Adapting cervical cancer screening for women vaccinated against human papillomavirus infections: The value of stratifying guidelines

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We analysed patterns in the incidence of cervical intraepithelial neoplasia grades 2 and 3 (CIN2, CIN3) and adenocarcinoma in situ (AIS) by age and histology in 1992–2016 in Norway and described changes in screening tests. Incident cases of CIN2, CIN3, AIS and cervical cancer were identified in the Cancer Registry of Norway, as were all women with at least one screening test. The annual percentage change statistic was used to assess point estimates and changes in age‐specific and age‐standardised incidence rates (IR). Women aged 25–29 years had the highest incidence of cervical precancerous lesions (CIN2: 192.9/10, CIN3: 737.2/10, AIS: 32.5/105 in 2016). The IR of CIN2 increased for all screening ages (25–69 years) from 3.6% to 6.7% per year. CIN3 incidence increased by 1.6% (95% confidence interval [CI] 0.6–2.6) annually. A steep increase in AIS incidence was observed in all age groups (7.1% per year, 95% CI 5.3–8.8). Changes in screening tests and the histological verification of cervical precancerous lesions alone cannot explain the steady increase in incidence we observed over the 25‐year study period, and increased exposure to human papillomavirus (HPV) likely plays a role. Age‐appropriate treatment of screening‐detected cervical precancerous lesions is needed for effective cervical cancer control while avoiding overtreatment and related health risks. In order to perform an appropriate harm‐benefit evaluation of cervical cancer control efforts, detailed information on screening technology and background risks, including HPV vaccination status, is needed to create optimal public health policy.

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Recent increase in incidence of cervical precancerous lesions in Norway: Nationwide study from 1992 to 2016

Orumaa

Leinonen

Campbell

et al. 2019

Self Cite

“…Finally, from a screening laboratory operational perspective, HPV assays with extended genotyping for cervical cancer screening are already available, and these assays have the capacity for returning detailed genotype results on an HPV‐positive sample without further analysis required. On the other hand, assays with limited genotyping reporting HPV16 and 18 individually combined with bulk detection of the remaining hrHPV genotypes will have limited value in such strategy as well as in screening populations with increasing proportions of HPV16/18 vaccinated women reducing the assay to a simple hrHPV “yes/no” assay …”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, assays with limited genotyping reporting HPV16 and 18 individually combined with bulk detection of the remaining hrHPV genotypes will have limited value in such strategy as well as in screening populations with increasing proportions of HPV16/18 vaccinated women reducing the assay to a simple hrHPV "yes/no" assay. [44][45][46][47][48]…”

Section: Discussionmentioning

confidence: 99%

Bayesian analysis of baseline risk of CIN2 and ≥CIN3 by HPV genotype in a European referral cohort

Bonde

Bottari

Parvu

et al. 2019

Whereas HPV16 and HPV18 have been the focus in current risk‐based cervical cancer screening algorithms using HPV genotype information, mounting evidence suggests that oncogenic HPV types such as HPV31, 33, 52 and 58 pose a ≥CIN3 risk equivalent to or greater than that of HPV18, and the combined risk of HPV31 and HPV33 rivals even HPV16 in women above 30 years of age. Here, we evaluate the baseline risk of CIN2 and CIN3 by genotype in a colposcopy referral population from Denmark and Italy. In total, 655 women were enrolled upon a referral to colposcopy after a positive screening sample. All samples were HPV analyzed using Onclarity HPV assay with extended genotyping and combined with the histology outcomes, a Bayesian probability modeling was used to determine the risk per genotype assessed. The combined data for this referral population showed that the ≥CIN2 risk of HPV16 was 69.1%, HPV31 at 63.3%, HPV33/58 at 52.7%, HPV18 at 46.6% and HPV52 at 40.8%. For ≥CIN3, the risks were 44.3%, 38.5%, 36.8%, 30.9% and 16.8% for HPV16, HPV31, HPV18, HPV33/58 and HPV52, respectively, indicating that the baseline risk of disease arising from HPV16 is, not surprisingly, the highest among the oncogenic HPV genotypes. We find that the HPV genotype‐specific ≥CIN2 and ≥CIN3 risk‐patterns are so distinct that, for example, 35/39/68 and 56/59/66 should be considered only for low intensive follow‐up, thereby proposing active use of this information in triage strategies for screening HPV‐positive women.

Reducing overtreatment associated with overdiagnosis in cervical cancer screening—A model‐based benefit–harm analysis for Austria

Sroczynski¹,

Esteban²,

Widschwendter

et al. 2020

A general concern exists that cervical cancer screening using human papillomavirus (HPV) testing may lead to considerable overtreatment. We evaluated the trade‐off between benefits and overtreatment among different screening strategies differing by primary tests (cytology, p16/Ki‐67, HPV alone or in combinations), interval, age and diagnostic follow‐up algorithms. A Markov state‐transition model calibrated to the Austrian epidemiological context was used to predict cervical cancer cases, deaths, overtreatments and incremental harm–benefit ratios (IHBR) for each strategy. When considering the same screening interval, HPV‐based screening strategies were more effective compared to cytology or p16/Ki‐67 testing (e.g., relative reduction in cervical cancer with biennial screening: 67.7% for HPV + Pap cotesting, 57.3% for cytology and 65.5% for p16/Ki‐67), but were associated with increased overtreatment (e.g., 19.8% more conizations with biennial HPV + Papcotesting vs. biennial cytology). The IHBRs measured in unnecessary conizations per additional prevented cancer‐related death were 31 (quinquennial Pap + p16/Ki‐67‐triage), 49 (triennial Pap + p16/Ki‐67‐triage), 58 (triennial HPV + Pap cotesting), 66 (biennial HPV + Pap cotesting), 189 (annual Pap + p16/Ki‐67‐triage) and 401 (annual p16/Ki‐67 testing alone). The IHBRs increased significantly with increasing screening adherence rates and slightly with lower age at screening initiation, with a reduction in HPV incidence or with lower Pap‐test sensitivity. Depending on the accepted IHBR threshold, biennial or triennial HPV‐based screening in women as of age 30 and biennial cytology in younger women may be considered in opportunistic screening settings with low or moderate adherence such as in Austria. In organized settings with high screening adherence and in postvaccination settings with lower HPV prevalence, the interval may be prolonged.