Human papillomaviruses (HPVs), which belong to the Papillomaviridae family, constitute a group of small nonenveloped double-stranded DNA viruses. HPV has a small genome that only encodes a few proteins, and it is also responsible for 5% of all human cancers, including cervical, vaginal, vulvar, penile, anal, and oropharyngeal cancers. HPV types may be classified as high- and low-risk genotypes (HR-HPVs and LR-HPVs, respectively) according to their oncogenic potential. HR-HPV 16 and 18 are the most common types worldwide and are the primary types that are responsible for most HPV-related cancers. The activity of the viral E6 and E7 oncoproteins, which interfere with critical cell cycle points such as suppressive tumor protein p53 (p53) and retinoblastoma protein (pRB), is the major contributor to HPV-induced neoplastic initiation and progression of carcinogenesis. In addition, the E5 protein might also play a significant role in tumorigenesis. The role of HPV in the pathogenesis of gynecological cancers is still not fully understood, which indicates a wide spectrum of potential research areas. This review focuses on HPV biology, the distribution of HPVs in gynecological cancers, the properties of viral oncoproteins, and the molecular mechanisms of carcinogenesis.

The aim of this review is to clarify the relative association between adenomyosis and infertility and the possible treatment for an infertile patient. Although adenomyosis is detected more often in women of late reproductive age, its influence on pregnancy rates is important, especially considering the tendency to delay pregnancy among women in developed countries. In this article, we present a critical analysis of the literature data concerning the impact of adenomyosis on fertility. The possible effects of treatment on the pregnancy rate will also be discussed. We conducted a literature search; publications from Pubmed, Embase and Cochrane databases published from 1982 to 2019 were retrieved using terms ’adenomyosis and infertility’ and ’adenomyosis and pregnancy outcomes’, extensively studied in the aspects of diagnosis, pathogenesis of infertility and possible treatment methods. Molecular studies have given deep insight into the pathogenesis of adenomyosis in the recent few years, but there is a huge discrepancy between in vitro studies and praxis. Oral contraceptive pills, anti-prostaglandins, oral or parenteral progestins, danazol and gonadotrophin-releasing hormone (GnRH) analogues have all been used to control menstrual pain and menorrhagia in women with adenomyosis, but they temporarily suppress the menstrual cycle. Additionally, endometrial ablation and hysterectomy used to alleviate pain caused by adenomyosis exclude pregnancy planning. The development of imaging techniques—ultrasound and MRI—enables the diagnosis of adenomyosis with very high accuracy nowadays, but the methods of treatment mentioned above have not given satisfactory results in women planning pregnancy. For these patients, the high-intensity-focused ultrasound method (HIFU) and combined treatment before assisted reproductive techniques can prove beneficial in adenomyosis patients.

Reproductive failure in humans is a very important social and economic problem, because nowadays women decide to conceive later in life and delay motherhood. Unfortunately, with increasing age they have less chance for natural fertilization and maintenance of pregnancy. Many of them need assisted reproductive technology. Approximately 10% of women after in vitro fertilization-embryo transfers experience recurrent implantation failure (RIF). Multiple factors may contribute to RIF, including oocyte and sperm quality, parental chromosomal anomalies, genetic or metabolic abnormalities of the embryo, poor uterine receptivity, immunological disturbances in the implantation site, and some gynecologic pathologies such as endometriosis, uterine fibroids, hydrosalpinx and endometrial polyps. Moreover, the procedure of in vitro fertilization itself could adversely influence the implantation. Nowadays, many studies are focused on the role of natural killer (NK) cells in normal and pathologic pregnancy because NK cells constitute the dominant cell population in the endometrium and they come in close contact with the allogeneic extravillous trophoblast cells in early pregnancy decidua. The majority of these cells are of CD56^bright phenotype. These cells can express killer immunoglobulin-like receptors (KIRs), which, upon recognition of HLA class I molecules (HLA-C and HLA-G) on trophoblasts, may either stimulate or inhibit NK cells to produce soluble factors, and display low cytotoxicity necessary for maintenance of the allogeneic embryo and fetus in the next steps of pregnancy. Moreover, some members of the leukocyte immunoglobulin-like receptor (LILR) family, also named ILT (immunoglobulin-like transcript), are present in the human placenta. LILRB1 (ILT2) was described mainly on stromal cells, while LILRB2 (ILT4), in addition to stromal cells, was also found around vessels in the smooth muscle layer. In this review we focus on the possible role of polymorphism of KIR, LILRB and their ligands (HLA-C, HLA-G) in susceptibility to recurrent implantation failure, which could serve as diagnostic biomarkers of this disease.