Currently, we consider imiquimod (Aldara) to be the most promising form of immunotherapy for high-grade CIN. Herfs et al. [22] have shown that high-grade CIN can originate exclusively from cells of the squamocolumnar junction.
BRIEF ARTICLE
Update on human papillomavirus vaccination: Where are we now?
Abstract
REVIEW
Top tip: Human papilloma virus (HPV) represents the main cause of pre-invasive and invasive lesions of the urogenital tract. This article will review the efficacy, safety, and approval of currently available HPV vaccines including bivalent, quadrivalent, and nine-valent vaccines.
INTRODUCTION
DISCUSSION
A population-based evaluation of the subtypes of HPV in women with CIN2+ was performed in the United States. Efficacy of the quadrivalent vaccine in men was established in a study by Giuliano et al.[25].
CONCLUSION
Countries such as Australia, the United Kingdom and Portugal have achieved coverage rates as high as 80%[52]. Programs that have achieved mass vaccination coverage rates have been able to show reductions in HPV viral prevalence in terms of high-grade precancerous lesions and overall disease burden.
Use of 9-valent human papillomavirus (HPV) vaccine: updated HPV vaccination recommendations from the Advisory Committee on Immunization Practices. Safety and immunogenicity of a quadrivalent human papillomavirus (type and 18) vaccine in HIV-infected children 7 to 12 years of age.
Human papilloma virus vaccination: Review article and an update
Loss of E2 leads to upregulation of E6 and E7 genes, leading to high expression of E6 and E7 proteins, genomic instability and disruption of cell cycle. E6 and E7 are oncogenes and play an important role in malignant transformation of the infected cells.
HPV INFECTION TRANSMISSION
During infection, HPV DNA integrates into the host DNA genome, leading to the disruption of the E2 gene and inability of late genes to express[7]. Viral particle formation is completed and the viral particles are released at the epithelial or mucosal surface, which can then cause additional tissue infection[6].
HPV AND ITS GLOBAL IMPACT
The life cycle of HPV requires a basal layer of epidermal or mucosal epithelial cells that can still proliferate. After entry into the suprabasal layers, viral DNA is replicated, late viral genes are activated, and capsid proteins are formed.
INCIDENCE OF HPV IN HUMAN
IMMUNODEFICIENCY VIRUS PATIENTS
Several studies from sub-Saharan Africa with limited generalizability have reported similar proportions of HPV 16 and 18-associated cervical cancer in HIV-infected women versus the general female population[33,34].
HPV ASSOCIATED DISEASES
HPV SUBTYPES AND THEIR ASSOCIATED DISEASES
It protects against cervical, vaginal and vulvar cancers and precancerous lesions, and against genital warts associated with HPV types and 18[76]. HPV types 16 and 18 have shown the strongest association between infection and cervical cancer and high-grade SILs (CIN II and 3), accounting for 70% of all cervical cancer and CIN II and CIN III[77].
HPV VACCINATION IN HIV-INFECTED PATIENTS
In the PATRICIA trial, analysis of naïve cohorts of young vaccinated women showed 100% efficacy to protect against high-grade CIN 3 associated with HPV types 16 and 18[72,89]. Gardasil showed high efficacy and protection against CIN 3 associated with HPV types 16 and 18 in the final intention-to-treat (ITT)-naive analyses.
ISSUES REGARDING HPV VACCINES
A study in boys aged 10 to 18 years who received 3 doses of bivalent HPV vaccine showed protection against HPV 16/18 after 24 months of follow-up. Importantly, HPV 16 and 18 antibody titers were up to three times higher in boys than in young women after vaccination, and HPV 16 and 18 antibody levels were four and two times higher at month 2, respectively.
OBSTACLES OF ACCEPTANCE OF HPV VACCINE
Despite the above facts, only 53% of American female youth initiate the HPV vaccine and among them only 35%. In Africa, knowledge gaps regarding HPV and cervical cancer, lack of access to HPV vaccine and its cost were among major barriers to receiving HPV vaccine[124,125].
STRATEGIES FOR THE FUTURE
Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions: a meta-analysis update. Review of current knowledge on the epidemiology, pathogenesis and prevention of human papillomavirus infection.
MicroRNAs: New players in endometriosis
PERITONEAL FACTORS AND ENDOMETRIOSIS
These authors also found increased expression levels of miR-451 and decreased MIF in ectopic endometriotic lesions (mainly peritoneal lesions) compared with matched eutopic tissue. Consequently, the aforementioned authors hypothesized that miR-451 overexpresses in ectopic lesions in an attempt to limit endometriotic lesion/cell survival[ 46 ].
MIRNAS IN ENDOMETRIOSIS
Thus, the overexpression of BCL-2 in the eutopic endometrium of patients with endometriosis[4,67] may be a consequence of the regulation of GLI1 by miR-202-3p. Interestingly, one of the most dysregulated miRNAs in ovarian endometrioma was miR-29c, consistent with our data[ 53 ].
ANGIOGENESIS-RELATED MIRNAS IN ENDOMETRIOSIS
Although efforts have been made to identify the role of miRNAs in the pathogenesis of endometriosis, we are aware that future research will provide novel regulatory functions for known miRNAs and that newly identified miRNAs will expand our knowledge of this condition. Provided that miR-29c-3p regulates different extracellular matrix genes, our results are consistent with previously published studies[11,78].
CLINICAL UTILITY OF MIRNAS AS BIOMARKERS OF ENDOMETRIOSIS
113 Vitonis AF, Vincent K, Rahmioglu N, Fassbender A, Buck Louis GM, Hummelshoj L, Giudice LC, Stratton P, Adamson GD, Becker CM, Zondervan KT, Missmer SA.
Pathobiological role of MUC16 mucin (CA125) in ovarian cancer: Much more than a tumor biomarker
Nevertheless, in recent years, a number of studies have begun to unravel the biological functions of MUC16. Here we will review the current knowledge on the oncological role of MUC16 in ovarian cancer.
CA125 AS A BIOMARKER
Indeed, there is a strong correlation between rising and falling serum CA125 levels with disease progression and regression. Not surprisingly, most early studies (before 2001) focused on the clinical applicability of CA125 as a biomarker.
CLONING OF MUC16 GENE
Interestingly, mutation of Ser106Ala or Thr84/85Ala in the cytoplasmic tail did not affect the cleavage of MUC16 [ 54 ]. This is unexpected because previous studies showed that the phosphorylation of MUC16 cytoplasmic tail (Ser/Thr phosphorylation) was associated with its secretion [56].
MUC16 AND TUMORIGENICITY OF CANCER CELLS
Ectopic expression of the MUC16 terminal domain induces an epithelial-to-mesenchymal transition, which has been associated with tumorigenesis and tumor progression[ 78 ]. In addition, both Akt and ERK pathways can be activated by constitutive expression of the MUC16 Cterminal domain[69,82].
MUC16 AND TRANSFORMATION
Most importantly, expression of the Cterminal domain appears to be sufficient to mediate these effects. Ectopic expression of MUC16 Cterminal domain in cancer cells was associated with altered gene expression profile with increased expression of genes encoding proteins involved in invasion such as MMP2, MMP9, CXCL12 and CDH1[ 85 ].
MUC16 AND DRUG RESISTANCE
Knockdown of MUC16 in breast cancer cells was associated with reduced expression of cyclin B1 and D1, both of which are involved in the regulation of cell cycle control [69]. Indeed, expression of the Cterminal domain of MUC1 induced resistance to cisplatin and etoposide in colon cancer cells [89, 95].
CONCLUSIONS AND FUTURE DIRECTIONS
A novel multi-marker bioassay using HE4 and CA125 to predict ovarian cancer in patients with a pelvic mass. Tumor antigen CA125 (MUC16) selectively modulates the susceptibility of ovarian cancer cells to drug-induced genotoxic apoptosis.
Implications of multigene testing for hereditary breast cancer in primary care
There are many risk factors for developing breast cancer, including increasing age, reproductive factors and family history of breast cancer. In the case of some mutations, there are interventions that can reduce the incidence of breast cancer and mortality in mutation carriers.
INDICATIONS FOR GENETIC
Proper identification of women who should undergo genetic counseling for hereditary breast cancer and implementation of recommended guidelines for those found to be at high risk can reduce breast cancer incidence and mortality. There are many risk factors for developing breast cancer, including increasing age, reproductive factors and family history of breast cancer.
ASSESSMENT IN HEREDITARY BREAST CANCER
MULTIGENE TESTING FOR HEREDITARY BREAST CANCER
Breast cancer and ≥ 1 Peutz-Jeghers polyp in the same person Lobular breast cancer and diffuse gastric cancer in the same person. Several studies have shown that mutations in PALB2 are associated with an increased risk of breast cancer[38-41].
INTERVENTIONS FOR HIGH RISK PATIENTS
Tamoxifen for the prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. Tamoxifen for the prevention of breast cancer: current status of the National Surgical Adjuvant Breast and Bowel Project P-1 study.
Amniocentesis: A contemporary review
Amniocentesis is also useful if intraamniotic infection is suspected, but the clinical picture is unclear. However, there are some cases when the timing of delivery is unclear and amniocentesis for fetal lung maturity can provide information to guide the timing of delivery.
HISTORICAL CONSIDERATIONS
TECHNIQUE
INDICATIONS
In utero, bilirubin from the fetal pulmonary and tracheal effusions is found in the amniotic fluid. Based on the findings of this study, MCA Doppler assessment has been widely accepted as the primary screening tool in the detection of fetal anemia[5].
COMPLICATIONS
We agree that amniocentesis should no longer be the first monitoring tool in this situation, as the non-invasive option has been shown to be superior. Given that recent literature suggests loss rates lower than seen in the 1970s, amniocentesis remains a safe option for genetic testing.
OTHER CONSIDERATIONS
Although additional RCTs are unlikely, based on current literature, the risk of pregnancy loss from amniocentesis in the second trimester is low in both singleton and twin pregnancies. Amniocentesis and the risk of second-trimester fetal loss in twin pregnancies: results from a prospective observational study.
Thyroid disease in pregnancy: A review of diagnosis, complications and management
MINIREVIEWS
All pregnant women with hypothyroidism should receive hormone replacement in the form of levothyroxine to maintain TSH in the normal to high normal range. They did not treat SCH in pregnancy, but recommended treatment for patients 
HYPERTHYROIDISM
The patient should be euthyroid before attempting cardioversion for atrial fibrillation because a spontaneous return to sinus rhythm may occur and even if cardioversion is successful, atrial fibrillation is likely to recur if hyperthyroidism is the cause and is not corrected [16]. TSI antibody titers should be measured between weeks 24 and 28 in all women with a current or history of Graves' disease.
POSTPARTUM THYROIDITIS
If thyroidectomy is required during pregnancy, it is ideally performed in the second trimester because of a possibly unwarranted concern about teratogenesis from anesthetics in the first trimester, and possible onset of labor leading to extreme prematurity during the third trimester. Weekly or bi-weekly non-stress testing in the interval between growth scans may be considered.
THYROID CANCER IN PREGNANCY
Low maternal free thyroxine concentrations during early pregnancy are associated with impaired psychomotor development in childhood. Downstream effects of maternal hypothyroxinemia during early pregnancy: nonverbal IQ and brain morphology in school-aged children.
Role of ultrasound imaging in advancing treatment of female patients with pelvic floor mesh complications
The role of ultrasound imaging in advancing the treatment of female patients with pelvic floor mesh complications. Repeat operations can be very involved, ranging from mesh removal to abdominal cystorrhaphy or partial cystectomy depending on the exact complications of the mesh[18].
DIAGNOSTIC ULTRASOUND
Commonly stated is the idea that surgeon skill is the most important factor in limiting mesh complications[1315]. While initial physical symptoms such as irritation, vaginal or pelvic pain, and dyspareunia may be the first manifestations of complications, vaginal mesh complications in particular can lead to feelings of hopelessness, isolation, shame, and emotional distress.
DIAGNOSTIC ALTERNATIVES TO ULTRASOUND
ROLE OF ULTRASOUND IN RE- OPERATIVE PLANNING AND
Meshes play a vital role in the treatment of female pelvic organ prolapse as well as urinary incontinence. Pelvic floor muscle training versus no treatment, or inactive control treatments, for urinary incontinence in women.
Evaluation of sentinel lymph nodes in vulvar, endometrial and cervical cancers
The application of SLN biopsy techniques in gynecological malignancies has been extensively studied over the past decade, because lymph node dissections in these cancers can lead to long-term morbidities. In breast and vulvar cancers, SLN biopsy is predictive of lymphatic disease status and has demonstrated a reduction in the significant short- and long-term morbidities seen with complete lymphadenectomy.
VULVAR CANCER
Another large multicenter study, conducted by Hampl et al[19], evaluated the accuracy and feasibility of SLN biopsy in women with T1-T3 vulvar cancer. In women with tumors measuring 2.0–3.9 cm, the rates of nodal metastasis and false-negative SLN biopsy were 26.4% and 2%, respectively.
ENDOMETRIAL CANCER
However, in many women with early-stage endometrial cancer, lymph node involvement is low and the survival benefit of adding an SLN biopsy is unknown. At this time, we believe that SLN biopsy is under investigation in women with endometrial cancer and should only be performed according to protocol.
CERVICAL CANCER
Lymphatic mapping and sentinel lymph node biopsy in women with squamous cell carcinoma of the vulva: a gynecologic oncology group study. Long-term follow-up of patients with vulvar cancer evaluated with sentinel lymph node biopsy alone.
Apoptosis and endometrial receptivity: Relationship with in vitro fertilization treatment outcome
Analysis of data obtained from different clinical centers shows that the maximum achievable pregnancy rate in IVF does not exceed 50%. And understanding the molecular mechanisms involved in the regulation of apoptosis in infertile women can be of great value and allow us to use them as predictors of endometrial dysfunctions to improve the implantation rate in the IVF program.
LITERATURE RESEARCH
APOPTOSIS IN THE NORMAL ENDOMETRIUM
It was also shown that the apoptosis of endometrial stromal cells in the secretory phase of the cycle was increased due to caspase activity, based on the upregulation of specific receptors Fas and TRAIL-R2 [47]. In normal endometrium, lowest DFF45 expression was detected in the secretory endometrium in the late proliferative phase and maximum staining of the endometrial tissue for DFF45 was observed in an early secretory phase of the menstrual cycle [48-50].
APOPTOSIS AND ENDOMETRIAL RECEPTIVITY
At the same time, an increase in the expression of the proapoptotic factor BAX in the endometrium has been observed in this phase of the cycle [33]. Simultaneous activation of p53 and estrogen receptor α has been reported to occur in the endometrium.
APOPTOSIS IN THE ENDOMETRIUM OF INFERTILE WOMEN
In the endometrium of women with ovarian endometriosis, the lower level of DFF45 expression was then observed. These results also directly prove in favor of reduced apoptosis in the endometrium of patients with endometriosis[48].
ENDOMETRIAL APOPTOSIS AND IVF TREATMENT OUTCOME
Expression of apoptosis-related genes in the endometrium of patients with polycystic ovary syndrome during the implantation window. Changes in the regulation of apoptosis in the endometrium of infertile women with tubal factor and endometriosis treated with in vitro fertilization.
Review of the current surgical management of vulval cancer
The objective of this paper is to review the current literature on the management of vulvar cancer and summarize new treatments and associated data. Currently in the UK, 1,200 cases of vulvar cancer are diagnosed each year, which is 6%.
RESEARCH
Inguinofemoral dissection for carcinoma of the vulva: effect of changes in size and technique on morbidity and survival. Regarding Katz et al.: The role of radiation therapy in preventing regional recurrences of invasive squamous cell carcinoma of the vulva (Int J Radiat Oncol Biol Phys.
Imperative for improvements and international
Cardiotocography (CTG) or interpretation of fetal heart rate (FHR) patterns has been the most widely accepted and practiced method of intrapartum fetal monitoring for over 50 years. This economic imperative (rightly or wrongly) pushes the issue of "intrapartum fetal monitoring" to the top of the patient safety agenda.
EFM AND EVIDENCE BASED MEDICINE
POSSIBLE REMEDIES TO IMPROVE CTG INTERPRETATION
VARIATIONS IN CATEGORIZATION OF FHR PARAMETERS
Indeed, FHR decelerations were the "low-hanging fruit" (generally highly correlated with outcomes) that were immediately captured by pioneers such as Hon et al[16] and CaldeyroBracia's group[17]. They categorized FHR decelerations based on the temporal relationship to contractions only as actually reflected in the terminology itself[16,17].
![Figure 1 Diagrammatic representation of early, late and variable decelerations as practiced in British Obstetrics before 2007 (Reproduced with kind per- per-mission from “Principles of Obstetrics” by Bryan Hibbard, 1988) [26]](https://thumb-ap.123doks.com/thumbv2/123dok/11492605.0/112.892.86.577.119.421/diagrammatic-representation-decelerations-practiced-obstetrics-reproduced-principles-obstetrics.webp)
CTG RECORDING SPEED
There is considerable observational and experimental evidence that the shape or rate of decline of FHR decelerations does not correlate with the etiology of the decelerations or the state of the fetus [17]. It would be very useful to reform the categorization of FHR decelerations in the US and Europe, correcting design/validation biases and errors – the compatibility of this with scientific practice is debatable.
CONFIRMATORY/ADJUNCTIVE TESTS OF FETAL WELL-BEING
Although more meaningful research is always welcome, it has been difficult to come by in this area and should not be a prerequisite for considering the validity of any aspect of CTG inter.
FETAL ECG
INTRAPARTUM FETAL PULSE OXIMETRY
COMPUTERISED CTG INTERPRETATION
COMMON PITFALLS IN INTRAPARTUM FETAL MONITORING
Critical evaluation of US categorization of fetal heart rate (FHR) decelerations and three tier classification -. Intermittent auscultation during labor: Can it miss many pathologic (late) fetal heart rate decelerations.
Overview of embryonal rhabdomyosarcoma of cervix in women over 40-year-old
Although radiotherapy was used infrequently, the longest survival in the age group > 40 years was observed in those who received radiotherapy, including a case with resected lung metastases. We examined how the outcomes of women >40 years old compared with younger women diagnosed with ERMS.
LITERATURE ON ERMS
In the series, the outcome of the 48-year-old patient was comparable to that of the younger patients. Of the 3 patients with follow-up, 1 was alive without evidence of disease 3 years later; this case received chemotherapy.
ACKNOWLEDGMENTS
Expression of the alpha1B receptor is a marker of reduced survival and increased tumor recurrence in patients with.
Alpha1B adrenoceptor expression is a marker of reduced survival and increased tumor recurrence in patients with
Basic Study
In this new study, we found that a1B adrenoceptor is a biomarker for tumor recurrence in endometrioid ovarian cancer. Alpha1B adrenoceptor expression is a marker for decreased survival and increased tumor recurrence in patients with endometrioid ovarian cancer.
MATERIALS AND METHODS
Increased levels of catecholamine hormones are associated with poor prognosis in ovarian cancer[35] possibly explained by their ability to promote cell invasion and proliferation via activation of adrenergic receptors (adrenoceptors, AR)[5,6]. ERK1/2 phosphorylation can occur after activation of α1B-adrenoceptor in ovarian cancer cells[15-17], but in contrast, α2C-adrenoceptor can preferentially inhibit cAMP and PKA gene transcription[17].
RESULTS
A Kaplan-Meier technique with a log-rank test was used to model the independence of adrenoceptor protein expression in predicting specific ovarian cancer survival and tumor recurrence in the entire patient cohort. 4 Figure 2 High alpha1B protein expression (green curve) showed an association with poor survival (P = 0.045) (A) and (B) tumor recurrence (P = 0.007) in the entire cohort of patients with ovarian cancer.
COMMENTS
The expression pattern of 3 AR proteins (aB1, a2C and b2) was investigated and its significance statistically related to survival and metastasis outcome in patients with different types of ovarian cancer. Stress-related mediators stimulate vascular endothelial growth factor secretion by two ovarian cancer cell lines.
Variation in use of menopausal hormone treatment on risk of health outcomes
Observational Study
Outcomes selected for their clinical significance included coronary artery disease, stroke, peripheral artery disease, and breast cancer. In conclusion, the study found that the use of MHT was not associated with any overall increased risk of coronary artery disease, stroke and breast cancer, and an increased risk of peripheral artery disease.
Postpartum intrauterine device contraception: A review
SYSTEMATIC REVIEWS
Ten evaluated the safety (infections, perforations) and efficacy (expulsion, pregnancy, continued use) of postpartum IUD insertion. IUD insertion is effective and safe during the immediate postpartum, early postpartum, and delayed postpartum periods [36].