Dirk Olaf Bauerschlag

Challenges in the Diagnosis and Individualized Treatment of Cervical Cancer

Cervical cancer is still the fourth most common cancer in women throughout the world; an estimated 604,000 new cases were observed in 2020. Better knowledge of its pathogenesis, gained in recent years, has introduced new preventive and diagnostic approaches. Knowledge of its pathogenesis has made it possible to provide individualized surgical and drug treatment. In industrialized countries, cervical cancer has become a less frequent tumor entity due to the accessibility of the human papilloma virus vaccination, systematic preventive programs/early detection programs, health care infrastructure and the availability of effective therapy options. Nevertheless, globally, neither mortality nor morbidity has been significantly reduced over the past 10 years, and therapy approaches differ widely. The aim of this review is to address recent advances in the prevention, diagnostic investigation and treatment of cervical cancer globally, focusing on advances in Germany, with a view toward providing an updated overview for clinicians. The following aspects are addressed in detail: (a) the prevalence and causes of cervical cancer, (b) diagnostic tools using imaging techniques, cytology and pathology, (c) pathomechanisms and clinical symptoms of cervical cancer and (d) different treatment approaches (pharmacological, surgical and others) and their impact on outcomes.

Assessing the Phenotype of a Homologous Recombination Deficiency Using High Resolution Array-Based Comparative Genome Hybridization in Ovarian Cancer

Ovarian cancer (OC) cells with homologous recombination deficiency (HRD) accumulate genomic scars (LST, TAI, and LOH) over a value of 42 in sum. PARP inhibitors can treat OC with HRD. The detection of HRD can be done directly by imaging these genomic scars, or indirectly by detecting mutations in the genes involved in HR. We show that HRD detection is also possible using high-resolution aCGH. A total of 30 OCs were analyzed retrospectively with high-resolution arrays as a test set and 19 OCs prospectively as a validation set. Mutation analysis was performed by HBOC TruRisk V2 panel to detect HR-relevant mutations. CNVs were clustered with respect to the involved HR genes versus the OC cases. In prospective validation, the HRD status determined by aCGH was compared with external HRD assessments. Two BRCA mutation carriers did not have HRD. OC could approximately differentiate into two groups with characteristic CNV patterns with different survival rates. Mutation frequencies have a linear regression on the HRD score. Mutations in individual HR-relevant genes do not always indicate HRD. This may depend on the mutation frequency in tumor cells. The aCGH shows the genomic scars of an HRD inexpensively and directly.