RESUMEN
AIMS: To assess colposcopic performance and determine indicators for competency within the new Australian primary human papillomavirus (HPV) cervical screening program. MATERIALS AND METHODS: A retrospective observational study of 4542 women seen at The Royal Women's Hospital Colposcopy Clinic in Melbourne, from 1 December 2017 to 31 July 2020 after a higher-risk cervical screening test (CST) result. RESULTS: Histological CIN2+ was detected in 25.1% up to two years from first colposcopy visit (FCV). The majority (86.7%) of CIN2+ was detected early within the first six months of presentation. Biopsy rate overall was 96.1% with abnormal colposcopic impression. Of four colposcopists with a lower biopsy rate, only one was able to achieve this early detection rate. Biopsy was also taken in over 30% of cases with negative reflex cytology and normal colposcopy, with CIN2+ detected in 5.0% among positive HPV16/18 and 3.8% with non-16/18 HPV. Positive predictive value of high-grade colposcopic impression at FCV averaged 66.4% (range: 54.9-81.6% among our colposcopists) and is poorly correlated with early detection rate of CIN2+. Overall accuracy of colposcopy is 84.5% (range: 78.7-90.3%), buoyed by high true negative colposcopic predictions secondary to high rates of negative reflex cytology referral with the new screening algorithm and is also unlikely to be a useful colposcopy indicator. CONCLUSIONS: Early detection rate of CIN2+ within the first six months of presentation is a useful measure of colposcopy competency and we would encourage our National Cancer Screening Register to explore this with the participating colposcopists.
Asunto(s)
Competencia Clínica , Colposcopía , Detección Precoz del Cáncer , Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Humanos , Femenino , Estudios Retrospectivos , Adulto , Infecciones por Papillomavirus/diagnóstico , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/patología , Australia , Detección Precoz del Cáncer/métodos , Persona de Mediana Edad , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/virología , Displasia del Cuello del Útero/patología , Biopsia , Tamizaje Masivo , Valor Predictivo de las PruebasRESUMEN
BACKGROUND AND OBJECTIVES: The impact of immunomodulatory therapies on the risk of cervical pre-cancer and invasive cancer development is important for the health and safety of women with multiple sclerosis (wwMS). We investigate the risk of cervical abnormalities in wwMS treated with disease-modifying therapies (DMTs). METHODS: This is a multicenter cohort study with data collected from 1998 to 2019 in Victoria, Australia. Data linkage was performed using matching records from the MSBase Registry, the National Human Papillomavirus (HPV) Vaccination Program Register, and the Victorian Cervical Cytology Register. The primary outcome was the detection of any type of cervical abnormality as determined by cytology or histology. Survival methods were used to assess the time to cervical abnormality detection on cervical screening tests (CSTs). Crude and adjusted Cox proportional hazards models were used to determine time to and magnitude of association of DMTs with the risk of cervical abnormality. In a sensitivity analysis, we constructed standardized survival curves averaged over the same set of covariates to determine the commensurate population-average (marginal) causal effects. RESULTS: We included 248 wwMS. The incidence of abnormal CSTs was lower (p < 0.001) for women not exposed to moderate-high-efficacy therapy (10.2 per 1,000 patient-years [95% confidence interval (CI) 5.5-14.9]), compared with those exposed (36.6 per 1,000 patient-years [95% CI 21.7-51.6]). Exposure to higher efficacy treatment was associated with a 3.79-fold increased hazard (95% CI 2.02-7.08, p < 0.001) of developing a cervical abnormality relative to those not exposed. When adjusted for vaccination status, smoking, hormonal contraceptive use, and socioeconomic status, the risk remained elevated at 3.79 (95% CI 1.99-7.21, p < 0.001). Marginal hazard ratios declined over time, ranging from 3.90 (95% CI 2.09-7.27) at 20 years of age to 2.06 (95% CI 1.14-3.73) at 70 years of age. DISCUSSION: A greater than three-and-a-half-fold increased risk of cervical abnormalities was found after exposure to moderate-high-efficacy DMTs. This risk persisted despite adjusting for HPV vaccination status, hormonal contraception use, smoking, and socioeconomic status. If confirmed in future studies, we would advocate for wwMS exposed to moderate-high-efficacy DMTs to be treated in line with immune-deficient paradigm in cervical screening and HPV vaccination programs. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that highly active MS therapy compared with less active therapy increases the risk of developing cervical abnormalities among women with MS.
Asunto(s)
Esclerosis Múltiple , Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Femenino , Humanos , Preescolar , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/patología , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/patología , Estudios de Cohortes , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/prevención & control , Detección Precoz del Cáncer/métodos , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/epidemiología , Esclerosis Múltiple/complicaciones , Victoria/epidemiologíaRESUMEN
AIMS: To examine outcomes in women aged 50-74 years after detection of oncogenic human papillomavirus (HPV) at cervical screening. MATERIALS AND METHODS: A retrospective observational study of 464 women seen in the Royal Women's Hospital Colposcopy Clinic from 1 January 2018 to 31 July 2020, 292 (62.9%) were positive for HPV16/18 and 172 (37.1%) for HPV (not 16/18). RESULTS: Fifty-four women (11.6%) had histologically proven CIN2+ including seven cancers, up to two years after first colposcopy visit (FCV): 48 (88.9%) detected at FCV or at excisional treatment (Excision) arranged after no CIN2+ detected at FCV. There was no significant difference (P = 0.14) in proportion of CIN2+ detected between the two groups, 'HPV16/18' (9.9%) or 'HPV (not 16/18)' (14.5%), nor with reflex cytology types. The positive predictive value (PPV) of high-grade impression at colposcopy was 63.6%. There were 243 (52.4%) who had Type 3 transformation zone (TZ3) with 20 CIN2+ detected, 13 at FCV including all three cancers and five at Excision. There were 214 (73.3%) with positive HPV16/18 who had reflex negative cytology, of which seven had CIN2+ including one cancer but only two (1.4%) CIN2+ when their repeat cytology at colposcopy was negative. CONCLUSIONS: Most CIN2+ were detected at first colposcopy or at subsequent excision. We would encourage high biopsy rates at colposcopy and vigilance in selection for excisional treatment in TZ3 cases if there is no significant suspicion of high-grade abnormality. There is a need to refine the algorithm for management of persistent HPV16/18 infections with reflex negative cytology to reduce colposcopy referrals in women aged 50 and above.
Asunto(s)
Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Femenino , Humanos , Embarazo , Displasia del Cuello del Útero/diagnóstico , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/cirugía , Neoplasias del Cuello Uterino/patología , Virus del Papiloma Humano , Colposcopía , Sensibilidad y Especificidad , Infecciones por Papillomavirus/diagnóstico , Detección Precoz del Cáncer , Papillomavirus Humano 16 , PapillomaviridaeRESUMEN
Australia's cervical screening program transitioned from cytology to HPV-testing with genotyping for HPV16/18 in Dec'2017. We investigated whether program data could be used to monitor HPV vaccination program impact (commenced in 2007) on HPV16/18 prevalence and compared estimates with pre-vaccination benchmark prevalence. Pre-vaccination samples (2005-2008) (n = 1933; WHINURS), from 25 to 64-year-old women had been previously analysed with Linear Array (LA). Post-vaccination samples (2013-2014) (n = 2989; Compass pilot), from 25 to 64-year-old women, were analysed by cobas 4800 (cobas), and by LA for historical comparability. Age standardised pre-vaccination HPV16/18 prevalence was 4.85% (95%CI:3.81-5.89) by LA; post-vaccination estimates were 1.67% (95%CI:1.21-2.13%) by LA, 1.49% (95%CI:1.05-1.93%) by cobas, and 1.63% (95%CI:1.17-2.08%) for cobas and LA testing of non-16/18 cobas positives (cobas/LA). Age-standardised pre-vaccination oncogenic HPV prevalence was 15.70% (95%CI:13.79-17.60%) by LA; post-vaccination estimates were 9.06% (95%CI:8.02-10.09%) by LA, 8.47% (95%CI:7.47-9.47%) by cobas and cobas/LA. Standardised rate ratios between post-vs. pre-vaccination rates were significantly different for HPV16/18, non-16/18 HPV and oncogenic HPV: 0.34 (95%CI:0.23-0.50), 0.68 (95%CI:0.55-0.84) and 0.58 (95%CI:0.48-0.69), respectively. Additional strategies (LA for all cobas positives; combined cobas and LA results on all samples) had similar results. If a single method is applied consistently, it will provide important data on relative changes in HPV prevalence following vaccination.
Asunto(s)
Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Femenino , Humanos , Adulto , Persona de Mediana Edad , Displasia del Cuello del Útero/diagnóstico , Neoplasias del Cuello Uterino/diagnóstico , Papillomavirus Humano 16 , Infecciones por Papillomavirus/diagnóstico , Detección Precoz del Cáncer/métodos , Papillomavirus Humano 18/genética , Vigilancia de la PoblaciónRESUMEN
OBJECTIVE: To review the first two years of the primary human papillomavirus (HPV) cervical screening programme in an HPV vaccinated population. DESIGN: Observational study. SETTING: Australia. PARTICIPANTS: 3 745 318 women with a primary HPV test between 1 December 2017 and 31 December 2019; most women aged <40 years had previously been offered vaccination against HPV16 and HPV18. INTERVENTIONS: Primary HPV screening with referral if HPV16 or HPV18 (HPV16/18) positive and triage with liquid based cytology testing (threshold atypical squamous cells-cannot exclude high grade squamous intraepithelial lesion) for women who were positive for high risk HPV types other than 16/18. A 12 month follow-up HPV test was recommended in triaged women with a negative or low grade cytology result, with referral if they tested positive for any high risk HPV type at follow-up. MAIN OUTCOME MEASURES: Proportion of women who had attended for their first HPV screening test, tested positive, and were referred for colposcopy; and short term risk of detecting cervical intraepithelial neoplasia (CIN) grade 2 or worse, CIN grade 3 or worse, or cancer. RESULTS: 54.6% (n=3 507 281) of an estimated 6 428 677 eligible women aged 25-69 had undergone their first HPV test by the end of 2019. Among those attending for routine screening, positivity for HPV16/18 and for HPV types not 16/18 was, respectively, 2.0% and 6.6% in women aged 25-69 (n=3 045 844) and 2.2% and 13.3% in highly vaccinated cohorts of women aged 25-34 (n=768 362). Colposcopy referral (ages 25-69 years) was 3.5%, increasing to an estimated 6.2% after accounting for women who had not yet had a 12 month repeat test. Cervical cancer was detected in 0.98% (456/46 330) of women positive for HPV16/18 at baseline, including 0.32% (89/28 003) of women with HPV16/18 and negative cytology. Women with HPV types not 16/18 and negative or low grade cytology at both baseline and 12 months were at low risk of serious disease (3.4% CIN grade 3 or worse; 0.02% cancer; n=20 019) but estimated to account for 62.0% of referrals for this screening algorithm. CONCLUSIONS: Colposcopy referral thresholds need to consider underlying cancer risk; on this basis, women with HPV16/18 in the first round of HPV screening were found to be at higher risk regardless of cytology result, even in a previously well screened population. Women with HPV types not 16/18 and negative or low grade cytology showed a low risk of serious abnormalities but constitute most referrals and could be managed safely with two rounds of repeat HPV testing rather than one. HPV16/18 driven referrals were low in HPV vaccinated cohorts.
Asunto(s)
Alphapapillomavirus , Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Adulto , Anciano , Detección Precoz del Cáncer , Femenino , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Humanos , Persona de Mediana Edad , Papillomaviridae , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/prevención & control , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/prevención & controlRESUMEN
OBJECTIVES: Previously, based on 6 months of follow-up, we showed that HPV self-sampling improved participation in cervical screening compared to a reminder letter for Pap testing for never- and under-screened women. Here, we report follow-up and related screening outcomes for women who participated in the initial self-sampling over two screening rounds. SETTING: The randomised controlled trial was conducted in Australia. METHODS: Never- and under-screened women were randomly allocated to the HPV self-sampling or the reminder for Pap test arm and followed at 6 and 36 months since the kits were first mailed. RESULTS: The first round of HPV self-sampling kits were mailed from May-July 2014 to 12 572 women. After 36 months, 19% of never-screened and 9% of under-screened women returned a kit for HPV testing; 2.7% were HPV 16/18 and 5.8% non-16/18 HPV positive. Compliance with first round follow-up was 84% (95% CI: 77.1-89.5%). Non-compliant and cytology triage negative women were mailed another kit at 12 months. Compliance at 12-month follow-up was 59.3% (49.4 to 68.6%). Of 37 women with a 12-month repeat HPV, 70% were positive. Of women who tested negative for HPV in the first round (n = 1573), 25% attended regular screening in the next round and none had CIN2 + detected. The overall prevalence of CIN2 + was 8.5 per 1000 screened (4.8 to 13.9 per 1000). CONCLUSION: While self-sampling can successfully engage women, compliance with repeat testing may require monitoring. The clinician-supported self-collection pathway now in use in Australia will likely improve women's engagement with follow-up.
Asunto(s)
Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Australia/epidemiología , Detección Precoz del Cáncer , Femenino , Estudios de Seguimiento , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Humanos , Tamizaje Masivo , Papillomaviridae , Infecciones por Papillomavirus/epidemiología , Autocuidado , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/prevención & control , Frotis VaginalRESUMEN
BACKGROUND: A number of retrospective and prospective studies have documented substantial rates of regression in cervical intraepithelial neoplasia grade 2 lesions in young women. Initial observational management of cervical intraepithelial neoplasia grade 2 is increasingly accepted as appropriate for women under 25 years of age with screen-detected abnormalities and is included in a number of clinical guidelines. However, there has been a paucity of large prospective studies on observational management with strict inclusion criteria. A number of important questions remain, specifically regarding the clinical variables that are associated with the risk of progression or persistence of disease. To investigate these factors and to ensure that young women with cervical intraepithelial neoplasia grade 2 undergoing observational management were being managed in a well-monitored and an appropriately informed fashion, we conducted a large, multicenter prospective study on observational management of cervical intraepithelial neoplasia grade 2 in women under 25 years. OBJECTIVE: This study aimed to determine the regression rates and clinical, cytologic, and pathologic predictors of regression of cervical intraepithelial neoplasia grade 2 in women under 25 years undergoing observational management over 24 months. STUDY DESIGN: This study was a multicenter prospective study on observational management of cervical intraepithelial neoplasia grade 2 (ie, repeat colposcopy, cytology, and cervical biopsy every 6 months) for up to 24 months. A total of 615 consenting women under 25 years with newly-diagnosed, biopsy-proven cervical intraepithelial neoplasia grade 2 were recruited (from 2010 to 2016) through 16 hospital-based colposcopy units in New Zealand and Australia. RESULTS: At completion, 326 women had confirmed regression, 156 had persistent high-grade cervical intraepithelial neoplasia grade 2 or 3 or adenocarcinoma in situ, and 24 had unconfirmed regression (ie, first regression at the 24-month follow-up). A total of 109 women did not complete the protocol (41 because of delayed follow-up, 41 lost to follow-up, 22 elected treatment, 4 refused a biopsy, and 1 died of an unrelated cause). Confirmed regression was observed in 53% (326 of 615) of all women enrolled in the study and, when missing data were imputed, it was estimated that 64% of women (95% confidence interval, 60%-68%) would have experienced regression. Similarly, lesions regressed in 64% (326 of 506) of women who completed the observational protocol. Based on a multivariable analysis, detection of human papillomavirus 16 in a liquid-based cytology sample at the time of initial colposcopy decreased the chance of regression by 31% (risk ratio, 0.69; 95% confidence interval, 0.56-0.86; P<.001). In addition, at initial colposcopy, low-grade or normal colposcopic impression, later year of diagnosis, low-grade or normal cytology, and being a nonsmoker were all independently associated with an increased chance of regression. CONCLUSION: More than half of women under 25 years with cervical intraepithelial neoplasia grade 2 will regress to cervical intraepithelial neoplasia grade 1 or normal within 24 months without destructive treatment. The absence of human papillomavirus 16 is the most important predictor of regression.
Asunto(s)
Regresión Neoplásica Espontánea/patología , Displasia del Cuello del Útero/patología , Neoplasias del Cuello Uterino/patología , Adolescente , Australia , Femenino , Humanos , Clasificación del Tumor , Nueva Zelanda , Infecciones por Papillomavirus/patología , Adulto JovenRESUMEN
While the benefits of human papillomavirus (HPV) vaccination relating to cervical cancer prevention have been widely documented, recent published evidence is suggestive of an impact on adverse pregnancy outcomes (APOs) in vaccinated mothers and their infants, including a reduction in rates of preterm births and small for gestational age infants. In this review, we examine this evidence and the possible mechanisms by which HPV vaccination may prevent these APOs. Large-scale studies linking HPV vaccination status with birth registries are needed to confirm these results. Potential confounding factors to consider in future analyses include other risk factors for APOs, and historical changes in both the management of cervical precancerous lesions and prevention of APOs. If confirmed, these additional benefits of HPV vaccination in reducing APO rates will be of global significance, due to the substantial health, social and economic costs associated with APOs, strengthening the case for worldwide HPV immunization.
Asunto(s)
Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Neoplasias del Cuello Uterino , Femenino , Humanos , Inmunización , Recién Nacido , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/prevención & control , Embarazo , Resultado del Embarazo , Neoplasias del Cuello Uterino/prevención & control , VacunaciónRESUMEN
AIM: To examine outcomes in women following cervical screening detection of oncogenic human papillomavirus (HPV), with reflex cytology showing possible high-grade squamous intraepithelial lesion (pHSIL). MATERIALS AND METHODS: A retrospective observational study of 523 women seen in the Royal Women's Hospital Colposcopy Clinic from 1 January 2018 to 31 July 2020. RESULTS: Two hundred eighty-two (53.9%) women had histology-confirmed HSIL, encompassing CIN2 or worse (CIN2+), including seven cancers (1.3%) and two adenocarcinoma in situ (AIS) (0.4%). In 81.2% (229/282) of women with CIN2+, this was detected on cervical biopsy at initial colposcopy, with another 8.9% (25/282) of CIN2+ detected at cervical excision following initial colposcopy and the remaining 9.9% (28/282) at follow-up colposcopy thereafter. When discordant cervical biopsy results were discussed at multidisciplinary meeting (MDM), 66.7% of women with pHSIL cytology upgraded to definite HSIL were found to have CIN2+, but only 20.8% when pHSIL cytology was retained and none when downgraded to low-grade (LSIL) or normal. No significant difference was found in the proportion of CIN2+ based on patient age above or below 40, HPV16 and/or 18 versus non 16/18, or whether discordant findings were reviewed at MDM. CONCLUSIONS: We propose a pathway for management of women with positive oncogenic HPV and reflex pHSIL cytology. MDM review is recommended when CIN2+ is not identified on cervical biopsy at initial colposcopy. Conservative management is safe with low risk of CIN2+ when LBC prediction of pHSIL is confirmed or downgraded at MDM with no high-grade change on colposcopy or repeat cytology.
Asunto(s)
Alphapapillomavirus , Infecciones por Papillomavirus , Lesiones Intraepiteliales Escamosas , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Detección Precoz del Cáncer , Femenino , Humanos , Papillomaviridae , Infecciones por Papillomavirus/complicaciones , ReflejoRESUMEN
OBJECTIVE: To measure menopausal symptoms and quality of life up to 12 months after risk-reducing salpingo-oophorectomy (RRSO) and to measure the effects of hormone therapy. METHODS: Prospective observational study of 95 premenopausal women planning RRSO and a comparison group of 99 who retained their ovaries. Vasomotor symptoms and menopausal-related quality of life (QoL) were measured by the Menopause-Specific QoL Intervention scale at baseline, 3, 6 and 12 months. Chi-square tests measured differences in prevalence of vasomotor symptoms between RRSO vs the comparison group and by hormone therapy use. Change in QoL were examined with multilevel modelling. RESULTS: Three months after RRSO hot flush prevalence increased from 5.3% to 56.2% and night sweats from 20.2% to 47.2%. Symptoms did not worsen between 3 and 12 months and remained unchanged in the comparison group (p<0.001). After RRSO, 60% commenced hormone therapy. However, 40% of hormone therapy uses continued to experience vasomotor symptoms. After RRSO, 80% of non-hormone therapy users reported vasomotor symptoms. Regardless of hormone therapy use, 86% categorized their vasomotor symptoms as "mild" after RRSO. Following RRSO, Menopause-related QoL deteriorated but was stable in the comparison group (adjusted coefficient = 0.75, 95%CI = 0.55-0.95). After RRSO, QoL was better in hormone therapy users vs non-users (adjusted coefficient = 0.49, 95%CI = 0.20-0.78). CONCLUSIONS: Vasomotor symptoms increase by 3 months after RRSO but do not worsen over the next 12 months. Hormone Therapy reduces but does not resolve vasomotor symptoms and may improve QoL, but not to pre-oophorectomy levels.
Asunto(s)
Menopausia/psicología , Calidad de Vida , Salpingooforectomía , Femenino , Humanos , Estudios Prospectivos , Conducta de Reducción del RiesgoRESUMEN
OBJECTIVE: Sleep difficulties impair function and increase the risk of depression at menopause and premenopausal oophorectomy may further worsen sleep. However, prospective data are limited, and it remains uncertain whether Hormone Therapy (HT) improves sleep. This prospective observational study measured sleep quality before and up to 12â¯months after risk-reducing salpingo-oophorectomy (RRSO) compared to a similar age comparison group who retained their ovaries. METHODS: Ninety-five premenopausal women undergoing RRSO and 99 comparisons were evaluated over a 12-month period using the Pittsburgh Sleep Quality Index (PSQI). RESULTS: Almost half reported poor sleep quality at baseline. Overall sleep quality was not affected by RRSO until 12â¯months (pâ¯=â¯0.007). However, sleep disturbance increased by 3â¯months and remained significantly elevated at 12â¯months (pâ¯<â¯0.001). Trajectory analysis demonstrated that 41% had increased sleep disturbance after RRSO which persisted in 17.9%. Risk factors for sleep disturbance included severe vasomotor symptoms, obesity and smoking. Around 60% initiated HT after RRSO. Sleep quality was significantly better in HT users vs non users (pâ¯=â¯0.020) but HT did not restore sleep quality to baseline levels. CONCLUSIONS: Overall sleep quality is not affected by RRSO, but new onset sleep disturbance is common, particularly in those with severe vasomotor symptoms. Clinicians should be alert to new-onset sleep disturbance and the potential for HT to improve sleep quality.
Asunto(s)
Neoplasias Ováricas/prevención & control , Complicaciones Posoperatorias/epidemiología , Procedimientos Quirúrgicos Profilácticos/efectos adversos , Salpingooforectomía/efectos adversos , Trastornos del Sueño-Vigilia/epidemiología , Adolescente , Adulto , Estudios de Casos y Controles , Comorbilidad , Femenino , Predisposición Genética a la Enfermedad , Humanos , Menopausia/fisiología , Persona de Mediana Edad , Obesidad/epidemiología , Neoplasias Ováricas/genética , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/fisiopatología , Premenopausia/fisiología , Estudios Prospectivos , Calidad de Vida , Factores de Riesgo , Conducta de Reducción del Riesgo , Sueño/fisiología , Trastornos del Sueño-Vigilia/diagnóstico , Trastornos del Sueño-Vigilia/etiología , Trastornos del Sueño-Vigilia/fisiopatología , Fumar/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Primary human papillomavirus (HPV) screening was introduced in Australia in December 2017. AIMS: Outcomes for women after positive HPV in their cervical screening test (CST). MATERIALS AND METHODS: A retrospective observational study of 4458 women seen at the Royal Women's Hospital Colposcopy Clinic from 1 January 2018 to 31 July 2020. RESULTS: HPV16/18 was positive (considered higher-risk CST) in 42.2% of women in the study, 16.6% with reflex possible with high-grade squamous intraepithelial lesions (pHSIL) or worse and 54.9% with normal cytology. There were 24.8% of women with positive HPV16/18 who had histological confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+), 10.3% CIN2+ (including six cancers) among women with reflex negative cytology and 87.7% CIN2+ among women with reflex HSIL cytology. In women with positive HPV (not 16/18), CIN2+ was found in 60.2% with reflex pHSIL or worse cytology (higher risk) and 10.2% with reflex low-grade SIL (LSIL) or normal cytology (intermediate risk). Median waiting time to colposcopy with the intermediate-risk group went up to 181 days. Our colposcopists were able to achieve a positive predictive value (PPV) for CIN2+ of 69.9%, higher than 57.8% PPV in the National Cervical Screening Program (NCSP) 2020 monitoring report. Women with type 3 transformation zone on colposcopy could be followed up with CST if no HSIL was suspected on screening or at colposcopy as their risk of CIN2+ was only 2.5%. CONCLUSIONS: Our findings support direct referral to colposcopy for women with higher-risk CST, with all cancers confined to this group. The NCSP recommendation to refer for colposcopy only after three intermediate-risk CST will need monitoring with the LSIL triage group.
Asunto(s)
Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Auditoría Clínica , Colposcopía , Detección Precoz del Cáncer , Femenino , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Humanos , Papillomaviridae , Infecciones por Papillomavirus/diagnóstico , Embarazo , Centros de Atención Terciaria , Neoplasias del Cuello Uterino/diagnóstico , Frotis Vaginal , Displasia del Cuello del Útero/diagnósticoRESUMEN
OBJECTIVE: Risk-reducing bilateral salpingo-oophorectomy (RRBSO) substantially reduces ovarian cancer risk in women with pathogenic gene variants and is generally recommended by age 34-45 years. Natural menopause is a vulnerable period for mood disturbance, but the risk of depression and anxiety in the first 12 months after RRBSO and potential modifying effect of hormone therapy are uncertain. METHODS: Prospective controlled observational study of 95 premenopausal women planning RRBSO and a Comparison group of 99 premenopausal women who retained their ovaries,- 95% of whom were at population level risk of ovarian cancer. Clinically significant symptoms of depression and anxiety were measured using standardised instruments at baseline, 3, 6 and 12 months. Chi-square tests and adjusted logistic regression models compared differences between groups. RESULTS: Baseline symptoms and previous depression or anxiety did not differ between groups. At 3 months after RRBSO clinically significant depressive symptoms were doubled (14.5% vs 27.1%, p = 0.010), which persisted at 12 months. Depressive symptoms were stable in comparisons. At 3 months after RRBSO, clinically significant anxiety symptoms almost trebled (6.1% vs 17.7%, p = 0.014) before plateauing at 6 months and returning to baseline at 12 months. Compared to comparisons, RRBSO participants were at 3.0-fold increased risk of chronic depressive symptoms (Wald 95% CI 1.27-7.26), 2.3-fold increased risk of incident depression (95% Wald CI 1.08-5.13) and 2.0-fold increase of incident anxiety (Wald 95% CI 0.78-5.00). Depression and anxiety were slightly more common in Hormone Therapy users after RRBSO vs non-users. CONCLUSIONS: RRBSO leads to a rapid increase in clinically significant depressive and anxiety symptoms despite Hormone Therapy use.
Asunto(s)
Ansiedad/etiología , Depresión/etiología , Menopausia/psicología , Neoplasias Ováricas/prevención & control , Posmenopausia/psicología , Salpingooforectomía/psicología , Adulto , Ansiedad/psicología , Depresión/psicología , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/psicología , Premenopausia/psicología , Estudios Prospectivos , Salpingooforectomía/efectos adversosRESUMEN
OBJECTIVE: Adenocarcinoma in situ (AIS) of the cervix is a precursor to cervical adenocarcinoma. When AIS is detected by cervical screening an excision biopsy is mandatory to exclude invasion. We aimed to compare margins status, specimen size and fragmentation after loop electrosurgical excision procedure (LEEP) and 'cold knife cone biopsy' (CKC). METHODS: The EXCISE Trial was an investigator-initiated, multicenter, open-label, parallel-group, phase 2, randomized study. Patients were enrolled at seven hospitals in Australia and New Zealand. We randomly assigned women aged ≥18 to ≤45 years with screen detected AIS to LEEP or CKC. Co-primary endpoints were margin status, specimen size and fragmentation. Analysis was by intention-to-treat. RESULTS: Between August 2, 2017 and September 6, 2019, 40 patients were randomly assigned 2:1 to LEEP or CKC. Margin status was evaluable in 36 cases. The proportion of patients with involved margins did not differ between groups. 25 of 26 LEEP and all 14 CKC biopsies were excised as single specimens (p = 1·00). There were no differences in specimen dimensions. Patients in the CKC group had more post-operative complications (64.3% compared to 15.4% for LEEP p = ·00). There were no differences in grade three complications (p = ·65). CONCLUSIONS: LEEP was not associated with a greater likelihood of positive margins, specimen fragmentation or smaller excision compared to CKC when performed according to a standardized protocol. However, the study was not powered to establish non-inferiority of LEEP and a definitive phase 3 trial to compare margin status and rates of treatment failure after LEEP and CKC is warranted.
Asunto(s)
Adenocarcinoma in Situ/cirugía , Electrocirugia/efectos adversos , Complicaciones Posoperatorias/epidemiología , Neoplasias del Cuello Uterino/cirugía , Adenocarcinoma in Situ/patología , Adulto , Biopsia/efectos adversos , Biopsia/instrumentación , Biopsia/métodos , Cuello del Útero/patología , Cuello del Útero/cirugía , Electrocirugia/instrumentación , Electrocirugia/métodos , Femenino , Humanos , Márgenes de Escisión , Proyectos Piloto , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Índice de Severidad de la Enfermedad , Neoplasias del Cuello Uterino/patologíaRESUMEN
BACKGROUND: Colposcopy has been recommended for all women with recurrent post-coital bleeding (PCB) even if their cervical cytology or co-test (involving oncogenic human papillomavirus (HPV) DNA testing and cytology) are negative. AIMS: To determine the risk of cervical cancer and its precursors among women with recurrent PCB with negative cytology or co-test. MATERIALS AND METHODS: A retrospective analysis of two cohorts of women with PCB referred to a tertiary colposcopy clinic. Cohort (1) (n = 1846) between 1 January 2000 and 31 December 2016 (cytology-based screening) and Cohort (2) (n = 215) from 1 January 2018 to 31 December 2019 after introduction of primary HPV screening. RESULTS: In 1217 (65.9%) women in Cohort (1) referred with negative cytology, there was one cancer (0.08%) and 22 high-grade squamous intraepithelial lesions (HSIL (cervical intraepithelial neoplasia 2/3)) on histopathology. In Cohort (2), there was no cancer or HSIL in 83 women with negative co-tests (negative for oncogenic HPV and cytology). False-negative cytology after a negative referral cytology or co-test was low with 2% of repeat cytology at initial colposcopy showing possible HSIL or worse. CONCLUSIONS: Women presenting with PCB and negative cytology alone have a low risk of cancer and could have HPV testing before being triaged to colposcopy. We showed that with the assurance of a negative co-test and the low likelihood of false-negative cytology, these women could avoid colposcopy unless cervical cancer is clinically suspected. There is a need for a larger cohort study to substantiate our findings with more precision.
Asunto(s)
Coito , Colposcopía/métodos , Hemorragia/etiología , Infecciones por Papillomavirus/diagnóstico , Adulto , Anciano , Estudios de Cohortes , Detección Precoz del Cáncer , Femenino , Humanos , Incidencia , Persona de Mediana Edad , Infecciones por Papillomavirus/epidemiología , Embarazo , Recurrencia , Estudios Retrospectivos , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/epidemiología , Frotis Vaginal , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/epidemiologíaRESUMEN
OBJECTIVES: Using laser capture microdissection (LCM) and sensitive human papillomavirus (HPV) genotyping, we aimed to determine the distribution of vaccine-preventable types in cervical intraepithelial neoplasia grade 3 (CIN3) lesions and adenocarcinoma in situ (AIS) in young women in Victoria, Australia, offered catch-up HPV vaccination, as a baseline for ongoing vaccine impact monitoring. We also compared findings with available pre-vaccination estimates from women with HPV detected on concurrently-collected cytology samples. METHODS: Consecutive histologically-confirmed CIN3/AIS biopsies were collected between May 2011 and December 2014 from vaccine-eligible women (born after 30th June 1981). Genotypes present in whole tissue sections (WTS) were determined by a sensitive reverse hybridisation assay; RHA kit HPV SPF10-LiPA25, v1 (Labo Bio-medical Products). Where multiple genotypes were detected, lesions were isolated using LCM and genotyped. Cervical cytology samples from a pre-vaccine cohort had been previously collected and genotyped using HPV Linear Array HPV Genotyping Test (Roche Diagnostics). Mixed-genotype detections in this cohort were resolved to single-lesion-attributable genotypes using hierarchical attribution. RESULTS: Overall, 213 and 530 cases were included from pre- and post-vaccine time-periods, respectively. In 18-25 year-olds, the proportion of HPV16/18-positive CIN3/AIS decreased significantly over time from 69% in 2001-2005 (pre-vaccine), to 62% in 2011-2012 (post-vaccine), to 47% in 2013-2014 (p-trend = 0.004). There was no significant change in HPV16/18 in 26-32 year-olds (p-trend = 0.15). In 2013/14, nonavalent vaccine types accounted for 80% of CIN3/AIS in 18-25 year old women and 90% in 26-32 year old women. CONCLUSION: Four to 8 years following implementation of HPV vaccination in Australia, approximately 70% of CIN3/AIS in young women was due to HPV16/18. Our data, despite some limitations due to change in methods between pre- and post-vaccine periods, suggests that for vaccine-eligible women aged 18-25 at the time of biopsy, the proportion of HPV16/18-attributable CIN3/AIS lesions is significantly declining post-vaccination.
Asunto(s)
Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Adolescente , Adulto , Femenino , Genotipo , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Humanos , Papillomaviridae/genética , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/prevención & control , Prevalencia , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/prevención & control , Vacunación , Victoria/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Autoimmune conditions (AICs) and/or their treatment may alter risk of human papilloma virus (HPV) infection and females with AICs are therefore at an increased risk of cervical dysplasia. However, inclusion of these at-risk populations in cervical cancer screening and HPV-vaccination guidelines, are mostly lacking. This study aimed to determine the prevalence of cervical dysplasia in a wide range of AICs and compare that to HIV and immunocompetent controls to support the optimisation of cervical cancer preventive health measures. METHODS: Data linkage was used to match cervical screening episodes to emergency department records of females with AICs or HIV to immunocompetent controls over a 14-year period. The primary outcome was histologically confirmed high-grade cervical disease. Results, measured as rates by cytology and histology classification per 1,000 females screened, were analysed per disease group, and intergroup comparisons were performed. RESULTS: Females with inflammatory bowel disease (2,683), psoriatic and enteropathic arthropathies (1,848), multiple sclerosis (MS) (1,426), rheumatoid arthritis (1,246), systemic lupus erythematosus and/or mixed connective tissue disease (SLE/MCTD) (702), HIV (44), and 985,383 immunocompetent controls were included. SLE/MCTD and HIV groups had greater rates of high-grade histological and cytological abnormalities compared to controls. Increased rates of low-grade cytological abnormalities were detected in all females with AICs, with the exception of the MS group. CONCLUSIONS: Females with SLE/MCTD or HIV have increased rates of high-grade cervical abnormalities. The increased low-grade dysplasia rate seen in most females with AICs is consistent with increased HPV infection. These findings support expansion of cervical cancer preventative programs to include these at-risk females.
Asunto(s)
Enfermedades Autoinmunes/patología , Displasia del Cuello del Útero/patología , Adulto , Artritis Reumatoide/complicaciones , Artritis Reumatoide/patología , Australia/epidemiología , Enfermedades Autoinmunes/complicaciones , Bases de Datos Factuales , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/patología , Humanos , Inmunocompetencia , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/patología , Persona de Mediana Edad , Clasificación del Tumor , Prevalencia , Factores de Riesgo , Displasia del Cuello del Útero/complicaciones , Displasia del Cuello del Útero/epidemiologíaRESUMEN
BACKGROUND: Human papillomavirus (HPV) infection, and its sequelae of precancerous cervical lesions and their subsequent treatment, have been linked with an increased risk of adverse pregnancy outcomes. Publicly funded HPV vaccination of female adolescents began in Australia in 2007 with initial catch-up to age 26 years. METHODS: Using data from the National Perinatal Data Collection we compared rates of preterm births and small-for-gestational-age infants born in Australia 2000-2015. We used generalized linear models, assuming a Poisson distribution and log link function, with single-year categories of infant birth year, maternal age, and age-specific HPV vaccination coverage as independent variables. RESULTS: In maternal cohorts with 60%-80% HPV vaccination coverage as achieved in Australia, there was a relative rate reduction of 3.2% (95% confidence interval, 1.1%-5.3%) in preterm births and 9.8% (8.2% to 11.4%) in small-for-gestational-age infants, after adjustment for infant's birth year and maternal age. CONCLUSION: This analysis provides provisional population-level evidence of a reduction in adverse pregnancy outcomes in cohorts of women offered HPV vaccination. Confounding by smoking or other variables and/or ecological analysis limitations, however, cannot be excluded. These findings indicate potential broader benefits of HPV vaccination than have been documented to date.
Asunto(s)
Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/administración & dosificación , Resultado del Embarazo/epidemiología , Vacunación/estadística & datos numéricos , Adolescente , Adulto , Australia , Femenino , Humanos , Recién Nacido de Bajo Peso , Recién Nacido , Recién Nacido Pequeño para la Edad Gestacional , Modelos Lineales , Edad Materna , Programas Nacionales de Salud , Embarazo , Nacimiento Prematuro/epidemiología , Adulto JovenRESUMEN
BACKGROUND: A high rate of regression in young women with cervical intraepithelial neoplasia grade 2 has been recorded. However, there are few prospective data by which to evaluate management guidelines. OBJECTIVE: This study evaluates the American Society for Colposcopy and Cervical Pathology recommendations for follow-up of young women with cervical intraepithelial neoplasia 2 using data created by a large prospective multicenter study of observational management. MATERIALS AND METHODS: Participants were 616 women under 25 years with biopsy-diagnosed cervical intraepithelial neoplasia 2 following a referral to colposcopy for an abnormal smear with no previous high-grade abnormality. The protocol included colposcopy, cytology, and colposcopically directed biopsy at the initial visit and at 6- and 12-month follow-ups visits, and these data were analyzed. Histology from the corresponding cervical biopsy was treated as the reference diagnostic test. For young women with cervical intraepithelial neoplasia 2, we aimed to determine the following: (1) the ability of colposcopy to identify women with cervical intraepithelial neoplasia 3 or worse at 6 months; and (2) the ability of colposcopy, cytology, and a combination of cytology and colposcopy to identify residual high-grade abnormalities at 12 months. In addition, although not specified in the guidelines, we investigated the ability of high-risk human papillomavirus positivity alone or with cytology as a co-test to identify residual high-grade abnormalities at 12 months. RESULTS: At 6 months, cervical intraepithelial neoplasia 3+ colposcopic appearance identified only 28% (95% confidence interval, 18-40%) of women diagnosed with cervical intraepithelial neoplasia 3. At 12 months, a high-grade colposcopic appearance identified only 58% (95% confidence interval, 48-68%) of women with residual histological cervical intraepithelial neoplasia 2 or 3. At 12 months, high-grade cytology identified only 58% (95% confidence interval, 48-68%) of women with cervical intraepithelial neoplasia 2 or 3. However, the combination of either high-grade cytology or colposcopic appearance proved substantially more sensitive (81%; 95% confidence interval, 72-88%). High-risk human papillomavirus positivity at 12 months was a sensitive (96%; 95% confidence interval, 89-99%) indicator of persisting high-grade histology. However, this sensitivity came at the expense of specificity (52%; 95% confidence interval, 45-58%). A co-test of high-risk human papillomavirus positivity or high-grade cytology at 12 months provided a high sensitivity (97%; 95% confidence interval, 90-99%) but low specificity (51%; 95% confidence interval, 45%-58%). CONCLUSION: Colposcopy and cytology are limited in their ability to exclude persistent high-grade abnormality for young women undergoing observational management for cervical intraepithelial neoplasia 2. We recommend biopsy for all women at 12 months. High-risk human papillomavirus positivity is a sensitive indicator of persistent abnormality and should be considered in those not having a biopsy.
Asunto(s)
Colposcopía/normas , Recurrencia Local de Neoplasia/prevención & control , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina/normas , Displasia del Cuello del Útero/prevención & control , Neoplasias del Cuello Uterino/prevención & control , Adolescente , Femenino , Humanos , Clasificación del Tumor , Recurrencia Local de Neoplasia/patología , Estudios Prospectivos , Sociedades Médicas , Estados Unidos , Neoplasias del Cuello Uterino/patología , Adulto Joven , Displasia del Cuello del Útero/patologíaRESUMEN
OBJECTIVE: Only risk-reducing bilateral salpingo-oophorectomy (RRBSO) has been shown to reduce ovarian cancer deaths in high-risk women. Uptake of RRBSO is, however, suboptimal and reasons are not well defined. More information is needed about the barriers to RRBSO and patient needs for information and care. METHODS: Cross-sectional study including the Perception of Cancer Risk Scale, factors affecting decision-making about RRBSO, and unmet information needs were measured using a purpose-designed questionnaire. RESULTS: Of the 193 high-risk women aged 30 to 50 approached, 60 (31%) agreed to participate. Respondents were either considering or had recently undergone premenopausal RRBSO. Most (49/60) had no personal history of cancer; 11/60 had previous breast cancer. Overall, responses did not differ between pre- and post-RRBSO participants. The main barriers to RRBSO were surgical menopause and loss of fertility. Other concerns included the impact on sexual function and bone health. Reduction in ovarian cancer risk and prolonged life expectancy were the main drivers for RRBSO. Participants understood that RRBSO reduced cancer risk, although most substantially overestimated their personal ovarian cancer risk. High-risk women wanted more information about how to manage the short- and long-term consequences of surgical menopause. CONCLUSIONS: Concerns about surgical menopause and loss of fertility are barriers to RRBSO for high-risk women despite understanding the benefits of reduced cancer risk. There is an unmet need for more information about effectively managing the noncancer consequences of RRBSO in premenopausal women. : Video Summary:http://links.lww.com/MENO/A478.