Risks for pregnancy-related complications after treatment from CIN-3 have declined over time

1. Risks for pregnancy-related complications after treatment from CIN-3 have declined over time

Women treated for these cervical lesions should be managed as ‘high risk’ to reduce risk of preterm birth, infant sepsis, and other adverse outcomes

Abstract: https://www.acpjournals.org/doi/10.7326/M21-2793

Editorial: https://www.acpjournals.org/doi/10.7326/M21-4666

URL goes live when the embargo lifts

A population-and-sibling-match cohort study of pregnant individuals found that a history of treatment for cervical intraepithelial neoplasia grade 3 (CIN3) is associated with adverse pregnancy outcomes even after accounting for familial factors, but the risk has declined over time and the risk for infant death no longer exists. A possible explanation for this is less invasive treatment methods for prodromal cervical cancer. Still, pregnancies after treatment of CIN3 should be managed as ‘high risk’ to decrease the risk for such outcomes. The findings are published in Annals of Internal Medicine.

CIN3 treatment may involve the removal or destruction of the cervix, possibly impacting its function. Observational studies have linked histories of treatment for CIN3 with higher risk of preterm delivery and other adverse outcomes. However, previous studies have compared individuals with histories of CIN3 treatment to patients in the same hospital or the general population without accounting for familial factors.

Researchers from Zhejiang University, Hangzhou, Zhejiang, China and the Karolinska Institutet, Stockholm, Sweden used data from 5 national Swedish registriesused data from 5 national Swedish registries with complete population data on pregnancies, cancer diagnoses, and demographic information to investigate pregnancy outcomes in women diagnosed with CIN3. The registry included data for a total of 4.6 million births between 1973 and 2018 and the researchers identified 78,450 births after a maternal CIN3 diagnosis and matched them to 784,500 births to women without a CIN3 diagnosis. The 2 cohorts were closely or exactly matched for factors including calendar period of delivery, age at delivery, Swedish health care region, years of education, country of birth, preeclampsia diagnosis, marital status, parity, pre-pregnancy body mass index, and smoking in early pregnancy. The authors also matched full sisters for scenarios in which one gave birth with a history of CIN3 treatment and the other gave birth without. The authors found that women with a prior CIN3 diagnosis had higher risks of preterm birth and related adverse pregnancy outcomes, such as chorioamnionitis and infant sepsis, than their CIN3-free sisters or population match. According to the authors, association of CIN3 with many adverse outcomes seems to decrease over the 46-year period for which data was available, suggesting that more conservative treatment methods may minimize subsequent adverse birth outcomes. The authors note that their results suggest that more caution should be taken for screen-and-treat approaches to CIN3, as overtreatment of the cervix may lead to more adverse pregnancy outcomes.

An editorial from Boston University School of Medicine notes that while pregnancies after treatment of CIN3 be managed as high risk to decrease adverse outcomes, the optimal clinical care remains unclear. The authors suggest that HPV vaccination will lead to fewer incidents of adverse pregnancy outcomes in the future. They cite Australia as an example, which has seen a 3.2% population-wide decrease in preterm births and a 9.8% decrease in small-for-gestational-age infants after widespread HPV vaccination.

Media contacts: For an embargoed PDF, please contact Angela Collom at acollom@acponline.org. The corresponding author, Wei He, PhD, contact the Karolinska Institutet press office at pressinfo@ki.se.

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2. Physicians debate best screening strategy for cervical cancer prevention after HPV vaccination

‘Beyond the Guidelines’ features are based on the Department of Medicine Grand Rounds at Beth Israel Deaconess Medical Center

Abstract: https://www.acpjournals.org/doi/10.7326/M21-0724

URL goes live when the embargo lifts

In a new Annals ‘Beyond the Guideline’s feature, two experts debate the most appropriate test and interval for a young patient who has not yet undergone cervical cancer screening but has received HPV vaccination. All ‘Beyond the Guidelines’ features are based on the Department of Medicine Grand Rounds at Beth Israel Deaconess Medical Center (BIDMC) in Boston and include print, video, and educational components published in Annals of Internal Medicine. 

Cervical cancer currently has one of the lowest case rates of any cancer due to improved screening methods and programs. In recent years, the U.S. Preventive Services Task Force (USPSTF) and the American Cancer Society (ACS) have released differing guidelines for screening. The USPSTF recommends that screening start at age 21, continue and through age 29 with cytologic screening every 3 years, then move to any of the following scenarios through age 65: cytology every 3 years, high-risk HPV (hrHPV) testing every 5 years, or cytology with hrHPV co-testing every 5 years. The ACS recommends that screening start at age 25 and then continue every 5 years until age 65, with hrHPV testing (alone) being the preferred screening method for any age.

BIDMC Grand Rounds discussants, Doctors Amy Weinstein and Huma Farid, recently debated the case of a 22-year-old woman who has not yet undergone cervical cancer screening and who has received HPV vaccination.

In their assessment, both Drs. Weinstein and Farid agree that the patient’s vaccination status should not impact screening choices or intervals at that time. Because of the patient’s age and medical history, Dr. Weinstein recommends that she begin hrHPV screening at age 25 to avoid unnecessary testing. Dr. Farid recommends that the patient should undergo screening now because she is overdue for screening under USPSTF guidelines. Both clinicians also agree that as the rate of HPV vaccination increases, cervical cancer will be less common, and guidelines will need to evolve to include later start ages, longer intervals, and less testing for patients who have been vaccinated.

A complete list of ‘Beyond the Guidelines’ topics is available at www.annals.org/grandrounds.

Media contacts: For an embargoed PDF, please contact Angela Collom at acollom@acponline.org. To speak with corresponding author, Eileen E. Reynolds, MD, contact Kendra McKinnon at Kmckinn1@bidmc.harvard.edu.

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