Human Papillomavirus Positivity at 3 Anatomical Sites Among Transgender Women in Central Brazil.

BACKGROUND: Transgender women (TGW) are susceptible to the acquisition of sexually transmitted infections (STIs), including human papillomavirus (HPV). Nonetheless, the exact data for this population are scarce. We estimated HPV positivity at the anal, genital, and oral sites among TGW and also identified the related characteristics and behaviors that could be risk factors for HPV infection in a sample of TGW in Brazil. Furthermore, we characterized the site-specific HPV genotypes among those who were positive for HPV at these 3 sites. METHODS: A cross-sectional study was conducted on TGW in Goiânia City (Central-Midwest region), Brazil, between April 2018 and August 2019. Respondent-driven sampling was applied for recruitment. Next, self-collected anal, genital, and oral samples were examined for HPV DNA using polymerase chain reaction (SPF-10 primer). Human papillomavirus genotypes were identified in 12 TGW. RESULTS: In the TGW included in the study, the anal, genital, and oral HPV positivity values were 77.2% (95% confidence interval [CI], 67.3%-84.6%), 33.5% (95% CI, 26.1%-48.9%), and 10.9% (95% CI, 5.8%-17.0%), respectively. In addition, the majority of 12 participants who tested for HPV had multiple genotypes. HPV-52 was the most prevalent genotype identified at the anal (66.6%) and genital (40.0%) sites, whereas HPV-62 and HPV-66 were the most common at the oral site (25.0%). CONCLUSIONS: A high HPV positivity was observed among TGW. Therefore, additional epidemiological studies on HPV genotypes should generate health intervention information, including the prevention, diagnosis, and treatment of sexually transmitted infections.

Tumoral and stromal expression of MMP-2, MMP-9, MMP-14, TIMP-1, TIMP-2, and VEGF-A in cervical cancer patient survival: a competing risk analysis.

BACKGROUND: Expression of matrix metalloproteases 2, 9 and 14 (MMP-2, MMP-9, MMP-14), tissue inhibitors of metalloprotease 1 and 2 (TIMP-1, TIMP-2) and vascular endothelial growth factor A (VEGF-A) is involved in tumor invasion and metastasis via extracellular matrix degradation and angiogenesis. This study aimed to assess whether the expression of MMP-2, MMP-9, MMP-14, TIMP-1, and TIMP-2 in tumors and in the adjacent stroma is associated with cervical cancer prognosis. METHODS: This study analyzed a retrospective cohort of 64 patients. Protein expression was previously obtained by immunohistochemistry from biopsies containing both tumor and stroma. The expression and percentage of stained cells were categorized as high or low according to the cutoff points by using ROC curves. The follow-up data was collected from diagnosis to the last clinical visit. Clinical status categorized as alive without disease, alive with disease, death due to other causes, and death from the disease. The relative risk of death from the disease was evaluated according to the proteins expression using a cause-specific Cox regression model with a 95% confidence interval (95%CI). For the significant associations (p < 0.05), survival curves of patients with low and high expression were plotted for the competing risk survival curve analyses. RESULTS: High expression levels of stromal MMP-2 (RR; 95%CI: 3.91; 1.17-13.02) and stromal TIMP-2 (RR, 95%CI: 8.67; 1.15-65.27) were associated with a greater relative risk of death from the disease and with lower survival (p = 0.03; p = 0.04) than lower expression levels. Low expression levels of stromal MMP-9 (RR, 95%CI: 0.19; 0.05-0.65) and tumoral MMP-9 (HR, 95%CI: 0.19; 0.04-0.90) were protective factors against death from the disease and were associated with poorer survival. CONCLUSIONS: High expression levels of MMP-2 and TIMP-2 in the stroma were significantly associated with poor survival in cervical cancer patients. High expression of MMP-9 was associated with a favorable cervical cancer prognosis.

Detection of Human papillomavirus and the role of p16INK4a in colorectal carcinomas.

INTRODUCTION: Human papillomavirus (HPV) infection is associated with the development of anogenital and head and neck cancers. In recent years a potential role of HPV in colorectal cancer (CRC) has been suggested. OBJECTIVE: To investigate the presence of HPV in colorectal carcinomas and to study the role of p16INK4a as a marker of transcriptionally active HPV infection. In addition, to investigate the correlation between these findings and the CRC prognostic factors. METHODS: Case control study with 92 cases of colorectal cancers, 75 controls of normal tissue adjacent to the tumor, and 30 controls of precursor lesions, including polyps and colorectal adenomas. Paraffinized samples were used, HPV detection and genotyping were performed by PCR and reverse hybridization by using the INNO LIPA kit, with SPF10 plus primers. The expression of the p16INK4a protein was investigated using immunohistochemistry. Data analysis was performed using descriptive, univariate statistics and survival curves were calculated by using the Kaplan Meier and log-rank method. RESULTS: HPV was detected in 13% of the cases and the most prevalent genotype was HPV 16. HPV DNA was not detected in either control groups. The high expression of p16INK4a was observed in 30% of the cases, but it was not associated to the presence of HPV. The overall survival was 53.3% and was influenced by prognostic factors such as later stage, lymph node and distant metastasis. CONCLUSIONS: Based on these results, HPV is unlikely to be involved in colorectal carcinogenesis and p16INK4a expression is not a relevant marker of transcriptionally active HPV infection in CRC.

Human papillomavirus and Chlamydia trachomatis infections in adolescents and young women: Prevalence and risk factors.

BACKGROUND: The objective of this study was to estimate the prevalence of Human papillomavirus (HPV) genotypes and Chlamydia trachomatis (CT) infections among adolescents and young adult women and to identify the risk factors associated. METHODS: This study included 276 sexually active participants, classified as adolescents (15-19 years) and young adult women (20-24 years) that realized conventional cytology and were tested for 27 HPV genotypes and for CT. Bivariate and multivariate analyses were performed to evaluate the factors associated with both infections. RESULTS: The prevalence of HPV infection was 50.7% in adolescents and 43.0% in young adult women. The HPV-16 was the most prevalent (27.7%), followed by HPV-68 (6.9%), HPV-52 (6.2%), HPV-39 (4.6%), and HPV-73 (4.6%). The prevalence of CT infection was 11.5% among adolescents and 6.2% among young adult women. Cytological abnormalities were found in 14.2% among adolescents, of which 80.9% were positive for HPV and 10% of young adult women of which 84.6% were positive for HPV infection. HPV16 and HPV 68 were detected in 35.7% and 32.1% of cases with cytological abnormalities. Factors independently associated with HPV infection obtained by multivariate analysis were unmarried or divorced marital status and the presence of cytological abnormalities. The same variables were analyzed for the association with CT infection, and the association with cytological abnormalities remained significant. CONCLUSION: HPV and CT infections are very prevalent in adolescent and young adult women; these findings reinforce the need of early vaccination, prior to the onset of sexual activity, and justify implementation of molecular screening tests.

Bacterial vaginosis, representation of endocervical and/or metaplastic cells, and cytological abnormalities in different age groups: Association study.

BACKGROUND: Studies have indicated that bacterial vaginosis (BV) might be a cofactor for the acquisition and persistence of high-risk papillomavirus, enabling the development of cytological abnormalities. The presence of endocervical and metaplastic cells makes the smear more adequate for the detection of these abnormalities once these cell types are representative of the transformation zone, a site of increased susceptibility to viral infection. METHODS: The purpose of this study was to evaluate the patterns of vaginal microbiota, the representation of endocervical and/or metaplastic cells, and the detection of cytological abnormalities in cervical smears from women 15 to 64 years old. Results from satisfactory cytological smears performed in a laboratory school from the Federal University of Goiás were analyzed. The degree of association between the categorical variables was evaluated by the χ2 test, Fisher's Exact test, and stratified analysis through the estimation of the prevalence ratio, with 95% confidence intervals and 5% statistical significance level (P < .05). RESULTS: The global prevalence of BV and cytological abnormalities was 22.02% and 8.21%, respectively. BV and the representation of endocervical and/or metaplastic cells were independently associated with the detection of high-grade cytological abnormalities in the cervical smears of women between 25 and 64 years old. CONCLUSIONS: BV and representation of endocervical and/or metaplastic cells were independently associated with the detection of high-grade cytological abnormalities reinforcing the importance of specimen adequacy and microbiota in the cervical microenvironment.

Human Papillomavirus and Anal Cancer: Prevalence, Genotype Distribution, and Prognosis Aspects from Midwestern Region of Brazil.

BACKGROUND: Approximately 90% of all anal cancers are associated with human papillomavirus (HPV), especially high-risk genotypes such as HPVs 16 and 18. OBJECTIVE: To investigate the clinical and prognostic aspects of anal cancers associated with the presence, as well as the genotypic distribution of human papillomavirus (HPV). METHODS: A retrospective study carried out over a 10-year period, using clinical and molecular data, with PCR analysis and reverse hybridization (INNO-LIPA kit), in anal cancers. The data analysis was done using descriptive univariate statistics, and the survival curves were made using the Kaplan-Meier and log-rank methods. RESULTS: Of the 81 formalin-fixed and paraffin-embedded specimens, HPV prevalence was 69% and was significantly higher in squamous cell carcinomas (SCC) than in other anal tumors (p=0.0001). Female patients had a higher prevalence of HPV (p=0.01). Multiple infections were detected in 14.3% of cases. The most prevalent genotypes were HPVs 16, 33, and 18. The overall survival at 60 months was 44.3%, and the prognostic factors included gender (p=0.008) with greater survival for men (52.9%) in comparison to women (29.6%), histological type (p=0.01), SCC (54.4%), adenocarcinomas (37.5%), other carcinomas (14.2%), and the presence of distant metastasis (p=0.01). Survival was not influenced by the presence of HPV (p=0.54). CONCLUSIONS: The association of HPV to anal cancer was found in this study, especially in SCC. However, the presence of HPV did not influence the prognosis of patients with anal cancer.

Swainsonine, an alpha-mannosidase inhibitor, may worsen cervical cancer progression through the increase in myeloid derived suppressor cells population.

Cervical cancer, caused by high oncogenic risk Human Papillomavirus (HPV) infection, continues to be a public health problem, mainly in developing countries. Using peptide phage display as a tool to identify potential molecular targets in HPV associated tumors, we identified α-mannosidase, among other enriched sequences. This enzyme is expressed in both tumor and inflammatory compartment of the tumor microenvironment. Several studies in experimental models have shown that its inhibition by swainsonine (SW) led to inhibition of tumor growth and metastasis directly and indirectly, through activation of macrophages and NK cells, promoting anti-tumor activity. Therefore, the aim of this work was to test if swainsonine treatment could modulate anti-tumor immune responses and therefore interfere in HPV associated tumor growth. Validation of our biopanning results showed that cervical tumors, both tumor cells and leukocytes, expressed α-mannosidase. Ex vivo experiments with tumor associated macrophages showed that SW could partially modulate macrophage phenotype, decreasing CCL2 secretion and impairing IL-10 and IL-6 upregulation, which prompted us to proceed to in vivo tests. However, in vivo, SW treatment increased tumor growth. Investigation of the mechanisms leading to this result showed that SW treatment significantly induced the accumulation of myeloid derived suppressor cells in the spleen of tumor bearing mice, which inhibited T cell activation. Our results suggested that SW contributes to cervical cancer progression by favoring proliferation and accumulation of myeloid cells in the spleen, thus exacerbating these tumors systemic effects on the immune system, therefore facilitating tumor growth.

Three Prime Repair Exonuclease 1 (TREX1) expression correlates with cervical cancer cells growth in vitro and disease progression in vivo.

Alterations in specific DNA damage repair mechanisms in the presence of human papillomavirus (HPV) infection have been described in different experimental models. However, the global effect of HPV on the expression of genes involved in these pathways has not been analyzed in detail. In the present study, we compared the expression profile of 135 genes involved in DNA damage repair among primary human keratinocytes (PHK), HPV-positive (SiHa and HeLa) and HPV-negative (C33A) cervical cancer derived cell lines. We identified 9 genes which expression pattern distinguishes HPV-positive tumor cell lines from C33A. Moreover, we observed that Three Prime Repair Exonuclease 1 (TREX1) expression is upregulated exclusively in HPV-transformed cell lines and PHK expressing HPV16 E6 and E7 oncogenes. We demonstrated that TREX1 silencing greatly affects tumor cells clonogenic and anchorage independent growth potential. We showed that this effect is associated with p53 upregulation, accumulation of subG1 cells, and requires the expression of E7 from high-risk HPV types. Finally, we observed an increase in TREX1 levels in precancerous lesions, squamous carcinomas and adenocarcinomas clinical samples. Altogether, our results indicate that TREX1 upregulation is important for cervical tumor cells growth and may contribute with tumor establishment and progression.

Human papillomavirus (HPV) genotype distribution in penile carcinoma: Association with clinic pathological factors.

BACKGROUND: Penile carcinoma (PC) is a rare, highly mutilating disease, common in developing countries. The evolution of penile cancer includes at least two independent carcinogenic pathways, related or unrelated to HPV infection. OBJECTIVES: To estimate the prevalence, identify HPV genotypes, and correlate with clinicopathological data on penile cancer. METHODS: A retrospective cohort study involving 183 patients with PC undergoing treatment in a referral hospital in Goiânia, Goiás, in Midwestern Brazil, from 2003 to 2015. Samples containing paraffin embedded tumor fragments were subjected to detection and genotyping by INNO-LiPA HPV. The clinicopathological variables were subjected to analysis with respect to HPV positivity and used prevalence ratio (PR), adjusted prevalence ratio (PRa) and 95% confidence interval (CI) as statistical measures. RESULTS: The prevalence of HPV DNA in PC was 30.6% (95% CI: 24.4 to 37.6), high-risk HPV 24.9% (95% CI: 18.9 to 31.3), and 62.5% were HPV 16. There was a statistical association between the endpoints HPV infection and HPV high risk, and the variable tumor grade II-III (p = 0.025) (p = 0.040), respectively. There was no statistical difference in disease specific survival at 10 years between the HPV positive and negative patients (p = 0.143), and high and low risk HPV (p = 0.325). CONCLUSIONS: The prevalence of HPV infection was 30.6%, and 80.3% of the genotypes were identified as preventable by anti-HPV quadrivalent or nonavalent vaccine. HPV infections and high-risk HPV were not associated with penile carcinoma prognosis in this study.

Strong SOD2 expression and HPV-16/18 positivity are independent events in cervical cancer.

It is well known that persistent infection with high-risk HPV (hr-HPV), mostly HPV-16 and 18, is the main cause of cervical cancer development. Manganese superoxide dismutase (MnSOD or SOD2) are highly expressed in different neoplasia. The present study investigated SOD2 protein expression and the presence of hr-HPV types in 297 cervical samples including non-neoplastic tissue, cervical intraepithelial neoplasia grade 3 (CIN3), squamous cell carcinoma (SCC) and adenocarcinoma (ADC). Strong SOD2 expression was significantly higher in ADC (82%) than CIN3 (52%) or SCC (64%). There was no association between SOD2 expression and HPV 16 and/or 18 detection for every lesion analyzed. Binary Logist Regression revealed that strong SOD2 expression (OR: 27.50, 6.16-122.81) and HPV 16 and/or HPV 18 (OR: 12.67, 4.04-39.74) were independently more associated with CIN3 than non-neoplastic cervix. Strong SOD2 expression (OR: 3.30, 1.23-8.86) and HPV 16 and/or HPV 18 (OR: 3.51, 1.03-11.87) were independently more associated with ADC than SCC. Similar findings for SOD2 expression were observed by the Cochran Mantel-Haenszel test, controlling for HPV-16 and/or HPV 18. In conclusion, the expression of SOD2 was increased in CIN3 and SCC, and more increased in cervical ADC than in SCC. Strong SOD2 expression was statistically independent of the presence of HPV 16 and/or 18. These findings suggest that the mitochondrial antioxidant system and HPV infection could follow independent pathways in the carcinogenesis of cervical epithelium and in the differentiation to SCC or ADC of the cervix.

Human papillomavirus genotypes 68 and 58 are the most prevalent genotypes in women from quilombo communities in the state of Maranhão, Brazil.

OBJECTIVES: To determine the frequency of human papillomavirus (HPV) types and behavioral characteristics related to cytological abnormalities in women descendants of slaves, who live in isolated communities known as quilombos in the state of Maranhão, Brazil. METHODS: Cervicovaginal specimens of 353 women were analyzed by conventional cytology and genotyping. HPV detection and genotyping was performed using a linear array HPV genotyping test kit. Behavioral factors and their association with cytological abnormalities were analyzed, as well as the association between cytological abnormalities and HPV infection. RESULTS: The frequency of HPV infection was 13%, and infection with high-risk HPV types was more frequent than with low-risk types (10.2% vs. 2.8%). The most prevalent genotypes were HPV 68 (3.1%) and HPV 58 (2.6%). HPV-positive women were 6.5 times more likely than HPV-negative women to be diagnosed with cytological abnormalities. There was a significant association between HPV infection and the presence of cytological abnormalities in women 31-40 years of age and in women 51-60 years of age. CONCLUSIONS: A distinct profile of high-risk HPV genotypes was detected, with predominance of types 68 and 58. It is possible that the results of the present study are due to specific characteristics of the population, which is geographically isolated and maintains conservative sexual habits.

Bacterial vaginosis and inflammatory response showed association with severity of cervical neoplasia in HPV-positive women.

Vaginal infections may affect susceptibility to and clearance of human papillomavirus (HPV) infection and chronic inflammation has been linked to carcinogenesis. This study aimed to evaluate the association between bacterial vaginosis (BV) and inflammatory response (IR) with the severity of cervical neoplasia in HPV-infected women. HPV DNA was amplified using PGMY09/11 primers and genotyping was performed using a reverse line blot hybridization assay in 211 cervical samples from women submitted to excision of the transformation zone. The bacterial flora was assessed in Papanicolaou stained smears, and positivity for BV was defined as ≥ 20% of clue cells. Present inflammatory response was defined as ≥ 30 neutrophils per field at 1000× magnification. Age higher than 29 years (OR:1.91 95% CI 1.06-3.45), infections by the types 16 and/or 18 (OR:1.92 95% CI 1.06-3.47), single or multiple infections associated with types 16 and/or 18 (OR: 1.92 CI 95% 1.06-3.47), BV (OR: 3.54 95% CI 1.62-7.73) and IR (OR: 6.33 95% CI 3.06-13.07) were associated with severity of cervical neoplasia (CIN 2 or worse diagnoses), while not smoking showed a protective effect (OR: 0.51 95% CI 0.26-0.98). After controlling for confounding factors, BV(OR: 3.90 95% CI 1.64-9.29) and IR (OR: 6.43 95% CI 2.92-14.15) maintained their association with the severity of cervical neoplasia. Bacterial vaginosis and inflammatory response were independently associated with severity of cervical neoplasia in HPV-positive women, which seems to suggest that the microenvironment would relate to the natural history of cervical neoplasia.

HPV infection and cervical neoplasia: associated risk factors.

BACKGROUND: Behavioral risks such as age at first sexual intercourse, number of sexual partners and partner's sexual behavior are associated with an increased risk of HPV infection, persistence of the infection and the development of neoplastic precursor lesions. The objective of this study was to evaluate the risk factors associated with HPV positivity and with a diagnosis of cervical neoplasia in women referred with an abnormal cervical smear. METHODS: This study evaluated a series of 198 women referred with an abnormal cervical smear. Risk factors for HPV infection were investigated using a questionnaire. All cervical specimens were tested for 27 HPV genotypes using the Roche polymerase chain reaction reverse line blot assay. RESULTS: The overall prevalence of HPV was 87 %. First sexual intercourse before 16 years of age was significantly associated with a positive HPV test (OR 4.41; 95 %CI: 1.20 - 19.33; p = 0.01). A significant association was also found between this risk factor and CIN 1 lesions or worse (OR 2.2; 95 %CI 0.94 - 5.08; p = 0.03). CONCLUSIONS: The age at which a woman begins to be sexually active is associated with HPV infection and with a diagnosis of cervical neoplasia.

Association between the human papillomavirus, bacterial vaginosis and cervicitis and the detection of abnormalities in cervical smears from teenage girls and young women.

BACKGROUND: Human papillomavirus (HPV) infection, bacterial vaginosis (BV), and cervicitis may play a role in the presence of cytological abnormalities in female adolescents and young women. This study aimed to estimate the prevalence of HPV, BV and cervicitis in female adolescents and young women and evaluate whether these conditions are associated with a finding of cytological abnormalities in cervical smears. METHODS: Cervical smears were screened using the conventional method and HPV-DNA detection was performed by PGMY-PCR. BV was defined as ≥20% clue cells in cervical smears. Cervicitis was assessed by counting leukocytes in five non-adjacent microscopic fields at 1000× magnification. Odds ratios and 95% confidence intervals were calculated. RESULTS: The study analyzed 251 samples, with cytological abnormalities being found in 9.5% (24/251). Atypical squamous cells of undetermined significance (50.0%) and low-grade squamous intraepithelial lesions (29.1%) were the most common findings. HPV, BV and cervicitis were found in 44.2% (111/251), 41.0% (103/251) and 83.2% (209/251) of cases, respectively. Of the variables investigated, BV and an abnormal cytological diagnosis were independently associated with HPV positivity. Cytological abnormalities were significantly associated with a finding of HPV and BV in the same woman, and also with a simultaneous finding of HPV, BV and cervicitis; however, the independent association of these combined variables did not remain significant in the multivariate analysis. CONCLUSIONS: BV and cytological abnormalities were independently associated with HPV infection in female adolescents and young women.

A portrait of single and multiple HPV type infections in Brazilian women of different age strata with squamous or glandular cervical lesions.

BACKGROUND: Cervical cancer ranks third in prevalence and fourth as cause of death in women worldwide. In Brazil, 17,540 women were diagnosed in 2012 with the disease. Persistent infection with high-risk HPV types is a necessary condition for the development of pre-invasive and invasive cervical neoplasia. Currently, over 100 HPV types have been identified, but HPV16 and 18 are recognized as the mayor culprits in cervical carcinogenesis. Our objective was to assess the relationships between single- (ST) and multiple-type (MT) HPV infections with patients' age and lesion pathological status. METHODS: 328 patients with either squamous or glandular intraepithelial or invasive cervical lesion were selected. All subjects were tested for HPV genotypes with reverse hybridization for 21 high- (hr-HPV) and 16 low-risk (lr-HPV) probes. Prevalence of ST and MT HPV infections was compared across histological types and age strata. RESULTS: 287 (87%) women had at least one HPV type detected and 149 (52%) had MT infections. The most prevalent HPV type was HPV16, present in 142 cases (49% of all HPV-positive cases), followed by HPV58, 52, 31, 35 and 33. HPV18, in single or multiple infections, occurred in 23 cases (8% of hr-HPV cases). Almost all glandular lesions were associated with HPV16 and 18 alone. Multiple infections were significantly more prevalent in squamous than in glandular lesion for HPV16 and 18 (P = 0.04 and 0.03 respectively). The prevalence of MT infections followed a bimodal distribution; peaking in women younger 29 years and in those aged 50 to 59. CONCLUSIONS: Our data indicate that prevention strategies for pre-invasive and invasive squamous lesions should be focused on HPV16 and a few alpha-9 HPV types. It is clear to us that in young women, prophylaxis must cover a large amalgam of HPV types beyond classic HPV16 and 18.

Association of HPV infection and Chlamydia trachomatis seropositivity in cases of cervical neoplasia in Midwest Brazil.

High-risk human papillomavirus (HPV) is considered the main etiological agent for cervical neoplasia. However, the presence of a single type HPV infection alone is unlikely to be sufficient to cause cervical cancer. There is epidemiologic evidence suggesting that HPV and Chlamydia trachomatis play a central role in the etiology of cervical intraepithelial neoplasia and subsequent cervical cancer. To evaluate the HPV prevalence and the seropositivity for C. trachomatis in women referred to the colposcopy clinic due to an abnormal cervical smear and to examine the effect of this association on the severity of cervical neoplasia. Following enrollment, 131 patients underwent colposcopy and biopsies when necessary. HPV DNA was detected by the polymerase chain reaction (PCR) and genotyping was performed by reverse line-blot hybridization assay. C. trachomatis seropositivity was tested by ELISA for the detection of IgG antibodies. The prevalence of HPV infection was 86.3%. Seropositivity for C. trachomatis was 26%. Thirty-one women (27.4%) were positive for C. trachomatis antibodies and HPV-DNA. The most prevalent HPV type in C. trachomatis-seropositive women were HPV 16 (51.6%) and this HPV type was present mainly in neoplasia cases. Positivity for HPV, particularly HPV types 16 and 18, and C. trachomatis seropositivity was significantly associated with a diagnosis of high grade neoplasia. Borderline significance was observed after adjustment for HPV. C. trachomatis seropositivity is associated with high grade neoplasia in women infected with HPV, mainly when the types 16 and 18 were involved.

Cytopathic effects of human papillomavirus infection and the severity of cervical intraepithelial neoplasia : A frequency study.

Cytopathic effects related to the human papillomavirus (HPV) infection are more frequently found in cervical intraepithelial neoplasia (CIN) 1; however, there are indications that at least half the histological diagnoses of CIN2 and CIN3 include koilocytosis areas. The objective of this study was to evaluate the frequency of the cytological criteria suggestive of HPV infection in the cervical smears of women with a histological diagnosis of CIN. One hundred and sixty-two women with abnormal cervical smears and a diagnosis of CIN confirmed by histopathology were selected, including 46 cases of CIN 1, 42 of CIN 2 and 74 cases of CIN 3. Koilocytosis was found in 63% of the smears from women with a histopathological diagnosis of CIN 1. This sign was observed in 26.2% and 25.7% of smears of women with a diagnosis of CIN 2 and CIN 3, respectively. Cytomegaly also was frequent in cervical smears of women with histopathological diagnosis of CIN 1 (71.8%). On the other hand, spindle cells and atypical metaplasia were more frequent in women with CIN 2 and CIN 3. Atypical parakeratosis showed similar frequency in all grades of CIN diagnosis. Koilocytois and cytomegaly were inversely correlated with the diagnosis of CIN2 or CIN 3, with OR values respectively of 0.30 (95%CI 0.13-0.68) and 0.26 (95%CI 0.11-0.58). The others signs analyzed did not show any significant association. Koilocitosis and cytomegaly can provides good reassurance that a patient with atypical cervical smear have CIN 1.

Value of HPV-DNA test in women with cytological diagnosis of atypical glandular cells (AGC).

OBJECTIVE: This study analyzed whether HPV (human papillomavirus) testing contributes towards defining histological abnormalities in women with atypical glandular cells (AGC) diagnosed at cervical cytology. STUDY DESIGN: One hundred and eight women with conventional cervical cancer screening smears suggestive of AGC not otherwise specified (AGC-NOS) and favor neoplastic (AGC-FN) were consecutively enrolled. All women underwent colposcopic examinations and biopsy was performed according to the cytopathologic and/or colposcopic abnormalities present. All specimens were tested for high risk HPV genotypes by Roche's polymerase chain reaction reverse line blot assay. The chi-square test was used to evaluate the association between HPV findings and a diagnosis of high-grade pre-invasive or invasive disease (CIN 2 or worse) taking negative tests or CIN 1 as a reference. Odds ratios (OR) with their respective 95% confidence intervals (95%CI) were used to evaluate the magnitude of the association between HPV testing and CIN 2 or worse. Sensitivity, specificity and their respective 95% confidence intervals (95%CI), positive predictive values (PPV) and negative predictive values (NPV) were also calculated. RESULTS: Final diagnosis revealed a negative outcome in 80 cases (74%), cervical epithelial neoplasia 1 (CIN 1) in 13 cases (12%), CIN 2 or worse in 12 cases (11%) and glandular neoplasia in 3 (3%) cases. The overall detection rate of HPV was 21% (23/108). Neoplasia was significantly associated with positive HPV-DNA in women with AGC-NOS (OR=15.21; 95%CI: 2.64-87.50); however, there was no significant association between a histological diagnosis of neoplasia and HPV positivity in women with AGC-FN (OR=3.00; 95%CI: 0.36-24.92). The sensitivity, specificity, positive predictive value and negative predictive value of HPV-DNA testing for the detection of CIN 2 or worse in women with AGC-NOS were 71%, 86%, 29% and 97%, respectively. In women with AGC-FN, these values were 50%, 75%, 66% and 60%, respectively. CONCLUSIONS: HPV testing at the time of colposcopy for patients with AGC in whom no colposcopic abnormality is found may be a powerful ancillary tool for identifying women at a high risk of underlying significant cervical lesions.

Association between HPV types and species groups and cervical neoplasia from a high-risk area for cervical cancer, Goiânia, Brazil.

This study was designed to evaluate the effect of single or multiple-human papillomavirus (HPV) infection and phylogenetic groups on the prevalence and severity of cervical intraepithelial neoplasia (CIN) in women undergoing colposcopy after an abnormal cervical smear. Colposcopy was performed in 198 cases and biopsy was performed in 193 patients. All specimens were tested for 27 HPV genotypes using the Roche polymerase chain reaction reverse line blot assay. The overall prevalence of HPV infection in women with an abnormal cervical smear was 86% (171 of 198). The prevalence of HPV 16 in high-grade CIN (2/3) was 52% (40 of 76), being detected in 88.8% of cases (8 of 9) of invasive carcinoma. The prevalence of HPV types 31 and 35 in high-grade CIN was 10.5% (8 of 76) and 6.6% (5 of 76), respectively. Single or multiple-type infection involving HPV 16 were significantly associated with a diagnosis of high-grade neoplasia (≥ CIN 2) [odds ratio (OR) 6.49; 95% confidence interval (CI): 1.88-23.44 and OR: 3.65; 95% CI: 1.13-12.15] even after adjustment for HPV-DNA. A statistically significant association was also found between HPV 16 and the other HPV types belonging to species α 9 and a diagnosis of high-grade neoplasia (OR: 7.62; 95% CI: 1.28-51.58); however, no association was found between HPV 16 and the other HPV types belonging to species α 7. HPV 16 is the most important predictor of high-grade cervical neoplasia. Multiple-type infections are predictors of high-grade cervical neoplasia when type 16 is present.

Cytomorphological criteria, subclassifications of endocervical glandular cell abnormalities, and histopathological outcome: a frequency study.

The objective of this study was to evaluate the frequency and the significance of cytomorphological criteria defined in studies as being predictive of neoplasia in cervical smears of women with a cytological diagnosis of atypical glandular cells (AGC) or adenocarcinoma in situ (AIS). Women (n = 103) with cytological findings suggestive of AGC or AIS, whose diagnoses were later established by histopathology, were included in the study. The criteria analyzed and classified as present or absent in cervical smears previously classified as AGC-NOS (not otherwise specified), AGC-FN (favor neoplasia), or AIS were as follows: irregular nuclear membranes; scanty cytoplasm; dyskeratotic cells; increased nuclear/cytoplasmic ratio; nucleoli; overlapping; papillary clusters, feathering; loss of polarity; nuclear enlargement; coarsely granular chromatin; and pseudostratified strips. Histopathology resulted in neoplastic diagnoses in 55 cases (53.3%) and nonneoplastic diagnoses in 48 cases (46.6%). Coarsely granular chromatin was observed in 62.5% of cases with a diagnosis of neoplasia. Feathering was present in 80% of cases of histopathological AIS. Loss of polarity and coarsely granular chromatin were significantly associated with neoplastic diagnosis considering all subcategories of glandular abnormalities diagnosis. In AGC-SOE subclassification, coarsely granular chromatin was significantly associated with neoplastic diagnosis. The presence of nucleoli was significantly associated with neoplastic diagnosis in cervical smears qualified as AGC-FN and AIS. Nuclear enlargement, increased nuclear/cytoplasmic ratio, coarsely granular chromatin and overlapping cells were found in all the subclassifications of glandular cell abnormalities irrespective of the histopathological results. Chromatin aspects, polarity, and presence of nucleoli can predict neoplasia.