Selvan Pather

The impact of primary human papillomavirus screening on negative loop excision histology following biopsy‐proven high‐grade cervical intra‐epithelial lesions: A review from a large tertiary colposcopy unit

BackgroundThe renewed National Cervical Screening Program incorporating primary human papillomavirus (HPV) screening was implemented in Australia in December 2017. In a previous study conducted in the UK, primary HPV screening was found to be associated with a 25% reduction in the incidence of negative histology following loop electrosurgery excision procedure (LEEP).AimTo examine the change in incidence and associated risk factors for a negative LEEP with introduction of primary HPV screening.Materials and MethodsA retrospective review of the records of all patients undergoing a LEEP excision for biopsy‐proven high‐grade cervical intra‐epithelial lesions between 1 January 2014 and 30 June 2019 in a specialised centre.ResultsThere were 1123 patients who underwent a LEEP included in the analysis. The incidence of a negative LEEP specimen was 7.5% (59/784) and 5.3% (18/339) in the pre‐ and post‐HPV screening cohort. More patients in the post‐HPV screening group had low‐grade cytology on referral (P < 0.001), smaller cervical lesions on colposcopy (P = 0.012) and longer biopsy to treatment interval (P = 0.020). Primary HPV screening was associated with a significant reduction in the incidence of a negative LEEP specimen in a propensity matched cohort (11.2% to 5.1%, P = 0.006) and a 41% (P = 0.045) decreased relative risk of a negative LEEP on multivariate analysis.ConclusionsPrimary HPV screening results in a lower incidence of negative LEEP histology, despite a longer biopsy to treatment wait time and higher proportion of low‐grade cytology at triage.

Clinical Trial Protocol for HyNOVA: Hyperthermic and Normothermic intraperitoneal chemotherapy following interval cytoreductive surgery for stage III epithelial OVArian, fallopian tube and primary peritoneal cancer (ANZGOG1901/2020)

Ovarian cancer is the most lethal gynecological cancer, causing over 200,000 deaths worldwide in 2020. Initial standard treatment for primary ovarian cancer is optimal cytoreductive surgery (CRS) preceded and/or followed by intravenous platinum-based chemotherapy. However, most women develop recurrence within the peritoneal cavity and die of disease. Results of the OVIHIPEC 1 trial (2018) showed improved survival of 34% when hyperthermic intraperitoneal chemotherapy (HIPEC) was given immediately following interval-CRS in women with stage III disease. However, it is unknown if the effect of HIPEC is due to hyperthermia, one extra cycle of intraperitoneal (IP) chemotherapy, or other factors. There is also concern that hyperthermia might be associated with an increase in adverse events (AEs) due to a heightened systemic inflammatory response. HyNOVA is a seamless, multi-stage randomized study that attempts to answer these questions by comparing HIPEC to normothermic intraperitoneal chemotherapy (NIPEC), focusing on safety (stage 1), then assessing activity (stage 2) and effectiveness (stage 3). In this initial study, we hypothesize that NIPEC will result in a lower rate of severe AEs compared to HIPEC. This initial stage of HyNOVA is a phase II study of 80 women with International Federation of Gynaecology and Obstetrics stage III epithelial ovarian cancer, with at least stable disease following 3-4 cycles of neoadjuvant chemotherapy, achieving interval-CRS to <2.5 mm residual disease. Participants are randomized 1:1 to receive IP cisplatin 100 mg/m² for 90 minutes either as HIPEC, heated to 42°C (41.5°C-42.5°C), or NIPEC, at 37°C (36.5°C-37.5°C). The primary outcome is the proportion of AEs ≥ grade 3 occurring within 90 days. Secondary outcomes are AE of interest, surgical morbidity, patient reported outcomes, resource allocation, feasibility, progression-free survival and overall survival. AEs are measured using both CTCAE v5.0 and Clavien-Dindo classification, particularly infection, pain, bowel dysfunction, and anemia. Tertiary outcomes are potential predictive biomarkers measured before and after HIPEC/NIPEC including circulating cell-free tumor DNA, tissue factors, and systemic inflammatory markers. There are 4 participating Australian sites with experience in CRS and HIPEC for peritoneal malignancy. HyNOVA is funded by an MRFF grant (APP1199155). ANZCTR Identifier: ACTRN12621000269831.

Follow‐up after treatment of high‐grade cervical dysplasia: The utility of six‐month colposcopy and cytology and routine 12‐month colposcopy

BackgroundAustralian Cervical Screening Program guidelines no longer recommend colposcopy and cytology at six months following treatment of cervical intraepithelial neoplasia (CIN2/3) and a co‐test of cure can be performed at 12 months without colposcopy.AimsTo determine the usefulness of six‐month colposcopy and cytology and routine colposcopy with co‐testing at 12 months in detecting persistent or recurrent disease in patients treated for CIN2/3.Materials and MethodsWe conducted a review of all patients with histologically proven CIN2/3 who underwent a cervical excisional procedure between March 2012 and March 2017 in one specialised centre.ResultsWe examined 1215 cases and 750 remained after exclusions for analysis. At six months (722 cases, 96.2%) seven of 42 (16.7%) patients with high‐grade cytology had a high‐grade colposcopy and 24 of 42 (57.1%) had a normal colposcopy. Persistent CIN2/3 was diagnosed in 12 cases (1.7%) and only 1/3 had a high‐grade colposcopy. Cytology was more useful than colposcopy in detecting persistent disease. At 12 months (638 cases, 85%) routine colposcopy at the time of co‐testing had a high false positive rate with all high‐grade changes negative on biopsy and co‐test. Recurrent CIN2/3 was diagnosed in five cases, and four had normal colposcopy at co‐testing.ConclusionsThere may be a delay in detection of persistent/recurrent CIN2/3 in a small number of cases without six‐month colposcopy and cytology; however, it is not likely to negatively impact overall clinical outcome. Co‐testing at 12 months following treatment of CIN2/3 without colposcopy is safe and routine colposcopy at collection of the co‐test can be omitted.