Sofie Lindquist

Clinical performance of human papillomavirus based cervical cancer screening algorithm: The result of a large Danish implementation study

AbstractIntroductionIn Denmark, where human papillomavirus (HPV) ‐based cervical cancer screening is being implemented, the aim of this pilot implementation study was to test a specific screening algorithm, assess follow‐up examination attendance, and measure the proportion of precancer lesions found in relation to the number of women referred for colposcopy.Material and MethodsFrom May 2017 to December 2020, 36 417 women in the uptake area of the Department of Pathology, Vejle Hospital, Region of Southern Denmark, were included in the HPV group. Women positive for HPV16/18 irrespective of cytology and women positive for other high‐risk HPV (hrHPV) types having concomitant abnormal cytology were referred directly to colposcopy. Women positive for other hrHPV types and normal cytology were referred to repeat screening after 12 months, and hrHPV negative to routine screening after three years. We obtained information on screening results and subsequent histological diagnosis from the Danish Pathology Databank through September 2022.Results3.6% of the women were referred to colposcopy after primary screening, 5% to repeat screening after 12 months, and 91.4% back to routine screening. High follow‐up rates were observed: 96% attended colposcopy after primary screening, with 91% attending colposcopy after repeat screening. CIN3+ was detected at colposcopy following the primary screening in 28.1% of HPV16/18‐positive women and 18.2% of those positive for other hrHPV types with concomitant abnormal cytology. Of the women with other hrHPV and simultaneous ASCUS/LSIL, 8% had CIN3+. At the repeat screening, 43% had become hrHPV negative, 55% were persistently positive for other hrHPV, and 2% had turned positive for HPV16/18. At the colposcopy following repeat screening, 10.1% of the women positive for other hrHPV were diagnosed with CIN3+, in comparison with 11.1% of the HPV16/18‐positive women.ConclusionsIn this pilot implementation study, an algorithm for HPV‐based screening was evaluated in a Danish setting. The results demonstrated high attendance at follow‐up examinations and provided insights into the number of colposcopy referrals and the detection of CIN2 and CIN3+ cases. The results suggest that women testing positive for other hrHPV in combination with ASCUS/LSIL at primary screening could potentially be referred to repeat screening instead of an immediate colposcopy.

The risk of vaginal, vulvar and anal precancer and cancer according to high‐risk HPV status in cervical cytology samples

AbstractHigh‐risk human papillomavirus (hrHPV) is the cause of virtually all cervical cancers, most vaginal and anal cancers, and some vulvar cancer cases. With HPV testing becoming the primary screening method for cervical cancer, understanding the link between cervical hrHPV infection and the risk of other anogenital cancers is crucial. We assessed the risk of vulvar, vaginal and anal cancer and precancer (VIN2+, VaIN2+ and AIN2+) in a prospective cohort study including 455,349 women who underwent cervical hrHPV testing in Denmark from 2005 to 2020. We employed Cox proportional hazard models, adjusting for age, calendar year and HPV vaccination status, and estimated hazard ratios (HRs) and 95% confidence intervals (CI). We used the Aalen Johansen estimator to calculate the absolute risks of VIN2+, VaIN2+ and AIN2+. In total, 15% of the women were hrHPV positive at baseline. A positive cervical hrHPV test was associated with increased incidence of vulvar, vaginal and anal squamous cell carcinoma (SCC). Five‐year risk estimates of VIN2+, VaIN2+ and AIN2+ among hrHPV‐positive women (0.45%, 0.14% and 0.12%) were higher than among hrHPV‐negative women (0.14%, 0.01% and 0.05%). Particularly high risk was observed among the hrHPV‐positive women of the oldest age, with a history of anogenital precancer and those not HPV vaccinated. In conclusion, our study confirms the association between cervical hrHPV infection and non‐cervical anogenital precancers and cancers. Currently, no established risk threshold or guidelines for follow‐up. As HPV testing becomes the primary method for cervical cancer screening, future data will help define high‐risk groups and acceptable risk thresholds.

Risk of Epithelial Ovarian Tumors among Women Diagnosed with Hypothyroidism and Hyperthyroidism: Findings from a Large Nationwide Cohort Study

Abstract Background: Prior research on the association between thyroid disease, ovarian cancer, and borderline ovarian tumors has been inconsistent. This nationwide cohort study investigated the risk of epithelial ovarian cancer and borderline ovarian tumors among 1,058,745 Danish women born between January 1, 1960, and December 31, 1997, and were followed until December 31, 2022, in relation to hypothyroidism and hyperthyroidism. Methods: Data on thyroid diagnoses, ovarian tumors, covariates, migration, and vital status were retrieved from Danish national registers. Hazard ratios (HR) and 95% confidence intervals (CI) for ovarian cancer and borderline ovarian tumors overall and for histologic subtypes were estimated using adjusted Cox proportional hazard models. A landmark analysis assessed ovarian tumor risk at age 60 years by thyroid disease status before age 40 years. Results: Over a median of 18.4 years of follow-up, 49,015 women developed hypothyroidism, 26,950 hyperthyroidism, 905 ovarian cancer, and 1,111 borderline ovarian tumors. No association was found between hypothyroidism and ovarian cancer (HR, 1.10; CI, 0.78–1.55) or borderline tumors (HR, 0.88; CI, 0.60–1.29). Hyperthyroidism was associated with increased rates of serous ovarian cancer (HR, 1.62; CI, 1–2.63) and borderline ovarian tumors (HR, 1.78; CI, 1.26–2.52), especially in postmenopausal and premenopausal women, respectively. However, absolute risk differences at age 60 years were small and not statistically significant. Conclusions: Hyperthyroidism may increase the rate of epithelial ovarian tumors, though clinical significance remains unclear, warranting further research. Impact: These findings indicate that hyperthyroidism may modestly influence epithelial ovarian tumor risk, underscoring the need to clarify shared biological mechanisms between thyroid and ovarian function.