Cervical cancer: Part I human papilloma virus vaccination in Taiwan.

A significant decline in both incidence and prevalence of cervical cancers after widespread-introducing cervical screening strategy by Papanicolau test (Pap test) has been found in the world, but cervical cancer is still one of the most common female cancers, reporting the fourth prevalence and also one of the leading causes to result in main women-associated morbidity and mortality, particularly for those women living in low- and middle-income countries. Cervical cancer is one of the most important health concerns directly destroying the global health-care system, partly because of not only increasing the disability either secondary to diseases themselves of victims or mediated by treatment-related adverse events to the survivors but also acting as a leading cause of death of diseased patients worldwide, alarming the urgent need to do something to minimize the catastrophic diseases-related heavy socioeconomic burden. It is fortunate that cervical cancer is a preventable disease, based on its strong association with human papillomavirus (HPV) infection (more than 95%), particularly for those high-risk HPV (HR-HPV) and its high possibility by detecting HPV infection before the development of cervical cancer as well as an effective prevention by HPV vaccination. That is why WHO (World Health Organization) considers cervical cancer as a public problem and attempts to accelerate the elimination of cervical cancer program by three-pillar approach (90:70:90% targets), including (1) 90% of girls are fully vaccinated with HPV vaccine by 15 years of age; (2) 70% of women are screened with a high-performance test by 35 and 45 years of age and precancerous lesions are treated early; and (3) 90% of women identified with cervical diseases receive appropriate and adequate treatment. Herein, this review focuses on the HPV vaccination as Part I, including global recommendations and Taiwan government's policy for HPV vaccination.

Front-line chemoimmunotherapy for treating epithelial ovarian cancer: Part II promising results of phase 2 study of paclitaxel-carboplatin-oregovomab regimen.

In the Part I, we have discussed the background of CA125 and the development of anti-CA125 monoclonal antibody (MAb) to highlight the potential role of CA125 and anti-CA125 MAb in the management of women with advanced stage epithelial ovarian cancer (EOC). Glycosylation change either by N-link or by O-link of CA125 is supposed to play a role in the modification of immunity. Anti-CA125 MAb, which can be classified as OC 125-like Abs, M11-like Abs, and OV197-like Abs, is often used for diagnosing, screening, monitoring and detecting the mesothelin-related diseases of the abdominal cavity, particular for those women with EOC. Additionally, anti-CA125 MAb also plays a therapeutic role, named as OvaRex MAb-B43.13 (oregovomab), which has also been extensively reviewed in the Part I review article. The main mechanisms include (a) forming CA125 immune complexes to activate the antigen-presenting cells; (b) triggering induction of CA125-specific immune responses, including anti-CA125 Abs against various epitopes and CA125-specific B and T cell responses; and (c) triggering CD4 and CD8 T-cell responses specific for B43.13 to produce specific and non-specific immune response. With success in vitro, in vivo and in primitive studies, phase II study was conducted to test the effectiveness of chemoimmunotherapy (CIT) for the management of EOC patients. In the 97 EOC patients after optimal debulking surgery (residual tumor <1 cm or no gross residual tumor), patients treated with CIT had a dramatical and statistically significant improvement of both progression-free survival (PFS) and overall survival (OS) compared to those treated with chemotherapy alone with a median PFS of 41.8 months versus 12.2 months (hazard ratio [HR] 0.46, 95 % confidence interval [CI] 0.28-0.7) and OS not yet been reached (NE) versus 42.3 months (HR 0.35, 95 % CI 0.16-0.74), respectively. The current review as Part II will explore the possibility of using CIT as front-line therapy in the management of advanced-stage EOC patients after maximal cytoreductive surgery based on the evidence by many phase 2 studies.

Front-line chemo-immunotherapy for treating epithelial ovarian cancer: Part I CA125 and anti-CA125.

The current standard therapy of epithelial ovarian cancer (EOC) is the combination of surgery (primary cytoreductive surgery or interval cytoreductive surgery) and platinum-based chemotherapy (mainly using paclitaxel and carboplatin either by neoadjuvant chemotherapy and/or by postoperative adjuvant chemotherapy) with/without adding targeted therapy (mainly using anti-angiogenesis agent- bevacizumab). After front-line chemotherapy, the advanced-stage EOC can be successfully controlled and three-quarters of patients can achieve a complete clinical remission. Unfortunately, nearly all patients will recur and progression-free survival (PFS) of these patients is seldom more than 3 years with a dismal median PFS of 12-18 months. With each recurrence, patients finally develop resistance to standard chemotherapy regimen, contributing to fewer than half of women who survive for more than 5 years after diagnosis with a median overall survival (OS) of 40.7 months. Due to the lower PFS and OS, particularly for those advanced-stage patients, novel therapeutic options during the front-line therapy are desperately needed to decrease the occurrence of recurrence, and the majority of them are still under investigation. It is well-known that overexpression of CA125 has been associated with attenuated cellular apoptosis, platinum chemotherapy resistance, tumor proliferation and disease progression, suggesting that anti-CA125 may play a role in the management of patients with EOC. The current review is a Part I which will focus on development of anti-CA125 monoclonal antibody, hoping that alternation of the front-line therapy by chemo-immunotherapy will be beneficial for prolonged survival of patients with EOC.