Economic burden of HPV9-related diseases: a real-world cost analysis from Italy.

INTRODUCTION: The objectives of this study were to estimate the economic burden of HPV in Italy, accounting for total direct medical costs associated with nine major HPV-related diseases, and to provide a measure of the burden attributable to HPV 6, 11, 16, 18, 31, 33, 45, 52, 58 infections. METHODS: A cost-of-illness incidence-based model was developed to estimate the incidences and costs of invasive cervical cancer, cervical dysplasia, cancer of the vulva, vagina, anus, penis, oropharyngeal, anogenital warts, and recurrent respiratory papillomatosis (RRP) in the context of the Italian National Health System (NHS). We used data from hospital discharge records (HDRs) of an Italian region and conducted a systematic literature review to estimate the lifetime cost per case, the number of incident cases, the prevalence of HPV9 types. Costs of therapeutic options not included in the diagnosis-related group (DRG) tariffs were estimated through a scenario analysis. RESULTS: In 2018, the total annual direct costs were €542.7 million, with a range of €346.7-€782.0 million. These costs could increase considering innovative therapies for cancer treatment (range €16.2-€37.5 million). The fraction attributable to the HPV9 genotypes without innovative cancers treatment was €329.5 million, accounting for 61% of the total annual burden of HPV-related diseases in Italy. Of this amount, €135.9 million (41%) was related to men, accounting for 64% of the costs associated with non-cervical conditions. CONCLUSIONS: The infections by HPV9 strains and the economic burden of non-cervical HPV-related diseases in men were found to be the main drivers of direct costs.

Clinical application of photodynamic diagnosis and photodynamic therapy for gynecologic malignant diseases: A review.

INTRODUCTION: Several types of photosensitizers such as 5-aminolevulinic acid are progenitors of protoporphyrin IX (PpIX). PpIX accumulates in cancer cells and has photosensitivity. Based on these characteristics, they are used in photodynamic diagnosis (PDD) and photodynamic therapy (PDT). These methods have recently been applied to gynecologic malignant diseases. Here, we review articles on clinical applications of PDD and PDT for these diseases. MATERIALS AND METHODS: A systematic literature search in Pubmed was performed with a combination of keywords to collect the articles. RESULT: There were eight articles on PDT for uterine cervical diseases, including one study that included patients with cervical cancer. The disease remission rate ranged from 31.6% to 100%. PDD under hysteroscopy had positive effects on endometrial cancer, endometrial hyperplasia and secretory endometrial tissue, and 7 of 11 patients were able to become pregnant after PDT for endometrial cancer. For ovarian cancer, the sensitivity and specificity of clinical PDD were high. DISCUSSION: There is a need to improve the disease remission rate in uterine cervical diseases, and application of PDT for cervical cancer should be considered. For endometrial cancer, the risks and benefits of PDD that should be compared with those of hysteroscopy using narrow band imaging, which already has been shown to have high efficacy and few side effects. For ovarian cancer, it will be necessary to collect more data to evaluate the effect of PDD on overall survival. CONCLUSION: PDD and PDT can contribute to diagnosis and therapy in clinical practice for gynecologic malignant diseases.

Vaginal progesterone for preventing preterm birth and adverse perinatal outcomes in singleton gestations with a short cervix: a meta-analysis of individual patient data.

BACKGROUND: The efficacy of vaginal progesterone for preventing preterm birth and adverse perinatal outcomes in singleton gestations with a short cervix has been questioned after publication of the OPPTIMUM study. OBJECTIVE: To determine whether vaginal progesterone prevents preterm birth and improves perinatal outcomes in asymptomatic women with a singleton gestation and a midtrimester sonographic short cervix. STUDY DESIGN: We searched MEDLINE, EMBASE, LILACS, and CINAHL (from their inception to September 2017); Cochrane databases; bibliographies; and conference proceedings for randomized controlled trials comparing vaginal progesterone vs placebo/no treatment in women with a singleton gestation and a midtrimester sonographic cervical length ≤25 mm. This was a systematic review and meta-analysis of individual patient data. The primary outcome was preterm birth <33 weeks of gestation. Secondary outcomes included adverse perinatal outcomes and neurodevelopmental and health outcomes at 2 years of age. Individual patient data were analyzed using a 2-stage approach. Pooled relative risks with 95% confidence intervals were calculated. Quality of evidence was assessed using the GRADE methodology. RESULTS: Data were available from 974 women (498 allocated to vaginal progesterone, 476 allocated to placebo) with a cervical length ≤25 mm participating in 5 high-quality trials. Vaginal progesterone was associated with a significant reduction in the risk of preterm birth <33 weeks of gestation (relative risk, 0.62; 95% confidence interval, 0.47-0.81; P = .0006; high-quality evidence). Moreover, vaginal progesterone significantly decreased the risk of preterm birth <36, <35, <34, <32, <30, and <28 weeks of gestation; spontaneous preterm birth <33 and <34 weeks of gestation; respiratory distress syndrome; composite neonatal morbidity and mortality; birthweight <1500 and <2500 g; and admission to the neonatal intensive care unit (relative risks from 0.47-0.82; high-quality evidence for all). There were 7 (1.4%) neonatal deaths in the vaginal progesterone group and 15 (3.2%) in the placebo group (relative risk, 0.44; 95% confidence interval, 0.18-1.07; P = .07; low-quality evidence). Maternal adverse events, congenital anomalies, and adverse neurodevelopmental and health outcomes at 2 years of age did not differ between groups. CONCLUSION: Vaginal progesterone decreases the risk of preterm birth and improves perinatal outcomes in singleton gestations with a midtrimester sonographic short cervix, without any demonstrable deleterious effects on childhood neurodevelopment.

Conservative management of cervical ectopic pregnancy: Single-center experience.

AIM: The aim of this study was to assess the results of conservative treatment of cervical ectopic pregnancy (CEP). METHODS: We retrospectively reviewed all cervical ectopic pregnancies diagnosed at the present department between January 2010 and July 2015. Patients with CEP who were treated with either systemic or intra-amniotic methotrexate (MTX) injection were included in the study. RESULTS: Ten CEP patients were identified. Median maternal age was 33 years (range, 23-40 years). Median gestational age at diagnosis was 47 days (range, 44-58 days). Before treatment, overall mean serum beta-human chorionic gonadotrophin (ß-hCG) was 29 706.9 ± 19 695.2 mIU/mL. Mean gestational sac size was 29.0 ± 6.24 mm. Eight patients had viable fetuses with detected cardiac activity. Six patients were treated primarily with systemic MTX, and four were treated with local MTX injection. One patient in the systemic MTX injection group was switched to local MTX treatment due to severe oral ulceration and increasing ß-hCG titers after the fourth dose. One patient in the local treatment group had severe hemorrhage 7 days after local MTX. Three of six women achieved spontaneous pregnancy and gave birth to term, healthy infants after treatment. CONCLUSION: Conservative treatment of CEP with both systemic and local MTX is generally successful with regard to maternal morbidity and reproductive function, but these patients must be closely followed due to the small but real risk of late hemorrhage.

Revisiting the cost-effectiveness of universal cervical length screening: importance of progesterone efficacy.

BACKGROUND: Preterm birth (PTB) is a significant cause of neonatal morbidity and mortality. Studies have shown that vaginal progesterone therapy for women diagnosed with shortened cervical length can reduce the risk of PTB. However, published cost-effectiveness analyses of vaginal progesterone for short cervix have not considered an appropriate range of clinically important parameters. OBJECTIVE: To evaluate the cost-effectiveness of universal cervical length screening in women without a history of spontaneous PTB, assuming that all women with shortened cervical length receive progesterone to reduce the likelihood of PTB. STUDY DESIGN: A decision analysis model was developed to compare universal screening and no-screening strategies. The primary outcome was the cost-effectiveness ratio of both the strategies, defined as the estimated patient cost per quality-adjusted life-year (QALY) realized by the children. One-way sensitivity analyses were performed by varying progesterone efficacy to prevent PTB. A probabilistic sensitivity analysis was performed to address uncertainties in model parameter estimates. RESULTS: In our base-case analysis, assuming that progesterone reduces the likelihood of PTB by 11%, the incremental cost-effectiveness ratio for screening was $158,000/QALY. Sensitivity analyses show that these results are highly sensitive to the presumed efficacy of progesterone to prevent PTB. In a 1-way sensitivity analysis, screening results in cost-saving if progesterone can reduce PTB by 36%. Additionally, for screening to be cost-effective at WTP=$60,000 in three clinical scenarios, progesterone therapy has to reduce PTB by 60%, 34% and 93%. Screening is never cost-saving in the worst-case scenario or when serial ultrasounds are employed, but could be cost-saving with a two-day hospitalization only if progesterone were 64% effective. CONCLUSION: Cervical length screening and treatment with progesterone is a not a dominant, cost-effective strategy unless progesterone is more effective than has been suggested by available data for US women. Until future trials demonstrate greater progesterone efficacy, and effectiveness studies confirm a benefit from screening and treatment, the cost-effectiveness of universal cervical length screening in the United States remains questionable.

Cervical amoebiasis mimicking cervical carcinoma: A rare presentation of a common infection.

Cervical amoebiasis is an extremely rare diagnosis with only a small number of published case reports. This disease may present as cervical growth mimicking cervical carcinoma. Owing to the similarity of the clinical presentation of bleeding per vagina and per speculum examination showing growth or ulcers, definitive diagnosis is made on microscopic examination only. We present a rare case of cervical amoebiasis in a 28-year-old, multiparous female who presented with a history of vaginal bleeding. The patient was treated with metronidazole and diloxanide furate, after which she recovered. Awareness of this rare entity is important for clinical suspicion and for the pathologist to identify trophozoites and make a diagnosis, preventing unwarranted investigations. Accurate diagnosis also facilitates quick management of a patient; as this disease is an infective pathology that can easily be treated by antibiotics.

Granulomatosis con poliangeítis de presentación atípica: revisión de la literatura a propósito de un caso de localización ginecológica / Cervicovaginal granuloma as the first manifestation of granulomatosis with polyangiitis

La granulomatosis con poliangeitis (GPA) es una vasculitis sistémica, granulomatosa, con compromiso de pequeños vasos y presencia de anticuerpos c-ANCA. Ocasionalmente es localizada y es rara su manifestación genitourinaria. Se presenta el caso de una mujer de 68 años con sangrado genital causado por una lesión cervicovaginal verrucosa ulcerada, cuya histopatología descartó malignidad, hongos y TBC, con mala respuesta a antibióticos, ácido tricloro acético y crioterapia. Por recidiva al año se practica histerectomía total y colpectomía parcial, pero reincide al mes acompañada de epistaxis, cuyo estudio pornasofibroscopía e imágenes concluye en una lesión de tipo granulomatosa, agregándose anticuerpo anti PR-3 positivo. Se diagnostica GPA y se trata con ciclofosfamida con buena respuesta. La revisión de la literatura permite concluir que la GPA con localización cervicovaginal es muy poco frecuente, especialmente como manifestación inicial, y se debe considerar en el diagnóstico diferencial con cáncer y otras lesiones granulomatosas localizadas.

Granulomatosis with polyangiitis (GPA) is a systemic vasculitis, granulomatous, with commitment of small vessels and the presence of c-ANCA antibodies. Occasionally it is located and its genitourinary manifestation is rare. Presented the case of a 68 year old woman with genital bleeding caused by a lesion cervicovaginal ulcerated verrucosa, whose histopathology ruled out fungal, malignancy and TBC, with poor response to antibiotics, acid trichloro acetic and cryotherapy. By relapse a year is practiced total hysterectomy and partial colpectomia, but repeated a month accompanied by epistaxis, whose study by nasofibroscopia and images concludes in a type granulomatous lesion, adding antibody anti PR-3 positive. GPA is diagnosed and treated with cyclophosphamide with good response. Review of the literature leads to th conclusion that the GPA with cervico-vaginal location is very rare, especially as an initial manifestation, and should be considered in the diagnosis diferenttial with cancer and other localized granulomatous lesions.

Therapeutic effects of traditional Chinese medicine in patients with symptomatic cervical ectopy.

PURPOSE: The aim of this study is to evaluate the treatment and efficacy of Badushengjigao, a traditional Chinese medicine (TCM) formula, for symptomatic cervical ectopy. METHOD: A patient self-selected two group comparison study was performed. One hundred patients with symptomatic cervical ectopy admitted to the Central Hospital of E-Zhou (Hubei, China) between July 2013 and July 2014 were enrolled in the study. The patients treated with Badushengjigao were the study group and the patients treated with policresulen suppository were the control group. The medicine was administered through vagina. Patients received a three-month follow-up (once a month). The treatment results were evaluated and analyzed by variance analysis and X(2) test. RESULTS: The curative rates of the two groups with symptomatic cervical ectopy grade 1 shows no statistical significance. As for grade 2 and grade 3, the curative rates of the study group (phase 2: 72.0%; phase 3: 62.5%) are higher than that of the control group (phase 2: 44.4%; grade 3: 54.5%) with statistical difference (P < 0.05). The study group has less adverse effects (2.5 ± 1.3 days of vagina bleeding, 6 cases of abdominal pain and 2 cases of increased discharge) than the control group (12.5 ± 1.1 days of vagina bleeding, 15 cases of abdominal pain and 42 cases of increased discharge) with distinctive statistical difference (P < 0.01). CONCLUSION: The TCM formula, Badushengjigao, seems to be more effective than policresulen suppositories in treating symptomatic cervical ectopy phase 2 and phase 3. We suggest that it could be used as an alternative method for symptomatic cervical ectopy treatment, but further study is needed.

Successful treatment of gynaecological involvement of granulomatosis with polyangiitis (Wegener's granulomatosis) by rituximab.

Granulomatosis with polyangiitis, formerly called Wegener's granulomatosis, is a disease for which the treatment options are increasing, with the recent publication of several studies concerning the use of rituximab. The disease typically involves the upper airways, lungs and kidneys, but other far less frequent localisations are possible. Here, we describe a case of isolated relapse of granulomatosis with polyangiitis affecting the uterine cervix and upper vagina which dramatically responded to rituximab therapy, after failure of methotrexate treatment. This is the first documented response to rituximab of gynaecological involvement in granulomatosis with polyangiitis.

Cervical ectopic pregnancy managed with methotrexate and tranexamic acid: A case report.

BACKGROUND: Cervical pregnancy is a rare life-threatening form of ectopic pregnancy and when it occurs, it is challenging to decide the management options. Surgical intervention has been documented to be complicated by intractable haemorrhage and most often necessitating hysterectomy. We hereby report a case of cervical pregnancy managed conservatively with medical agents prior to surgical intervention. CASE PRESENTATION AND MANAGEMENT: A 29 year old primiparous woman with gestational diabetes mellitus who presented at 10 weeks gestation with 5 days history of brownish vaginal discharge and 2 days history of painless vaginal bleeding. On pelvic examination the cervix was disproportionately larger than the uterus with a closed internal os. Transvaginal and abdominal ultrasound scanning confirmed a live cervical pregnancy. She had intramuscular methotrexate and tranexamic acid followed by suction evacuation combined with balloon tamponade. Examination at 6 weeks post procedure revealed a normal cervix. CONCLUSION: Cervical pregnancy still occurs in this environment despite its rarity. Surgical intervention usually results in hysterectomy and adopting medical management as a first line treatment option offers the benefit of uterine preservation.

Primary tuberculosis of the uterine cervix: keep it in mind.

INTRODUCTION: Primary tuberculosis of the cervix is extremely rare, with only 20 cases reported in the English literature since 1949. Here we report the 21st case--an Italian woman with no risk factors. CASE: A 50-year-old Italian nulliparous woman was referred to our gynecology unit for vaginal discharge. Her past history was negative. Colposcopy revealed an ulcerated lesion raising the suspicion of cervical cancer. A biopsy revealed a tuberculosis granuloma, and acid-fast bacillus was identified with Ziehl-Neelsen stain. As no other site of tuberculosis was found, primary cervical tuberculosis was diagnosed. CONCLUSIONS: Although rare in industrialized countries, cervical tuberculosis may affect even women without risk factors. It should thus be taken into account in the differential diagnosis of cervical cancer.

Cervical pregnancy: a report of four cases.

Various conservative treatments for cervical pregnancy have been reported. However, unlike tubal ectopic pregnancy, the treatment of cervical pregnancy has not been well established. For patients who desire fertility preservation, treatment with methotrexate chemotherapy carries a high success rate for preservation of the uterus. When methotrexate is injected i.v. or i.m., expulsion of pregnant tissue occasionally takes up to 1 month. In this report, we present four cases of cervical pregnancy which were successfully managed by methotrexate injection into the bilateral uterine arteries. In cases presenting with massive bleeding, embolization of the bilateral uterine arteries was performed. Cervical pregnancy was aborted within 8 days safely, and fertility could be preserved without harmful side-effects.

Conservative management of cervical pregnancy with embryonic heart activity by ultrasound-guided local injection: an eight case series.

OBJECTIVE: To evaluate the efficacy of conservative management of cervical pregnancy with embryonic heart activity by ultrasound-guided local injection. METHODS: Retrospective case series at University tertiary care Hospital. Eight patients diagnosed with cervical pregnancy with embryonic heart activity managed conservatively. The intervention was ultrasound-guided local injection of methotrexate (1 mg/kg) and potassium chloride (2 meq/mL). Measurements were occurrence of morbidity, necessity for further intervention, the initial titers of beta-hCG, interval of time in which the levels of beta-hCG became negative, period for regression of cervical pregnancy at ultrasound and future pregnancy. RESULTS: All patients were treated successfully. The initial levels of beta-hCG ranged from 3013 to 71199 mUI/mL. One case evaluated with infection. There was no need for additional intervention in our series study. The interval of time for the levels of beta-hCG becomes negative range from 2 to 12 weeks. The period for the regression of the cervical pregnancy at ultrasound range from 3 to 14 weeks. In two cases intrauterine pregnancies occurred after the treatment. CONCLUSION: Conservative management of cervical pregnancy with embryonic heart activity by ultrasound-guided injection is an effective treatment avoiding the need of further intervention.

[Clinical efficacy of fluconazole, tinidazole and clindamycin vs fluconazole, tinidazole and azithromycin in the treatment of mixed cervical-vaginal infections, included those caused by Mycoplasma and Chlamydia trachomatis]. / Eficacia clínica de fluconazol, tinidazol y clindamicina vs fluconazol, tinidazol y azitromicina en el tratamiento de infecciones cérvico- vaginales mixtas, incluidas las causadas por Mycoplasma y Chlamydia trachomatis.

BACKGROUND: In the United States 19 million people acquire a sexually transmitted disease every year. Sexually transmitted diseases impact in gynecological terms because they may cause sterility, infertility and ectopic pregnancy. OBJECTIVE: To compare the effectiveness of two combinations of three oral antimicrobial drugs in the treatment of mixed cervical-vaginal infections, included those caused by Mycoplasma and Chlamydia trachomatis. MATERIAL AND METHOD: Aclinical, random, comparative, double-blind study included 50 patients assisting to infectology consult with diagnosis of mixed cervical-vaginal infection. Patients were divided into two groups: Group A (n = 25): fluconazole 37.5 mg, tinidazole 500 mg and azithromycin 250 mg; group B (n = 25): fluconazole 37.5 mg, tinidazole 500 mg and clindamycin 312.5 mg. Patients of both groups received two tablets twice p.o. for one day. Cultures were performed to corroborate the diagnosis and then to demonstrate effectiveness of the schemes studied. For the analysis of the data we used measures of central tendency, dispersion and inferential statistics for comparison of proportions by c2 and Fisher's exact tests with a significance level of p < 0.05. RESULTS: All patient got clinical cure; however, regarding the microbiologic eradication a positive case was identified in group A, requiring rescue treatment. The compliance in both groups was of 100%. In both groups, statistical analysis did not show significant differences. Three patients in group A had mild adverse effects. Patients mean age was 33.4 +/- 5.3 years. CONCLUSIONS: Both treatments showed similar effectiveness against mixed cervical-vaginal infections. Microbiological efficacy was of 96% and 100% in group A and B, respectively, besides, scheme of group B was better tolerated.

Genital tuberculosis with variable presentation: a series of three cases.

Tuberculosis (TB) is still frequently observed in third-world countries like Africa and Asia. Here we report three cases of genital TB with variable presentation. First case was a lady of reproductive age group who presented with polymenorrhagia and postcoital bleeding with unhealthy cervix. Histopathology of cervical tissue revealed tubercular cervicitis. Second and third cases presented with different complaints like discharge per vaginum, postcoital bleeding and pain in lower abdomen with growth over the cervix. Cervical biopsy was inconclusive of TB but endometrial tissue sampling for TB PCR was positive. This shows that newer diagnostic marker test can help us to detect secondary genital TB.

Schistosomiasis: an unusual finding of the cervix.

BACKGROUND: Schistosomiasis remains a major threat to women's health in many resource-poor countries and is being seen with increasing frequency in developed countries among immigrants and tourists who have a history of freshwater exposure in endemic areas. CASE: A 28-year-old asymptomatic African immigrant presented with an abnormal Pap test result showing rare atypical squamous cells. Colposcopy examination showed pale-yellow, finely granular cervical lesions. Calcified Schistosoma hematobium eggs were identified by histology but were absent in urine and stool specimens. Praziquantel treatment was initiated promptly, avoiding significant morbidity. CONCLUSION: The differential diagnosis of female genital schistosomiasis should be considered for patients who have a history of residence in or travel to endemic areas, including asymptomatic patients and patients presenting a long time after exposure.