Association between p16/Ki-67 dual stain cytology results prior to and 6 months after LLETZ treatment for CIN and the follow-up regimen three years after treatment: a retrospective cohort study.

OBJECTIVE: Investigate the association between p16/Ki-67 dual stain cytology test (DST) results, obtained prior to- and 6 months after LLETZ surgery for treatment of CIN, and the follow-up regimen three years after treatment. METHODS: Secondary analysis of a prospective cohort study. Cervical cytology samples were obtained just prior to- and 6 months after LLETZ and underwent conventional liquid-based cytology (LBC) and p16/Ki-67 dual staining, as well as high-risk HPV genotyping. Clinical management after the LLETZ was according to Belgian national guidelines, with clinicians being blinded to DST results at both time points. Case records were reviewed in 01/2023 to document the follow-up regimen on average three years afterwards: women had either been advised to return to routine screening (i.e., three-annual LBC testing according to the Belgian guideline at that time), or were still subject to more frequent posttreatment surveillance (i.e., more frequent visits because of persistent hrHPV infection or absence of cytological regression). RESULTS: The follow-up regimen was recorded in 79/110 women originally recruited (72%). The need for continued intense posttreatment surveillance was associated with hrHPV infection 6 months after treatment (79.3% vs. 18.0%, p < 0.001), a positive DST result at baseline and follow-up (41.4% vs. 84.0%, p < 0.001-55.2% vs. 16.0%, p < 0.001), and persistent cytological anomalies at 6 months (at an ASCUS or worse threshold, 37.9% vs. 16.0%, p = 0.028). In multivariable logistic regression analysis, a positive DST at baseline (aOR 20.1, 95%CI 2.03-199.1) was independently associated with the need for intense post-treatment surveillance multiple years after treatment. CONCLUSION: This exploratory study suggests a possible role of dual-stain cytology in predicting treatment outcome multiple years after LLETZ surgery.

p16/Ki-67 dual stain, PAP cytology and HR-HPV test results prior to and 6 months after a LLETZ procedure: a prospective observational cohort study.

OBJECTIVES: To investigate the effect of a LLETZ procedure on p16/Ki-67 dual stain, PAP cytology and HR-HPV test results on cervical cytology samples obtained prior to and 6 months after the procedure. Secondary aims are to assess dependency between test results at the time of follow-up and explore dual stain positivity rates according to known risk factors for persistence/recurrence of cervical intra-epithelial neoplasia (CIN). STUDY DESIGN: Prospective observational cohort study conducted in the Department of Gynaecology at the University Hospitals of Leuven, Belgium. All patients referred for a LLETZ procedure were invited to participate. A cervical cytology sample was obtained just prior to and 6 months after the procedure. Every sample was used for PAP staining (cytology), p16/Ki-67 dual staining (dual stain test, DST) and HR-HPV genotyping. Test results were compared between both timepoints using the McNemar test. Dependency was assessed cross-sectionally at the time of follow-up using a chi-squared test. RESULTS: From the 110 participants originally included, 83 attended follow-up (75.5%). Mean duration of follow-up was 187.91 days (SD 21.47) and mean age was 41.4 years (SD 11.08). DST positivity rates were 70.9 and 30.1% prior to and 6 months after the procedure (p < 0.001). HR-HPV testing (positive or negative) and abnormal PAP cytology (evaluated at an ASCUS or worse threshold) showed a similar significant reduction in positivity rates (84.5 vs 42.2% and 72.7 vs 28.9%, respectively, p < 0.001). Results of all three assays showed high dependency at the time of follow-up (DST and PAP, PAP and HR-HPV test, DST and HR-HPV test-p values < 0.001). The highest proportion of positive DST results was seen in patients carrying HPV16 (84.6%), followed by any HR-HPV type (60%), those treated for CIN2 + (27.3%) and those with positive margins on the cone specimen (26.7%). CONCLUSION: A LLETZ procedure results in a significant decrease in abnormal DST, PAP cytology and HR-HPV test results in this diverse cohort of patients. The highest proportion of abnormal DST results was seen in patients carrying HR-HPV at the time of follow-up, especially HPV 16.

Intrauterine Fluid Instillation and Transtubal Flow: A Randomized Controlled In vitro Trial Comparing Gel and Water.

BACKGROUND: Possible transtubal spillage of malignant cells is a major concern in fluid instillation sonography, as it is in hysteroscopy. This study aims to compare the transtubal flow of gel and saline and validate the clinical hypothesis that application of fluids with higher viscosity causes less spillage. METHODS: Randomized controlled in vitro trial comparing gel and saline infusion on 15 tissue specimens after hysterectomy with bilateral salpingectomy. Instillations are performed with saline and gel dyed with a 1% ink solution. Qualitative assessment of tubal spill is investigated as primary outcome. Secondary outcomes are instillation-volume and -pressure, assessed by measuring endometrial cavity dilation at in vitro ultrasound examination and subjective numeric 10-point scoring of the instillation pressure by a dedicated examiner. RESULTS: Tubal flow was more often observed during saline instillation (odds ratio 4.88, P = 0.008). Median subjectively assessed instillation pressures were nine arbitrary units for gel and three for saline (P < 0.001). Tubal flow occurred from 2 cc onward in the saline group versus five cc in the gel instillation group. Cavitary dilation did not differ between both groups. CONCLUSION: Gel instillation sonography is in vitro associated with less tubal flow and therefore could be a safer diagnostic test compared to saline infusion sonography or hysteroscopy. In vivo studies are necessary to confirm these results.

Prior human papillomavirus-16/18 AS04-adjuvanted vaccination prevents recurrent high grade cervical intraepithelial neoplasia after definitive surgical therapy: Post-hoc analysis from a randomized controlled trial.

We evaluated the efficacy of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine in preventing HPV-related disease after surgery for cervical lesions in a post-hoc analysis of the PApilloma TRIal against Cancer In young Adults (PATRICIA; NCT00122681). Healthy women aged 15-25 years were randomized (1:1) to receive vaccine or control at months 0, 1 and 6 and followed for 4 years. Women were enrolled regardless of their baseline HPV DNA status, HPV-16/18 serostatus, or cytology, but excluded if they had previous or planned colposcopy. The primary and secondary endpoints of PATRICIA have been reported previously; the present post-hoc analysis evaluated efficacy in a subset of women who underwent an excisional procedure for cervical lesions after vaccination. The main outcome was the incidence of subsequent HPV-related cervical intraepithelial neoplasia grade 2 or greater (CIN2+) 60 days or more post-surgery. Other outcomes included the incidence of HPV-related CIN1+, and vulvar or vaginal intraepithelial neoplasia (VIN/VaIN) 60 days or more post-surgery. Of the total vaccinated cohort of 18,644 women (vaccine = 9,319; control = 9,325), 454 (vaccine = 190, control = 264) underwent an excisional procedure during the trial. Efficacy 60 days or more post-surgery for a first lesion, irrespective of HPV DNA results, was 88.2% (95% CI: 14.8, 99.7) against CIN2+ and 42.6% (-21.1, 74.1) against CIN1+. No VIN was reported and one woman in each group had VaIN2+ 60 days or more post-surgery. Women who undergo surgical therapy for cervical lesions after vaccination with the HPV-16/18 vaccine may continue to benefit from vaccination, with a reduced risk of developing subsequent CIN2+.

Efficacy of fewer than three doses of an HPV-16/18 AS04-adjuvanted vaccine: combined analysis of data from the Costa Rica Vaccine and PATRICIA Trials.

BACKGROUND: There is some evidence to suggest that one or two doses of the HPV vaccine provides similar protection to the three-dose regimen. The main aim of the study was to ascertain HPV-16/18 vaccine efficacy in both full and naive cohorts and to explore protection conferred against non-vaccine HPV types, by number of doses received. METHODS: Summary data from the Costa Rica Vaccine Trial (CVT; NCT00128661) and ~the PATRICIA trial (NCT001226810), two phase 3, double-blind, randomised controlled clinical trials of the HPV-16/18 AS04-adjuvanted vaccine in young women, were combined in a post-hoc analysis (GlaxoSmithKline [GSK] e-track number 202142) to investigate the efficacy of fewer than three doses of the HPV-16/18 vaccine after 4 years of follow-up. Women were randomly assigned to receive three doses of the HPV-16/18 vaccine or to a control vaccine; yet, some received fewer doses. After exclusion of women with less than 12 months of follow-up or those who were HPV-16/18 DNA-positive at enrolment (for the HPV-16/18 endpoint), we calculated vaccine efficacy against one-time detection of incident HPV infections after three, two, and one dose(s). The primary study endpoint was one-time detection of first incident HPV-16/18 infections accumulated during the follow-up phase. FINDINGS: We assessed vaccine efficacy against incident HPV-16/18 infection in the modified total vaccinated cohort (22 327 received three doses, 1185 two doses, 543 one dose). Vaccine efficacy against incident HPV-16/18 infections for three doses was 77·0% (95% CI 74·7-79·1), two doses was 76·0% (62·0-85·3), and one dose was 85·7% (70·7-93·7). Vaccine efficacy against incident HPV-31/33/45 infections for three doses was 59·7% (56·0-63·0), two doses was 37·7% (12·4-55·9), and one dose was 36·6% (-5·4 to 62·2). Vaccine efficacy against incident HPV-16/18 infection for two-dose women who received their second dose at 1 month was 75·3% (54·2-87·5) and 82·6% (42·3-96·1) for those who received the second dose at 6 months (CVT data only). Vaccine efficacy against HPV-31/33/45 for two-dose women who received their second dose at 6 months (68·1%, 27·0-87·0; CVT data only), but not those receiving it at one month (10·1%, -42·0 to 43·3), was similar to the three-dose group. INTERPRETATION: 4 years after vaccination of women aged 15-25 years, one and two doses of the HPV-16/18 vaccine seem to protect against cervical HPV-16/18 infections, similar to the protection provided by the three-dose schedule. Two doses separated by 6 months additionally provided some cross-protection. These data argue for a direct assessment of one-dose efficacy of the HPV-16/18 vaccine. FUNDING: US National Cancer Institute, National Institutes of Health Office of Research on Women's Health, and Ministry of Health of Costa Rica (CVT); GlaxoSmithKline Biologicals SA (PATRICIA).

Sexual functioning in women after surgical treatment for endometrial cancer: a prospective controlled study.

INTRODUCTION: Endometrial cancer (EC) can affect sexual functioning based on anatomical, physiological, psychological, and relational mechanisms. AIM: The aim of this study was to prospectively investigate sexual adjustment of women with EC during a follow-up period of 2 years after surgical treatment and to compare the results with women who underwent a hysterectomy for a benign gynecological condition and healthy control women. METHODS/MAIN OUTCOME MEASURES: In this prospective controlled study, participants completed the Short Sexual Functioning Scale, Specific Sexual Problems Questionnaire, Beck Depression Inventory Scale, World Health Organization-5 Well-being Scale, and Dyadic Adjustment Scale to assess various aspects of sexual and psychosocial functioning before undergoing a hysterectomy and 6 months, 1 year, and 2 years after surgery. RESULTS: Eighty-four women with EC, 84 women with a benign gynecological condition, and 84 healthy controls completed the survey. In EC survivors, no differences were found in sexual functioning during prospective analyses. In comparison with women with a benign gynecological condition, significantly more EC patients reported entry dyspareunia 1 year after surgical treatment. Moreover, compared with healthy women, pre- and postoperatively, significantly more EC patients reported sexual dysfunctions, including sexual desire dysfunction, arousal dysfunction, entry dyspareunia, and a reduced intensity of orgasm. Furthermore, compared with healthy controls, EC patients reported significantly lower overall well-being 1 year after surgical treatment. Nevertheless, consensus in the partner relationship was significantly higher in EC patients compared with healthy controls. Moreover, before treatment, quality of partner relationship was negatively associated with sexual arousal dysfunction and orgasm dysfunction. CONCLUSIONS: In EC patients, no differences were found in sexual functioning when prospectively comparing the situation before surgery with the situation after surgery. However, when compared with healthy controls, EC patients are at high risk for sexual dysfunctions, both before and after surgical treatment.

Risk of newly detected infections and cervical abnormalities in women seropositive for naturally acquired human papillomavirus type 16/18 antibodies: analysis of the control arm of PATRICIA.

BACKGROUND: We examined risk of newly detected human papillomavirus (HPV) infection and cervical abnormalities in relation to HPV type 16/18 antibody levels at enrollment in PATRICIA (Papilloma Trial Against Cancer in Young Adults; NCT00122681). METHODS: Using Poisson regression, we compared risk of newly detected infection and cervical abnormalities associated with HPV-16/18 between seronegative vs seropositive women (15-25 years) in the control arm (DNA negative at baseline for the corresponding HPV type [HPV-16: n = 8193; HPV-18: n = 8463]). RESULTS: High titers of naturally acquired HPV-16 antibodies and/or linear trend for increasing antibody levels were significantly associated with lower risk of incident and persistent infection, atypical squamous cells of undetermined significance or greater (ASCUS+), and cervical intraepithelial neoplasia grades 1/2 or greater (CIN1+, CIN2+). For HPV-18, although seropositivity was associated with lower risk of ASCUS+ and CIN1+, no association between naturally acquired antibodies and infection was demonstrated. Naturally acquired HPV-16 antibody levels of 371 (95% confidence interval [CI], 242-794), 204 (95% CI, 129-480), and 480 (95% CI, 250-5756) EU/mL were associated with 90% reduction of incident infection, 6-month persistent infection, and ASCUS+, respectively. CONCLUSIONS: Naturally acquired antibodies to HPV-16, and to a lesser extent HPV-18, are associated with some reduced risk of subsequent infection and cervical abnormalities associated with the same HPV type.

Risk of first cervical HPV infection and pre-cancerous lesions after onset of sexual activity: analysis of women in the control arm of the randomized, controlled PATRICIA trial.

BACKGROUND: More information is needed about time between sexual initiation and human papillomavirus (HPV) infection and development of cervical precancer. METHODS: The objectives were to investigate the time between first sexual activity and detection of first cervical HPV infection or development of first cervical intraepithelial neoplasia (CIN), and associated factors in women from the double-blind, multinational, 4-year PATRICIA trial. PATRICIA enroled women aged 15-25 years with no more than 6 lifetime sexual partners. Women were randomized 1:1 to the HPV-16/18 AS04-adjuvanted vaccine or to control, but only women from the control arm who began sexual intercourse during the study or within 6 months before enrolment, and had no HPV infection detected before the recorded date of their first sexual intercourse, were included in the present analysis. The time between onset of sexual activity and detection of the first cervical HPV infection or development of the first CIN lesion was analyzed using Kaplan-Meier and univariate and multivariable Cox proportional-hazards models. RESULTS: A total of 9337 women were enroled in the control arm of PATRICIA of whom 982 fulfilled the required inclusion criteria for analysis. A cumulative total of 28%, 44%, and 62% of the subjects had HPV infection within 12, 24, and 48 months, respectively. The overall incidence rate was 27.08 per 100 person-years. The most common oncogenic types associated with 6-month persistent infection were HPV-16 (incidence rate: 2.74 per 100 person-years), HPV-51 (2.70), HPV-52 (1.66), HPV-66 (1.14), and HPV-18 (1.09). Increased infection risk was associated with more lifetime sexual partners, being single, Chlamydia trachomatis history, and duration of hormone use. CIN1+ and CIN2+ lesions were most commonly associated with HPV-16, with an overall incidence rate of 1.87 and 1.07 per 100 person-years, respectively. Previous cervical HPV infection was most strongly associated with CIN development. CONCLUSIONS: More than 25% of women were infected with HPV within 1 year of beginning sexual activity. Without underestimating the value of vaccination at older ages, our findings emphasize its importance before sexual initiation. TRIAL REGISTRATION: clinicaltrials.gov: NCT00122681 .

Long-term sexual functioning in women after surgical treatment of cervical cancer stages IA to IB: a prospective controlled study.

OBJECTIVE: Women with cervical cancer (CC) may be faced with changes in sexual functioning resulting from the cancer itself and/or its surgical treatment. The aims of this study were to prospectively investigate sexual adjustment of CC patients during a follow-up period of 2 years after radical hysterectomy without adjuvant treatment and to compare the results with women who underwent a hysterectomy for a benign gynecological condition and with healthy control women. METHODS: In this prospective controlled study, participants completed the Short Sexual Functioning Scale, Specific Sexual Problems Questionnaire, Beck Depression Inventory Scale, World Health Organization-5 Well-Being Scale, and Dyadic Adjustment Scale to assess various aspects of sexual and psychosocial functioning at certain time intervals, namely, before surgery and 6 months, 1 year, and 2 years after surgical treatment. RESULTS: Thirty-one women with CC, 93 women with a benign gynecological condition, and 93 healthy controls completed the survey. In CC survivors, no differences were found in sexual functioning during prospective analyses and in comparison with women with a benign gynecological condition. However, compared with healthy women, preoperatively and postoperatively, significantly more CC patients reported sexual dysfunctions, including sexual arousal dysfunction, entry dyspareunia, deep dyspareunia, abdominal pain during intercourse, and reduced intensity of the orgasm. Furthermore, compared with healthy controls, CC patients reported worse psychological functioning before surgery and at 6 months after surgery. Finally, before surgery, quality of partner relationship was rated significantly better by CC patients compared with healthy controls; however, quality of the partner relationship declined during the first year of follow-up compared with the situation before surgery. CONCLUSIONS: In CC patients, no differences were found in sexual functioning when prospectively comparing the situation before and after surgery. However, when compared with healthy controls, CC patients are at high risk for sexual dysfunctions, both before and after surgical treatment.

2D versus 3D roadmap for uterine artery catheterization: impact on several angiographic parameters.

BACKGROUND: Three-dimensional (3D) roadmap is a recently developed imaging technique used to guide diagnostic and interventional catheter-directed procedures and mainly evaluated for neurovascular procedures. Few data with regard to efficacy and radiation dose are currently available in literature. PURPOSE: To evaluate the use of 3D roadmap technique as compared with the conventional two-dimensional (2D) roadmap for uterine artery catheterization and embolization during uterine fibroid embolization and assess the potential impact on radiation dose, contrast load, and total procedure time. MATERIAL AND METHODS: In this prospective study, 40 patients were randomly assigned to the 2D or 3D roadmap technique for uterine artery catheterization. Demographic data, specifically the patient's age, weight, height, pelvic circumference, and total uterine and fibroid volume were recorded. Exposure parameters, contrast load, and procedure time were recorded and organ doses for ovaries and uterus were calculated. RESULTS: Demographic data did not differ between the groups. Catheterization and embolization of both uterine arteries were feasible in all patients, although in one patient in the 3D group, a focal dissection of the proximal uterine artery occurred. No significant difference in estimated ovarian dose was found in the 3D versus 2D group (P = 0.07). Total procedure time was shorter in the 2D group (P = 0.01) and no difference in total contrast load was seen (P = 0.17). CONCLUSION: Both roadmap techniques are effective imaging-guided tools for uterine artery catheterization, without difference in terms of radiation exposure or contrast load. The total procedure time is shorter in the 2D group.

Efficacy of the HPV-16/18 AS04-adjuvanted vaccine against low-risk HPV types (PATRICIA randomized trial): an unexpected observation.

BACKGROUND: Public Health England has reported a decrease of up to 20.8% in new diagnoses of external genital warts (GWs) among women aged <19 years since the national vaccination program with the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine began in 2008. A post hoc analysis of the phase III PATRICIA (PApilloma TRIal against Cancer In young Adults) trial (NCT00122681) was performed to ascertain whether protection against low-risk HPV types was apparent. METHODS: Vaccine efficacy (VE) at 48 months was assessed against 6-month persistent infection (6MPI) with low-risk HPV types in the total vaccinated cohort (TVC) and in the TVC naive (for 25 HPV types tested) populations. RESULTS: In the TVC naive cohort, VE against 6MPI (95% confidence interval) was 34.5% (11.3 to 51.8) for HPV-6/11, 34.9% (9.1 to 53.7) for HPV-6, 30.3% (-45.0 to 67.5) for HPV-11, and 49.5% (21.0 to 68.3) for HPV-74. CONCLUSIONS: The HPV-16/18 AS04-adjuvanted vaccine appears to have moderate efficacy against persistent infections with a number of low-risk HPV types (HPV-6/11/74), which are responsible for the majority of external GWs, and recently, antibody and cell-mediated immune response to HPV-6/11 have been observed. These findings may help to explain the decrease in external GW diagnoses seen in England.

Cross-protective efficacy of HPV-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by non-vaccine oncogenic HPV types: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial.

BACKGROUND: We evaluated the efficacy of the human papillomavirus HPV-16/18 AS04-adjuvanted vaccine against non-vaccine oncogenic HPV types in the end-of-study analysis after 4 years of follow-up in PATRICIA (PApilloma TRIal against Cancer In young Adults). METHODS: Healthy women aged 15-25 years with no more than six lifetime sexual partners were included in PATRICIA irrespective of their baseline HPV DNA status, HPV-16 or HPV-18 serostatus, or cytology. Women were randomly assigned (1:1) to HPV-16/18 vaccine or a control hepatitis A vaccine, via an internet-based central randomisation system using a minimisation algorithm to account for age ranges and study sites. The study was double-blind. The primary endpoint of PATRICIA has been reported previously; the present analysis evaluates cross-protective vaccine efficacy against non-vaccine oncogenic HPV types in the end-of-study analysis. Analyses were done for three cohorts: the according-to-protocol cohort for efficacy (ATP-E; vaccine n=8067, control n=8047), total vaccinated HPV-naive cohort (TVC-naive; no evidence of infection with 14 oncogenic HPV types at baseline, approximating young adolescents before sexual debut; vaccine n=5824, control n=5820), and the total vaccinated cohort (TVC; all women who received at least one vaccine dose, approximating catch-up populations that include sexually active women; vaccine n=9319, control=9325). Vaccine efficacy was evaluated against 6-month persistent infection, cervical intraepithelial neoplasia grade 2 or greater (CIN2+) associated with 12 non-vaccine HPV types (individually or as composite endpoints), and CIN3+ associated with the composite of 12 non-vaccine HPV types. This study is registered with ClinicalTrials.gov, number NCT00122681. FINDINGS: Consistent vaccine efficacy against persistent infection and CIN2+ (with or without HPV-16/18 co-infection) was seen across cohorts for HPV-33, HPV-31, HPV-45, and HPV-51. In the most conservative analysis of vaccine efficacy against CIN2+, where all cases co-infected with HPV-16/18 were removed, vaccine efficacy was noted for HPV-33 in all cohorts, and for HPV-31 in the ATP-E and TVC-naive. Vaccine efficacy against CIN2+ associated with the composite of 12 non-vaccine HPV types (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68), with or without HPV-16/18 co-infection, was 46·8% (95% CI 30·7-59·4) in the ATP-E, 56·2% (37·2-69·9) in the TVC-naive, and 34·2% (20·4-45·8) in the TVC. Corresponding values for CIN3+ were 73·8% (48·3-87·9), 91·4% (65·0-99·0), and 47·5% (22·8-64·8). INTERPRETATION: Data from the end-of-study analysis of PATRICIA show cross-protective efficacy of the HPV-16/18 vaccine against four oncogenic non-vaccine HPV types-HPV-33, HPV-31, HPV-45, and HPV-51-in different trial cohorts representing diverse groups of women. FUNDING: GlaxoSmithKline Biologicals.

Overall efficacy of HPV-16/18 AS04-adjuvanted vaccine against grade 3 or greater cervical intraepithelial neoplasia: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial.

BACKGROUND: Cervical intraepithelial neoplasia grade 2 or greater (CIN2+) is the surrogate endpoint used in licensure trials of human papillomavirus (HPV) vaccines. Vaccine efficacy against CIN3+, the immediate precursor to invasive cervical cancer, is more difficult to measure because of its lower incidence, but provides the most stringent evidence of potential cancer prevention. We report vaccine efficacy against CIN3+ and adenocarcinoma in situ (AIS) in the end-of-study analysis of PATRICIA (PApilloma TRIal against Cancer In young Adults). METHODS: Healthy women aged 15-25 years with no more than six lifetime sexual partners were included in PATRICIA, irrespective of their baseline HPV DNA status, HPV-16 or HPV-18 serostatus, or cytology. Women were randomly assigned (1:1) to receive an HPV-16/18 AS04-adjuvanted vaccine or a control hepatitis A vaccine via an internet-based central randomisation system using a minimisation algorithm to account for age ranges and study sites. The patients and study investigators were masked to allocated vaccine. The primary endpoint of PATRICIA has been reported previously. In the present end-of-study analysis, we focus on CIN3+ and AIS in the populations of most clinical interest, the total vaccinated cohort (TVC) and the TVC-naive. The TVC comprised all women who received at least one vaccine dose, approximating catch-up populations and including sexually active women (vaccine n=9319; control=9325). The TVC-naive comprised women with no evidence of oncogenic HPV infection at baseline, approximating early adolescent HPV exposure (vaccine n=5824; control=5820). This study is registered with ClinicalTrials.gov, number NCT00122681. FINDINGS: Vaccine efficacy against CIN3+ associated with HPV-16/18 was 100% (95% CI 85·5-100) in the TVC-naive and 45·7% (22·9-62·2) in the TVC. Vaccine efficacy against all CIN3+ (irrespective of HPV type in the lesion and including lesions with no HPV DNA detected) was 93·2% (78·9-98·7) in the TVC-naive and 45·6% (28·8-58·7) in the TVC. In the TVC-naive, vaccine efficacy against all CIN3+ was higher than 90% in all age groups. In the TVC, vaccine efficacy against all CIN3+ and CIN3+ associated with HPV-16/18 was highest in the 15-17 year age group and progressively decreased in the 18-20 year and 21-25 year age groups. Vaccine efficacy against all AIS was 100% (31·0-100) and 76·9% (16·0-95·8) in the TVC-naive and TVC, respectively. Serious adverse events occurred in 835 (9·0%) and 829 (8·9%) women in the vaccine and control groups, respectively; only ten events (0·1%) and five events (0·1%), respectively, were considered to be related to vaccination. INTERPRETATION: PATRICIA end-of-study results show excellent vaccine efficacy against CIN3+ and AIS irrespective of HPV DNA in the lesion. Population-based vaccination that incorporates the HPV-16/18 vaccine and high coverage of early adolescents might have the potential to substantially reduce the incidence of cervical cancer. FUNDING: GlaxoSmithKline Biologicals.

Prevalence and risk factors for cervical HPV infection and abnormalities in young adult women at enrolment in the multinational PATRICIA trial.

OBJECTIVE: We evaluated baseline data from the PApilloma TRIal against Cancer In young Adults (PATRICIA; NCT00122681) on the association between behavioral risk factors and HPV infection and cervical abnormalities. METHODS: Women completed behavioral questionnaires at baseline. Prevalence of HPV infection and cervical abnormalities (detected by cytological or histological procedures) and association with behavioral risk factors were analyzed by univariate and stepwise multivariable logistic regressions. RESULTS: 16782 women completed questionnaires. Among 16748 women with data for HPV infection, 4059 (24.2%) were infected with any HPV type. Among 16757 women with data for cytological abnormalities, 1626 (9.7%) had a cytological abnormality, of whom 1170 (72.0%) were infected with at least one oncogenic HPV type including HPV-16 (22.7%) and HPV-18 (9.3%). Multivariable analysis (adjusted for age and region, N=14404) showed a significant association between infection with any HPV type and not living with a partner, smoking, age <15 years at first sexual intercourse, higher number of sexual partners during the past 12 months, longer duration of hormonal contraception and history of sexually transmitted infection (STI). For cervical abnormalities, only history of STI (excluding Chlamydia trachomatis) remained significant in the multivariable analysis after adjusting for HPV infection. CONCLUSIONS: Women reporting 3+ sexual partners in the past 12 months had the highest risk of HPV infection at baseline. HPV infection was the main risk factor for cervical abnormalities, and history of STIs excluding Chlamydia trachomatis increased risk to a lesser extent. Although behavioral factors can influence risk, all sexually active women are susceptible to HPV infection.

Sexual, psychological, and relational functioning in women after surgical treatment for vulvar malignancy: a literature review.

INTRODUCTION: Vulvectomy is an intrusive treatment option for women with vulvar malignancy that theoretically may affect sexual function. AIM: This study aims to provide a comprehensive review of the literature on the impact of surgical treatment for vulvar malignancy on sexual functioning, overall quality of life, and partner relationship. METHODS: Systematic search of the medical literature on PubMed, PsycINFO, Cochrane database, Google Scholar and Embase using a number of related terms including vulvar malignancy, vulvar cancer, vulva cancer, vulval cancer, vulvectomy, sexual function, partner relation, quality of life, and psychological functioning. MAIN OUTCOME MEASURE: Measures and indicators of sexual function, overall quality of life, and partner relationship following vulvectomy for vulvar malignancy. RESULTS: There is evidence that women who undergo surgical treatment for vulvar cancer or vulvar intraepithelial neoplasia are at high risk for sexual dysfunctions, dissatisfaction with partner relationship, and psychological difficulties. Factors associated with posttreatment sexual dysfunction include patient's increased age, poor overall well-being, history of depression, anxiety, and excision size of vulvar malignancy. CONCLUSIONS: Surgical treatment of vulvar cancer has a negative impact on sexual function, quality of life, and satisfaction with partner relationship. However, hitherto only little research effort has been directed to postoperative sexual well-being in vulvar cancer survivors. There is a need for more methodological sound prospective studies that explore sexual function, quality of life, and partner relationship and its predictors over time in vulvar cancer patients.

Sexual functioning in women using levonorgestrel-releasing intrauterine systems as compared to copper intrauterine devices.

INTRODUCTION: There has been little research published on the impact of intrauterine contraceptive (IUC) methods on sexual functioning. AIMS: This study aimed: (i) to assess different aspects of sexual functioning, including the prevalence of sexual dysfunction in women using a levonorgestrel intrauterine system (LNG-IUS); (ii) to compare this prevalence with that among copper-releasing intrauterine device (Cu-IUD) users; and (iii) to identify the relationship between psychological variables and sexual functioning in women using one of the aforementioned IUCs. METHODS: In a multicenter cross-sectional study, 845 women with an IUC were invited to fill out a questionnaire. The latter was returned by 402 (48%) of them: 353 women were LNG-IUS users (88%) and 49 were Cu-IUD users (12%). The questions asked pertained to depression, well-being, marital relation quality, and sexual functioning. MAIN OUTCOME MEASURES: Sexual functioning was measured with the short sexual functioning scale. RESULTS: One-third of LNG-IUS users (33%) reported a sexual dysfunction. Of those, 20% reported an increased sexual desire, 25% a decreased sexual desire, 5% arousal problems, and 8% orgasm problems. Women using a LNG-IUS did not differ significantly in distribution, type, or prevalence (32.9% vs. 36.7%) of sexual dysfunction, nor in depressive symptoms (Beck Depression Inventory score; 4.7 vs. 3.9; P = 0.33), general well-being (WHO-5 well-being scale score; 16.8 vs. 17.7; P = 0.170), or partner relationship quality (Dyadic Adjustment Scale score; 107 vs. 108; P = 0.74) compared to Cu-IUD users. Overall, the perceived influence of IUCs on sexual functioning was in the lower range and did not differentiate LNG-IUS greatly from Cu-IUD-users. CONCLUSION: Women using a LNG-IUS do not differ from those wearing a Cu-IUD with regard to psychological and sexual functioning. The perceived impact of IUD use on sexuality should not be overestimated.

Type-specific HPV geno-typing improves detection of recurrent high-grade cervical neoplasia after conisation.

The aim of this case-control study was to examine if type-specific human papillomavirus (HPV) DNA geno-typing before and after treatment of high-grade cervical intra-epithelial neoplasia (CIN) improves prediction of recurring or persisting CIN 2 or 3 compared with follow-up cytology or high-risk (hr)HPV testing. Women with biopsy-proven recurrence of CIN 2 or 3 (cases) in a follow-up period of at least 24 months after treatment of high-grade CIN were compared with women without recurrence (controls). These cohorts were identified by a database search of the Riatol Laboratoria (Antwerp, Belgium). In a cohort of 823 women treated with conisation for high-grade CIN between January 2001 and December 2007, 21 patients with a histologically proven recurrence of CIN2+ were identified. A group of women (n=42) from the same cohort without recurrence was randomly chosen. We found that hrHPV testing at 6 months post-treatment is significantly more sensitive compared with follow-up cytology (ratio: 1.31, 95% confidence interval (CI): 1.10-1.54), but less specific (ratio: 0.85, 95% CI: 0.81-0.90) to predict failure of treatment. When compared with hrHPV testing, HPV geno-typing is more efficient (equal sensitivity, but higher specificity, ratio: 1.43, 95% CI: 1.280-1.62). When compared with follow-up cytology, HPV geno-typing is more sensitive (ratio: 1.31, 95% CI: 1.10-1.54) and more specific (ratio: 1.22, 95% CI: 1.14-1.36). All women who developed a recurrence tested positive for hrHPV. The negative predictive value in the absence of hrHPV DNA was 100%. Six months after treatment HPV geno-typing is the most sensitive and specific method to predict recurrent or persistent CIN 2-3 in the next 24 months.

Intravascular Leiomyomatosis as a Rare Cause of Nonthrombotic Pulmonary Embolism.

Intravascular leiomyomatosis (IVL) is a very rare condition. It is characterized by the proliferation of benign smooth muscle cells within vascular structures without invasion of these tissues. Symptoms depend on the site of origin and the extent of invasion. Rarely, this neoplasm is located in the inferior vena cava or in the pulmonary vasculature potentially causing symptoms of dyspnea, chest pain, or syncope. We report the case of a 53-year-old woman who was referred to our hospital with extensive pulmonary embolism comprising of a subtotal occlusion of the right pulmonary artery with extension into the left pulmonary artery. Due to persistent dyspnea (New York Heart Association class II) despite anticoagulation, after a six-week period, imaging was repeated and showed stable findings. As she was not responding to adequate anticoagulant therapy, intima sarcoma of the pulmonary artery was suspected, and a pulmonary endarterectomy (PEA) was performed. A smooth, white, intravascular mass was easily and completely removed. Analysis demonstrated a lesion consisting of cells without atypia, showing expression of alpha-smooth muscle actin (alpha SMA) and desmin with partial expression of estrogen receptor (ER) and progesterone receptor (PR), leading to the diagnosis of intravascular leiomyomatosis. The patient fully recovered. Complete surgical removal of the intravascular tumor is recommended to relieve symptoms and prevent possible complications. Clinicians have to be aware that in unresolved pulmonary embolism, nonthrombotic and rare causes, like an intima sarcoma or intravascular leiomyomatosis, should be considered.

Incidence of vaginal intraepithelial neoplasia after hysterectomy for cervical intraepithelial neoplasia: a retrospective study.

OBJECTIVE: Hysterectomy with concomitant cervical intraepithelial neoplasia (CIN), is often considered a definitive treatment for CIN, but development of subsequent vaginal intraepithelial neoplasia (VAIN) is known to range from 0.9% to 6.8%. STUDY DESIGN: In a retrospective analysis of 3030 women with CIN2+ without history of VAIN in the University Hospital Gasthuisberg, Leuven, Belgium, from January 1989 until December 2003, we identified 125 women who underwent a hysterectomy within 6 months after diagnosis of CIN2+ and reviewed their postoperative Papanicolaou smears. RESULTS: Thirty-one patients (24.8%) were lost to follow-up. Seven of the 94 women in the follow-up group (7.4%) developed VAIN2+, of which 2 were invasive vaginal cancers. Median interval between hysterectomy and diagnosis of VAIN2+ was 35 months (5-103 months). Women with recurrence were significantly older (P = .003). CONCLUSION: Hysterectomy may not be considered as a definitive therapy for CIN2+ because the incidence rate of subsequent VAIN2+ is as high as 7.4%.