Older women testing positive for HPV16/18 on cervical screening and risk of high-grade cervical abnormality.

In Australia's HPV-based cervical screening program, we previously showed that risk of histological high-grade abnormality at 1 year post screening decreased with age in women with oncogenic HPV. In this study, we followed 878 HPV16/18 positive women aged 55 years and over for up to 3 years post screening test, to determine the proportion with histological high-grade abnormality (HGA, incorporating high-grade squamous intraepithelial abnormality (HSIL), adenocarcinoma in situ (AIS), squamous cell carcinoma (SCC) and adenocarcinoma) and to correlate risk of HGA with liquid-based cytology result and with prior screening history. HGA was detected in 7.8% at 1 year and 10.0% at 3 years, with no significant difference (P = .136), despite the number of women with follow-up information significantly increasing from 82.9% to 91.0% (P < .0001). The proportion of HPV16/18 positive women with HGA at 3 years was highest in those with an HSIL cytology result (79.0%) and lowest in those with negative cytology (6.2%). Women with an adequate screening history had fewer HGA than such women with inadequate prior screening (6.6% vs 16.0%, P = .001) or with a history of an abnormality (6.6% vs 14.4%, P = .001). HPV16/18 infection in women over 55 years may have a different natural history from that in younger women, in whom HGA are more common after HPV16/18 detection. In HPV-based cervical screening programs, management algorithms for screen-detected abnormalities based on risk stratification should include factors such as age, screening history and index cytology result, so that women receive appropriate investigation and follow-up.

Histological outcomes of anal high-grade cytopredictions.

BACKGROUND: Longitudinal studies of histological outcomes after anal cytological screening in men who have sex with men (MSM) are rare. This study measured the positive predictive values (PPVs) of each level of baseline cytological abnormality in MSM in Sydney, Australia, over a 12-month period. METHODS: The Study of the Prevention of Anal Cancer is a 3-year prospective study of the natural history of anal human papillomavirus infection in MSM at least 35 years old. For each participant with a baseline cytological abnormality, the worst histology was recorded at the baseline high-resolution anoscopy and at 6 and 12 months. PPVs for a histological high-grade squamous intraepithelial lesion (HSIL) diagnosis were calculated for each level of baseline cytological abnormality at each time point. RESULTS: Among 424 men who completed 3 visits, the PPV of a cytological HSIL increased from 71.6% at the baseline to 86.4% at 6 months and to 92.6% at 12 months (P < .001). For cytological atypical squamous cells, cannot rule out high-grade squamous intraepithelial lesion (ASC-H), the PPV increased from 51.5% at the baseline to 69.7% at 6 months and to 75.8% at 12 months (P = .004). At each time point, the PPV of a cytological HSIL was significantly higher than the PPV of ASC-H. The PPV of low-grade cytology reports was significantly lower than the PPV of ASC-H at each time point. CONCLUSIONS: In a cohort of MSM, a baseline histological HSIL diagnosis after an HSIL cytoprediction is high, and it increases with further examinations over the course of 12 months. Lower levels of cytological abnormalities have significantly lower PPVs. These data can inform patient management and the quality assessment of each aspect of the screening pathway. Cancer Cytopathol 2018;126:136-44. © 2017 American Cancer Society.

The reporting of anal cytology and histology samples: establishing terminology and criteria.

Our understanding of the human papillomavirus (HPV) related cytomorphology and histopathology of the anal canal is underpinned by our knowledge of HPV infection in the cervix. In this review, we utilise cervical reporting of cytological and histological specimens as a foundation for the development of standardised and evidence-based terminology and criteria for reporting of anal specimens. We advocate use of the Australian Modified Bethesda System 2004 for reporting anal cytology. We propose the use of a two-tiered histological reporting system for noninvasive disease - low-grade and high-grade anal intraepithelial neoplasia. These classification systems reflect current understanding of the biology of HPV and enhance diagnostic reproducibility. Biomarkers such as p16(INK4A) may prove useful in further improving diagnostic accuracy. Standardisation is important because it will increase the value of the data collected as Australian centres develop programs for screening for anal neoplasia.

Comparison of the performance of anal cytology and cervical cytology as screening tests.

Cervical cytology screening has a long history and has successfully reduced the impact of cervical cancer in many countries. Anal cytology is a relative newcomer and anal screening is currently offered in only a few centres around the world. Many questions need to be answered before anal screening is more widely adopted. While there are many similarities between cervical and anal squamous cell carcinoma, there are also important differences: differences in the prevalence of disease, in the 'at-risk' target populations and possibly in the robustness of the reference standard of biopsy. The performance of cytology as a screening test in the literature varies widely but it is essential to understand that some of this variability is due to differences in the definitions of key parameters in the various studies. For cervical screening, estimates of sensitivity have ranged from 19% to 94% and specificity from 94% to 98%. For anal screening, data are fewer and more limited. Estimates of the sensitivity of anal cytology in men who have sex with men and HIV-positive populations have ranged from 55% to 87% and specificity from 37% to 76%. Ultimately, rather than comparing anal with cervical cytology, it may be more helpful to assess the value of anal cytology independently through well designed trials.