Primary human papillomavirus DNA screening for cervical cancer prevention: Can the screening interval be safely extended?

Abstract

Cytological screening has substantially decreased the cervical cancer incidence, but even better protection may be achieved by primary high-risk human papillomavirus (hrHPV) screening. In the Netherlands, five-yearly cytological screening for women aged 30-60 years will be replaced by primary hrHPV screening in 2016. The new screening guidelines involve an extension of the screening interval from 5 to 10 years for hrHPV-negative women aged 40 or 50 years. We investigated the impact of this program change on the lifetime cancer risks in women without an hrHPV infection at age 30, 35, 40, 45 or 50 years. The time to cancer was estimated using 14-year follow-up data from a population-based screening intervention trial and the nationwide database of histopathology reports. The new screening guidelines are expected to lead to a reduced cervical cancer risk for all age groups. The average risk reduction was 34% and was smallest (25%) among women aged 35 years. The impact of hrHPV screening on the cancer risk was sensitive to the duration from cervical intraepithelial neoplasia grade 2/3 (CIN2/3) to cancer; a small increase in the cancer risk was estimated for women aged 35 or 40 years in case a substantial proportion of CIN2/3 showed fast progression to cancer. Our results indicate that primary hrHPV screening with a ten-yearly interval for hrHPV-negative women of age 40 and beyond will lead to a further reduction in lifetime cancer risk compared to five-yearly cytology, provided that precancerous lesions progress slowly to cancer.Screening for cervical cancer has been implemented in many countries starting in the 1960s 1 and has led to a large reduction in cervical cancer incidence since. [2][3][4] Most countries use a cytology-based screening instrument (the Pap test). The success of cervical screening is largely determined by the opportunity for timely detection and treatment of precancerous lesions and the accuracy of the screening instrument. The time spent in the screen-detectable, precancerous state is thought to be long enough to prevent the majority of cervical cancer cases, 5,6 but the sensitivity of cytology for detection of cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3) is only moderate and varies considerably between countries (see for example Cuzick et al. 7 ). Repeated screening is therefore necessary to compensate for test inaccuracy.Cervical cancer is caused by a persistent high-risk human papillomavirus (hrHPV) infection. HrHPV testing has been shown to have a higher sensitivity than cytology for detection of CIN2/3 (96% vs. 53% 7 ) at the cost of a 2.5 to 4% lower specificity. 7,8 Moreover, hrHPV screening provides up to 70% better protection against CIN3 and cancer compared to cytology. 9,10 Despite its lower specificity, organized screening by hrHPV testing in cervical smears is considered cost-effective on the basis of modeling studies 11-13 and several countries are considering implementation of the hrHPV DNA test as primary screening instrument, either used alone or in combination wit...

Cost-effective management of women with minor cervical lesions: Revisiting the application of HPV DNA testing

“…HPV testing has been recommended to triage women with cytology results indicating minor cervical lesions (i.e., atypical squamous cells of undetermined significance (ASC-US) and/or low-grade squamous intraepithelial lesion (LSIL)) since the beginning of the 2000s; recent applications involve replacing cytology as the primary screening test [6, 7]. In Norway, a randomized implementation study was initiated in 2015 to evaluate switching women from primary cytology-based screening to HPV-based screening at age 34 years [8]; however, national scale-up is not scheduled for several years.…”

Transitioning to a new era in cervical cancer screening

“…For example, the issue of how long to wait after a negative screening test, depending on the kind of test, remains controversial in practice despite published guidelines (3 years following negative cytology, 5 years following negative cotest and, based on preliminary guidance, 3 years following negative HPV test alone) [10,16]. In European settings, higher risk tolerance is leading to acceptance of longer screening intervals [17]. Ideally, we should debate and agree to a US standard, recognizing that no screening program will prevent all cervical cancer.…”

Reconsidering Primary HPV Testing in Cervical Cancer Screening

“…Nonetheless in the Netherlands, five-yearly cytological screening for women aged 30-60 years will be replaced by primary HPV screening in 2016. Not only, but these newly developed guidelines involve an extension of the screening interval from 5 to 10 years for HPV-negative women aged 40 or 50 years [33].…”