How will transitioning from cytology to HPV testing change the balance between the benefits and harms of cervical cancer screening? Estimates of the impact on cervical cancer, treatment rates and adverse obstetric outcomes in Australia, a high vaccination coverage country

Abstract

Primary HPV screening enables earlier diagnosis of cervical lesions compared to cytology, however, its effect on the risk of treatment and adverse obstetric outcomes has not been extensively investigated. We estimated the cumulative lifetime risk (CLR) of cervical cancer and excisional treatment, and change in adverse obstetric outcomes in HPV unvaccinated women and cohorts offered vaccination (>70% coverage in 12-13 years) for the Australian cervical screening program. Two-yearly cytology screening (ages 18-69 years) was compared to 5-yearly primary HPV screening with partial genotyping for HPV16/18 (ages 25-74 years). A dynamic model of HPV transmission, vaccination, cervical screening and treatment for precancerous lesions was coupled with an individual-based simulation of obstetric complications. For cytology screening, the CLR of cervical cancer diagnosis, death and treatment was estimated to be 0.649%, 0.198% and 13.4% without vaccination and 0.182%, 0.056% and 6.8%, in vaccinated women, respectively. For HPV screening, relative reductions of 33% and 22% in cancer risk for unvaccinated and vaccinated women are predicted, respectively, compared to cytology. Without the implementation of vaccination, a 4% increase in treatment risk for HPV versus cytology screening would have been expected, implying a possible increase in pre-term delivery (PTD) and low birth weight (LBW) events of 19 to 35 and 14 to 37, respectively, per 100,000 unvaccinated women. However, in vaccinated women, treatment risk will decrease by 13%, potentially leading to 4 to 41 fewer PTD events and from 2 more to 52 fewer LBW events per 100,000 vaccinated women. In unvaccinated women in cohorts offered vaccination as 12-13 year olds, no change to lifetime treatment risk is expected with HPV screening. In unvaccinated women in cohorts offered vaccination as 12-13 year olds, no change to lifetime treatment risk is expected with HPV screening. HPV screening starting at age 25 in populations with high vaccination coverage, is therefore expected to both improve the benefits (further decrease risk of cervical cancer) and reduce the harms (reduce treatments and possible obstetric complications) associated with cervical cancer screening.

Comparison of human papillomavirus genotyping and cytology triage, COMPACT Study: Design, methods and baseline results in 14 642 women

“…23 However, the global consensus is that there is strong and uniform evidence for the efficacy of HPV-based screening, as it allows earlier detection of cervical precancers and is more effective than cytology-based screening because it permits an extension of screening intervals at equal or better safety while reducing harm from too frequent screening. 24,25 Most national and international organizations also agree there is little evidence for the usefulness of adding cytology to primary HPV screening in the form of co-testing.…”

“…A third study with MHLW funding, the JCHO‐HPV study enrolling 20 000 women >20 years and using the Hybrid Capture 2 HPV test (Qiagen, Germantown, MD, USA), which does not allow for partial genotyping, and comparing cytology to HPV co‐testing, is also about to start . However, the global consensus is that there is strong and uniform evidence for the efficacy of HPV‐based screening, as it allows earlier detection of cervical precancers and is more effective than cytology‐based screening because it permits an extension of screening intervals at equal or better safety while reducing harm from too frequent screening . Most national and international organizations also agree there is little evidence for the usefulness of adding cytology to primary HPV screening in the form of co‐testing.…”

CIN III and cervical SCC with negative oncogenic HPV PCR: A case series

“…Regarding broadening the number of HPV subtypes included in NAT for primary cervical screening, harms to be considered are increases in the number of colposcopies and the treatment for lesions that may have otherwise spontaneously regressed. These are both expected to decrease under the renewed NCSP, in addition to a $50 million reduction in the annual cost of the NCSP . Aside from the cost‐benefit analysis that must be undertaken if broadening primary HPV testing to include all the probably oncogenic HPV subtypes, the positive predictive value of the screening will be reduced.…”

“…These are both expected to decrease under the renewed NCSP, in addition to a $50 million reduction in the annual cost of the NCSP. 4,14,16 Aside from the cost-benefit analysis that must be undertaken if broadening primary HPV testing to include all the probably oncogenic HPV subtypes, the positive predictive value of the screening will be reduced.…”

Gaps and opportunities for cervical cancer prevention, diagnosis, treatment and care: evidence from midterm review of the Zimbabwe Cervical Cancer Prevention and Control strategy (2016-2020).

“…In addition, women younger than 25 years and HIV negative and those older than 49 years were also screened, resulting in ine cient use of resources. Young women tend to have HPV infections which are transient and do not require treatment due to possible harms in later pregnancies [12].…”