F Pesola

Introducing human papillomavirus (HPV) primary testing in the age of HPV vaccination: projected impact on colposcopy services in Wales

ObjectiveTo determine the demand for colposcopy in the Cervical Screening Wales programme after the introduction of human papillomavirus (HPV) cervical screening, which coincided with the start of screening of women vaccinated against HPV types 16/18.DesignThe study used a computational model that assigns screening and screening‐related colposcopy events to birth cohorts in individual calendar years.SettingCervical Screening Wales.PopulationWomen aged 25–64 years from birth cohorts 1953–2007.Methods and main outcome measuresWe estimated the numbers of colposcopies and high‐grade cervical intraepithelial lesions (CIN2+) within Cervical Screening Wales in 2018–32, using official population projections for Wales and published estimates of the effects of HPV screening and vaccination.ResultsVaccination will reduce the number of colposcopies by 10% within the first 3–4 years after the national roll‐out of HPV screening, and by about 20% thereafter. The number of screening colposcopies is estimated to increase from 6100 in 2018 and peak at 8000 (+31%) in 2021, assuming current screening intervals are maintained. The numbers of CIN2+ lesions follow similar patterns, stabilising at around 1000 diagnoses per year by 2026, approximately 60% lower than at present. Extending the screening intervals to 5 years for all women shows similar trends but introduces peaks and troughs over the years.ConclusionsVaccination will not fully prevent an increase in colposcopies and detected CIN2+ lesions during the first 2–3 years of HPV‐based screening but the numbers are expected to decrease substantially after 5–6 years.Tweetable abstractHPV‐based cervical screening will initially increase colposcopy referral. In 6 years, this increase will be reversed, partly by HPV vaccination.

Recovery strategies following COVID-19 disruption to cervical cancer screening and their impact on excess diagnoses

Abstract Background The COVID-19 pandemic has disrupted cervical cancer screening services. Assuming increases to screening capacity are unrealistic, we propose two recovery strategies: one extends the screening interval by 6 months for all and the other extends the interval by 36/60 months, but only for women who have already missed being screened. Methods Using routine statistics from England we estimate the number of women affected by delays to screening. We used published research to estimate the proportion of screening age women with high-grade cervical intraepithelial neoplasia and progression rates to cancer. Under two recovery scenarios, we estimate the impact of COVID-19 on cervical cancer over one screening cycle (3 years at ages 25–49 and 5 years at ages 50–64 years). The duration of disruption in both scenarios is 6 months. In the first scenario, 10.7 million women have their screening interval extended by 6 months. In the second, 1.5 million women (those due to be screened during the disruption) miss one screening cycle, but most women have no delay. Results Both scenarios result in similar numbers of excess cervical cancers: 630 vs. 632 (both 4.3 per 100,000 women in the population). However, the scenario in which some women miss one screening cycle creates inequalities—they would have much higher rates of excess cancer: 41.5 per 100,000 delayed for screened women compared to those with a 6-month delay (5.9 per 100,000). Conclusion To ensure equity for those affected by COVID-19 related screening delays additional screening capacity will need to be paired with prioritising the screening of overdue women.

Extension of cervical screening intervals with primary human papillomavirus testing: observational study of English screening pilot data

Abstract Objectives To provide updated evidence about the risk of cervical intraepithelial neoplasia grade 3 or higher (CIN3+) and cervical cancer after a negative human papillomavirus (HPV) test in primary cervical screening, by age group and test assay. Design Observational study. Setting Real world data from the English HPV screening pilot’s first and second rounds (2013-16, follow-up to end of 2019). Participants 1 341 584 women. Interventions Cervical screening with HPV testing or liquid based cytological testing (cytology or smear tests). Women screened with cytology were referred to colposcopy after high grade cytological abnormalities or after borderline or low grade abnormalities combined with a positive HPV triage test. Women screened with HPV testing who were positive were referred at baseline if their cytology triage test showed at least borderline abnormalities or after a retest (early recall) at 12 and 24 months if they had persistent abnormalities. Main outcome measures Detection of CIN3+ and cervical cancer after a negative HPV test. Results For women younger than 50 years, second round detection of CIN3+ in this study was significantly lower after a negative HPV screen in the first round than after cytology testing (1.21/1000 v 4.52/1000 women screened, adjusted odds ratio 0.26, 95% confidence interval 0.23 to 0.30), as was the risk of interval cervical cancer (1.31/100 000 v 2.90/100 000 woman years, adjusted hazard ratio 0.44, 0.23 to 0.84). Risk of an incident CIN3+ detected at the second screening round in the pilot five years after a negative HPV test was even lower in women older than 50 years, than in three years in women younger than 50 years (0.57/1000 v 1.21/1000 women screened, adjusted odds ratio 0.46, 0.27 to 0.79). Women with negative HPV tests at early recall after a positive HPV screening test without cytological abnormalities had a higher detection rate of CIN3+ at the second routine recall than women who initially tested HPV negative (5.39/1000 v 1.21/1000 women screened, adjusted odds ratio 3.27, 95% confidence interval 2.21 to 4.84). Detection after a negative result on a clinically validated APTIMA mRNA HPV test was similar to that after clinically validated cobas and RealTime DNA tests (for CIN3+ at the second round 1.32/1000 v 1.14/1000 women screened, adjusted odds ratio 1.05, 0.73 to 1.50). Conclusions These data support an extension of the screening intervals, regardless of the test assay used: to five years after a negative HPV test in women aged 25-49 years, and even longer for women aged 50 years and older. The screening interval for HPV positive women who have negative HPV tests at early recall should be kept at three years.

The impact of catch-up bivalent human papillomavirus vaccination on cervical screening outcomes: an observational study from the English HPV primary screening pilot

Abstract Background In England, bivalent vaccination (Cervarix) against high-risk human papillomavirus (HR-HPV) genotypes 16/18 was offered in a population-based catch-up campaign in 2008–2010 to girls aged 14–17 years. These women are now entering the national cervical screening programme. We determined the impact of catch-up bivalent vaccination on their screening outcomes. Methods We studied the overall and genotype-specific screening outcomes in 108,138 women aged 24–25 (offered vaccination) and 26–29 years (not offered vaccination) included in the English HPV screening pilot between 2013 and 2018. Results At 24–25 years, the detection of high-grade cervical intraepithelial neoplasia (CIN2+) associated with HPV16/18 decreased from 3 to 1% (p < 0.001), with estimated vaccine effectiveness of 87% (95% CI: 82–91%). The detection of any CIN2+ halved from 6 to 3% (p < 0.001), with an estimated vaccine effectiveness of 72% (95% CI: 66–77%). The positive predictive value of a colposcopy for CIN2+ decreased for both low-grade (p < 0.001) and high-grade (p = 0.02) abnormalities on triage cytology. The decreases in screen-detected abnormalities at age 26-29 were of a substantially smaller magnitude. Conclusions These data confirm high effectiveness of bivalent HPV vaccination delivered through a population-based catch-up campaign in England. These findings add to the rationale for extending screening intervals for vaccinated cohorts.

Age‐specific outcomes from the first round of HPV screening in unvaccinated women: Observational study from the English cervical screening pilot

AbstractObjectiveTo report detailed age‐specific outcomes from the first round of an English pilot studying the implementation of high‐risk human papillomavirus (HR‐HPV) testing in primary cervical screening.DesignObservational study with screening in 2013–2016, followed by two early recalls and/or colposcopy until the end of 2019.SettingSix NHS laboratory sites.PopulationA total of 1 341 584 women undergoing screening with HR‐HPV testing or liquid‐based cytology (LBC).MethodsEarly recall tests and colposcopies were recommended, depending on the nature of the screening‐detected abnormality.Main outcome measuresWe reported standard screening process indicators, e.g. proportions with an abnormality, including high‐grade cervical intraepithelial neoplasia (CIN2+) or cancer, and the positive predictive value (PPV) of colposcopy for CIN2+, by screening test and age group.ResultsAmong unvaccinated women screened with HR‐HPV testing at age 24–29 years, 26.9% had a positive test and 10.4% were directly referred to colposcopy following cytology triage, with a PPV for CIN2+ of 47%. At 50–64 years of age, these proportions were much lower: 5.3%, 1.2% and 27%, respectively. The proportions of women testing positive for HR‐HPV without cytological abnormalities, whose early recall HR‐HPV tests returned negative results, were similar across the age spans: 54% at 24–29 years and 55% at 50–64 years. Two‐thirds of infections at any age were linked to non‐16/18 genotypes. Among women with CIN2, CIN3 or cervical cancer, however, the proportion of non‐16/18 infections increased with age. As expected, the detection of abnormalities was lower following screening with LBC.ConclusionsThese data provide a reliable reference for future epidemiological studies, including those concerning the effectiveness of HPV vaccination.Tweetable abstractData from the English pilot study provide a comprehensive overview of abnormalities detected through HPV screening.