Karoliina Aro

Clinicopathologic stratification demonstrates survival differences between endometrial carcinomas with mismatch repair deficiency and no specific molecular profile: a cohort study

Endometrial carcinomas with mismatch repair deficiency (MMRd) and no specific molecular profile (NSMP) are considered to have intermediate prognoses. However, potential prognostic differences between these molecular subgroups remain unclear due to the lack of standardized control for clinicopathologic factors. This study aims to evaluate outcomes of MMRd and NSMP endometrial carcinomas across guideline-based clinicopathologic risk groups. This study analyzed patients treated at a single tertiary center. Immunohistochemistry and polymerase-ϵ sequencing were performed for molecular classification. MLH1-deficient tumors underwent methylation-specific multiplex ligation-dependent probe amplification. Carcinomas were classified into clinicopathologic risk groups according to European guidelines. The analysis included 420 MMRd and 399 NSMP carcinomas. Among MMRd cases, 224 were subcategorized as MLH1-methylated or MLH1-non-methylated. Median follow-up was 71 months (range; 1-136). Survival differences were most notable in clinicopathologic medium-risk carcinomas, with the MMRd subgroup exhibiting poorer progression-free, disease-specific, and overall survival compared to NSMP. Adjusting for age and adjuvant therapy, MMRd still showed an association with progression-free survival. Both MLH1-methylated (n = 154) and MLH1-non-methylated tumors (n = 70) were associated with more aggressive clinicopathologic risk groups compared to NSMP, but only methylated tumors showed poorer outcomes. The distinct outcomes for MMRd and NSMP in the clinicopathologic medium-risk group suggest that uterine risk factors may worsen the prognosis for MMRd endometrial carcinomas. Advanced stage may be the primary factor contributing to poor outcomes in high-risk-advanced metastatic carcinomas. Clinicopathologic factors may particularly worsen the prognosis of MLH1-methylated carcinomas.

Predictors for regression and progression of actively surveilled cervical intraepithelial neoplasia grade 2: A prospective cohort study

AbstractIntroductionTo evaluate predicting clinical factors for regression and progression of cervical intraepithelial neoplasia (CIN) grade 2 (CIN2) in young women during two years of active surveillance.Material and MethodsThis was a single‐center prospective observational cohort study. Women under 31 years of age giving written informed consent with histologically confirmed CIN2 were followed with colposcopy, cytology, and biopsies every 6 months up to 24 months. At baseline, HPV genotyping was performed on cervical samples. The rates of regression and progression were recorded for every timepoint and at the end of study overall and stratified according to clinical factors and HPV genotypes at baseline. Risk ratio (RR) was used to estimate the relative risks for regression and progression. The study was registered in the ISRCTN registry (ISRCTN91953024).ResultsIn total, 205/243 (84.4%) women completed the study. Complete regression (normal histology and/or normal or atypical squamous cells of undetermined significance (ASC‐US) cytology) was detected in 64.4.% (n = 132) while 16.1% (n = 33) of the lesions progressed to CIN grade 3 (CIN3) or worse including 31 CIN3 cases, one adenocarcinoma in situ and one cervical cancer case. Factors associated with progression were initial large (>50% of the transformation zone) lesion size, risk ratio (RR) 3.06 (95% confidence interval (CI) 1.40–6.69), and high‐grade referral cytology RR 4.73 (95% CI 1.18–19.03). Compared with baseline HPV negativity or having only low‐risk HPV genotypes present, high‐risk HPV (hrHPV) positivity was associated with lower likelihood of regression RR 0.74 (95% CI 0.60–0.91). Age, cigarette smoking, use of combined oral contraceptives or baseline high‐risk HPV genotype, including HPV16, were not associated with the outcomes.ConclusionsThe majority of CIN2 lesions regress in young women. Women with large lesions and/or high‐grade referral cytology should perhaps more often be treated instead of active surveillance. Initial hrHPV genotype does not appear to predict outcomes while not harboring hrHPV favors regression.

Randomised trial on treatment of vaginal high‐grade squamous intraepithelial lesion: Self‐administered vaginal imiquimod and laser vaporisation

AbstractHigh grade vaginal squamous intraepithelial lesion (HSIL) (or vaginal intraepithelial neoplasia; VAIN) is a rare human papillomavirus (HPV)‐related cancer precursor, which is commonly treated with laser vaporisation or other surgical methods to prevent progression to invasion. Vaginal HSIL has a substantial tendency to relapse despite treatment, for which HPV persistence is a known risk factor. Imiquimod is a topically applied immunomodulator and has shown promise in the treatment of high‐grade HPV‐related genital cancer precursors. The aim of this study was to assess the efficacy and patient compliance of self‐administered vaginal imiquimod in comparison to laser vaporisation in the treatment of vaginal HSIL. We recruited 56 women with histological vaginal HSIL into a randomised controlled trial of laser vaporisation and self‐administered vaginal imiquimod with follow‐up up to 6 months. Follow‐up visits included colposcopy, punch biopsies, and cervical or vaginal swabs for HPV genotyping. In per protocol analyses of 26 women in the laser arm and 27 women in the imiquimod arm, 53.8% and 77.8% (p = 0.07), respectively, showed histological regression at the end of the study. No progressions to invasion were detected during the study period. Genotype‐specific post‐treatment negativity for HPV occurred in 16.7% of the laser group and in 39.1% of the imiquimod group (p = 0.12). Imiquimod had short‐term adverse effects, but 93% completed treatment as instructed. We conclude that vaginal imiquimod is an effective treatment for vaginal HSIL and could be considered an alternative to laser vaporisation.