Accuracy of reading liquid based cytology slides using the ThinPrep Imager compared with conventional cytology: prospective study

Objective To compare the accuracy of liquid based cytology using the computerised ThinPrep Imager with that of manually read conventional cytology

Routine cervical screening by primary HPV testing: early findings in the renewed National Cervical Screening Program

Objectives: To report human papillomavirus (HPV) testing patterns and rates of oncogenic HPV‐positivity for specimens submitted during the first 6 months after the National Cervical Screening Program switched from cytology‐ to primary HPV‐based screening. Design, participants: Retrospective cross‐sectional review of 195 606 specimens submitted for HPV testing, 1 December 2017 – 31 May 2018. Setting: Large community‐based general pathology laboratory in metropolitan Sydney. Main outcome measures: Prevalence of oncogenic HPV types (all, HPV16/18, non‐HPV16/18) by reason for HPV test (primary screening, non‐screening); for oncogenic HPV‐positive women in the age band recommended for primary HPV screening (25–74 years), prevalence of cytologic abnormality and rates of 12‐month follow‐up and colposcopy recommendations. Results: 195 606 samples were received: 157 700 (80.6%) for primary screening, 37 906 (19.4%) for non‐screening tests. Oncogenic HPV was detected in 8.1% of screening tests (95% CI, 7.9–8.2%) and 20.9% of non‐screening tests (95% CI, 20.5–21.3%); 35.5% (95% CI, 34.7–36.4%) of women of recommended screening age with positive oncogenic HPV screening test results also had a cytologic abnormality. The proportion of HPV16/18‐positive samples with high grade abnormality was 15.3% (95% CI, 14.2–16.6%); for samples positive for other oncogenic HPV types, the proportion was 6.3% (95% CI, 5.8–6.8%). Repeat HPV testing after 12 months was recommended for 5.4% (95% CI, 5.3–5.5%) and direct colposcopy for 2.6% (95% CI, 2.5–2.7%) of screened women aged 25–74 years. Conclusions: High grade cytologic abnormalities were more common in women positive for HPV16/18, supporting their higher risk classification. Colposcopy referral rates were higher than during primary cytology‐based testing, as predicted by clinical trial and modelling data. The prevalence of HPV was much higher in non‐screening than in primary screening samples. Our findings indicate the renewed program is performing as expected during the initial HPV screening round

Diffuse melanosis cutis in the setting of BRAF V

Case Report: A 79-year-old Caucasian male presented with a 1-week history of diffuse progressive blue-gray discoloration of the skin subsequently found to due to diffuse melanosis cutis (DMC) in the setting of metastatic melanoma. Mutation testing demonstrated BRAFV 600E mutation status, an unexpected finding given his age. He died two weeks after presentation. Discussion: As our understanding of the molecular subtypes of melanoma increases, in the future it may be possible to predict which melanoma patients have a predilection to developing DMC. Mutation testing of DMC patients should be considered as BRAF inhibitors, and other novel targeted therapies may improve the bleak prognosis associated with this unusual presentation of metastatic melanoma

Diffuse melanosis cutis in the setting of BRAFV 600E metastatic melanoma

Case Report: A 79-year-old Caucasian male presented with a 1-week history of diffuse progressive blue-gray discoloration of the skin subsequently found to due to diffuse melanosis cutis (DMC) in the setting of metastatic melanoma. Mutation testing demonstrated BRAFV 600E mutation status, an unexpected finding given his age. He died two weeks after presentation. Discussion: As our understanding of the molecular subtypes of melanoma increases, in the future it may be possible to predict which melanoma patients have a predilection to developing DMC. Mutation testing of DMC patients should be considered as BRAF inhibitors, and other novel targeted therapies may improve the bleak prognosis associated with this unusual presentation of metastatic melanoma

Prevalence and risk factors associated with high-grade anal squamous intraepithelial lesions (HSIL)-AIN2 and HSIL-AIN3 in homosexual men

Background: Anal intraepithelial neoplasia grade 2 (AIN2) and AIN grade 3 (AIN3) are commonly grouped together as high grade squamous intraepithelial lesions (HSIL). We assessed risk factors for HSIL-AIN2 and HSIL-AIN3 in a cohort of homosexual men. Methods: At the baseline visit in the Study for the Prevention of Anal Cancer (SPANC), all men completed a questionnaire and underwent anal swabbing for cytology and HPV genotyping, followed by high resolution anoscopy. Results: Composite-HSIL prevalence was 47% and 32% among 220 HIV-positive and 396 HIV-negative men, respectively. HSIL-AIN3 (37.7% versus 24.7%; p<0.001), but not HSIL-AIN2 (9.5% versus 7.6%; p=0.395) was more common in HIV-positive men. Recent receptive anal partners (p-trend=0.045), and increasing number of high-risk (HR)-HPV types (p-trend<0.001) were associated with HSIL-AIN2. Lifetime receptive partners (p-trend<0.001), HIV status (OR 1.74; 95% CI: 1.05–2.87) and HPV16 (OR 3.00; 95% CI: 1.56–5.75) were associated with HSIL-AIN3. HPV16 was the most common HR-HPV type detected in men with HSIL-AIN3, both HIV-negative (61.1%) and HIV-positive (54.9%). HPV16 was less commonly detected in men with HSIL-AIN2. Conclusions: Grouping HSIL-AIN2 and HSIL-AIN3 as HSIL may mask considerable heterogeneity in anal cancer risk. Given the strong link between HPV16 and anal cancer, men with HSIL-AIN3 and HPV16 are likely to be at greatest risk of cancer. Keywords: Risk factors, Surrogate endpoints, HSIL, Cancer screening, Human papillomaviru

The Natural History of Anal High-grade Squamous Intraepithelial Lesions in Gay and Bisexual Men (vol 72, pg 853, 2021)

In the original publication of this article [Poynten IM, Jin F, Roberts JM et al. The Natural History of Anal High-grade Squamous Intraepithelial Lesions in Gay and Bisexual Men. Clin Infect Dis. Volume 72 Issue 5; March 1 2021, 853-861. https://doi.org/10.1093/cid/ciaa166], the term HSIL was erroneously used in the Methods and Results section of the abstract and has been replaced where necessary with cHSIL. The authors regret this error

Cervical screening with primary HPV testing or cytology in a population of women in which those aged 33 years or younger had previously been offered HPV vaccination: Results of the Compass pilot randomised trial

<div><p>Background</p><p>Using primary human papillomavirus (HPV) testing for cervical screening increases detection of high-grade cervical intraepithelial neoplastic lesions and invasive cancer (cervical intraepithelial neoplasia grade 2+ [CIN2+]) compared to cytology, but no evaluation has been conducted in a population previously offered HPV vaccination. We aimed to assess colposcopy referral and CIN2+ detection rates for HPV-screened versus cytology-screened women in Australia’s HPV-vaccinated population (by 2014, resident women ≤33 years had been age-eligible for HPV vaccination, with 3-dose uptake across age cohorts being about 50%–77%).</p><p>Methods and findings</p><p>Compass is an open-label randomised trial of 5-yearly HPV screening versus 2.5-yearly liquid-based cytology (LBC) screening. In the first phase, consenting women aged 25–64 years presenting for routine screening at 47 primary practices in Victoria, Australia, provided a cervical sample and were randomised at a central laboratory at a 1:2:2 allocation to (i) image-read LBC screening with HPV triage of low-grade cytology (‘LBC screening’), (ii) HPV screening with those HPV16/18 positive referred to colposcopy and with LBC triage for other oncogenic (OHR) types (‘HPV+LBC triage’), or (iii) HPV screening with those HPV16/18 positive referred to colposcopy and with dual-stained cytology triage for OHR types (‘HPV+DS triage’). A total of 5,006 eligible women were recruited from 29 October 2013 to 7 November 2014 (recruitment rate 58%); of these, 22% were in the group age-eligible for vaccination. Data on 4,995 participants were analysed after 11 withdrawals; 998 were assigned to, and 995 analysed (99.7%) in, the LBC-screened group; 1,996 assigned to and 1,992 analysed (99.8%) in the HPV+LBC triage group; and 2,012 assigned to and 2,008 analysed (99.8%) in the HPV+DS triage group. No serious trial-related adverse events were reported. The main outcomes were colposcopy referral and detected CIN2+ rates at baseline screening, assessed on an intention-to-treat basis after follow-up of the subgroup of triage-negative women in each arm referred to 12 months of surveillance, and after a further 6 months of follow-up for histological outcomes (dataset closed 31 August 2016). Analysis was adjusted for whether women had been age-eligible for HPV vaccination or not. For the LBC-screened group, the overall referral and detected CIN2+ rates were 27/995 (2.7% [95% CI 1.8%–3.9%]) and 1/995 (0.1% [95% CI 0.0%–0.6%]), respectively; for HPV+LBC triage, these were 75/1,992 (3.8% [95% CI 3.0%–4.7%]) and 20/1,992 (1.0% [95% CI 0.6%–1.5%]) and 20/1,992 (1.0% [95% CI 0.6%–1.5%); and for HPV+DS triage, these were 79/2,008 (3.9% [95% CI 3.1%–4.9%]) and 24/2,008 (1.2% [95% CI 0.8%–1.6%]) (<i>p =</i> 0.09 for difference in referral rate in LBC versus all HPV-screened women; <i>p =</i> 0.003 for difference in CIN2+ detection rate in LBC versus all HPV-screened women, with <i>p =</i> 0.62 between HPV screening groups). Limitations include that the study population involved a relatively low risk group in a previously well-screened and treated population, that individual women’s vaccination status was unknown, and that long-term follow-up data on disease detection in screen-negative women are not yet available.</p><p>Conclusions</p><p>In this study, primary HPV screening was associated with significantly increased detection of high-grade precancerous cervical lesions compared to cytology, in a population where high vaccine uptake was reported in women aged 33 years or younger who were offered vaccination. It had been predicted that increased disease detection might be associated with a transient increase in colposcopy referral rates in the first round of HPV screening, possibly dampened by HPV vaccine effect; in this study, although the point estimates for referral rates in women in each HPV-screened group were 41%–44% higher than in cytology-screened women, the difference in referral rate between cytology- and HPV-screened women was not significant. These findings provide initial support for the implementation of primary HPV screening in vaccinated populations.</p><p>Trial registration</p><p>Australian New Zealand Clinical Trials Registry <a href="https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=364244" target="_blank">ACTRN12613001207707</a></p></div