳性检出率为18.0%。hrHPV感染情况在不同年龄段分布有显著差异,hrHPV病毒载量越高宫颈病变的程度越重。结论:不同年龄段hrHPV感染情况不同,hrHPV病毒载量与宫颈病变之间存在剂量-效应关系。     

Prevalence of high-risk human papillomavirus cervical infection in female kidney graft recipients: an observational study

ABSTRACT: BACKGROUND: Immunosuppressive therapy protects the transplanted organ but predisposes the recipient to chronic infections and malignancies. Transplant patients are at risk of cervical intraepithelial neoplasia (CIN) and cervical cancer resulting from an impaired immune response in the case of primary infection or of reactivation of a latent infection with human papillomavirus of high oncogenic potential (HR-HPV). METHODS: The aim of this study was to assess the prevalence of HR-HPV cervical infections and CIN in 60 female kidney graft recipients of reproductive age in comparison to that in healthy controls. Cervical swabs were analyzed for the presence of HR-HPV DNA. HR-HPV-positive women remained under strict observation and were re-examined after 24 months for the presence of transforming HR-HPV infection by testing for HR-HPV E6/E7 mRNA. All the HR-HPV-positive patients were scheduled for further diagnostic tests including exfoliative cytology, colposcopy and cervical biopsy. RESULTS: The prevalence of HR-HPV did not differ significantly between the study group and the healthy controls (18% vs 25%, p=0.37). There was no correlation between HR-HPV presence and the immunosuppresive regimen, underlying disease, graft function or time interval from transplantation. A higher prevalence of HR-HPV was observed in females who had had [greater than or equal to]2 sexual partners in the past. Among HR-HPV-positive patients, two cases of CIN2+ were diagnosed in each group. In the course of follow-up, transforming HR-HPV infections were detected in two kidney recipients and in one healthy female. Histologic examination confirmed another two cases of CIN2+ developing in the cervical canal. CONCLUSIONS: Female kidney graft recipients of reproductive age are as exposed to HR-HPV infection as are healthy individuals. Tests detecting the presence of HR-HPV E6/E7 mRNA offer a novel diagnostic opportunity in those patients, especially in those cases where lesions have developed in the cervical canal.     

Human Papillomavirus Prevalence in a Population of Women Living in Port-au-Prince and Leogane,Haiti

Background

There have been no published studies of carcinogenic human papillomavirus (HPV)--the necessary cause of cervical cancer--in Haiti, a nation that has one of the greatest burdens of cervical cancer globally.

Objective

Characterize prevalence of carcinogenic HPV and the prevalence of individual carcinogenic HPV genotypes in women with cervical precancer or cancer, cervical intraepithelial neoplasia grade 2 (CIN2) or more severe (CIN2+).

Methods

Women (n=9,769; aged 25-60 years) were screened for carcinogenic HPV by Hybrid Capture 2 (HC2; Qiagen, Gaithersburg, MD). Carcinogenic HPV positives underwent colposcopy and visible lesions were biopsied. A subset of carcinogenic HPV positives was tested for individual HPV genotypes using a GP5+/6+ assay.

Results

The prevalence of carcinogenic HPV was 19.0% (95% confidence interval: 18.4%-19.9%) and decreased with increasing age (p_trend < 0.001). Women with 3 or more sexual partners and who started sex before the age of 18 years had twice the age-adjusted prevalence of carcinogenic HPV of women with one partner and who started sex after the age of 21 (24.3% vs. 12.9%, respectively). HPV16 and HPV35 were the most common HPV genotypes detected in CIN2+ and more common in women with CIN2+ than those without CIN2+. HPV16 and/or HPV18 were detected in 21.0% of CIN2 (n = 42), 46.2% of CIN3 (n = 52), and 80% of cancers (n = 5).

Conclusions

The prevalence of carcinogenic HPV in Haiti was much greater than the prevalence in other Latin American countries. High carcinogenic HPV prevalence and a lack of cervical cancer screening may explain the high burden of cervical cancer in Haiti.     

Prevalence of chlamydial genital infection and associated risk factors in adolescent females at an urban reproductive health care center in Croatia

The study was undertaken to determine the prevalence of chlamydial genital infection in sexually active, urban adolescent females 15-19 years; to identify behavioral, demographic, and clinical factors associated with chlamydial infections; and to develop criteria for potential screening strategies. 500 adolescent women, median age 17.7 years, who visited gynecological outpatient clinic in Children's Hospital Zagreb for different reasons were enrolled in this study. Gynecological exam, colposcopy, detection of chlamydial infection by the rapid direct immunoassay of endocervical swab (Clearview Chlamydia-Unipath), endocervical cytological examination--Papanicolaou smear, and questionnaire to obtain demographic, social, behavioral and presence of symptoms data were performed. Positive Chlamydia trachomatis test were found in 16.4% of participants, cytologic cervical abnormalities--cervical intraepithelial neoplasia (CIN I-CIN III) were found in 25.2% and cytological signs of Human papilloma virus were found in 11.4%. Stepwise multivariate logistic regression analysis identified five factors associated with infection: the age of menarche < or =13 years, > or =4 lifetime sexual partners, non-use of contraception (rare or never), cervical friability, and abnormal Papanicolaou test. Urban adolescent sexually active women are at high risk for chlamydial infection and other sexually transmitted diseases including HIV infection. Association between chlamydial genital infection and risk-taking sexual and contraceptive behavior was found. Routine Chlamydia trachomatis testing for this population is recommended as well as implementation of school based sexual health education because of their risk-taking sexual behavior.     

Risk factors for cervical precancer and cancer in HIV-infected, HPV-positive Rwandan women

Background

Although cervical cancer is an AIDS-defining condition, infection with human immunodeficiency virus (HIV) may only modestly increase the risk of cervical cancer. There is a paucity of information regarding factors that influence the natural history of human papillomavirus (HPV) in HIV-infected women. We examined factors associated with cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) in Rwandan women infected with both HIV and HPV (HIV+/HPV+).

Methods

In 2005, 710 HIV+ Rwandan women ≥25 years enrolled in an observational cohort study; 476 (67%) tested HPV+. Each woman provided sociodemographic data, CD4 count, a cervical cytology specimen and cervicovaginal lavage (CVL), which was tested for >40 HPV genotypes by MY09/MY11 PCR assay. Logistic regression models calculated odds ratios (OR) and 95% confidence intervals (CI) of associations of potential risk factors for CIN3+ among HIV+/HPV+ women.

Results

Of the 476 HIV+/HPV+ women 42 (8.8%) were diagnosed with CIN3+. Factors associated with CIN3+ included ≥7 (vs. 0-2) pregnancies, malarial infection in the previous six months (vs. never), and ≥7 (vs. 0-2) lifetime sexual partners. Compared to women infected by non-HPV16 carcinogenic HPV genotypes, HPV16 infection was positively associated and non-carcinogenic HPV infection was inversely associated with CIN3+. CD4 count was significantly associated with CIN3+ only in analyses of women with non-HPV16 carcinogenic HPV (OR = 0.62 per 100 cells/mm³, CI = 0.40-0.97).

Conclusions

In this HIV+/HPV+ population, lower CD4 was significantly associated with CIN3+ only in women infected with carcinogenic non-HPV16. We found a trend for higher risk of CIN3+ in HIV+ women reporting recent malarial infection; this association should be investigated in a larger group of HIV+/HPV+ women.     

Prevalence and correlation of human papillomavirus genotypes with clinical factors in cervical samples from Mexican women

In the last decade, the inclusion of HPV DNA testing in cervical cancer screening has provided one of the best strategies for the prevention and timely detection of HPV. We conducted a high-throughput HPV genotyping study based on MALDI-TOF mass spectrometry to determine the prevalence of 24 HPV genotypes, including oncogenic genotypes, in Mexican women and correlated the results with cytological findings and clinical variables. We likewise identified the risk factors in patients with the HPV infection. Our study included 1000 women from Sonora, Mexico, who participated in cervical cancer screening campaigns and who underwent a Pap smear and HPV DNA test. The results showed that the overall prevalence of HPV was 27.2%, 18.5% with single, and 8.7% multiple infections. The low-risk HPV genotype 6 (8.5%) and oncogenic genotypes 31 (8.1%) and 53 (4.4%) were the most prevalent in the study population. The number of lifetime sexual partners, previous STIs, and age at first intercourse was significantly associated with HPV infection (P ≤ 0.05). Smoking (OR = 1.5609; 95% IC 1.062–2.292) and more than three lifetime sexual partners (OR = 1.609; 95% IC = 1.124–2.303) represented risk factors for HPV infection. Cytological abnormalities were found in 3.4% of the HPV-positive samples. CIN 1–3 occurred in 0.6% of high-risk HPV cases. In general, the prevalence of the HPV genotypes is high in Mexican women with normal cytological findings. This issue highlights the importance of HPV research in seemingly healthy women and could help guide screening strategies for cervical cancer prevention in Mexico.Impact statementWe are submitting data regarding the prevalence and type distribution of the HPV infection and the risk factors associated with it, which may provide a valuable reference to reinforce screening strategies, and to maintain HPV genotype surveillance in Mexico. We discuss the overall prevalence of HPV infection as detected in normal cytological samples stratified by age, different types of infection, and oncogenic capacity. One of the most important findings was that common HPV genotypes detected in healthy women were the genotype numbers: 6, 31, 16, and 56, likewise, smoking and having a history of more than three sexual partners over their lifetime, represented the main risk factors in this study. Furthermore, we found a low frequency of cytological abnormalities and CIN 1–3 in women with HR-HPV.     

553例女性宫颈高危型HPV感染与宫颈病变的相关性研究

目的：研究女性生殖道高危型人乳头瘤病毒（high risk human papilloma virus,hrHPV）感染现状及子宫颈上皮内瘤样病变（cervical intraepithelial neoplasia,CI N）的现患率,并分析该人群年龄与HPV感染及宫颈癌前病变的相关性以及hrHPV病毒载量与宫颈病变之间剂量-效应关系。方法：对553例30岁-78岁有性生活史的女性进行以人群为基础的横断面调查。对所有接受筛查的妇女均行宫颈HPV检测及电子阴道镜下病理活检,并以病理结果作为诊断子宫颈病变的金标准。资料采用EXCEL整理,利用x2检验和非条件Logistic回归分析危险因素和CI N的关系。结果：553例受检对象总体阳性检出率为18.0%。hrHPV感染情况在不同年龄段分布有显著差异,hrHPV病毒载量越高宫颈病变的程度越重。结论：不同年龄段hrHPV感染情况不同,hrHPV病毒载量与宫颈病变之间存在剂量-效应关系。     

Sexual dysfunction among middle aged women in the community

In a community survey of women aged 35-59 sexual functioning was studied in the 436 women with partners. One third of these women had operationally defined sexual dysfunction: impaired sexual interest was identified in 17% of women (68/406), vaginal dryness in 17% (73/434), infrequency of orgasm in 16% (60/379), and dyspareunia in 8% (30/379). Sexual dysfunctions were statistically significantly associated with increasing age and also with psychiatric disorder, neuroticism, and marital disharmony. One in 10 women regarded themselves as having a sexual problem. These women were no older than women with sexual dysfunction who did not regard themselves as having a sexual problem. Nevertheless, they differed from the rest of the sample in having more psychiatric disorder, neuroticism, marital disharmony, and (in women still menstruating) psychological symptoms of the premenstrual syndrome. In the whole sample 16 women (4%) said that they would like help for a sexual problem.The prevalence of sexual dysfunction in this series of women suggests that general practitioners should increase their alertness to the problem in their patients.     

A Study of Cervical Cancer In Ethiopian Women

In common with many African countries, Ethiopia has a very limited cytological service, smears are only taken in a hospital or clinic setting and until very recently most had to be sent abroad for analysis. We describe the results of a clinical and cytological investigation of 2111 women attending hospitals and clinics in Addis Ababa: 33 invasive or microinvasive cancers and 10 dysplasias (CIN) were detected. The prevalence of invasive cervical cancer in that population was 15.6/1000. Risk factors were shown to be age over 35 (especially over 50), parity over six (especially more than 10), very low income or subsistence economy, particularly in those from the rural areas, and prostitution. Less significant factors, possibly related to age, were sexual activity of more than 20 years and first coitus before the age of 15; and more than five sexual partners. Most (66%) of women with invasive cancer were at stage 3 or 4.     

Prevalence of human papillomavirus among Croatian women attending regular gynecological visit

Human papillomavirus (HPV) infection has been identified as major risk factor for cervical intraepithelial neoplasia (CIN) and invasive cervical cancer. About 40 HPV viral types are commonly found in the genital tract. Most HPV infections resolve spontaneously, while persistent infection with oncogenic types, namely HPV 16 and 18 is necessary for CIN to occur and progress to cancer. Cervical screening is presently based on the Pap smear that is designed to diagnose precancerous lesions and cervical cancer The aim of this study was to investigate the prevalence of HPV DNA and to determine HPV types distribution among 361 women attending regular gynecological visit. There were 205 women (29+/-8 years old) without determined abnormal cervical lesions and 156 women (34+/-15 years old) with abnormal Pap smear; low grade squamous intraepitehelial lesions (LSIL, n=69), high grade squamous intraepithelial lesions (HSIL, n=72) and atypical squamous cells of undetermined significance (ASCUS, n=15). HPV DNA detection and genotyping was performed by Hybrid Capture 2 assay and additionally by consensus and type-specific primers directed PCR. The overall prevalence of high-risk HPV (hrHPV) in women with abnormal Pap smears was 67.9% (106/156), of which in ASCUS 33.4% (5/15), LSIL 62.3% (43/69) and HSIL 80.6% (58/72). In HPV positive specimens, HPV 16 was found as predominant type in 60.4% cases, followed by HPV 31 (8.5%), HPV 33 (6.6%) and HPV 18 (3.7%). In the group of women without obvious cervical changes the overall hrHPV prevalence was 35.6% with HPV 16 found in 43.8% cases, followed by HPV 31 (17.8%), HPV33 (9.5%) and HPV18 (6.8%). In both study groups, women with and without cervical lesions, the prevalence of HPVof indeterminate type was 14.2% and 13.7%, respectively. Our results indicate that cervical intraepithelial lesions are largely associated with HPV type 16, followed by HPV types 31, 33, 18 and HPV of indeterminate type. Although there is a significant difference in hrHPV DNA prevalence among two groups, no significant differences between particular hrHPV types distribution were observed.     

Mild and moderate dyskaryosis: can women be selected for colposcopy on the basis of social criteria?

OBJECTIVE--To describe the distribution of cervical intraepithelial neoplasia grades among women with mild and moderate dyskaryosis after a single cervical smear and to determine whether social criteria could help identify women who are at increased risk of grade II or III disease. DESIGN--Cross sectional analysis within a randomised prospective study. Subjects had a repeat smear, a colposcopic examination, and an excision biopsy of the transformation zone. In addition, women were asked to complete a social questionnaire. SETTING--Colposcopy clinic, Aberdeen. SUBJECTS--228 women with a single smear test showing mild or moderate dyskaryosis. MAIN OUTCOME MEASURES--Histology, age, sexual and contraceptive history, cigarette smoking. RESULTS--159 (70%) women had cervical intraepithelial neoplasia grades II or III. Among current smokers the prevalence of grade II and III disease was higher in women who smoked greater than or equal to 20 cigarettes a day (84%) than among those who smoked less (66%; p less than 0.04). Women with more than one sexual partner also had a higher prevalence (75%) than women with only one partner (50%; p = 0.0028). Use of oral contraceptives and younger age were not significantly associated. The prevalence of grade II or III disease was up to 66% in the lower risk groups. CONCLUSIONS--Because of the high prevalence of cervical intraepithelial neoplasia grades II and III in both the high and the low risk groups social factors are not useful for selecting women with mild or moderate dyskaryosis for either early referral to colposcopy or cytological surveillance.     

Risk factors associated with human papillomavirus prevalence and cervical neoplasia among Cameroonian women

BackgroundThis study used community-based cervical cancer screening for high-risk human-papillomavirus (HPV) to determine demographic and lifestyle factors associated with HPV prevalence and cervical intraepithelial neoplasia grade 2 or worse (CIN2+).MethodsWomen (n = 838) aged 25–65 years were recruited in two sequential studies in Cameroon. Demographic and historical data were obtained from participants and specimens were self-collected for HPV-testing using real-time PCR. HPV-positive women underwent biopsy and endocervical curettage. Associations were determined using bivariate analysis and logistic regression.ResultsHPV and self-reported HIV prevalence were 39.0% and 9.2%, respectively. Eighteen (9.3%) CIN2+ lesions were found among HPV-positive women. Housewives had a higher risk of being HPV infected (OR = 1.60, p = 0.010). HIV co-infection (aOR = 3.44, p < 0.001) and hormonal contraception (aOR = 1.97, p = 0.007) were associated with increased HPV prevalence. HPV-positive women who used condoms during sexual intercourse were at lower risk of CIN2+ (aOR = 0.15, p = 0.029). CIN2–3 lesions were found in women younger than 50 years, with a median age of 36 years (31–44). HPV-16/18-positive women had a 4.65-fold increased risk of CIN2+ (p = 0.015).ConclusionsYoung, single women and housewives were at higher risk of HPV infection. Preventive strategies for cervical cancer in low-resource settings should target women aged 30–50 years for HPV screening, and should focus treatment and follow-up on HPV-16/18-positive women. Further studies are needed to clarify if other risk factors require attention.     

Single nucleotide polymorphisms in the PRDX3 and RPS19 and risk of HPV persistence and cervical precancer/cancer

Background

Host genetic factors might affect the risk of progression from infection with carcinogenic human papillomavirus (HPV), the etiologic agent for cervical cancer, to persistent HPV infection, and hence to cervical precancer and cancer.

Methodology/Principal Findings

We assessed 18,310 tag single nucleotide polymorphisms (SNPs) from 1113 genes in 416 cervical intraepithelial neoplasia 3 (CIN3)/cancer cases, 356 women with persistent carcinogenic HPV infection (median persistence of 25 months) and 425 randomly selected women (non-cases and non-HPV persistent) from the 10,049 women from the Guanacaste, Costa Rica HPV natural history cohort. For gene and SNP associations, we computed age-adjusted odds ratio and p-trend. Three comparisons were made: 1) association with CIN3/cancer (compared CIN3/cancer cases to random controls), 2) association with persistence (compared HPV persistence to random controls), and 3) progression (compared CIN3/cancers with HPV-persistent group). Regions statistically significantly associated with CIN3/cancer included genes for peroxiredoxin 3 PRDX3, and ribosomal protein S19 RPS19. The single most significant SNPs from each gene associated with CIN3/cancer were PRDX3 rs7082598 (P _trend<0.0001), and RPS19 rs2305809 (P _trend=0.0007), respectively. Both SNPs were also associated with progression.

Conclusions/Significance

These data suggest involvement of two genes, RSP19 and PRDX3, or other SNPs in linkage disequilibrium, with cervical cancer risk. Further investigation showed that they may be involved in both the persistence and progression transition stages. Our results require replication but, if true, suggest a role for ribosomal dysfunction, mitochondrial processes, and/or oxidative stress, or other unknown function of these genes in cervical carcinogenesis.     

Clinical and pathological heterogeneity of cervical intraepithelial neoplasia grade 3

Objective

Cervical intraepithelial neoplasia grade 3 (CIN3), the immediate cervical cancer precursor, is a target of cervical cancer prevention. However, less than half of CIN3s will progress to cancer. Routine treatment of all CIN3s and the majority of CIN2s may lead to overtreatment of many lesions that would not progress. To improve our understanding of CIN3 natural history, we performed a detailed characterization of CIN3 heterogeneity in a large referral population in the US.

Methods

We examined 309 CIN3 cases in the SUCCEED, a large population-based study of women with abnormal cervical cancer screening results. Histology information for 12 individual loop electrosurgical excision procedure (LEEP) segments was evaluated for each woman. We performed case-case comparisons of CIN3s to analyze determinants of heterogeneity and screening test performance.

Results

CIN3 cases varied substantially by size (1–10 LEEP segments) and by presentation with concomitant CIN2 and CIN1. All grades of CINs were equally distributed over the cervical surface. In half of the women, CIN3 lesions were found as multiple distinct lesions on the cervix. Women with large and solitary CIN3 lesions were more likely to be older, have longer sexual activity span, and have fewer multiple high risk HPV infections. Screening frequency, but not HPV16 positivity, was an important predictor of CIN3 size. Large CIN3 lesions were also characterized by high-grade clinical test results.

Conclusions

We demonstrate substantial heterogeneity in clinical and pathological presentation of CIN3 in a US population. Time since sexual debut and participation in screening were predictors of CIN3 size. We did not observe a preferential site of CIN3 on the cervical surface that could serve as a target for cervical biopsy. Cervical cancer screening procedures were more likely to detect larger CIN3s, suggesting that CIN3s detected by multiple independent diagnostic tests may represent cases with increased risk of invasion.     

Cervical intraepithelial neoplasia and the risk of spontaneous preterm birth: A Dutch population-based cohort study with 45,259 pregnancy outcomes

BackgroundExcisional procedures of cervical intraepithelial neoplasia (CIN) may increase the risk of preterm birth. It is unknown whether this increased risk is due to the excision procedure itself, to the underlying CIN, or to secondary risk factors that are associated with both preterm birth and CIN. The aim of this study is to assess the risk of spontaneous preterm birth in women with treated and untreated CIN and examine possible associations by making a distinction between the excised volume of cervical tissue and having cervical disease.Methods and findingsThis Dutch population-based observational cohort study identified women aged 29 to 41 years with CIN between 2005 and 2015 from the Dutch pathology registry (PALGA) and frequency matched them with a control group without any cervical abnormality based on age at and year of pathology outcome (i.e., CIN or normal cytology) and urbanization (<100,000 inhabitants or ≥100,000 inhabitants). All their 45,259 subsequent singleton pregnancies with a gestational age ≥16 weeks between 2010 and 2017 were identified from the Dutch perinatal database (Perined). Nineteen potential confounders for preterm birth were identified. Adjusted odds ratios (ORs) were calculated for preterm birth comparing the 3 different groups of women: (1) women without CIN diagnosis; (2) women with untreated CIN; and (3) women with treated CIN prior to each childbirth.In total, 29,907, 5,940, and 9,412 pregnancies were included in the control, untreated CIN, and treated CIN group, respectively. The control group showed a 4.8% (1,002/20,969) proportion of spontaneous preterm birth, which increased to 6.9% (271/3,940) in the untreated CIN group, 9.5% (600/6,315) in the treated CIN group, and 15.6% (50/321) in the group with multiple treatments. Women with untreated CIN had a 1.38 times greater odds of preterm birth compared to women without CIN (95% confidence interval (CI) 1.19 to 1.60; P < 0.001). For women with treated CIN, these odds 2.07 times increased compared to the control group (95% CI 1.85 to 2.33; P < 0.001). Treated women had a 1.51 times increased odds of preterm birth compared to women with untreated CIN (95% CI 1.29 to 1.76; P < 0.001). Independent from cervical disease, a volume excised from the cervix of 0.5 to 0.9 cc increased the odds of preterm birth 2.20 times (37/379 versus 1,002/20,969; 95% CI 1.52 to 3.20; P < 0.001). These odds further increased 3.13 times and 5.93 times for women with an excised volume of 4 to 8.9 cc (90/724 versus 1,002/20,969; 95% CI 2.44 to 4.01; P < 0.001) and ≥9 cc (30/139 versus 1,002/20,969; 95% CI 3.86 to 9.13; P < 0.001), respectively. Limitations of the study include the retrospective nature, lack of sufficient information to calculate odds of preterm birth <24 weeks, and that the excised volume could only be calculated for a select group of women.ConclusionsIn this study, we observed a strong correlation between preterm birth and a volume of ≥0.5 cc excised cervical tissue, regardless of the severity of CIN. Caution should be taken when performing excisional treatment in women of reproductive age as well as prudence in case of multiple biopsies. Fertile women with a history of performing multiple biopsies or excisional treatment for CIN may benefit from close surveillance during pregnancy.

In a population-based study, Diede Loopik and colleagues investigate associations between cervical intraepithelial neoplasia and risk of preterm birth among Dutch women.     

Long-Term Follow-Up of HPV16-Positive Women: Persistence of the Same Genetic Variant and Low Prevalence of Variant Co-Infections

HPV16 variants correlate with geographic origin and ethnicity. The association between infection with a specific variant and the cervical disease risk remains unclear. We studied the prevalence, persistence and association with cervical intraepithelial neoplasia (CIN) of different HPV16 variants, using cervical swabs and whole tissue sections (WTS) of biopsies from 548 women in the placebo group of a HPV16/18 vaccine trial. In HPV16-positive samples, HPV16 variants were identified by a reverse hybridization assay (RHA). Laser-capture micro-dissection (LCM) was performed for localized detection of HPV. HPV16 variants were determined in 47 women. Frequency of mixed HPV16 variant infections was lower (8.5%) than for multiple HPV genotypes (39.1%). Among 35 women having consecutive HPV16 variant-positive swabs, 32 (91.4%) had the same variant while in three (8.6%) women a change in variant(s) was observed. HPV16-positive WTS were obtained from 12 women having consecutive HPV16 variant-positive swabs. The same variant was present in WTS of 10 women, while two were negative. WTS of five women were histologically normal. A single HPV16 variant was detected in four women having CIN1-3, while additional HPV genotypes were found in three other women having CIN2 and CIN3. In the WTS of one woman with mixed genotypes, the HPV16 variant was assigned to a CIN2 lesion by LCM. HPV16 variant infections can be effectively studied in cervical swabs and tissue specimens by the HPV16 variant RHA. Multiple HPV16 variants in one woman are rare. The HPV16 genotype consistently detected in follow-up samples usually involves a persistent infection with the same variant.     

Detection of human papillomavirus types by the polymerase chain reaction and the differentiation between high-risk and low-risk cervical lesions

By means of a consensus polymerase chain reaction (PCR) method, the prevalence of HPV types was determined in cervical biopsies from 137 women referred to the gynecological outpatient clinic for colposcopy because of an abnormal cervical smear. The prevalence of HPV was 80.3%. There was a statistically highly significant rise in the prevalence of the oncogenic HPV types (16, 18, 31, 33) with increasing severity of cervical intraepithelial neoplasia (CIN I to III), indicating a role for these HPV types in the pathogenesis of cervical cancer. The prevalence of other HPV types decreased significantly with the severity of the lesion, suggesting that these HPV types play a less significant role in this process. These data indicate that HPV typing with PCR may be a valuable tool for distinguishing between highrisk and low-risk cervical lesions. Furthermore, our results suggest that the detection of HPV types by consensus PCR in the cervix of patients with an abnormal smear but without histologically detectable CIN is a useful tool for predicting which of these patiens will eventually develop CIN. Finally, a relatively low percentage (3%) of HPV double infections is reported in this study.     

Detection of human papillomavirus types by the polymerase chain reaction and the differentiation between high-risk and low-risk cervical lesions.

By means of a consensus polymerase chain reaction (PCR) method, the prevalence of HPV types was determined in cervical biopsies from 137 women referred to the gynecological outpatient clinic for colposcopy because of an abnormal cervical smear. The prevalence of HPV was 80.3%. There was a statistically highly significant rise in the prevalence of the oncogenic HPV types (16, 18, 31, 33) with increasing severity of cervical intraepithelial neoplasia (CIN I to III), indicating a role for these HPV types in the pathogenesis of cervical cancer. The prevalence of other HPV types decreased significantly with the severity of the lesion, suggesting that these HPV types play a less significant role in this process. These data indicate that HPV typing with PCR may be a valuable tool for distinguishing between high-risk and low-risk cervical lesions. Furthermore, our results suggest that the detection of HPV types by consensus PCR in the cervix of patients with an abnormal smear but without histologically detectable CIN is a useful tool for predicting which of these patients will eventually develop CIN. Finally, a relatively low percentage (3%) of HPV double infections is reported in this study.