Background Cervical cancer screening might contribute to the prevention of anal cancer in women. We aimed to investigate if routine cervical cancer screening results-namely high-risk human papillomavirus (HPV) infection and cytohistopathology-predict anal HPV16 infection, anal high-grade squamous intraepithelial lesions (HSIL) and, hence, anal cancer. MethodsWe did a systematic review of MEDLINE, Embase, and the Cochrane library for studies of cervical determinants of anal HPV and HSIL published up to Aug 31, 2018. We centrally reanalysed individual-level data from 13 427 women with paired cervical and anal samples from 36 studies. We compared anal high-risk HPV prevalence by HIV status, cervical high-risk HPV, cervical cytohistopathology, age, and their combinations, using prevalence ratios (PR) and 95% CIs. Among 3255 women with anal cytohistopathology results, PRs were similarly calculated for all anal HSIL and HPV16-positive anal HSIL. Findings Cervical and anal HPV infections were highly correlated. In HIV-negative women, anal HPV16 prevalence was 41% (447/1097) in cervical HPV16-positive versus 2% (214/8663) in cervical HPV16-negative women (PR 16•5, 95% CI 14•2-19•2, p<0•0001); these values were 46% (125/273) versus 11% (272/2588) in HIV-positive women (4•4, 3•7-5•3, p<0•0001). Anal HPV16 was also associated with cervical cytohistopathology, with a prevalence of 44% [101/228] for cervical cancer in HIV-negative women (PR vs normal cytology 14•1, 11•1-17•9, p<0•0001). Anal HSIL was associated with cervical high-risk HPV, both in HIV-negative women (from 2% [11/527] in cervical highrisk HPV-negative women up to 24% [33/138] in cervical HPV16-positive women; PR 12•9, 95% CI 6•7-24•8, p<0•0001) and HIV-positive women (from 8% [84/1094] to 17% [31/186]; 2•3, 1•6-3•4, p<0•0001). Anal HSIL was also associated with cervical cytohistopathology, both in HIV-negative women (from 1% [5/498] in normal cytology up to 22% [59/273] in cervical HSIL; PR 23•1, 9•4-57•0, p<0•0001) and HIV-positive women (from 7% [105/1421] to 25% [25/101]; 3•6, 2•5-5•3, p<0•0001). Prevalence of HPV16-positive anal HSIL was 23-25% in cervical HPV16-positive women older than 45 years (5/20 in HIV-negative women, 12/52 in HIV-positive women).Interpretation HPV-based cervical cancer screening programmes might help to stratify anal cancer risk, irrespective of HIV status. For targeted secondary anal cancer prevention in high-risk groups, HIV-negative women with cervical HPV16, especially those older than 45 years, have a similar anal cancer risk profile to that of HIV-positive women.

Chlamydia trachomatis (CT) is the most common bacterial cause of sexually transmitted disease. High-risk human papillomavirus (HR-HPV) is considered the main etiological agent for cervical neoplasia. Evidences showed that the presence of co-infection of CT and HR-HPV plays a central role in the etiology of cervical intraepithelial neoplasia (CIN) and cervical cancer. The goals of this study were: evaluate the human papillomavirus (HPV) and CT prevalence among Brazilian women with abnormal cytology and provide the effect of this association on the severity of cervical neoplasia. The population of this study was composed by 142 women with incident histological incidence of CIN grades I, II, III or cervical cancer from Recife, Northeast of Brazil. The polymerase chain reaction method on a cervical brush specimen was used to detect both agents and the automatic sequencing method was used for HPV genotyping assay. The prevalence of HPV and CT was 100 and 24.65 %, respectively. Thirteen types of HPV were detected; HPV 16, 18, 31 and 33 were the most common. The most prevalent HPV types were HPV 16 and 18. A significant association between CT positive and HPV 16 infection was found (p < 0.0106; OR = 5.31; 95 % IC 1.59-17.67). In the study population, there was diversity of HPV infections, with high-risk types being the most common. Also, the data collected suggest that CT infection may play an important role in the natural history of HPV infection.

The Human Papillomavirus (HPV) is a sexually transmitted organism associated with Cervical Intraepithelial Neoplasia (CIN) and cervical cancer, the second main cause of malignancy in women worldwide. The virus itself, however, is not enough to cause lesions on the cervix. Several studies suggest that some polymorphic sites changes the cytokines levels and influence the cancer development in HPV infected patients. In this study, we evaluated the presence of functional polymorphisms at +874 (T/A) IFNG and +1188 (A/C) IL-12B genes in cervical smears samples from 76 healthy women and 162 women, HPV positive, with CIN lesion--CIN I (45), CIN II (55), CIN III (53) and cervical cancer (9)--in Brazilian population. There was no significant differences in genotype (p = 0.4192) and allele (p = 0.370; OR = 1.20) distributions between CIN patients and control groups on IFNG allelic polymorphism. Moreover, for IL-12B gene, there was a significant difference in genotype (p = 0.015) and allele distribution (p = 0.014; OR = 0.5754) between the groups. When samples were stratified according to grade of cervical lesion, the AA genotype and A allele were less frequent in the group with low-grade cervical lesions than in group with high-grade cervical lesions (p = 0.0036 and p = 0.0010; OR = 0.3819, respectively), suggesting that the C allele (mutant) may protect against the emergence of CIN lesions and its progression.

In the present study, we compared the performance of a ThinPrep cytological method with the conventional Papanicolaou test for diagnosis of cytopathological changes, with regard to unsatisfactory results achieved at the Central Public Health Laboratory of the State of Pernambuco. A population-based, cross-sectional study was performed with women aged 18 to 65 years, who spontaneously sought gynecological services in Public Health Units in the State of Pernambuco, Northeast Brazil, between April and November 2011. All patients in the study were given a standardized questionnaire on sociodemographics, sexual characteristics, reproductive practices, and habits. A total of 525 patients were assessed by the two methods (11.05% were under the age of 25 years, 30.86% were single, 4.4% had had more than 5 sexual partners, 44% were not using contraception, 38.85% were users of alcohol, 24.38% were smokers, 3.24% had consumed drugs previously, 42.01% had gynecological complaints, and 12.19% had an early history of sexually transmitted diseases). The two methods showed poor correlation (k=0.19; 95%CI=0.11–0.26; P<0.001). The ThinPrep method reduced the rate of unsatisfactory results from 4.38% to 1.71% (χ2=5.28; P=0.02), and the number of cytopathological changes diagnosed increased from 2.47% to 3.04%. This study confirmed that adopting the ThinPrep method for diagnosis of cervical cytological samples was an improvement over the conventional method. Furthermore, this method may reduce possible losses from cytological resampling and reduce obstacles to patient follow-up, improving the quality of the public health system in the State of Pernambuco, Northeast Brazil.

Polymorphisms in chemokine receptors play an important role in the progression of cervical intraepithelial neoplasia (CIN) to cervical cancer (CC). Our study examined the association of CCR2-64I (rs1799864) andCCR5-Δ32 (rs333) polymorphisms with susceptibility to develop cervical lesion (CIN and CC) in a Brazilian population. The genotyping of 139 women with cervical lesions and 151 women without cervical lesions for the CCR2-64I and CCR5-Δ32 polymorphisms were performed using polymerase chain reaction-restriction fragment length polymorphism. The individuals carrying heterozygous or homozygous genotypes (GA+AA) for CCR2-64I polymorphisms seem to be at lower risk for cervical lesion [odds ratio (OR) = 0.37, p = 0.0008)]. The same was observed for the A allele (OR = 0.39, p = 0.0002), while no association was detected (p > 0.05) with CCR5-Δ32 polymorphism. Regarding the human papillomavirus (HPV) type, patients carrying the CCR2-64Ipolymorphism were protected against infection by HPV type 16 (OR = 0.35, p = 0.0184). In summary, our study showed a protective effect ofCCR2-64I rs1799864 polymorphism against the development of cervical lesions (CIN and CC) and in the susceptibility of HPV 16 infection.

A number of recent studies have catalogued global gene expression patterns in a panel of normal, tumoral cervical tissues so that potential biomarkers can be identified. The qPCR has been one of the most widely used technologies for detecting these potential biomarkers. However, few studies have investigated a correct strategy for the normalization of data in qPCR assays for cervical tissues. The aim of this study was to validate reference genes in cervical tissues to ensure accurate quantification of mRNA and miRNA levels in cervical carcinogenesis. For this purpose, some issues for obtaining reliable qPCR data were evaluated such as the following: geNorm analysis with a set of samples which meet all of the cervical tissue conditions (Normal + CIN1 + CIN2 + CIN3 + Cancer); the use of individual Ct values versus pooled Ct values; and the use of a single (or multiple) reference genes to quantify mRNA and miRNA expression levels. Two different data sets were put on the geNorm to assess the expression stability of the candidate reference genes: the first dataset comprised the quantities of the individual Ct values; and the second dataset comprised the quantities of the pooled Ct values. Moreover, in this study, all the candidate reference genes were analyzed as a single “normalizer”. The normalization strategies were assessed by measuring p16INK4a and miR-203 transcripts in qPCR assays. We found that the use of pooled Ct values, can lead to a misinterpretation of the results, which suggests that the maintenance of inter-individual variability is a key factor in ensuring the reliability of the qPCR data. In addition, it should be stressed that a proper validation of the suitability of the reference genes is required for each experimental setting, since the indiscriminate use of a reference gene can also lead to discrepant results.

Objective: To evaluate agreement between 3 methods for screening anal intraepithelial lesions: anal cytology, anoscopy and human papillomavirus (HPV) detection by PCR. Study Design: This prospective, cross-sectional study screened 324 women with cervical neoplasia for anal neoplasia. Agreement between methods was calculated using the ĸ coefficient. Results: Of 324 anal cytologies performed, 31.5% (n = 102) were found to be abnormal: low-grade anal lesions were detected in 19.1% (n = 62) of cases, high-grade lesions in 3.1% (n = 10) and atypical squamous cells of undetermined significance in 9.3% (n = 30). With respect to the biopsies, 25.7% (n = 20) were positive, consisting of 7 cases of HPV infection, 5 anal intraepithelial neoplasia (AIN) grade 1, 6 AIN grade 2, and 2 AIN grade 3. Twenty-one samples (6.5%) were inadequate for HPV analysis. Of the 303 adequate samples, 84.2% (n = 255) tested positive for HPV. Agreement between cytology and anoscopy was fair (ĸ = 0.31). Agreement between PCR for HPV and cytology was slight (ĸ = 0.08) and no agreement was found between PCR for HPV and anoscopy (ĸ = 0.00). Conclusion: Agreement between the different methods of diagnosing HPV-induced anal lesions is slight to fair; however, anal cytology permits identification of cases in which lesions are present, allowing them to be referred for anoscopy and biopsy.

The prevalence of anal intraepithelial neoplasia was high among patients with cervical neoplasia who did not have HIV, particularly patients older than 35 years.