(1) Background: This population-based study aimed at identifying the factors associated with the likelihood of detection of stage IA cervical carcinoma-versus the detection of stage IB through IV cervical carcinoma-and the patterns of surgical treatment. (2) Methods: Between 1995-2016, 3750 patients living in the Emilia-Romagna Region (northern Italy) were registered with cervical carcinoma, including 2942 eligible patients (median age, 53). Multivariate analysis was performed using binary logistic regression models. (3) Results: The likelihood of stage IA cervical carcinoma (n = 876, 29.8%) did not change over time, decreased with increasing patient age, and was lower for patients with adenocarcinoma and grade 3-4 disease. Three hundred and fifty (40.0%) patients had a conservative treatment, 317 (36.2%) had hysterectomy, 197 (22.5%) had hysterectomy with lymph node dissection (LND), and 12 (1.4%) had a conservative treatment with LND. The proportion of hysterectomy decreased from 70.6% in 1995-1999 to 46.9% in 2011-2016. The likelihood of hysterectomy increased above the age of 40. Among screening-aged (25-64 years) patients, the likelihood of hysterectomy did not differ between screen-detected and non-screen-detected ones. Hysterectomy was increasingly combined with LND. High tumour grade was the strongest determinant of LND during hysterectomy. (4) Conclusions: This study provided a multifaceted overview of stage IA cervical carcinoma over the last decades.

Acute respiratory distress syndrome (ARDS) is a life-threatening lung injury. After injury, severe inflammation, alveolar-capillary barrier permeability and alveolar epithelial cell (AEC) death lead to lung dysfunction. Glycogen synthase kinase-3 (GSK-3) is an important molecule in cell proliferation and differentiation. CHIR99021 (CHIR), a GSK-3 inhibitor, modulates the maturation of epithelial progenitor cells in lung 3D model. Thus, we aimed to understand the effects of CHIR on AEC regeneration using LPS-induced acute lung injury (ALI) mouse model. GSK-3 was inhibited 30min or 18h after LPS injection to investigate effects on disease progression in the early and late inflammatory response. Animals treated with CHIR for 30min were evaluated after 12h and 24h, and animals treated with CHIR for 18h were studied after 30h and 72h. We analyzed lung injury by H&E staining, barrier permeability by Evan Blue dye, inflammatory recruitment by flow cytometry, apoptosis by TUNEL and Cleaved Caspase-3 expression, proliferation by Cyclin D1 and PCNA expression. Moreover, the presence of AEC lineage was assessed by expression of HOPX (AECII-to-AECI differentiation), pro-SPC (AECII) and PDPN, AQP5 (AECI). GSK-3 inhibition reduced lung injury at 24 and 72h with no effect on inflammatory cell recruitment nor barrier permeability. CHIR enhanced cell proliferation at all times analyzed, increased AECII cell proliferation at 24h and bipotent cell proliferation at 24h and 72h. AECI-related molecules showed an increase at 24h, 30h and 72h and AECII-related markers were enhanced at 30h and 72h. In conclusion, our preliminary data suggest that CHIR promotes AEC proliferation and transdifferentiation, restores alveolar epithelial population, and thus promotes lung regeneration in LPS-induced ALI.

OBJECTIVE Human PapillomaVirus (HPV) vaccination has been introduced in recent years in clinical practice as the most effective primary prevention strategy for cervical cancer and HPV-induced lesions, either pre-malignant or benign. Since its introduction, HPV vaccination has been progressively demonstrated as extremely effective in preventing extra-genital and male diseases also; furthermore, non only adolescents but adult subjects have been investigated and reported as positively responding to vaccine immunostimulation. More recently, effectiveness of post-treatment vaccine administration has been preliminarily investigated with very promising results in terms of decreased recurrences. On this basis, we report an Italian-focused picture of the state of the art and take a position in favour of the extension of HPV vaccination to male adolescents, to older age groups and to already treated subjects.

HPV vaccination has been introduced in clinical practice in recent years and represents the most effective strategy of primary prevention of cervical carcinoma and of female genital preneoplastic conditions. One of the major issues of the subject is represented by vaccination coverage of the target population. Since its introduction, HPV vaccine efficacy has been progressively demonstrated also towards extragenital HPV-correlated conditions and in males too. Moreover, even subjects of older age groups or subjects who already had HPV infections have been demonstrated to received benefits from vaccination, due to improvements of their immunological response. Recently, vaccine efficacy has also been investigated in terms of adjuvant administration after treatments of preneoplastic or benign conditions of the female lower genital tract caused by HPVs; preliminary results indicate an interesting and promising field of application. On this basis, in this article an analysis of the state of the art has been performed, with specific regard to the Italian scenario and with the focus of future perspectives of implementation of the HPV vaccination policy. From the available evidences, the Italian HPV Study Group recommends the extension of systematic HPV vaccination to males too, to adult subjects and also after conservative treatment of genital HPV correlated conditions.

Introduction:Diffuse large B-cell lymphoma (dlbcl) accounts for 30%-40% of all non-Hodgkin lymphomas. Approximately 60% of patients are cured with standard treatment. Targeted treatments are being investigated and might improve disease outcomes; however, their effect on cancer drug budgets will be significant. For the present study, we conducted an analysis of real-world costs for dlbcl patients treated in British Columbia, useful for health care system planning.Methods:Patient records from a retrospective cohort of patients diagnosed with dlbcl in British Columbia during 2004-2013 were anonymously linked across multiple administrative data sources: systemic therapy, radiotherapy, hospitalizations, oncologist services, outpatient medications, and fee-for-service physician services. Using generalized linear modelling regression, time-dependent costs (in 2015 Canadian dollars) were estimated in 6-month intervals over a 5-year period. The inverse probability weighting method was applied to account for censored observations. Nonparametric bootstrapping was used to estimate standard errors for the mean cost at each time interval.Results:The cohort consisted of 678 patients (5-year overall survival: 67%). Mean age at diagnosis was 64 ± 14 years; median follow-up was 3.2 years. Mean total cost of care was highest in the first 6 months after diagnosis ($29,120; 95% confidence interval: $28,986 to $29,170) and after disease progression ($18,480; 95% confidence interval: $15,187 to $24,772). Systemic therapy and hospitalization costs were the largest cost drivers. At each time interval, costs were observed to be positively skewed.Conclusions:Our results depict real-world costs for the treatment of dlbcl patients with standard chop-r therapy. Cost-model parameters are also provided for economic modelling of dlbcl interventions.

In Canada, the approved frontline therapy for advanced-stage Hodgkin’s Lymphoma (HL) is doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). Recently, the clinical efficacy of brentuximab vedotin (A+AVD) compared to ABVD has been demonstrated through a randomized controlled trial in these patients. The objective of this study is to evaluate the cost-effectiveness of A+AVD compared to ABVD. We constructed a time-dependent Markov model to calculate the incremental costs and effects (in terms of quality-adjusted life-years (QALYs)) of A+AVD versus ABVD. Patients could cycle through a series of health states over a time horizon of 15 years. The length of each cycle was 6 months. Data for the treatment effect of ABVD was obtained from a database of patients at the British Columbia Cancer Agency between 2004 and 2013. A series of scenario analyses were carried out employing differing treatment effect estimates obtained from the published literature for both A+AVD and ABVD. A probabilistic analysis was conducted to estimate concurrent parameter uncertainty on incremental costs and effects. All costs are reported in 2015 Canadian dollars. We took a healthcare system perspective and used a discount rate of 1.5%, as per Canadian guidelines. The incremental cost for A+AVD versus standard therapy (ABVD) as frontline therapy in HL patients is $87,000. Treatment with A+AVD resulted in small additional effects, with the incremental QALYs gained estimated at 0.30. The estimated ICER was $280,000/QALY (95% CI: 150,000 to 3,410,000). In the probabilistic analysis, only 24% of simulations resulted in an ICER of less than $100,000 per QALY. Treatment with A+AVD compared to ABVD in patients with HL resulted in a limited QALY gain at substantial cost to the drugs budget. While future analyses based on emerging evidence for A+AVD may decrease decision uncertainty, there is a low probability that ABVD would be considered cost-effective at current prices.

To investigate knowledge of school-aged children and their perception on intestinal parasites, and to assess knowledge reconstruction on prevention practices after specific training in the subject. We performed an activity package that included the analysis of children's drawings of intestinal parasites, and information and communication technologies (ITCs) to transfer knowledge about these pathogens and prevention measures. Retrieval learning activities were performed to fixation of general and specific prevention and control measures.Overall, we found that there is a knowledge gap in many aspects of parasite biology and ecology, and therefore on the risk of infection and acquisition mechanisms. After ITCs, the children improved their knowledge over non-trained children.The approaches used to transfer knowledge and for learning, fixation were valuable tools for incorporating changes in misconceptions and in the deep-rooted habits that favour entero-parasitic diseases. This has important implications for the specific design of future education materials and campaigns. Understanding of perceptions helps to provide justifications and knowledge to achieve changes in unhealthy habits, and it constitutes the basis for the transformation of many risky practices.

The Fixed-Time Artificial Insemination (FTAI) is an animal reproduction biotechnique which has been widely used in dairy and beef herds in Brazil. The use of this tool offers substantial advantages on reproductive management of dairy herd, allowing the improvement of reproductive performance of high production cows, which is currently low. However, the conception subsequent to FTAI protocols are variable due to several factors as differences among the ovulation induction hormones, hormonal concentration and doses and the dominant follicle diameter at the moment of Artificial Insemination (AI). Accordingly, the aim of this current study, was to evaluate the diameter of the largest follicle in heifers receiving two different FTAI protocols, with different methods of follicular wave synchronization. Heifers Girolando (3/4 to 7/8 Holstein-Zebu) were submitted to two FTAI protocols: Protocol I (PI) (n = 30): injection via intramuscular (IM) of 10.5μg GnRH and the placing of intravaginal device containing progesterone (P4) (D0-day zero); injection IM of 150μg prostaglandin F2alfa (PGF2a), removal of P4 device on the fifth day (D5); injection IM of PGF2α on the sixth day (D6) and AI and injection IM of 10.5μg GnRH on the eighth day of the protocol (D8). Protocol II (PII) (n = 30): injection IM of 2.0mg of estradiol benzoate (EB) and the placing of intravaginal device containing progesterone (P4) (D0); injection IM of 150μg of PGF2α on the seventh day (D7); removal of P4 device and injection IM of 1mg of estradiol cypionate (EC) on the ninth day (D9) and AI on the eleventh day of the protocol (D11). Transrectal ultrasonography was performed in the beginning of the protocols (D0), two days after the beginning (D2) and on AI day (D8 of Protocol I and D11 of Protocol II). Vaginal device used were Primer (Tecnopec, Sao Paulo, Brazil) and hormones GnRH (Gonaxal), EB (Bioestrogen), EC (Croni-cip), PGF2α (Croniben) of Biogenesis Bago SA (Garin, Buenos Aires, Argentina). Aiming to confirm the ovulation of the animals, it was also performed transrectal ultrasonography seven days after the AI in each protocol. The follicles diameters in different days of the protocols, were statistically evaluated (ANOVA), means were compared using Mann Whitney Test and ovulation rate analyzed using Chi-Square Test, considering P < 0.05. The follicles diameters at D0, D2 and AI day, expressed as means ± SEM, were: 13.1 ± 0.4mm and 12.8 ± 0.6mm, 8.1 ± 0.5mm and 12.0 ± 0.6mm, 12.6 ± 0.6mm and 10.6 ± 0.7mm, respectively for protocol I and II. Significant differences P < 0.05 were observed between the follicular diameters at D2 and AI day. The ovulation rates were 83.3% and 60.0% for PI and PII, respectively. The follicles diameters differences observed, occurred due to the distinct wave synchronization methods in each protocol.

Objective: An innovative web-based colposcopy quality assurance programme was implemented in population-based cervical screening services in three north-eastern Italian administrative regions with different colposcopists' training background. In this study, the levels of intra- and interregional intercolposcopist diagnostic agreement were evaluated.Study design: Of the 158 registered colposcopists, 125 accessed the website of the programme, logged-in, viewed a posted set of 50 digital colpophotographs selected by an expert steering committee, and classified them for the colposcopic impression, the visibility of the squamocolumnar junction, and the need for biopsy. Anonymous data were downloaded and analysed using the crude, or observed, proportion of agreement and the kappa coefficient.Results: There were 113 eligible colposcopists. Overall, crude agreement on the colposcopic impression, the visibility of the squamocolumnar junction, and the need for biopsy was 0.72, 0.72, and 0.87, with kappa values of 0.60, 0.36, and 0.69, respectively. The homologous kappa values were 0.61, 0.41, and 0.69 in one region, 0.57, 0.36, and 0.69 in another, and 0.66, 0.38, and 0.74 in the third. Total intra- and interregional agreement were nearly identical, with kappa values of 0.59 and 0.60 for the colposcopic impression, 0.38 and 0.35 for the visibility of the squamocolumnar junction, and 0.69 and 0.69 for the need for biopsy. The width of 95% confidence intervals around the above kappa values was <= 0.01.Conclusions: The levels of agreement varied between moderate and substantial both within and between regions. Regional differences in training background had minor effects. The interpretation of colposcopy is potentially well-reproducible. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

Persistent positivity of HPV-DNA testing is considered a prognostic index of recurrent disease in patients treated for CIN2+. HPV detection, and particularly genotyping, has an adequate high rate of sensitivity and specificity (along with an optimal reproducibility), for accurately predicting treatment failure, allowing for an intensified monitoring activity. Conversely, women with a negative HPV-test 6 months after therapy have a very low risk for residual/recurrent disease, which leads to a more individualized follow-up schedule, allowing for a gradual return to the normal screening scheme. HPV testing should be routinely included (with or without cytology) in post-treatment follow-up of CIN2+ patients for early detection of recurrence and cancer progression. HPV genotyping methods, as a biological indicator of persistent disease, could be more suitable for a predictive role and risk stratification (particularly in the case of HPV 16/18 persistence) than pooled HPV-based testing. However, it is necessary to be aware of the performance of the system, adhering to strict standardization of the process and quality assurance criteria.

We have recently read with interest the important article entitled “Is cervical screening preventing adenocarcinoma and adenosquamous carcinoma of the cervix?” by Castanon et al.1 that provides a new insight into the impact of cervical cytology screening on glandular lesions. In the developed countries, the incidence of cervical squamous cell carcinoma (SCC) has decreased for decades, whereas an opposite trend has been noted for adenocarcinoma (AC), especially among younger women.2 The latter has been attributed to selective deficiencies of the screening process in detecting the precursors of AC: first, the glandular lesions, often located in the cervical canal, are more difficult to sample and less amenable to early detection by exfoliation cytology;3 second, glandular precancerous lesions can be hard to detect cytologically because their distinguishing features are subtle; and, third, firm criteria upon which to base a colposcopic suspicion of glandular precancerous lesion are lacking. The study by Castanon et al.1 provides an elegant confirmation that cytology screening is less sensitive for glandular than squamous precancerous lesions. Conversely, and this is an equally important result, the study demonstrates that cytology screening is capable to detect early invasive AC and to prevent the disease progression to FIGO stage 1B or greater. The poor sensitivity of cytology screening for glandular precancerous lesions is a long-standing problem but is attracting new attention today. Over the last years, the upward incidence trend of AC has levelled off, and even reversed, in some countries. Some have related these changes to improvements in the screening process.4 If this hypothesis is true, it means that quality assurance efforts and technological advances may favourably affect the detectability of glandular precancerous lesions and, conceivably, of AC itself. With this rationale, we have assessed the patient's screening history, the FIGO stage, and the incidence and survival trends of AC among women aged 25–64 years (currently 1,220,000) living in the Emilia-Romagna Region (northern Italy) in 1997–2012, and we have compared them with those of SCC. Since 1997, the area has been targeted by a cervical screening programme for women in the above age range, in which innovative quality assurance schemes for local cytology, pathology and colposcopy services have been implemented.5, 6 The data for the study were from the regional cervical cancer registry. ICD-O 3 codes were categorised according to standard criteria. With respect to statistical methods, univariate comparisons were performed using the median test and the Pearson's χ2 test. Annual incidence rates per 100,000 women were age-standardised to the European standard population. The joinpoint regression analysis was used to investigate the trends in rates and to test for significant changes. Relative survival rates were calculated with the actuarial method. Multivariate analysis of survival was performed using the Cox proportional hazards model. Table 1 shows an overview of results. AC patients were younger. The proportions of screen-detected cancers and of FIGO stage I cancers were comparable between SCC and AC, although AC patients were less likely to have a stage IA disease. The incidence declined steadily for SCC and was stable for AC, causing (data not shown) the relative incidence of the latter to increase from 9.6% in 1997 to 25.5% in 2012. In the period, a 50% decrease in the risk of dying was observed for both diseases, that was more rapid for AC. Because both Cox proportional hazard models were adjusted for the FIGO stage, the decrease was most likely due to downstaging within stage categories. Finally, and contrary to many previous studies showing a prognostic disadvantage for AC patients,1 the five-year relative survival rate and the crude hazard ratio over the 16-year period were not significantly different between the two diseases. A non-significant 17% increased risk of death for AC patients was found only after adjustment for patient age—a factor inversely associated with survival—and other weaker confounders (data not shown). In interpreting these data, it must be considered that the observed survival trend is unlikely to be biased by changes in the patterns of treatment. Few randomised controlled clinical trials have been conducted in the period and the marginal improvements obtained cannot have had a measurable public health impact. The proportion of patients with AC at stage IA, that was smaller than that of patients with SCC but greater than expected,1 the high proportion of screen-detected ACs and—more important—the rapid and strong increase in survival from AC suggest that the sensitivity of the local screening programme for the disease has improved. The fact that the 5-year relative survival of AC patients was equivalent to that of SCC patients despite their worse FIGO stage distribution confirms a favourable within-stage distribution. We relate the downstaging of AC to stringent quality assurance initiatives5, 6 and to a partial introduction of liquid-based cytology, that is known to improve the sensitivity of the Pap smear for glandular cell abnormalities.7 In addition, we suggest that a more systematic and accurate treatment of high-grade squamous intraepithelial lesions, resulting from a permanent colposcopy training programme6 and documented by the decreasing incidence of SCC, has probably led to the incidental detection of many early ACs, since the two types of disease often coexist.8 Unfortunately, the second key finding of the study was that all of these improvements had no apparent effect on the incidence of AC. Of course, the effect of early detection of precursors would be delayed by an interval equal to the lead time. However, with an estimated time span of 5 to 13 years for the transition from preinvasive to invasive AC,9, 10 the observation time of the study was sufficient to capture a discontinuity in the stable incidence trend line (if any). In conclusion, the observed incidence and survival changes suggest that quality assurance activities and technological advances have increased the effectiveness of cytology screening in downstaging AC but not in detecting its precursors and in preventing the disease. Our study corroborates the results of Castanon et al.1 especially considering that both researches were conducted in highly quality-assured screening settings and that the introduction of liquid-based cytology occurred earlier in the Emilia-Romagna Region (2006–2008) than in England (2008) and Wales (2012) (Castanon A, Landy R, Sasieni PD, personal communication, 2016).

Background: Genomic technologies are increasingly used to guide clinical decision-making in cancer control. Economic evidence about the cost-effectiveness of genomic technologies is limited, in part because of a lack of published comprehensive cost estimates. In the present micro-costing study, we used a time-and-motion approach to derive cost estimates for 3 genomic assays and processes—digital gene expression profiling (GEP), fluorescence in situ hybridization (FISH), and targeted capture sequencing, including bioinformatics analysis—in the context of lymphoma patient management. Methods: The setting for the study was the Department of Lymphoid Cancer Research laboratory at the BC Cancer Agency in Vancouver, British Columbia. Mean per-case hands-on time and resource measurements were determined from a series of direct observations of each assay. Per-case cost estimates were calculated using a bottom-up costing approach, with labour, capital and equipment, supplies and reagents, and overhead costs included. Results: The most labour-intensive assay was found to be FISH at 258.2 minutes per case, followed by targeted capture sequencing (124.1 minutes per case) and digital GEP (14.9 minutes per case). Based on a historical case throughput of 180 cases annually, the mean per-case cost (2014 Canadian dollars) was estimated to be $1,029.16 for targeted capture sequencing and bioinformatics analysis, $596.60 for FISH, and $898.35 for digital GEP with an 807-gene code set. Conclusions: With the growing emphasis on personalized approaches to cancer management, the need for economic evaluations of high-throughput genomic assays is increasing. Through economic modelling and budget-impact analyses, the cost estimates presented here can be used to inform priority-setting decisions about the implementation of such assays in clinical practice.

Two-thirds of 152 patients treated for high-grade cervical disease, free of persistence/recurrence, and followed-up both with human papillomavirus (HPV) DNA testing and HPV genotyping cleared their high-risk HPV infection within 1 year. Viral clearance continued at diminishing rates during the second and the third year, at the end of which it was virtually complete.

Usual vulvar intraepithelial neoplasia (uVIN) is the most common VIN type, generally related to a human papillomavirus (HPV) infection, predominantly type 16. The incidence of uVIN has been increasing over the last decades, and a bimodal peak is observed at the age of 40-44 and over 55 years. Almost 40% of patients with uVIN have a past, concomitant or future HPV-associated lesion of the lower genital tract. HPV-related malignancies are associated with a persistent HPV infection. The host immune response is of crucial importance in determining clearance or persistence of both HPV infections and HPV-related VIN. About 60% of the patients present with symptoms. Clinical features of uVIN vary in site, number, size, shape, colour, and thickness of lesions. Multicentric disease is often present. Most uVIN lesions are positive at immunohistochemistry to p16(ink4a) and p14(arf), but negative to p53. Irrespective of surgical treatment used, uVIN recurrence rates are high. Positive margins do not predict the development of invasive disease and the need to re-excide the tissue around the scare remains to be demonstrated. Therefore, considering the low progression rate of uVIN and psycosexual sequelae, treatments should be as conservative as possible. Medical treatments available are mainly based on immunotherapy to induce normalisation of immune cell count in uVIN. None are approved by the food and drug administration (FDA) for the treatment of uVIN. If medical treatment is performed, adequate biopsies are required to reduce the risk of unrecognised invasive disease. Some studies suggest that failure to respond to immunotherapy might be related to a local immunosuppressive microenvironment, but knowledge of the uVIN microenvironment is limited. Moreover, our knowledge of the potential mechanisms involved in the escape of HPV-induced lesions from the immune system has many gaps. HPV vaccines have been demonstrated to be effective in preventing uVIN, with 94.9% efficacy in the HPV-naive population, while studies on therapeutic vaccines are limited. The low incidence of VIN requires large multicentre studies to determine the best way to manage affected patients and to investigate the immunological characteristics of the 'vulvar microenviroment' which leads to the persistence of HPV.

Background: Although it is hypothesised that human papillomavirus (HPV) testing may have a role in surveillance of patients conservatively treated for stage IA squamous cell cervical carcinoma, research on this topic has been minimal.Objectives: To determine: (1) the changes in HPV test result from treatment onward; (2) the time to viral clearance; and (3) the negative predictive value (NPV) and positive predictive value (PPV) of HPV test result for the detection of CIN2 or worse (CIN2+) during follow-up.Study design: In a multicentre retrospective follow-up study of a consecutive series (1997-2009) of 91 patients, longitudinal outcome measures were estimated as cumulative probabilities using the Kaplan-Meier method.Results: For patients testing HPV-positive at the first follow-up visit (n = 44), the probability of change to negative rose from 0 to 0.78 between 7 and 21 months after treatment. For HPV-negative patients (n = 47), the probability of change to positive rose to 0.13 between 9 and 26 months. After a median follow-up of 50 months (range, 2-80), the NPV for CIN2+ was 1.00. The PPV was 0.60 (95% confidence interval, 0.43-0.77) after 26 months. The median time to detection was 5 months.Conclusions: If adequately confirmed, these findings would indicate that HPV testing is capable to identify the patients who have had their lesions fully removed, and would make it possible to focus follow-up efforts on a subset of patients at high risk of residual or progressive disease. (C) 2015 Elsevier B.V. All rights reserved.

BACKGROUND:Over the last two decades it has become clear that distinct types of human papillomavirus (HPV), the so-called high-risk types (hrHPV), are the major cause of cervical cancer. The hrHPV-DNA testing has shown excellent performance in several clinical applications from screening to the follow-up of conservatively treated patients.METHODS:We conducted a systematic review of the recent literature on the performance of HPV DNA testing in follow-up after treatment of high-grade cervical lesions, adenocarcinoma in situ, and microinvasive carcinoma compared to Pap smear cytology.RESULTS:Observational studies have demonstrated that the high risk hrHPV-DNA test is significantly more sensitive (95%) compared to follow-up cytology(70%) in detecting post-treatment squamous intraepithelial high-grade lesions. Moreover, in patients treated conservatively for cervical adenocarcinoma in situ, the hrHPV-DNA test is the most significant independent predictor of recurrent disease or progression to invasive cancer, and the combination of viral DNA testing and cytology reaches 90% sensitivity in detecting persistent lesions at the first follow-up visit and 100% at the second follow-up visit. The cause of microinvasive squamous cervical carcinoma is increasingly treated with conservative therapies in order to preserve fertility, and an effective strategy allowing early detection of residual or progressive disease has become more and more important in post-treatment follow-up. Primary results seem to indicate that the median time for viral clearance is relatively longer compared with patients treated for CIN and suggest a prolonged surveillance for these patients. However, the potential clinical value of HPV-DNA testing in this clinical setting needs to be confirmed by further observations.CONCLUSIONS:The excellent sensitivity, negative predictive value, and optimal reproducibility of the hrHPV DNA testing, currently is considered a powerful tool in the clinicians' hands to better manage post-treatment follow-up either in cervical squamous lesion or in situ adenocarcinoma.

Background: Human papillomavirus (HPV) plays a role in the development of benign and malign neoplasms in both sexes. The Italian recommendations for HPV vaccines consider only females. The BEST II study (Bayesian modelling to assess the Effectiveness of a vaccination Strategy to prevent HPV-related diseases) evaluates 1) the cost-effectiveness of immunization strategies targeting universal vaccination compared with cervical cancer screening and female-only vaccination and 2) the economic impact of immunization on various HPV-induced diseases. Objective: The objective of this study was to evaluate whether female-only vaccination or universal vaccination is the most cost-effective intervention against HPV. Methods: We present a dynamic Bayesian Markov model to investigate transmission dynamics in cohorts of females and males in a follow-up period of 55 years. We assumed that quadrivalent vaccination (against HPV 16, 18, 6, and 11) is available for 12-year-old individuals. The model accounts for the progression of subjects across HPV-induced health states (cervical, vaginal, vulvar, anal, penile, and head/neck cancer as well as anogenital warts). The sexual mixing is modeled on the basis of age-, sex-, and sexual behavioral-specific matrices to obtain the dynamic force of infection. Results: In comparison to cervical cancer screening, universal vaccination results in an incremental cost-effectiveness ratio of 1,500. When universal immunization is compared with female-only vaccination, it is cost-effective with an incremental cost-effectiveness ratio of (sic)11,600. Probabilistic sensitivity analysis shows a relatively large amount of parameter uncertainty, which interestingly has, however, no substantial impact on the decision-making process. The intervention being assessed seems to be associated with an attractive cost-effectiveness profile. Conclusions: Universal HPV vaccination is found to be a cost-effective choice when compared with either cervical cancer screening or female-only vaccination within the Italian context.