Gynecological Cancer Survivors' Experiences of Dyspareunia and Factors Influencing Care-Seeking Behavior: A Qualitative Study.

Pain during sexual intercourse, also called dyspareunia, affects most women after treatment for gynecological cancer. Previous work adopted a biomedical approach to depict dyspareunia in this population, which provided a narrow perspective of this condition. Taking into account women's experiences of dyspareunia and the factors influencing their care-seeking behaviors would provide insight to improve care in the context of gynecological cancer. The aim of this study was to describe gynecological cancer survivors' experiences of dyspareunia and factors influencing care-seeking behavior. A qualitative study was performed with 28 gynecological cancer survivors with dyspareunia. Individual telephone interviews were conducted based on the Common-Sense Model of Self-Regulation. Interviews were recorded and transcribed for analysis using the interpretative description framework. Concerning their experience, participants reported the oncological treatments as the primary cause of dyspareunia. Loss of libido, lower vaginal lubrication, and smaller vaginal cavity were described as being linked with dyspareunia. Women explained how dyspareunia and these changes had led them to engage less in, and even interrupt, sexual activity. They expressed that they were distressed, felt less of a woman, and experienced low control and/or self-efficacy. Regarding the factors influencing women's care-seeking behaviors, participants emphasized that they were provided with insufficient information and support. Balancing priorities, denial or reluctance, misbeliefs, resignation and acceptance, and negative emotions were reported as barriers, whereas acknowledgement of sexual dysfunction, desire for improvement, awareness of treatment possibilities, willingness to undertake treatment and treatment acceptability were reported as facilitators to seeking care. Findings suggest that dyspareunia is a complex and impactful condition after gynecological cancer. While this study highlights the importance of alleviating the burden of sexual dysfunction in cancer survivors, it identified factors that should be considered in the provision of services to improve care.

Acceptability of multimodal pelvic floor physical therapy to treat dyspareunia after gynecological malignancies: a qualitative study of women's views and experiences.

INTRODUCTION AND HYPOTHESIS: Multimodal pelvic floor physical therapy (PFPT) is recommended after gynecological malignancies to treat dyspareunia. However, data to strongly support its implementation in the cancer care continuum are lacking. The aim of this study was to explore the views and experiences of gynecological cancer survivors with dyspareunia regarding the acceptability of multimodal PFPT. METHODS: This qualitative study was conducted with the participants (n = 28) of a study investigating a 12-week multimodal PFPT treatment. Individual semi-structured telephone interviews served to collect qualitative data pertaining to women's views and experiences of the treatment they received. Interviews were recorded and transcribed for analysis using the interpretative description framework. RESULTS: Our cohort described the appropriateness of the treatment in terms of modalities, physical therapist, care delivery, and intensity (Theme 1). While the intensity was reported as demanding by a few, all participants stressed that it was relevant to see significant improvements (Theme 2). In addition to the treatment characteristics and women's beliefs and attitudes, noticing the treatment effects motivated their participation (Theme 2). Women expressed being highly satisfied with the treatment based on their positive experiences and the balance between their efforts and the results they obtained (Theme 3). As a result, they all recommended this treatment (Theme 3). CONCLUSIONS: This is the first study to examine the acceptability of multimodal PFPT in the context of gynecological malignancies. This treatment was found acceptable and can be offered to gynecological cancer survivors.

Human papillomavirus genotype concordance between Anyplex II HPV28 and linear array HPV genotyping test in anogenital samples.

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.

Risk factors for placental human papillomavirus infection.

OBJECTIVE: Human papillomavirus (HPV) has been associated with adverse pregnancy outcomes but placental HPV infection has been rarely studied. The objective was to determine the proportion of HPV-positive placentas and the associated risk factors among HPV-positive women during pregnancy. METHODS: We analysed data from pregnant women enrolled in HERITAGE cohort study between 2010 and 2016 with positive vaginal HPV infection during the first trimester of pregnancy (n=354). Placental swabs and biopsies were collected. HPV genotyping was performed using Linear Array. The predictors of placental HPV detection were identified by generalised estimating equations models. RESULTS: HPV was detected in 78 placentas (22.0%) (one among 96 caesarean sections and 77 among 258 vaginal deliveries). Overall, 91% of HPV-positive placentas were positive for a genotype that was detected in vaginal samples during pregnancy. Among women who delivered vaginally, abnormal cytology (adjusted OR (aOR) 1.78 (95% CI 1.02 to 3.10)), other genitourinary infection (aOR 2.41 (95% CI 1.31 to 4.44)), presence of multiple HPV genotypes in the first trimester (aOR 2.69 (95% CI 1.76 to 4.12)) and persistence of high-risk HPV infections during pregnancy (HPV-16/18: aOR 3.94 (95% CI 2.06 to 7.55) and other than HPV-16/18: aOR 2.06 (95% CI 1.05 to 4.02)) were independently associated with placental HPV. CONCLUSIONS: HPV was frequently detected in the placenta of women who delivered vaginally and may be associated with host immune response characteristics.

Racial/ethnic inequalities in cervical cancer screening in the United States: An outcome reclassification to better inform interventions and benchmarks.

In the United states (U.S.), prevailing understanding suggests significant racial/ethnic inequalities in cervical cancer screening exist. However, recent findings elsewhere in North America indicate the magnitude of these inequalities depend on the way screening is defined: lifetime screening versus up-to-date screening. As those who have never been screened are most at risk for invasive cancer, an improved understanding of inequalities in this outcome is necessary to better inform interventions. To describe racial/ethnic inequalities in 1) never screening and 2) not being up-to-date with screening among women who have been screened at least once in their lifetime, three years (2014-2016) of the U.S. Behavioral Risk Factor Surveillance Survey were utilized to estimate cervical cancer screening prevalence ratios via Poisson regression (N = 123,070). The sample was limited to women age 21 to 65 years. Women from racial/ethnic minority groups were more likely to never have been screened in comparison to White women, particularly women of Asian descent (Prevalence Ratio (PR) = 3.8, 95% CI = 3.3-4.3). However, among women who had been screened at least once in their lifetime, an inverse association was observed between being a member of a racial/ethnic minority group and not being up-to-date with screening (e.g. PRasian vs white = 0.7, 95% CI = 0.6-0.9). Physicians and public health institutions concerned with monitoring racial/ethnic inequalities should consider adding lifetime screening as a primary benchmark, as this outcome implies different intervention targets to address inequalities and the differential burden of cervical cancer.

University of Montreal's Clinician-Investigator Program: A 10-Year Descriptive Evaluation.

PURPOSE: Clinician-investigators have an important role in the development and implantation of new therapies and treatment modalities; however, there have been several reports highlighting a pending shortage in the clinician-investigators' workforce. In Canada, the Royal College has promoted the development of clinician-investigators programs (CIP) to facilitate the training of these individuals. There is currently a paucity of data regarding the outcomes of such programs. This study aims to identify the strengths and areas of improvement of the Montreal University CIP.  Methods: An internet-based 51-question survey was distributed to all the alumni from the University of Montreal CIP. Participation was voluntary and no incentives were provided. The response rate was 64%.  Results: Among respondents, 50% (n=16) had completed their clinical residency and all CIP requirements. The majority of these individuals (63%) had become independent investigators and had secured provincial and national funding. Satisfaction of the respondents was high regarding the overall program (85%), the research skills developed during the CIP (84%) and the financial support obtained during the program (72%). The satisfaction rate regarding career planning was lower (63%).  Conclusion: This survey demonstrates that, while indicators are favorable, some areas still require improvement. Several steps to improve the CIP have been identified; notably, the transition from the CIP to early independent career has been identified as critical in the development of clinician-investigators and steps have been taken to improve this progression.

Endometrial Biopsy in Low-Risk Women: Are We Over-Investigating?

The appropriate age at which to perform endometrial biopsy for abnormal uterine bleeding (AUB) is controversial. This study aimed to determine the prevalence of malignant and premalignant pathologies in women aged 41-49 years with AUB and without risk factors for endometrial cancer. Records of women who had undergone a biopsy at the gynaecology clinic of the Centre hospitalier de l'Université de Montréal between 2014 and 2018 were reviewed. Of the 209 women included in the study, 2 had atypical hyperplasia, which resolved without treatment, and 3 had hyperplasia without atypia. The remaining women had benign results, showing that the prevalence of malignant and premalignant endometrial pathologies is low in this subgroup of patients.

Multimodal physical therapy versus topical lidocaine for provoked vestibulodynia: a multicenter, randomized trial.

BACKGROUND: 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. OBJECTIVE: The purpose of this study was to establish the efficacy of multimodal physical therapy compared with topical lidocaine, a frequently used first-line treatment. STUDY DESIGN: 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. RESULTS: 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). CONCLUSION: 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.

A Prospective Single-Arm Study Evaluating the Effects of a Multimodal Physical Therapy Intervention on Psychosexual Outcomes in Women With Dyspareunia After Gynecologic Cancer.

BACKGROUND: Dyspareunia affects most women after treatment for gynecologic malignancies. However, to date, evidence-based interventions remain limited and no study has examined the effects of multimodal physical therapy on psychosexual outcomes in these patients. AIM: To assess the effects of multimodal physical therapy on psychosexual outcomes including sexual distress, body image concerns, pain anxiety, pain catastrophizing, pain self-efficacy and depressive symptoms in women with dyspareunia after treatment for gynecologic malignancies. METHODS: Thirty-one gynecologic cancer survivors with dyspareunia enrolled in this prospective single-arm interventional study. The participants undertook 12 weekly sessions of physical therapy incorporating education, pelvic floor muscle exercises with biofeedback, manual therapy and home exercises. Outcome measures were evaluated pre- and post-treatment. Paired t-tests were conducted to investigate the changes from pre-treatment (P-value Ë‚ 0.05) while effect sizes (Cohen's d) were calculated to measure the magnitude of the change. MAIN OUTCOME MEASURES: Sexual distress (Female Sexual Distress Scale-Revised), body image concerns (Body Image Scale), pain anxiety (Pain Anxiety Symptoms Scale), pain catastrophizing (Pain Catastrophizing Scale), pain self-efficacy (Painful Intercourse Self-Efficacy Scale) and depressive symptoms (Beck Depression Inventory-II). RESULTS: Significant changes were found from pre- to post-treatment for all psychosexual outcomes. Women reported reductions in sexual distress (P Ë‚ 0.001, d = 1.108), body image concerns (P Ë‚ 0.001, d = 0.829), pain anxiety (P Ë‚ 0.001, d = 0.980), pain catastrophizing (P Ë‚ 0.001, d = 0.968) and depression symptoms (P = 0.002, d = 0.636) with an increase in pain self-efficacy (P Ë‚ 0.001, d ≥ 0.938) following the intervention. CLINICAL IMPLICATIONS: The results suggest that multimodal physical therapy significantly improves sexual distress, body image concerns, pain anxiety, pain catastrophizing, pain self-efficacy and depressive symptoms in our sample of women with dyspareunia after treatment for gynecologic malignancies. The medium to large effect sizes obtained with the high proportion of women presenting meaningful changes according to the known minimal clinically important difference or clinical cut-off underlines the significance of these effects. STRENGTHS & LIMITATIONS: The current study used validated questionnaires to assess the psychosexual outcomes of a well-designed physical therapy intervention using multiple modalities to address the multifaceted aspect of dyspareunia in cancer survivors. This study did not include a control group, which may limit drawing definitive conclusions. CONCLUSION: Findings showed that multimodal physical therapy yielded significant improvements in psychosexual outcomes in gynecologic cancer survivors with dyspareunia. A randomized controlled trial is indicated to confirm these results. Cyr M-P, Dumoulin C, Bessette P, et al. A Prospective Single-Arm Study Evaluating the Effects of a Multimodal Physical Therapy Intervention on Psychosexual Outcomes in Women With Dyspareunia After Gynecologic Cancer. J Sex Med 2021;18:946-954.

Pelvic floor morphometrical and functional changes immediately after pelvic floor muscle training and at 1-year follow-up, in older incontinent women.

AIMS: To compare the effects of group-based and individual physiotherapy for stress or mixed urinary incontinence (UI) on pelvic floor morphometry, pelvic floor muscle (PFM) function, and related self-efficacy, immediately after treatment and at 1 year. METHODS: This is a planned secondary analysis of the group rehabilitation or individual physiotherapy study, an assessor-blinded, randomized, noninferiority trial. Eligible participants included 362 community-dwelling older women with symptoms of stress/mixed UI. After learning how to contract PFMs, participants completed 12 weeks of PFM training, either individually (one-on-one) or as part of a group (eight women). Pelvic floor transperineal ultrasound volumes (morphometry), PFM intravaginal dynamometric data (function), and self-efficacy in performing PFM exercises were acquired at baseline, posttreatment, and at 1 year. RESULTS: Groups were comparable at all time points. Immediately posttreatment, both groups demonstrated significant changes in pelvic floor morphometry during coughs, and in PFM function during contractions and coughs. Participants also reported improved self-efficacy in performing PFM exercises. Results were sustained at 1 year. When participants coughed, pelvic floor structures were better supported (reflected by less caudal movement of the puborectalis sling and a smaller opening of the levator hiatus) in a pattern consistent with the "knack" strategy. Furthermore, both interventions resulted in stronger, faster, more coordinated, and more endurant PFMs. CONCLUSION: In older women with stress or mixed UI, both individual and group-based PFM training resulted in comparable improvements in overall PFM function, pelvic floor morphometry during coughs, and related self-efficacy in performing PFM exercises, which were sustained at 1 year.

Association Between Maternal Human Papillomavirus Infection and Adverse Pregnancy Outcomes: Systematic Review and Meta-Analysis.

BACKGROUND: Experimental studies provide evidence of the harmful effect of human papillomavirus (HPV) infection on pregnancy, but observational studies are inconclusive. We systematically assessed the association between HPV and adverse pregnancy outcomes. METHODS: We searched electronic databases up to December 1, 2019. We included observational studies on the association between HPV and adverse pregnancy outcomes. We conducted a random-effect meta-analysis for each outcome and assessed heterogeneity between studies. RESULTS: From 3034 citations, we included 38 studies and quantitatively synthesized 36 studies. Human papillomavirus was significantly associated with preterm birth (age-adjusted odds ratio [aOR], 1.50; 95% confidence interval [CI], 1.19-1.88), preterm premature rupture of membranes (aOR, 1.96; 95% CI, 1.11-3.45), premature rupture of membranes (aOR, 1.42; 95% CI, 1.08-1.86), intrauterine growth restriction (aOR, 1.17; 95% CI, 1.01-1.37), low birth weight (aOR, 1.91; 95% CI, 1.33-2.76), and fetal death (aOR, 2.23; 95% CI, 1.14-4.37). No significant association was found for spontaneous abortion (aOR, 1.14; 95% CI, 0.40-3.22) and pregnancy-induced hypertensive disorders (aOR, 1.24; 95% CI, 0.80-1.92). Most of the studies were of moderate or low quality, and substantial between-studies heterogeneity remained unexplained. CONCLUSIONS: We found a consistent and significant association between HPV and preterm birth and preterm premature rupture of membranes. Human papillomavirus may also be associated with intrauterine growth restriction, low birth weight, and fetal death, but findings are limited by suboptimal control of biases.

Feasibility, acceptability and effects of multimodal pelvic floor physical therapy for gynecological cancer survivors suffering from painful sexual intercourse: A multicenter prospective interventional study.

OBJECTIVES: Painful sexual intercourse (dyspareunia) is a distressing condition affecting a large proportion of gynecological cancer survivors, yet treatments remain limited and poorly studied. This multicenter prospective interventional study examined the feasibility, acceptability and effects of multimodal pelvic floor physical therapy in gynecological cancer survivors with dyspareunia. METHODS: Thirty-one endometrial and cervical cancer survivors with dyspareunia participated in 12 weekly 60-min physical therapy sessions combining education, manual therapy, pelvic floor muscle exercises using biofeedback and home exercises, which included the use of a dilator. The adherence rate to home exercises (≥80%), the attendance rate at physical therapy sessions (≥80% of participants attending ≥10 sessions) and the dropout rate (˂15%) served as feasibility and acceptability outcomes and benchmarks. Pain intensity, pain quality, sexual function, pelvic floor dysfunction symptoms and quality of life were measured at baseline and post-treatment. Treatment satisfaction and participants' perceived improvement were also assessed. RESULTS: The adherence rate was 88% (SD 10), 29/31 (94%) women attended ≥10 treatment sessions, and the dropout rate was 3%. Moreover, women experienced significant improvements in all outcomes after the intervention (p ≤ 0.044). They also reported being highly satisfied with the treatment (9.3/10 (SD 1.2)), and 90% of them were very much or much improved. CONCLUSIONS: Our findings support the feasibility and acceptability of multimodal pelvic floor physical therapy for gynecological cancer survivors with dyspareunia. The intervention also led to significant improvements in pain, sexual function, pelvic floor dysfunction symptoms and quality of life. A randomized controlled trial is needed to confirm these results.

Efficiency and Cost: E-Recruitment Is a Promising Method in Gynecological Trials.

BACKGROUND: Recruitment of participants is crucial to the success of any trial as it can have a major impact on study costs, the duration of the study itself, and, more critically, trial failure. Given that vulvodynia particularly affects young women, the use of social media and e-recruitment could prove efficient for enrollment. AIM: To compare the efficiency, effectiveness, and cost-effectiveness of three different recruitment methods. METHODS: The comparison data were collected as part of a bicentric randomized controlled trial evaluating the efficacy of physiotherapy in comparison with topical lidocaine in 212 women suffering from provoked vestibulodynia. The recruitment methods included: (i) conventional methods (eg, posters, leaflets, business cards, newspaper ads); (ii) health professional referrals, and (iii) e-recruitment (eg, Facebook ads and web initiatives). Women interested in participating were screened by telephone for eligibility criteria and were assessed by a gynecologist to confirm their diagnosis. Once included, structured interviews were undertaken to describe their baseline characteristics. MAIN OUTCOME MEASURES: The outcomes of this study were the recruitment efficiency (the number of patients screened/enrolled), recruitment effectiveness (the number of participants enrolled), cost-effectiveness (cost per enrolled participant), and retention rate, and baseline characteristics of participants were monitored for each method. RESULTS: The conventional methods (n = 101, 48%) were more effective as they allowed for greater enrollment of participants, followed by e-recruitment (n = 60, 28%) and health professional referrals (n = 33, 16%) (P < 0.007). Recruitment efficiency was found to be similar for e-recruitment and referrals (60/122 and 33/67, 49%, P = 0.055) but lower for conventional methods (101/314, 32%, P < 0.011). Nonsignificant differences were found between the three groups for baseline characteristics (P ≥ 0.189) and retention rate (91%, P ≥ 0.588). The average cost per enrolled participant was fairly similar for e-recruitment ($117) and conventional methods ($110) and lower for referrals ($60). CLINICAL IMPLICATIONS: Our results suggest that having a variety of recruitment methods is beneficial in promoting clinical trial recruitment without affecting participant characteristics and retention rates. STRENGTH & LIMITATIONS: Although recruitment methods were used concomitantly, this study gives an excellent insight into the advantages and limitations of recruitment methods owing to a large sample size. CONCLUSION: The study findings revealed that e-recruitment is a valuable recruitment method because of its comparable efficiency and cost-effectiveness to health professional referrals and conventional methods, respectively. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, number NCT01455350. Benoit-Piau J, Dumoulin C, Carroll MS, et al. Efficiency and Cost: E-Recruitment Is a Promising Method in Gynecological Trials. J Sex Med 2020;17:1304-1311.

Assessing the time dependence of prognostic values of cytology and human papillomavirus testing in cervical cancer screening.

Accurate assessment of risks for developing cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) after a given set of screening test results is instrumental to reaching valid conclusions and informing cervical cancer screening recommendations. Using data from the Canadian Cervical Cancer Screening Trial (CCCaST), we assessed prognostic values of enrollment screening test results to predict CIN2+ among women attending routine cervical screening using multivariable Cox proportional hazards (PH) regression and its flexible extension during each of two follow-up periods (protocol-defined and extended). Nonproportional (time-dependent (TD)) and/or nonlinear effects were modeled, as appropriate. Women with abnormal cytology had hazard ratios (HRs) for CIN2+ detection of 17.61 (95% CI: 11.25-27.57) and 10.46 (95% CI: 5.41-20.24) relative to women with normal cytology during the protocol-defined and extended follow-up periods, respectively. High-risk human papillomavirus (HR-HPV) positivity was an even stronger predictor of CIN2+ risk, with significant TD effects during both follow-up periods (p <0.001 for both TD effects). Risks among women co-testing HR-HPV+ with and without abnormal cytology (relative to women co-testing negative) were highest immediately after baseline, and decreased significantly thereafter (p <0.001 for both TD effects). HRs for HPV16+ and HPV18+ women (relative to those testing HR-HPV-) did not vary significantly over time (HR = 182.96; 95% CI: 95.16-351.77 and HR = 111.81; 95% CI: 44.60-280.31, respectively). Due to TD effects, conventional Cox model estimates considerably underestimated adjusted HRs associated with positive HR-HPV testing results early on in the follow-up periods.

Age at last screening and remaining lifetime risk of cervical cancer in older, unvaccinated, HPV-negative women: a modelling study.

BACKGROUND: There is a paucity of empirical evidence to inform the age at which to stop cervical cancer screening. The recommended age to stop screening generally varies between age 50-70 years worldwide. However, cervical cancer incidence and mortality remain high in older women. We used a Markov model of cervical cancer screening to estimate the remaining lifetime risk of cervical cancer at different ages and with different exit screening tests, with the aim of informing recommendations of the age at which to stop cervical cancer screening in developed countries. METHODS: For this modelling study, we developed a state transition (Markov) model of cervical cancer natural history and screening. We developed, calibrated, and validated our model using Canadian provincial registries and survey data. To simulate an age-structured population in the model, a new cohort of 236 564 women (one fifth of the population of Canadian women aged 20-24 years in 2012) entered the model every year and were successively modelled in parallel. Successive cohorts entered the model at age 10 years, creating an age-structured population of women aged 10-100 years. Women who had a total hysterectomy were excluded from the analyses. We calibrated our model to human papillomavirus (HPV) infection and cancer incidence with data from Statistics Canada, which compiles the data from 13 individual provincial registries. We chose a three-stage progressive cervical intraepithelial neoplasia model to include differences in management and treatment decisions depending on lesion severity. We modelled infections with four high-risk HPV groups: HPV16 and HPV18; HPV31, HPV33, HPV45, HPV52, and HPV58; HPV35, HPV39, HPV51, HPV56, HPV59, HPV66, and HPV68; and a generic group of other potentially oncogenic HPVs. We estimated 5-year, 10-year, and remaining lifetime risk of cervical cancer for older, unvaccinated women who stopped screening at different ages and underwent different screening tests. FINDINGS: Cervical cancer incidence excluding women with hysterectomies underestimated the incidence of cervical cancer in women with a cervix by up to 71% in women aged 80-84 years. Our model predicted that women without HPV vaccination who have been never screened have a 1 in 45 (95% percentile interval 1 in 32 to 1 in 64) lifetime risk of cervical cancer. Perfect adherence (100% of women screened) to cytology screening every 3 years between the ages of 25 years and 69 years could reduce the lifetime risk of cervical cancer to 1 in 532 women (95% percentile interval 1 in 375 to 1 in 820) without HPV vaccination. Increasing the age at which women stopped cytology screening from 55 years to 75 years led to incremental decreases in cancer risk later in life. A 70-year old woman whose screening history was unknown had an average remaining lifetime risk of 1 in 588 (<1%; 95% percentile interval 1 in 451 to 1 in 873) if she stopped screening. Her remaining lifetime risk at age 70 years was reduced to 1 in 1206 (2·0 times reduction; 95% percentile interval 1 in 942 to 1 in 1748) if she had a negative cytology test, 1 in 6525 (12·9 times reduction; 95% percentile interval 1 in 3167 to 1 in 18 664) if she had a negative HPV test, and 1 in 9550 (18·1 times reduction; 95% percentile interval 1 in 4928 to 1 in 23 228) if she had a negative co-test for cytology and HPV. INTERPRETATION: Cervical cancer risk reductions might be achieved by screening with cytology up to age 75 years, although with diminishing returns. A negative exit oncogenic HPV test or negative HPV test plus cytology correlates with a low remaining lifetime cervical cancer risk for unvaccinated women with a cervix after the age of 55 years. FUNDING: Canadian Institutes of Health Research.

Final efficacy, immunogenicity, and safety analyses of a nine-valent human papillomavirus vaccine in women aged 16-26 years: a randomised, double-blind trial.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: Merck & Co, Inc.

Pelvic Floor Muscle Morphometry and Function in Women With Primary and Secondary Provoked Vestibulodynia.

INTRODUCTION: Provoked vestibulodynia (PVD) can be categorized as primary PVD affecting women from their first sexual intercourse or secondary PVD, which appears after a period of pain-free intercourse. There is growing evidence that these subgroups may be distinct entities presenting different pathophysiological mechanisms. Although there are documented pelvic floor muscle alterations in provoked vestibulodynia, no study has yet evaluated whether the pelvic floor muscle morphometry or function differed between women with primary and secondary provoked vestibulodynia. AIM: To assess and compare pelvic floor muscle morphometry and function in women with primary and secondary provoked vestibulodynia. METHODS: A total of 212 women with provoked vestibulodynia (primary = 75 and secondary = 137) participated in the study after completing a gynecologic exam to confirm their diagnosis. MAIN OUTCOME MEASURE: Pelvic floor muscle morphometry was evaluated at rest and during maximal contraction using 3D/4D transperineal ultrasound and pelvic floor muscle function (tone, strength, speed of contraction, endurance) was assessed with a dynamometric speculum. RESULTS: Pelvic floor muscle morphometry at rest and during contraction was not statistically different between women with primary and secondary provoked vestibulodynia (P > .327 adjusted for the duration of symptoms; P > .137 unadjusted t-tests). Regarding pelvic floor muscle function assessed with the dynamometric speculum, no differences were found in tone, strength, speed of contraction, endurance between the 2 groups (P > .144 adjusted for duration of symptoms; P > .118 unadjusted t-tests). CLINICAL IMPLICATIONS: Women with primary and secondary PVD do not differ on pelvic floor muscle morphometric or dynamometric characteristics, suggesting that physical therapy modalities should be offered to both subgroups of PVD. STRENGTHS & LIMITATIONS: The current study used a large and mixed clinical and community sample providing more representative findings. Moreover, the analyses were adjusted for relevant variables such as duration of symptoms. Although the inclusion of nulliparous women below 45 years of age ensured the homogeneity of the sample, it may limit the external validity. CONCLUSION: These findings suggest that primary and secondary subgroups of provoked vestibulodynia cannot be differentiated by morphometric or dynamometric characteristics. Pelvic floor muscles alterations in provoked vestibulodynia are therefore not influenced by the onset of the symptoms. Fontaine F, Dumoulin C, Bergeron S, et al. Pelvic floor muscle morphometry and function in women with primary and secondary provoked vestibulodynia. J Sex Med 2018;15:1149-1157.

Cervical cancer screening in Montreal: Building evidence to support primary care and policy interventions.

In Canada, over 40% of invasive cervical cancers occur among women who have never been screened. Although 12% of Canadian women have never been screened, this number can be as high as 43% among certain social groups. Little is published on factors associated with screening uptake and inequalities among women residing in Quebec. Four waves of the Canadian Community Health Survey (2003, 2005, 2008, 2012, N = 6393) were utilized to assess lifetime screening and screening in the previous 3 years among women residing in Montreal. Chi-squared statistics were calculated, Poisson regression was utilized to model prevalence ratios, and prevalence differences were calculated. In total, 13.6% of women had never been screened and 12.1% had not been screened in the previous 3 years. Immigrant status was the strongest predictor of never being screened [recent vs non-immigrant: Prevalence Ratio (PR), 3.9 (95% Confidence Interval (CI): 2.9-5.4)] and not having a primary care physician (PCP) was the strongest predictors of not being screened recently [PR = 3.0 (95% CI: 2.3-3.9)]. The two most common reasons for not being screened were not "know[ing] it was necessary" and not "get[ting] around to it." These results provide a description of sub-populations which might benefit from cervical screening interventions: immigrants and women without a PCP. Interventions targeting access to PCPs, expanding training of non-physicians to conduct screening, organized screening, or autoadministered screening test may mitigate inequalities. Future work should assess their acceptability and feasibility, and evaluate the impact of these types of primary care and policy interventions.

Impact of Acetic Acid on HPV Testing Using Hybrid Capture 2.

As per the American Society for Colposcopy and Cervical Pathology guidelines, human papillomavirus (HPV) testing is currently used as part of cervical cancer screening and during colposcopy follow-up. The present project evaluated if the application of acetic acid (AA) impacts HPV test results. METHODS: We conducted a prospective nonrandomized interventional study. Participants referred for colposcopy were eligible if immunocompetent, older than 18 years, and not pregnant. Women in group A (controls) received 2 consecutive HPV tests without application of AA. Women in group B had a first HPV sample collected before the application of AA and a second sample collected 3 minutes after application of AA. Samples were tested for HPV DNA with Hybrid Capture 2 (HC2) according to the manufacturer's instructions. RESULTS: From October 17, 2012, to January 10, 2013, approximately 101 women were recruited in 2 colposcopy clinics. In each group, concordance was 98%, with only 1 participant having discordant results (testing negative on the first sample and positive on the second sample). We found no statistically significant difference in relative light units(RLUs) between groups (median of difference, - 0.02 vs -0.05 RLU; p = .93). CONCLUSIONS: The results of this study suggest that acetic acid at concentrations of 3% to 5% and sequential cervical sampling do not modify the result of HPV testing by Hybrid Capture 2.