Diagnostic outcomes after colposcopy at a tertiary clinic for women aged 50-74 referred after detection of oncogenic human papillomavirus at primary screening.

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.

Exploring monitoring strategies for population surveillance of HPV vaccine impact using primary HPV screening.

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.

Evaluation of p16INK4a immunostaining for the detection of high-grade changes in cervical cytology.

Since its introduction in Australia in 2007, the human papillomavirus (HPV) vaccine has led to a markedly lower prevalence of vaccine targeted HPV genotype infections as well as HPV disease including genital warts and histologically confirmed high-grade (HG) cervical abnormalities. To increase the ability to identify abnormal cells in lower prevalence, adjunct markers can be incorporated to improve the sensitivity and specificity of cytology test. One such marker is p16(p16), which is detectable in cells expressing the E7 oncogene encoded by high-risk HPVs (HR-HPV). In this study, the sensitivity and specificity of p16 immunostaining in detection of underlying HG lesions was evaluated in a cohort of 454 women undergoing surgical treatment for biopsy proven cervical dysplasia. Overall, p16 positive cells were detected in 321 (71%) of cytology preparations evaluated. Comparison of p16 staining on cytological preparations to histology diagnosis available on 212 patients, showed 26 (54%), 41 (78%) and 80 (90%) of cytology preparations to be p16 positive in women with CIN1, CIN2 and CIN3, respectively (p < 0.005). HPV16 and 18 were the most prevalent genotypes in HG lesions and were highly correlated with p16 staining. p16 staining provides an additional marker which can assist in better detecting underlying HG lesion in cytology smears with low disease prevalence.

Comparison of the Roche Cobas(®) 4800 HPV assay to Digene Hybrid Capture 2, Roche Linear Array and Roche Amplicor for Detection of High-Risk Human Papillomavirus Genotypes in Women undergoing treatment for cervical dysplasia.

BACKGROUND: The recently FDA (U.S. food and drug administration) approved Roche Cobas(®) 4800 (Cobas) human papillomavirus (HPV) has limited performance data compared to current HPV detection methods for test of cure in women undergoing treatment for high grade lesions. OBJECTIVE: Evaluation of Cobas HPV assay using historical samples from women undergoing treatment for cervical dysplasia. STUDY DESIGN: A selection of 407 samples was tested on the Cobas assay and compared to previous results from Hybrid Capture 2, HPV Amplicor and Roche Linear Array. RESULTS: Overall, a correlation between high-risk HPV positivity and high grade histological diagnosis was 90.6% by the Cobas, 86.1% by Hybrid Capture 2, 92.9% by HPV Amplicor and 91.8% by Roche Linear Array. CONCLUSION: The Cobas HPV assay is comparative to both the HPV Amplicor and Roche Linear Array assays and better than Hybrid capture 2 assay in the detection of High-Risk HPV in women undergoing treatment for cervical dysplasia.

Radiosurgery facilitates resection of brain arteriovenous malformations and reduces surgical morbidity.

OBJECTIVE: Stereotactic radiosurgery makes brain arteriovenous malformations (AVM) more manageable during their microsurgical resection. To better characterize these effects, we compared results of microsurgical resection of radiated (RS) and nonradiated (RS) AVMs to demonstrate that previous radiosurgery facilitates surgery and decreases operative morbidity. METHODS: From our series of 344 patients who underwent AVM resections at the University of California, San Francisco (1997-2007), 21 RS patients were matched with 21 RS patients based on pretreatment clinical and AVM characteristics. Matching was blinded to outcomes, which were assessed with the modified Rankin Scale. RESULTS: Mean AVM volume was reduced by 78% (P < 0.01), and Spetzler-Martin grades were reduced in 52% of RS patients (P < 0.001). Preoperative embolization was used less in RS than in RS patients (P < 0.001). Mean operative time (P < 0.01), blood loss (P < 0.05), and length of hospital stay (P < 0.05) were lower in the RS group. Surgical morbidity was 14% higher in RS patients, and they demonstrated significant worsening in modified Rankin Scale scores after surgery, whereas RS patients did not (P < 0.01). RS patients deteriorated between AVM diagnosis and surgery owing to hemorrhages during the latency period (P < 0.05). CONCLUSION: Previous radiosurgery facilitates AVM microsurgery and decreases operative morbidity. Radiosurgery is recommended for unruptured AVMs that are not favorable for microsurgical resection. Microsurgical resection is recommended for radiated AVMs that are not completely obliterated after the 3-year latency period but are altered favorably for surgery, even in asymptomatic patients. Prompt resection of persistent AVMs should be considered to avoid the risk of postlatency hemorrhage and to optimize patient outcomes.