Anyplex II HPV‐28 (HPV‐28) can detect individually 28 HPV genotypes. We assessed the agreement between linear array HPV genotyping (LA‐HPV) and HPV‐28 for detection of 27 HPV genotypes in 410 stored ...anogenital samples (75 anal samples, 335 physician‐collected cervical samples) collected over 5 years from 410 individuals (13 men, 397 women), including 202 HIV‐seropositive individuals. HPV DNA was detected in 393 (95.9%, 95% confidence interval CI: 93.4–97.4) and 382 (93.2%, 95% CI: 90.3–95.3) samples with HPV‐28 and LA‐HPV (p = 0.13), respectively, for a good agreement of 96.3% (κ = 0.65). Of the 10503 HPV typing results, 10195 (780 positive, 9577 negative) were concordant, for an agreement of 97.1% (95% CI: 96.7–97.4) and an excellent of κ = 0.82 (95% CI: 0.80–0.84). The mean type‐specific concordance for 27 genotypes was 97.0%, 95% CI: 95.8–98.5 (κ = 0.86 ± 0.07, 95% CI: 0.83–0.88). Excellent agreement was obtained individually for all high‐risk genotypes (κ = 0.81–0.97) and for most other genotypes except for types 42, 44, 54, 68, and 69. The mean number of types per sample in discordant samples detected with LA‐HPV (3.0, 95% CI: 2.7–3.4) was greater than in concordant samples (1.4, 95% CI: 1.3–1.5; p< 0.001). In conclusion, HPV‐28 compared favorably with LA‐HPV, but was more frequently positive for HPV42 and HPV68.
HIGHLIGHTS
Anyplex II HPV‐28 (HPV‐28) can detect individually 28 HPV genotypes including high‐risk HPV types.
Excellent agreement between HPV‐28 and the linear array was obtained individually for all high‐risk genotypes and for most other genotypes except for types 42, 44, 54, 68, and 69.
The mean number of types per sample in discordant samples was greater than in concordant samples.
Concordance between HPV‐28 and linear array was greater on cervical samples than anal samples, and greater in samples from women not living with HIV compared to HIV‐seropositive participants.
Primary analyses of a study in young women aged 16–26 years showed efficacy of the nine-valent human papillomavirus (9vHPV; HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58) vaccine against infections and ...disease related to HPV 31, 33, 45, 52, and 58, and non-inferior HPV 6, 11, 16, and 18 antibody responses when compared with quadrivalent HPV (qHPV; HPV 6, 11, 16, and 18) vaccine. We aimed to report efficacy of the 9vHPV vaccine for up to 6 years following first administration and antibody responses over 5 years.
We undertook this randomised, double-blind, efficacy, immunogenicity, and safety study of the 9vHPV vaccine study at 105 study sites in 18 countries. Women aged 16–26 years old who were healthy, with no history of abnormal cervical cytology, no previous abnormal cervical biopsy results, and no more than four lifetime sexual partners were randomly assigned (1:1) by central randomisation and block sizes of 2 and 2 to receive three intramuscular injections over 6 months of 9vHPV or qHPV (control) vaccine. All participants, study investigators, and study site personnel, laboratory staff, members of the sponsor's study team, and members of the adjudication pathology panel were masked to vaccination groups. The primary outcomes were incidence of high-grade cervical disease (cervical intraepithelial neoplasia grade 2 or 3, adenocarcinoma in situ, invasive cervical carcinoma), vulvar disease (vulvar intraepithelial neoplasia grade 2/3, vulvar cancer), and vaginal disease (vaginal intraepithelial neoplasia grade 2/3, vaginal cancer) related to HPV 31, 33, 45, 52, and 58 and non-inferiority (excluding a decrease of 1·5 times) of anti-HPV 6, 11, 16, and 18 geometric mean titres (GMT). Tissue samples were adjudicated for histopathology diagnosis and tested for HPV DNA. Serum antibody responses were assessed by competitive Luminex immunoassay. The primary evaluation of efficacy was a superiority analysis in the per-protocol efficacy population, supportive efficacy was analysed in the modified intention-to-treat population, and the primary evaluation of immunogenicity was a non-inferiority analysis. The trial is registered with ClinicalTrials.gov, number NCT00543543.
Between Sept 26, 2007, and Dec 18, 2009, we recruited and randomly assigned 14 215 participants to receive 9vHPV (n=7106) or qHPV (n=7109) vaccine. In the per-protocol population, the incidence of high-grade cervical, vulvar and vaginal disease related to HPV 31, 33, 45, 52, and 58 was 0·5 cases per 10 000 person-years in the 9vHPV and 19·0 cases per 10 000 person-years in the qHPV groups, representing 97·4% efficacy (95% CI 85·0–99·9). HPV 6, 11, 16, and 18 GMTs were non-inferior in the 9vHPV versus qHPV group from month 1 to 3 years after vaccination. No clinically meaningful differences in serious adverse events were noted between the study groups. 11 participants died during the study follow-up period (six in the 9vHPV vaccine group and five in the qHPV vaccine group); none of the deaths were considered vaccine-related.
The 9vHPV vaccine prevents infection, cytological abnormalities, high-grade lesions, and cervical procedures related to HPV 31, 33, 45, 52, and 58. Both the 9vHPV vaccine and qHPV vaccine had a similar immunogenicity profile with respect to HPV 6, 11, 16, and 18. Vaccine efficacy was sustained for up to 6 years. The 9vHPV vaccine could potentially provide broader coverage and prevent 90% of cervical cancer cases worldwide.
Merck & Co, Inc.
Provoked vestibulodynia is the most common subtype of chronic vulvar pain. This highly prevalent and debilitating condition is characterized by acute recurrent pain located at the entry of the vagina ...in response to pressure application or attempted vaginal penetration. Although physical therapy is advocated as a first-line treatment for provoked vestibulodynia, evidence supporting its efficacy is scarce.
The purpose of this study was to establish the efficacy of multimodal physical therapy compared with topical lidocaine, a frequently used first-line treatment.
We conducted a multicenter, parallel-group, randomized clinical trial in women diagnosed as having provoked vestibulodynia recruited from the community and 4 Canadian university hospitals. Women were randomly assigned (1:1) to receive either weekly sessions of physical therapy or overnight topical lidocaine (5% ointment) for 10 weeks. Randomization was stratified by center using random permuted blocks from a computer-generated list managed by an independent individual. Physical therapy entailed education, pelvic floor muscle exercises with biofeedback, manual therapy, and dilation. Assessments were conducted at baseline, posttreatment, and 6-month follow-up. Outcome assessors, investigators, and data analysts were masked to allocation. The primary outcome was pain intensity during intercourse evaluated with the numeric rating scale (0–10). Secondary outcomes included pain quality (McGill-Melzack Pain Questionnaire), sexual function (Female Sexual Function Index), sexual distress (Female Sexual Distress Scale), satisfaction (numeric rating scale of 0–10), and participants’ impression of change (Patient Global Impression of Change). Intention-to-treat analyses were conducted using piecewise linear-growth models.
Among 212 women who were recruited and randomized, 201 (95%) completed the posttreatment assessment and 195 (92%) completed the 6-month follow-up. Multimodal physical therapy was more effective than lidocaine for reducing pain intensity during intercourse (between-group pre-post slope difference, P<.001; mean group postdifference, 1.8; 95% confidence interval, 1.2–2.3), and results were maintained at 6-month follow-up (mean group difference, 1.8; 95% confidence interval, 1.2–2.5). The physical therapy group also performed better than the lidocaine group in all secondary outcomes (pain quality, sexual function, sexual distress, satisfaction, and participants’ impression of change) at posttreatment and 6-month follow-up. Moreover, the changes observed after physical therapy were shown to be clinically meaningful. Regarding participants’ impression of change, 79% of women in the physical therapy group reported being very much or much improved compared with 39% in the lidocaine group (P<.001).
The findings provide strong evidence that physical therapy is effective for pain, sexual function, and sexual distress and support its recommendation as the first-line treatment of choice for provoked vestibulodynia.
High-risk human papillomavirus (HR-HPV) testing has become a preferred cervical cancer screening strategy in some countries due to its superior sensitivity over cytology-based methods for identifying ...cervical intraepithelial neoplasia of grade 2 or worse (CIN2
). Improved sensitivity has been accompanied by reductions in specificity and concerns regarding overscreening and overtreatment of women with transient or nonprogressing HR-HPV infections. Triage of HR-HPV
women to colposcopy is, thus, warranted for appropriate management and treatment.
Using data from the Canadian Cervical Cancer Screening Trial (CCCaST), we compared the performance of cytology and HR-HPV strategies to detect CIN2
among HR-HPV
women (age, 30-69 years). Colposcopy referral rates and performance gains from adding other HR-HPV genotypes to HPV16/18
triage were also evaluated.
A strategy referring all women HPV16/18
and HPV16/18
, but with atypical squamous cells of undetermined significance or worse cytology (ASC-US
) had the highest sensitivity 82.5%; 95% confidence interval (CI), 70.9%-91.0% but yielded the highest colposcopy referral rate. HPV16/18
triage was the next most sensitive strategy (64.1%; 95% CI, 51.1%-75.7%). Low-grade squamous intraepithelial lesion or worse cytology (LSIL
) triage yielded a low sensitivity (32.8%; 95% CI, 21.9%-45.4%) but had the most favorable specificity (93.6%; 95% CI, 91.0%-95.6%), positive predictive value (41.5%; 95% CI, 28.1%-55.9%), and colposcopy referral rate of strategies examined. HPV viral load triage strategies did not perform optimally overall. Inclusion of HR-HPV genotypes 31 and 52 to HPV16/18
triage provided the highest sensitivities.
Concerns surrounding HPV-based screening can be effectively mitigated via triage.
Balancing the benefits of HPV-based primary cervical screening with informed management recommendations for HR-HPV
women may decide the success of its widening utilization.
.
Women living with HIV (WLHIV) have a high risk of anal cancer. Identifying risk factors for anal HPV 16 infection, the most significant risk factor for anal cancer, is essential for prevention and ...screening strategies.
In the EVVA Cohort study, 151 WLHIV had cervical and anal HPV testing with genotyping every 6 months for 2 years, while demographic and clinical data were collected via questionnaires and chart reviews. Here, we present results of baseline data analyzed using multivariable logistic regression.
Among 150 women with adequate HPV test results at baseline, HPV 16 DNA was detected anally in 23 (15.3%; 95%CI:10.4-22.1) and cervically in 5 (3.3%; 95%CI:1.4-7.8). In multivariable analysis, current smoking (OR = 6.0; 95%CI: 1.5-23.9), nadir CD4 count ≤ 200 cells/μL (OR = 8.4; 95%CI: 2.0-34.3), prevalent cervical HPV 16 (OR = 14.7; 95%CI: 1.0-222.5) and anogenital herpes in previous 6 months (OR = 9.8, 95%CI: 1.7-56.8) were associated with prevalent anal HPV 16.
Knowledge of risk factors can help identify WLHIV at greatest risk of anal HPV 16 infection and, potentially, developing subsequent anal cancer. Identification of the subgroup of these women in whom HPV 16 persists could be an early step in the algorithm of anal cancer screening.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Recent evidence shows increased preterm birth risk with human papillomavirus-16 (HPV16) infection during pregnancy. This study aimed to measure the association between HPV16 viral load during ...pregnancy and preterm birth. We used data from participants in the HERITAGE study. The Linear Array assay was used for HPV DNA testing on vaginal samples collected during the first and third trimesters of pregnancy. The HPV16 viral load was measured with a real-time polymerase chain reaction. We used logistic regression to measure the associations between HPV16 viral load during pregnancy and preterm birth (defined as birth before 37 weeks of gestation). The adjusted odd ratios (aORs) and the 95% confidence intervals CIs were estimated with inverse probability treatment weighting of the propensity score. This study included 48 participants who tested positive for HPV16 during the first trimester of pregnancy. The aOR for the association between first-trimester HPV16 viral load (higher viral load categorized with a cutoff of 0.5 copy/cell) was 13.04 95% CI: 1.58-107.57). Similar associations were found using different cutoffs for the categorization of viral load during the first and third trimesters. Our findings suggest a strong association between a high HPV16 viral load during pregnancy and preterm birth, demonstrating a biological gradient that reinforces the biological plausibility of a causal association.
Abstract Substantial evidence exists to support the introduction of molecular testing for human papillomavirus (HPV) as the primary technology in cervical cancer screening. While HPV testing is much ...more sensitive than cytology for detection of high-grade precancerous lesions, it is less specific. To improve efficiency, it is therefore recommended that a specific test (like cytology) be used in triaging HPV positive women to colposcopy. A number of studies have been conducted that support the use of cytology alone or in conjunction with HPV genotyping for triage. The decision to incorporate genotyping also depends on the commercial HPV test that is selected since not all tests provide results for certain individual high-risk types. Regardless of whether policy officials decide to adopt a triage approach that incorporates genotyping, the use of liquid based cytology (LBC) may also improve screening performance by reducing diagnostic delays. With LBC, the same cell suspension from a single collection may be used for HPV testing and a smear can be immediately prepared if HPV status is positive. This was a critical lesson from a community based demonstration project in Montreal (VASCAR study), where conventional cytology exists and specimen co-collection was not permitted for ethical reasons, requiring HPV positive women to return for an additional screening visit prior to colposcopy.
The purpose of this paper is to provide evidence-based guidance on the management of a positive human papilloma virus (HPV) test and to provide guidance around screening and HPV testing for specific ...patient populations. The guideline was developed by a working group in collaboration with the Gynecologic Oncology Society of Canada (GOC), Society of Colposcopists of Canada (SCC), and the Canadian Partnership Against Cancer. The literature informing these guidelines was obtained through a systematic review of relevant literature by a multi-step search process led by an information specialist. The literature was reviewed up to July 2021 with manual searches of relevant national guidelines and more recent publications. The quality of the evidence and strength of recommendations were developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. The intended users of this guideline include primary care providers, gynecologists, colposcopists, screening programs, and healthcare facilities. The implementation of the recommendations will ensure an optimum implementation of HPV testing with a focus on the management of positive results. Recommendations for appropriate care for underserved and marginalized groups are made.
Human papillomavirus (HPV) can be vertically transmitted. Our objective was to measure the association between the mode of delivery and the detection of HPV in infants. We used data collected from ...pregnant women during the HERITAGE study. Self-collected vaginal samples from the first and third trimester were obtained for HPV testing. Specimens from oral, pharyngeal, conjunctival and anogenital mucosa were collected from infants 36-48 h after delivery and at 3 months of age. All samples were tested for HPV DNA by the Linear Array assay. Adjusted odd ratios (aOR) and 95% confidence interval (CI) were estimated using multivariate logistic regressions. From the 282 women revealed to be HPV-positive in both the first and third trimesters, 25 infants were born HPV-positive. The overall probability of transmission was 8.9% (25/282); 3.7% (3/81) in participants with a caesarean section and 10.9% (22/201) for those who delivered vaginally. Vaginal delivery increased the risk of HPV in infants compared to caesarean (aOR: 3.63, 95%CI: 1.03-12.82). Infants born after a caesarean with ruptured membranes were not at increased risk of HPV compared to infants born after an elective caesarean section with intact membranes (aOR: 1.31, 95%CI: 0.10-17.76). Our results support the hypothesis that transmission occurs mostly during the passage in the vaginal canal.
The disrupted introduction of the HPV-based cervical screening program in several jurisdictions has demonstrated that the attitudes and beliefs of screening-eligible persons are critically implicated ...in the success of program implementation (including the use of self-sampling). As no up-to-date and validated measures exist measuring attitudes and beliefs towards HPV testing and self-sampling, this study aimed to develop and validate two scales measuring these factors. In October-November 2021, cervical screening-eligible Canadians participated in a web-based survey. In total, 44 items related to HPV testing and 13 items related to HPV self-sampling attitudes and beliefs were included in the survey. For both scales, the optimal number of factors was identified using Exploratory Factor Analysis (EFA) and parallel analysis. Item Response Theory (IRT) was applied within each factor to select items. Confirmatory Factor Analysis (CFA) was used to assess model fit. After data cleaning, 1027 responses were analyzed. The HPV Testing Attitudes and Beliefs Scale (HTABS) had four factors, and twenty-two items were retained after item reduction. The HPV Self-sampling Attitudes and Beliefs Scale (HSABS) had two factors and seven items were retained. CFA showed a good model fit for both final scales. The developed scales will be a valuable resource to examine attitudes and beliefs in anticipation of, and to evaluate, HPV test-based cervical screening.
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