Towards the eradication of HPV infection through universal specific vaccination.

BACKGROUND: The Human Papillomavirus (HPV) is generally recognized to be the direct cause of cervical cancer. The development of effective anti-HPV vaccines, included in the portfolio of recommended vaccinations for any given community, led to the consolidation in many countries of immunization programs to prevent HPV-related cervical cancers. In recent years, increasing evidence in epidemiology and molecular biology have supported the oncogenic role of HPV in the development of other neoplasm including condylomas and penile, anal, vulvar, vaginal, and oro-pharyngeal cancers. Men play a key role in the paradigm of HPV infection: both as patients and as part of the mechanisms of transmission. Data show they are affected almost as often as women. Moreover, no screening procedures for HPV-related disease prevention are applied in men, who fail to undergo routine medical testing by any medical specialist at all. They also do not benefit from government prevention strategies. DISCUSSION: A panel of experts convened to focus on scientific, medical, and economic studies, and on the achievements from health organizations' intervention programs on the matter. One of the goals was to discuss on the critical issues emerging from the ongoing global implementation of HPV vaccination. A second goal was to identify contributions which could overcome the barriers that impede or delay effective vaccination programs whose purpose is to eradicate the HPV infection both in women and men. SUMMARY: The reviewed studies on the natural history of HPV infection and related diseases in women and men, the increasing experience of HPV vaccination in women, the analysis of clinical effectiveness vs economic efficacy of HPV vaccination, are even more supportive of the economic sustainability of vaccination programs both in women and men. Those achievements address increasing and needed attention to the issue of social equity in healthcare for both genders.

The 'incessant menstruation' hypothesis: a mechanistic ovarian cancer model with implications for prevention.

Serous, endometrioid, clear cell and mucinous histotypes are the most common epithelial ovarian cancer. Most serous cancers appear to originate from precursor lesions at the fimbriated tubal end, whereas most endometrioid and clear cell cancers seem to derive from atypical endometriosis. Data regarding hormonal factors and associated gynaecologic conditions were critically analysed with the objective of defining a carcinogenic model for sporadic epithelial ovarian cancer complying with epidemiologic and pathologic findings. Oral contraceptives and tubal ligation substantially reduce the risk of serous, endometrioid and clear cell subgroups, but have no significant effect on mucinous tumours, which probably follow a different oncogenic pathway. We hypothesize that serous, endometrioid and clear cell cancers share a common pathogenic mechanism, i.e. iron-induced oxidative stress derived from retrograde menstruation. Fimbriae floating in bloody peritoneal fluid are exposed to the action of catalytic iron and to the genotoxic effect of reactive oxygen species, generated from haemolysis of erythrocytes by pelvic macrophages. This would explain the distal site of tubal intraepithelial neoplasia. Collection of blood inside endometriomas would lead to the same type of genotoxic insult on gonadal endometrial implants. This would explain why endometriosis-associated cancers develop much more frequently in the ovary than at extragonadal sites. In women not seeking conception, bilateral salpingectomy could be advised whenever planning surgery for independent indications, thus possibly reducing cancer risk, while preserving ovarian function. The use of oral contraceptives should be favoured for prolonged periods of time, especially in women with endometriosis, a population at doubled risk of gonadal malignancy.

Assisted reproduction: what factors interfere in the professional's decisions? Are single women an issue?

BACKGROUND: With the development of medical technology, many countries around the world have been implementing ethical guidelines and laws regarding Medically Assisted Reproduction (MAR). A physician's reproductive decisions are not solely based on technical criteria but are also influenced by society values. Therefore, the aim of this study was to analyze the factors prioritized by MAR professionals when deciding on whether to accept to perform assisted reproduction and to show any existing cultural differences. METHODS: Cross-sectional study involving 224 healthcare professionals working with assisted reproduction in Brazil, Italy, Germany and Greece. Instrument used for data collection: a questionnaire, followed by the description of four special MAR cases (a single woman, a lesbian couple, an HIV discordant couple and gender selection) which included case-specific questions regarding the professionals' decision on whether to perform the requested procedure as well as the following factors: socio-demographic variables, moral and legal values as well as the technical aspects which influence decision-making. RESULTS: Only the case involving a single woman who wishes to have a child (without the intention of having a partner in the future) demonstrated significant differences. Therefore, the study was driven towards the results of this case specifically. The analyses we performed demonstrated that professionals holding a Master's Degree, those younger in age, female professionals, those having worked for less time in reproduction, those in private clinics and Brazilian health professionals all had a greater tendency to perform the procedure in that case. A multivariate analysis demonstrated that the reasons for the professional's decision to perform the procedure were the woman's right to gestate and the duty of MAR professionals to help her. The professionals who decided not to perform the procedure identified the woman's marital status and the child's right to a father as the reason to withhold treatment. CONCLUSION: The study indicates differences among countries in the evaluation of the single woman case. It also discloses the undervaluation of bioethics committees and the need for a greater participation of healthcare professionals in debates on assisted reproduction laws.

'Waiting for Godot': a commonsense approach to the medical treatment of endometriosis.

Conservative surgical treatment for symptomatic endometriosis is frequently associated with only partial relief of pelvic pain or its recurrence. Therefore, medical therapy constitutes an important alternative or complement to surgery. However, no available compound is cytoreductive, and suppression instead of elimination of implants is the only realistic objective of pharmacological intervention. Because this implies prolonged periods of treatments, only medications with a favourable safety/tolerability/efficacy/cost profile should be chosen. In the past few years, innumerable new drugs for endometriosis, which would interfere with several hypothesized pathogenic mechanisms, have been studied and their use foreseen. However, robust evidence of in vivo safety and efficacy is lacking and, at the moment, the principal modality to interfere with endometriosis metabolism is still hormonal manipulation. Regrettably, in spite of consistent demonstration of a major effect on pain even in patients with deeply infiltrating lesions, progestins are underestimated and dismissed in favour of more scientifically fashionable and up-to-the-minute alternatives. Moreover, oral contraceptives (OCs) dramatically reduce the rate of post-operative endometrioma recurrence and should now be considered an essential part of long-term therapeutic strategies in order to limit further damage to future fertility. Finally, women who have used OC for prolonged periods will be protected from an increased risk of endometriosis-associated ovarian cancer. To avoid the several subtle modalities for distorting facts and orientating opinions in favour of specific compounds, progestins and monophasic OC used continuously are here proposed as the reference comparator in all future randomized controlled trials on medical treatment for endometriosis.

Effect of the ethinylestradiol/norelgestromin contraceptive patch on body composition. Results of bioelectrical impedance analysis in a population of Italian women.

BACKGROUND: As weight gain is one of the most frequently cited reasons for not using and for discontinuing hormonal contraceptives, in an open-label, single-arm, multicentre clinical study we evaluated the effect of the ethinylestradiol/norelgestromin contraceptive patch (EVRA, Janssen-Cilag International, Belgium) on body composition using bioelectrical impedance analysis (BIA). METHODS: Body weight and impedance vector components (resistance (R) and reactance (Xc), at 50 kHz frequency, Akern-RJL Systems analyzer) were recorded before entry, after 1, 3 and 6 months in 182 Italian healthy women aged 29 yr (18 to 45), and with BMI 21.8 kg/m2 (16 to 31). Total body water (TBW) was estimated with a BIA regression equation. Vector BIA was performed with the RXc mean graph method and the Hotelling's T2 test for paired and unpaired data. RESULTS: After 6 months body weight increased by 0.64 kg (1.1%) and TBW increased by 0.51 L (1.7%). The pattern of impedance vector displacement indicated a small increase in soft tissue hydration (interstitial gel fluid). Body composition changes did not significantly differ among groups of previous contraceptive methods. Arterial blood pressure did not significantly change over time. CONCLUSION: After 6 months of treatment with the ethinylestradiol/norelgestromin contraceptive patch we found a minimal, clinically not relevant, increase in body weight less than 1 kg that could be attributed to an adaptive interstitial gel hydration. This fluctuation is physiological as confirmed by the lack of any effect on blood pressure. This could be useful in increasing women's choice, acceptability and compliance of the ethinylestradiol/norelgestromin contraceptive patch.

Advances in the management of endometriosis: an update for clinicians.

Endometriosis is a chronic and recurrent disease characterized by the presence and proliferation of endometrial tissue outside the uterine cavity, which occurs in approximately 10% of women of reproductive age. In this estrogen-dependent disorder, lesions become inactive and gradually undergo regression during states of ovarian down-regulation, such as amenorrhoea or menopause. The impact of endometriosis includes impaired fertility potential, as well as symptoms of dysmenorrhoea, dyspareunia and chronic non-menstrual pain, all of which adversely affect quality of life. Management of endometriosis focuses on pain relief and includes medical and surgical treatment. Pharmacologic therapies currently in use include combination oral contraceptives (COCs), danazol, GnRH analogues and progestins. Although some agents show efficacy in relieving pain, all differ in their side effects, making it difficult to achieve a balance between efficacy and safety. Efficacy has been demonstrated with danazol or GnRH analogues; however, treatment is limited to 6 months because of significant metabolic side effects. Alternatives for longer-term management of symptoms include add-back therapy with GnRH analogues, COCs or progestins. Newer options for treatment of endometriosis include depot medroxyprogesterone acetate subcutaneous injection, as well as several agents under investigation that may prove to have therapeutic potential.