Low‐ and middle‐income countries carry a high burden of preventable cervical cancer cases and deaths. Because human papillomavirus DNA‐based testing is increasingly becoming the preferred method of screening for cervical cancer prevention, this commentary discusses next steps and key considerations for its expansion.

Many studies have suggested that renal T cell infiltration contributes to the pathogenesis of salt-sensitive hypertension. To investigate this mechanism further, we determined T cell profiles in the kidney and lymphoid tissues as a function of blood pressure in the female Envigo Dahl salt-sensitive (SS) rat maintained on low-Na+ (LS) diet. Mean arterial pressure and heart rate were measured by telemetry in SS rats from 1 mo old (juvenile) to 4 mo old. Normotensive salt-resistant (SR) rats were included as controls. Frequencies of T helper (CD4+) cells were greater in the kidney, lymph nodes, and spleen in 4-mo-old hypertensive SS rats compared with normotensive SR animals and SS juvenile rats, suggesting that renal T cell infiltration contributes to hypertension in the SS rat on a LS diet. At 1.5 mo, half of the SS rats were treated with vehicle (Veh), and the rest received hydralazine (HDZ; 25 mg·kg−1·day−1) for 11 wk. HDZ impeded the development of hypertension compared with Veh-treated control rats [mean arterial pressure: 157 ± 4 mmHg in the Veh-treated group ( n = 6) vs. 133 ± 3 mmHg in the HDZ-treated group ( n = 7), P < 0.001] without impacting T helper cell frequencies in the tissues, suggesting that HDZ can overcome mechanisms of hypertension driven by renal T cell infiltration under the LS diet. Renal frequencies of CD4+CD25+ and CD4+CD25+FoxP3+ regulatory T cells were significantly higher in 4-mo-old hypertensive rats compared with normotensive SR rats and SS juvenile rats, suggesting that these T cell subpopulations play a compensatory role in the development of hypertension. Greater understanding of these T cell populations could lead to new therapeutic targets for treating inflammatory diseases associated with hypertension.

Introduction: Several studies have shown that ovariectomy increases blood pressure and that 17beta-estradiol ( E 2 ) treatment can attenuate this effect; however, the majority of these studies were conducted in young animals in which E 2 replacement was initiated soon after ovariectomy. Since most women who experience ovarian hormone loss are middle aged rather than young, this study investigated the effect of E 2 replacement in middle aged Dahl salt-sensitive ( DS ) rats. In addition, the time at which E 2 replacement was initiated was examined. Methods: DS rats were ovariectomized ( OVX ) at 4.5 months ( mo ) ( DS-OVX Y ) and 7mo ( DS-OVX O ). At 7mo, half of OVX DS rats in each group were treated with E 2 for 4 weeks ( DS-OVX Y +E 2 , DS-OVX O +E 2 ). Mean arterial pressure ( MAP ) was measured by telemetry in all treatment groups from 7-8mo. Body weights were measured throughout the experiment and plasma angiotensin II ( AngII ) was determined at time of sacrifice (8mo) by RAS fingerprint. Results: E 2 treatment at 7mo had no effect on MAP in the DS rats OVX at early age [MAP (mmHg) at 8mo: DS-OVX Y , 180±5.3 vs. DS-OVX Y +E 2 , 179±4.6, ns; n=4/group]. In contrast, one month of E 2 treatment prevented the ovariectomy-induced increase in MAP when OVX at late age [MAP (mmHg): DS-OVX O , 191±1.6 vs. DS-OVX O +E 2 , 177±2.9, p<0.0001 (Two-way ANOVA); n=4/group]. E 2 reduced the body weight ( BW ) by 26g in the DS-OVX Y group and prevented the ovariectomy-induced gain in BW by 39g in the DS-OVX O rats [BW(g): DS-OVX Y , 349±9 vs. DS-OVX Y +E 2 323±7, p<0.05; DS-OVX O , 334±7 vs. DS-OVX O +E 2 , 295±6, p<0.01; n=7-9/group]. E 2 also reduced plasma AngII in both the DS-OVX Y and DS-OVX O groups to similar extents [AngII (pg/ml): DS-OVX Y , 112±19 vs. DS-OVX Y +E 2 , 68.0±7.8, p<0.05; DS-OVX O , 113±11 vs. DS-OVX O +E 2 , 63.9±6.1, p<0.05; n=7-9/group]. Conclusions: These findings suggest E 2 replacement can attenuate the increase in MAP in middle age as a result of ovarian hormone loss. This study also supports the timing hypothesis that suggests E 2 treatment loses its protective blood pressure lowering effects if there is a significant time delay between ovarian hormone loss and E 2 replacement. These findings have implications for women who are ovarian hormone deficient and are considering E 2 replacement therapy.