Search

Tumor cells release fragments of their DNA into the circulation, so called cell-free tumor DNA (ctDNA), allowing for analysis of tumor DNA in a simple blood test, that is, liquid biopsy. Cervical cancer is one of the most common malignancies among women worldwide and high-risk human papillomavirus (HR-HPV) is the cause of the majority of cases. HR-HPV integrates into the host genome and is often present in multiple copies per cell and should thus also be released as ctDNA. Such ctHPV DNA is therefore a possible biomarker in cervical cancer. In this review, we first give a background on ctDNA in general and then a comprehensive review of studies on ctHPV DNA in cervical cancer and pre-malignant lesions that may develop in cervical cancer. Furthermore, studies on ctHPV DNA in other HPV related malignancies (eg, head-and-neck and anogenital cancers) are briefly reviewed. We conclude that detection of ctHPV DNA in plasma from patients with cervical cancer is feasible, although optimized protocols and ultra-sensitive techniques are required for sufficient sensitivity. Results from retrospective studies in both cervical cancer and other HPV-related malignancies suggests that ctHPV DNA is a promising prognostic biomarker, for example, for detecting relapses early. This paves the way for larger, preferably prospective studies investigating the clinical value of ctHPV DNA as a biomarker in cervical cancer. However, there are conflicting results whether ctHPV DNA can be found in blood from patients with pre-malignant lesions and further studies are needed to fully elucidate this question.

Tubal ligation results in less advanced stages and lower risk of metastatic spread at diagnosis of endometrial cancer (EC) but the primary preventive effect of the procedure is unclear. In a Swedish nationwide population-based cohort study, we crosslinked registry data for tubal ligation, EC, and death for Swedish women between 1973 and 2010. All women were followed until EC, emigration, hysterectomy for non-cancerous reasons, death, or end of follow-up. Primary outcome was incidence of EC and secondary outcome overall survival. We calculated adjusted incidence rates (IR) per 100,000 person-years and hazard ratios (HR) using Cox regression models. A total of 35,711 cases of EC were identified among 5,385,186 women. The IR of EC among exposed was 17.7 (95% CI 15.7-19.9) versus 29.0 (95% CI 28.7-29.3) among unexposed (per 100,000 women years). Exposed individuals had significantly reduced risk of EC (HR 0.73, 95% CI 0.65-0.83). The mortality rate among women with EC was 72% lower in exposed compared to unexposed (IR 1,441; 95% CI 1,089-1,907 and IR 5,136; 95% CI 5,065-5,209, respectively) which following adjustment corresponded to a HR of 0.71 (95% CI 0.49-1.03). Tubal ligation was associated with lower risk of EC as well as mortality rates in women with EC. Elective tubal ligation may be adopted in future cancer preventive strategies but must be balanced against the irreversibility of the procedure, which preclude further unassisted reproduction.

Hysterectomy on benign indications is associated with an increased risk for adverse health effects. However, little is known about the association between hysterectomy and subsequent cancer occurrence later in life. The purpose of this study was to assess the effect of hysterectomy on the incidence of cancer. In this population-based cohort study, we used data on 111,595 hysterectomized and 537,9843 nonhysterectomized women from nationwide Swedish Health Care registers including the Inpatient Register, the Cancer Register and the Cause of Death Register between 1973 and 2009. Hysterectomy with or without concomitant bilateral salpingo-ophorectomy (BSO) performed on benign indications was considered as exposure and incidence of primary cancers was used as outcome measure. Rare primary cancers (

Tubal ligation results in less advanced stages and lower risk of metastatic spread at diagnosis of endometrial cancer (EC) but the primary preventive effect of the procedure is unclear. In a Swedish nationwide population-based cohort study, we crosslinked registry data for tubal ligation, EC, and death for Swedish women between 1973 and 2010. All women were followed until EC, emigration, hysterectomy for non-cancerous reasons, death, or end of follow-up. Primary outcome was incidence of EC and secondary outcome overall survival. We calculated adjusted incidence rates (IR) per 100,000 person-years and hazard ratios (HR) using Cox regression models. A total of 35,711 cases of EC were identified among 5,385,186 women. The IR of EC among exposed was 17.7 (95% CI 15.7-19.9) versus 29.0 (95% CI 28.7-29.3) among unexposed (per 100,000 women years). Exposed individuals had significantly reduced risk of EC (HR 0.73, 95% CI 0.65-0.83). The mortality rate among women with EC was 72% lower in exposed compared to unexposed (IR 1,441; 95% CI 1,089-1,907 and IR 5,136; 95% CI 5,065-5,209, respectively) which following adjustment corresponded to a HR of 0.71 (95% CI 0.49-1.03). Tubal ligation was associated with lower risk of EC as well as mortality rates in women with EC. Elective tubal ligation may be adopted in future cancer preventive strategies but must be balanced against the irreversibility of the procedure, which preclude further unassisted reproduction.

Hysterectomy on benign indications is associated with an increased risk for adverse health effects. However, little is known about the association between hysterectomy and subsequent cancer occurrence later in life. The purpose of this study was to assess the effect of hysterectomy on the incidence of cancer. In this population-based cohort study, we used data on 111,595 hysterectomized and 537,9843 nonhysterectomized women from nationwide Swedish Health Care registers including the Inpatient Register, the Cancer Register and the Cause of Death Register between 1973 and 2009. Hysterectomy with or without concomitant bilateral salpingo-ophorectomy (BSO) performed on benign indications was considered as exposure and incidence of primary cancers was used as outcome measure. Rare primary cancers (100 cases for the two groups combined) were excluded from analysis. A marginal risk reduction for any cancer was observed for women with previous hysterectomy and for those with hysterectomy and concurrent BSO (HR 0.93, 95% CI 0.91-0.95 and HR 0.92, 95% CI 0.87-0.96, respectively). Compared to nonhysterectomized women, significant risks were observed for thyroid cancer (HR 1.76, 95% CI 1.45-2.14). For both hysterectomy and hysterectomy with BSO, an association with brain cancer was observed (HR 1.48, 95% CI 1.32-1.65 and HR 1.45, 95% CI 1.15-1.83, respectively). Hysterectomy, with or without BSO, was not associated with breast, lung or gastrointestinal cancer. We conclude that hysterectomy on benign indications is associated with an increased risk for thyroid and brain cancer later in life. Further research efforts are needed to identify patient groups at risk of malignancy following hysterectomy.