Detection of Human Papillomavirus among Women with Atypical Squamous Cells of Undetermined Significance Referred to Colposcopy: Implications for Clinical Management in Low and MiddleIncome Countries.

To determine the prevalence of human papillomavirus (HPV) among women with atypical squamous cells of undetermined significance (ASC-US) referred to colposcopy and the implications for clinical management in low- and middle-income countries (LMIC), the present study was conducted. We included 200 women living in Maringa÷Brazil referred to colposcopy service between August 2012 and March 2013 due to an abnormal cytology from ASC-US until high-grade intraepithelial lesion (HSIL). HPV was detected and genotyped by polymerase chain reaction (PCR). The mean age was 36.8±10.5 years, and women with and without ASC-US had similar mean ages (37.4±11.5 and 36.4±9.96 years, respectively). The highest prevalence of ASC-US occurred at 20-24 years (40%). HPV-DNA was positive in 164 (82.0%) women.Of the 57 women with ASC-US, 30 (52.6%) were HPV-DNA-positive and 21 (70%) were high-risk HPV-positive (HR-HPV); the latter was similar to women without ASC-US (76.9%) but with other abnormal cytological findings present. Our data demonstrated that performing tests for HR-HPV can be used for management of women with ASC-US to support the decision of which women should be referred for an immediate or later colposcopy. The same conclusions can be applied to other LMICs for which HPV testing for primary screening has not been adopted.

Association of human papillomavirus, Neisseria gonorrhoeae and Chlamydia trachomatis co-infections on the risk of high-grade squamous intraepithelial cervical lesion.

The link between high-risk human Papillomavirus (HR-HPV) and other sexually transmitted diseases (STDs) in the risk of developing cervical cancer still unclear. Thus, in this report we investigated the rates of co-infections between HPV and other important non-HPV STDs in different cervical findings using a multiplex polymerase chain reaction (M-PCR) to simultaneously detect Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Trichomonas vaginalis, HSV-1 and -2, and Treponema pallidum. A total of 838 women aged 18 to 68 years were screened using Papanicolaou smears for cervical abnormalities, HPV and non-HPV STDs using PCR and M-PCR methods. A total of 614 (73.3%) of the women had normal cytology (NILM) and 224 (26.7%) women exhibited abnormal cytology (≥ ASC-US). HPV-DNA prevalence was 33.9%, and HPV-16 was the most prevalent genotype in women with NILM and ≥ ASC-US cytology. Non-HPV STDs were detected in 30.4% women and T. vaginalis was the most prevalent one (11.6%). A higher increased risk of ≥ ASC-US and HSIL occurred in co-infections of HR-HPV with C. trachomatis and N. gonorrhoeae. Co-infections of HPV-DNA and HR-HPV with HSV-2 exhibited a similar increased risk but only with ≥ ASC-US. Co-infections of HPV-DNA and HR-HPV with T. vaginalis demonstrated a similar increased risk of ≥ ASC-US and HSIL. We found that C. trachomatis and N. gonorrhoeae were the primary pathogens associated with HR-HPV for the increased risk for all grades of cervical abnormalities but mainly for HSIL, suggesting a possible synergistic action in cervical lesions progression. Our results reinforce the hypothesis that some non-HPV STDs might play a role as co-factors in HPV-mediated cervical carcinogenesis. These data improve our understanding of the etiology of SCC and may also be useful for disease prevention.

HPV Infection and Cervical Abnormalities in HIV Positive Women in Different Regions of Brazil, a Middle-Income Country.

Human papillomavirus is a virus that is distributed worldwide, and persistent infection with high-risk genotypes (HR-HPV) is considered the most important factor for the development of squamous cell cervical carcinoma (SCC). However, by itself, it is not sufficient, and other factors may contribute to the onset and progression of lesions. For example, infection with other sexually transmitted diseases such as human immunodeficiency virus (HIV) may be a factor. Previous studies have shown the relationship between HPV infection and SCC development among HIV-infected women in many regions of the world, with great emphasis on low- and middle- income countries (LMICs). Brazil is considered a LMIC and has great disparities across different regions. The purpose of this review was to highlight the current knowledge about HPV infection and cervical abnormalities in HIV+ women in Brazil because this country is an ideal setting to evaluate HIV impact on SCC development and serves as model of LMICs and low-resource settings.

Animal models for the effective development of atrophic vaginitis therapies: possibilities and limitations.

INTRODUCTION: Vaginal atrophy (VA) is an inflammation of the vagina that develops when there is a significant decrease in levels of the estrogen. Prolonged periods of hypoestrogenism may induce severe VA and treatment is essential. This is a significant problem which requires more focused attention for the development of existing and future therapies. AREAS COVERED: This review evaluates the suitable animal models of VA, including: mice, rodents and non-human primates. It focuses particularly on the possibilities and limitations of these in vivo models for the effective development of VA therapies. EXPERT OPINION: Hormone replacement therapy (HRT) has been prescribed and successfully used for VA. However, some studies have shown that HRT may be linked to an increased risk of breast cancer, coronary heart diseases and others risks. Thus, there is a growing interest in effective and safe alternatives to VA symptoms. There are, however, a number of things that must be considered for future drug discovery efforts. One major consideration is what animal model should be used and whether the model is appropriate for the study aim. Similarly, research studies must also consider the influencing factors on these animal models, so that these models can effectively mimic the actual disease. The authors also highlight the need to standardize research parameters to produce more reliable and reproducible data.

Differences in the mutation of the p53 gene in exons 6 and 7 in cervical samples from HIV- and HPV-infected women.

BACKGROUND: Human Papillomavirus (HPV) infection is a serious problem for human immunodeficiency virus (HIV)-infected women, increases their risk of cervical lesions and cancer. In cervical carcinogenesis, mutations in the p53 gene occur most frequently within exons 5-8. To our knowledge, no previous studies have analyzed mutations in exons 5-8 of the p53 gene in HIV- and HPV-infected women. In our study, we verified these mutations in women with and without cervical abnormalities. FINDINGS: The study included 160 women, divided into three groups: (1) 83 HPV- and HIV-infected women (HIV group); (2) 37 HPV-infected/HIV-uninfected (control group); and (3) 40 normal cytology/DNA-HPV negative/HIV-uninfected women (negative control p53 reactions). HPV-DNA was detected using polymerase chain reaction (PCR) and genotyping by PCR-restriction fragment length polymorphism analysis. Using primers for exons 5-8, the mutation of the p53 gene was verified by PCR-single strand conformational polymorphism. The total mutation of the p53 gene in exons 5-8 was not significantly associated with the HIV and control groups. The mutations in exon 7 were the highest in the HIV group (43.8%) and in exon 6 in the control group (57.2%) (p = 0.0793) suggesting a tendency toward differential mutation in exon 7 in the HIV group. CONCLUSIONS: Our study provides preliminary evidence that the mutation in exon 7 might be an important differentiating factor for cervical carcinogenesis in HIV-infected women. This aspect deserves an additional cross-sectional and longitudinal study using a larger sample size with a higher number of High-grade squamous intraephitelial lesion (HSIL) to observe the evolution of cervical lesions.