Background

Invasive cervical carcinoma is associated with a human immunodeficiency virus (HIV) prevalence of >0.1%, and screening is recommended and cost-effective for cancer populations exceeding this threshold. HIV status is also prognostic for cancer-specific survival, but compliance with HIV screening is poor in the USA and abroad.

Objectives

This study aims to describe HIV screening practices in a US comprehensive cancer center. To guide quality improvement, we identify characteristics which may predict compliance with screening.

Study design

Women treated for invasive cervical cancer from January 2007 to December 2017 were identified by local cancer registry and billing data. We assessed age, race, ethnicity, insurance status, histology, stage, pregnancy, drug use, and HIV testing status. Univariate logistical regression was performed to assess predictors of completed HIV screening.

Results

Of 492 eligible women, the cumulative screening rate was 7.6%. Race, ethnicity, histology, and funding source were not predictive of screening. Every 5 year increase in age was associated with a lower chance of screening (OR 0.86, p=0.015), as was earlier stage at diagnosis (OR 0.43, p=0.017). Pregnancy during, or antecedent to, invasive cervical cancer diagnosis was significantly more predictive of screening compliance (OR 10.57, p=0.0007). Only 8/492 (1.6%) women in the cohort were active or former drug users, but within this group HIV screening was performed more frequently (OR 22.7, p<0.0001).

Conclusion

Despite US and international recommendations for HIV screening in AIDS-defining cancers, compliance remains low. In our centers, factors including earlier age, advanced stage, active pregnancy at diagnosis, and any drug use history were predictive of greater compliance with screening. These data will inform a tailored intervention to improve compliance with HIV screening in our population.

Purpose

Ovarian and uterine clear cell carcinomas (CCCs) are rare but associated with poor prognosis. This study explored RNA transcription patterns characteristic of these tumors.

Experimental design

RNA sequencing (RNA-seq) of 11 ovarian CCCs and five uterine CCCs was performed and compared to publicly available data from high grade serous ovarian cancers (HGSOCs). Ingenuity Pathway Analyses were performed. CIBERSORT analyses estimated relative fractions of 22 immune cell types in each RNA-seq sample. Sequencing data was correlated with PD-L1 immunohistochemical expression.

Results

RNA-seq revealed 1,613 downregulated and 1,212 upregulated genes (corrected p < 0.05, |FC |≥10) in ovarian CCC versus HGSOC. Two subgroups were identified in the ovarian CCC, characterized by ethnicity and expression differences in ARID1A. There were 3,252 differentially expressed genes between PD-L1+/- ovarian CCCs, revealing immune response, cell death, and DNA repair networks, negatively correlated with PD-L1 expression, whereas cellular proliferation networks positively correlated with expression. In clear cell ovarian versus clear cell uterine cancer, 1,607 genes were significantly upregulated, and 109 genes were significantly downregulated (corrected p < 0.05, |FC|≥10). Comparative pathway analysis of late and early stage ovarian CCCs revealed unique metabolic and PTEN pathways, whereas uterine CCCs had unique Wnt/Ca+, estrogen receptor, and CCR5 signaling. CIBERSORT analysis revealed that activated mast cells and regulatory T cell populations were relatively enriched in uterine CCCs. The PD-L1+ ovarian CCCs had enriched resting NK cells and memory B cell populations, while PD-L1- had enriched CD8 T-cells, monocytes, eosinophils, and activated dendritic cells.

Conclusions

Unique transcriptional expression profiles distinguish clear cell uterine and ovarian cancers from each other and from other more common histologic subtypes. These insights may aid in devising novel therapeutics.

Objectives

To compare clinical outcomes for stage IIIC and IV ovarian cancer patients receiving neoadjuvant chemotherapy and interval cytoreductive surgery followed by up to three versus more cycles of post-operative chemotherapy.

Methods

We conducted a multi-institution retrospective cohort study of patients treated from January 2005 to February 2016 with neoadjuvant platinum-based therapy followed by interval surgery and post-operative chemotherapy. The following were exclusion criteria: more than four cycles of neoadjuvant chemotherapy, bevacizumab with neoadjuvant chemotherapy, non-platinum therapy, prior chemotherapy, and elevated CA125 values after three post-operative chemotherapy cycles. Progression-free and overall survival and toxicity profiles were compared between groups receiving up to three cycles versus more that three cycles post-operatively.

Results

A total of 100 patients met inclusion criteria: 41 received up to three cycles and 59 received more than three cycles. The groups were similar in terms of age, body mass index, performance status, tumor histology, optimal cytoreduction rates, and median number of neoadjuvant chemotherapy cycles. Median progression-free survival was 14 vs 16.6 months in those receiving up to three cycles versus more than three cycles, respectively (HR 0.99, 95% CI 0.58 to 1.68, p=0.97). Similarly, median overall survival was not different at 47.1 vs 69.4 months, respectively (HR 1.96, 95% CI 0.87 to 4.42, p=0.10). There were no differences in grade 2 or higher chemotherapy-related toxicities.

Conclusions

Extending post-operative chemotherapy beyond three cycles in patients receiving neoadjuvant chemotherapy and interval cytoreductive surgery with normalization of CA125 levels was not associated with improved survival or greater toxicity. Future study in a larger cohort is warranted to define optimal length of cytotoxic treatment.