Science.gov

Sample records for human cervical squamous

  1. Proteomic identification of potential biomarkers for cervical squamous cell carcinoma and human papillomavirus infection.

    PubMed

    Qing, Song; Tulake, Wuniqiemu; Ru, Mingfang; Li, Xiaohong; Yuemaier, Reziwanguli; Lidifu, Dilare; Rouzibilali, Aierken; Hasimu, Axiangu; Yang, Yun; Rouziahong, Reziya; Upur, Halmurat; Abudula, Abulizi

    2017-04-01

    It is known that high-risk human papillomavirus infection is the main etiological factor in cervical carcinogenesis. However, human papillomavirus screening is not sufficient for early diagnosis. In this study, we aimed to identify potential biomarkers common to cervical carcinoma and human papillomavirus infection by proteomics for human papillomavirus-based early diagnosis and prognosis. To this end, we collected 76 cases of fresh cervical tissues and 116 cases of paraffin-embedded tissue slices, diagnosed as cervical squamous cell carcinoma, cervical intraepithelial neoplasia II-III, or normal cervix from ethnic Uighur and Han women. Human papillomavirus infection by eight oncogenic human papillomavirus types was detected in tissue DNA samples using a quantitative polymerase chain reaction. The protein profile of cervical specimens from human papillomavirus 16-positive squamous cell carcinoma and human papillomavirus-negative normal controls was analyzed by proteomics and bioinformatics. The expression of candidate proteins was further determined by quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry. We identified 67 proteins that were differentially expressed in human papillomavirus 16-positive squamous cell carcinoma compared to normal cervix. The quantitative reverse transcriptase-polymerase chain reaction analysis verified the upregulation of ASAH1, PCBP2, DDX5, MCM5, TAGLN2, hnRNPA1, ENO1, TYPH, CYC, and MCM4 in squamous cell carcinoma compared to normal cervix ( p < 0.05). In addition, the transcription of PCBP2, MCM5, hnRNPA1, TYPH, and CYC was also significantly increased in cervical intraepithelial neoplasia II-III compared to normal cervix. Immunohistochemistry staining further confirmed the overexpression of PCBP2, hnRNPA1, ASAH1, and DDX5 in squamous cell carcinoma and cervical intraepithelial neoplasia II-III compared to normal controls ( p < 0.05). Our data suggest that the expression of ASAH1, PCBP2, DDX5

  2. Chronic estrogen-induced cervical and vaginal squamous carcinogenesis in human papillomavirus type 16 transgenic mice.

    PubMed

    Arbeit, J M; Howley, P M; Hanahan, D

    1996-04-02

    High-risk human papillomaviruses (HPVs), including type 16, have been identified as factors in cervical carcinogenesis. However, the presence and expression of the virus per se appear to be insufficient for carcinogenesis. Rather, cofactors most likely are necessary in addition to viral gene expression to initiate neoplasia. One candidate cofactor is prolonged exposure to sex hormones. To examine the possible effects of estrogen on HPV-associated neoplasia, we treated transgenic mice expressing the oncogenes of HPV16 under control of the human keratin-14 promoter (K14-HPV16 transgenic mice) and nontransgenic control mice with slow release pellets of 17beta-estradiol. Squamous carcinomas developed in a multistage pathway exclusively in the vagina and cervix of K14-HPV16 transgenic mice. Estrogen-induced carcinogenesis was accompanied by an incremental increase in the incidence and distribution of proliferating cells solely within the cervical and vaginal squamous epithelium of K14-HPV16 mice. Expression of the HPV transgenes in untreated transgenic mice was detectable only during estrus; estrogen treatment resulted in transgene expression that was persistent but not further upregulated, remaining at low levels at all stages of carcinogenesis. The data demonstrate a novel mechanism of synergistic cooperation between chronic estrogen exposure and the oncogenes of HPV16 that coordinates squamous carcinogenesis in the female reproductive tract of K14-HPV16 transgenic mice.

  3. RNA interference targeting CD147 inhibits the invasion of human cervical squamous carcinoma cells by downregulating MMP-9.

    PubMed

    Fan, Xiaobin; Wu, Weiguang; Shi, Haixia; Han, Jianqiu

    2013-07-01

    Cervical squamous carcinoma is a highly invasive tumour that has a great capacity to metastasise. Extracellular matrix metalloproteinase inducer (EMMPRIN or CD147), a member of the immunoglobulin superfamily, is a widely distributed cell surface glycoprotein. It is highly expressed on malignant tumour cell surfaces, including human cervical squamous carcinoma. It also plays a critical role in the invasive and metastatic activity of malignant cells by stimulating the expression of matrix metalloproteinases (MMPs). The anti-invasive effect of small interfering RNA (siRNA) against CD147 on human cervical squamous carcinoma cells and its possible pathways has been investigated. The downregulation of CD147 by transfection with siRNA resulted in MMP-9 expression and decreased activity in the cervical squamous carcinoma cell line SiHa. In vitro analysis showed that the invasive capacity of SiHa cells decreased. Thus CD147 inhibition and subsequent MMP-9 deletion may have anti-tumour effects by inhibiting the invasiveness of human cervical squamous carcinoma cells.

  4. Reduced expression of autophagy markers correlates with high-risk human papillomavirus infection in human cervical squamous cell carcinoma

    PubMed Central

    WANG, HUA-YI; YANG, GUI-FANG; HUANG, YAN-HUA; HUANG, QI-WEN; GAO, JUN; ZHAO, XIAN-DA; HUANG, LI-MING; CHEN, HONG-LEI

    2014-01-01

    Infection by an oncogenic human papillomavirus (HPV), in particular HPV16 and 18, is a high risk factor for developing cervical cancer; however, viral infection alone is not sufficient for cancer progression. Autophagy is hypothesized to be an important process during carcinogenesis. The aim of the present study was to investigate the association between autophagy and high-risk HPV (hrHPV) infection in human cervical squamous cell carcinomas (SCCs), and to analyze the clinical significance of this association. Quantum dot (QD)-based immunofluorescence histochemistry was used to detect the expression of autophagy markers, Beclin-1 and microtubule-associated proteins 1A/1B light chain 3B (LC3B) proteins, in 104 cases of cervical cancer (including 80 SCCs and 24 adenocarcinomas) and 20 normal cervical tissues. hrHPV (HPV16/18) infection was detected by QDs based fluorescence in situ hybridization in cervical cancers. The results revealed that the expression levels of Beclin-1 and LC3B were significantly lower in cervical cancer cells when compared with those of normal cervical squamous epithelial cells, and were found to negatively correlate with hrHPV infection. The expression levels of Beclin-1 and LC3B were not associated with age, tumor grade, tumor stage, tumor node metastasis stage or lymph node metastasis. However, a positive correlation was identified between Beclin-1 and LC3B protein expression. In addition, the absence of autophagy in combination with hrHPV infection may accelerate the progression of cervical SCC. In conclusion, decreased expression of Beclin-1 and LC3B may be important in cervical carcinogenesis. The hrHPV-host cell interaction may inhibit autophagy, which may aid virus duplication and infection, as well as cervical cancer development. PMID:25202355

  5. Human papilloma virus genotypes in women from Nayarit, Mexico, with squamous intraepithelial lesions and cervical cancer.

    PubMed

    Ortega-Cervantes, Laura; Aguilar-Lemarroy, Adriana; Rojas-García, Aurora Elizabeth; Barrón-Vivanco, Briscia Socorro; Vallejo-Ruiz, Verónica; León, David Cantú-De; Hernández, Yael Yvette Bernal; Jáuregui-Martínez, Armando; Medina-Díaz, Irma Martha

    2016-07-01

    In Mexico cervical cancer (CC) is the most common cause of death from neoplasia in women. Study aimed to analyze the current distribution of Human papillomavirus (HPV) types in women from Nayarit, Mexico, with Squamous intraepithelial lesions (SIL) and Cervical cancer (CC). Between January 2011 and July 2013, cervical samples were collected from female residents of the Mexican state of Nayarit and were analyzed by means of a LINEAR ARRAY® HPV genotyping test. Data analyses were performed using Stata ver. 8.0 statistical software. Of the samples analyzed, 91.2%, HPV DNA was detected. Of these positive samples, 82% were High-risk (HR) viral types. The most prevalent HPV genotypes identified were 16, 58, 31, 18, and 70. Forty two percent of participants had a single infection, while 23 and 26% of participants were infected with two or more HPV genotypes, respectively. HPV 16 was the most prevalent genotype identified and was frequently present as a co-infection with HPV types 18, 51, 52, 59, 66, or 70. Women <20 years of age were most often infected with HPV, and the HPV Quadrivalent vaccine (types 16, 18, 6, and 11), currently available in Mexico, no confers protection against a subset of the HPV genotypes identified in the present study (58, 31, 70, and 35). Thus, it is important evaluate the geographical distribution of specific HPV genotypes in all health of center across Mexico in order to implement a successful vaccination program and to diagnose CC in its early stages.

  6. Human papilloma virus genotypes in women from Nayarit, Mexico, with squamous intraepithelial lesions and cervical cancer

    PubMed Central

    Ortega-Cervantes, Laura; Aguilar-Lemarroy, Adriana; Rojas-García, Aurora Elizabeth; Barrón-Vivanco, Briscia Socorro; Vallejo-Ruiz, Verónica; León, David Cantú-De; Hernández, Yael Yvette Bernal; Jáuregui-Martínez, Armando; Medina-Díaz, Irma Martha

    2016-01-01

    Objective In Mexico cervical cancer (CC) is the most common cause of death from neoplasia in women. Study aimed to analyze the current distribution of Human papillomavirus (HPV) types in women from Nayarit, Mexico, with Squamous intraepithelial lesions (SIL) and Cervical cancer (CC). Methodology Between January 2011 and July 2013, cervical samples were collected from female residents of the Mexican state of Nayarit and were analyzed by means of a LINEAR ARRAY® HPV genotyping test. Data analyses were performed using Stata ver. 8.0 statistical software. Results Of the samples analyzed, 91.2%, HPV DNA was detected. Of these positive samples, 82% were High-risk (HR) viral types. The most prevalent HPV genotypes identified were 16, 58, 31, 18, and 70. Forty two percent of participants had a single infection, while 23 and 26% of participants were infected with two or more HPV genotypes, respectively. HPV 16 was the most prevalent genotype identified and was frequently present as a co-infection with HPV types 18, 51, 52, 59, 66, or 70. Conclusion Women <20 years of age were most often infected with HPV, and the HPV Quadrivalent vaccine (types 16, 18, 6, and 11), currently available in Mexico, no confers protection against a subset of the HPV genotypes identified in the present study (58, 31, 70, and 35). Thus, it is important evaluate the geographical distribution of specific HPV genotypes in all health of center across Mexico in order to implement a successful vaccination program and to diagnose CC in its early stages. PMID:27610056

  7. New approaches to pathogenic gene function discovery with human squamous cell cervical carcinoma by gene ontology.

    PubMed

    Seo, Min-Jae; Bae, Su Mi; Kim, Yong-Wan; Kim, Yong Wook; Hur, Soo Young; Ro, Duck Young; Lee, Joon Mo; Namkoong, Sung Eun; Kim, Chong Kook; Ahn, Woong Shick

    2005-03-01

    This study utilized mRNA differential display and the Gene Ontology (GO) analysis to characterize the multiple interactions of a number of genes with gene expression profile involved in squamous cell cervical carcinoma. mRNA differential displays were used to identify potential transcripts that were differentially expressed between cervix cancers of 13 patients (invasive cancer stages Ib-IIb) and universal reference RNAs comprised of 17 different normal cervixes. Aberrant bands were excised and used to make cDNA, which was sequenced. DNA sequences were compared to other nucleic acids in the NCBR database for homology. Transcript expression was verified in select samples using RT-PCR and North blotting. The specific functions were correlated with gene expression patterns via gene ontology. Fifty-eight genes were up- or down-regulated above 2-fold and organized into reciprocally dependent sub-function sets depending on the cervical cancer pathway. The GO analysis showed that squamous cell cervical carcinogenesis underwent complete up-regulation of cell cycle, transport, epidermal differentiation, protein biosynthesis, and RNA metabolism. Also, genes belonging to protein metabolism and catabolism activity were significantly up-regulated. In contrast, significant down-regulation was shown in muscle development, cell adhesion, and damaged DNA binding activity. The GO analysis can overcome the complexity of the gene expression profile of the squamous cell cervical carcinoma-associated pathway and identify several cancer-specific cellular processes as well as genes of unknown function. Also, GO analysis can serve as a powerful basis for a molecular classification of carcinogenesis.

  8. Impact of human papillomavirus coinfections on the risk of high-grade squamous intraepithelial lesion and cervical cancer.

    PubMed

    Carrillo-García, Adela; Ponce-de-León-Rosales, Sergio; Cantú-de-León, David; Fragoso-Ontiveros, Verónica; Martínez-Ramírez, Imelda; Orozco-Colín, Asunción; Mohar, Alejandro; Lizano, Marcela

    2014-09-01

    The molecular and epidemiologic effect of human papillomavirus (HPV) coinfections in the risk of developing cervical cancer is yet unclear. The aim of this study was to determine the frequency HPV coinfections at different stages of cervical lesions in the development of cervical cancer and the impact of HPV specific type interactions on high-grade squamous intraepithelial lesions (HSIL) and invasive cervical cancer (ICC) risk. HPV testing was performed in 931 cervical samples diagnosed as: negative for intraepithelial lesion or malignancy (NILM); low-grade squamous intraepithelial lesion (LSIL); HSIL; and ICC. For HPV detection and typing two sets of primers from the L1 region were used in the polymerase chain reaction method (PCR) (MY09/MY11/HMB01 and L1C1/L1C2.1/L1C2.2) and HPV type was determined by PCR product sequence. To look for multiple HPV infections, the E6 nested multiplex PCR method was performed in all DNA samples. Odds ratios were calculated as indexes of the strength of the association between the sample category (LSIL/NILM or ICC/HSIL) and the presence of a given viral combination. In HPV positive samples, coinfections are as common in ICC/HSIL as in LSIL/NILM (47.12% and 40.17%, respectively). There is an increased risk to ICC/HSIL when multiple high-risk HPV types are present. The coinfection of HPV68 with HPV16 increases the risk of ICC/HSIL (OR=14.54, P=0.012, after multivariate adjustment), related to the presence of HPV16 or HPV68 alone. These results sustain that specific HPV coinfections confer an increased risk to develop ICC/HSIL. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Identification of high-risk human papillomavirus (hrHPV)-associated genes in early stage cervical squamous cell carcinomas.

    PubMed

    Hu, Y; Liu, Y; Liu, C-B; Ling, Z-Q

    2011-01-01

    This retrospective study investigated gene expression in tumour samples from 38 patients with early stage human papillomavirus (HPV)-associated cervical squamous cell carcinoma (CSCC). The patients were divided into two groups based on the presence of viral markers of HPV16 or HPV18 infection. Gene expression profiles of tumour samples and the corresponding normal cervical epithelium were analysed using cDNA microarrays. Several genes showed differential expression between the two groups of HPV-infected CSCC patients, although seven genes showed similar changes in both groups. The four genes encoding cyclin-dependent kinase inhibitor 2A, matrix metallopeptidase 9, laminin γ-1, and epidermal growth factor receptor were up-regulated, and the three genes encoding transforming growth factor β receptor 1, interleukin-1α and insulin-like growth factor-binding protein 6 were down-regulated, in both HPV16(+) and HPV18(+) CSCC. These proteins are involved in cell proliferation, cell structure and cell attachment, so their expression might be involved in the mechanism of HPV-induced carcino genesis. A clearer understanding of HPV type-specific gene expression might aid diagnosis and treatment.

  10. Demethylation restores SN38 sensitivity in cells with acquired resistance to SN38 derived from human cervical squamous cancer cells

    PubMed Central

    TANAKA, TETSUJI; BAI, TAO; TOUJIMA, SAORI; UTSUNOMIYA, TOMOKO; MATSUOKA, TOSHIHIDE; KOBAYASHI, AYA; YAMAMOTO, MADOKA; SASAKI, NORIYUKI; TANIZAKI, YUKO; UTSUNOMIYA, HIROTOSHI; TANAKA, JUNKO; YUKAWA, KAZUNORI

    2012-01-01

    Using seven monoclonal SN38-resistant subclones established from ME180 human cervical squamous cell carcinoma cells, we examined the demethylation effects of 5-aza-2′-deoxycytidine (5-aza-CdR) on the SN38-sensitivity of the cells as well as the expression of death-associated protein kinase (DAPK) in the SN38-resistant cells. The DAPK expression levels were evaluated among parent ME180 cells, SN38-resistant ME180 cells and cisplatin-resistant ME180 cells by methylation-specific DAPK-PCR, quantitative RT-PCR and western blot analysis. The SN38-resistant cells co-treated with SN38 and 5-aza-CdR strongly exhibited enhanced SN38-sensitivities resembling those found in the parent cells. In the SN38-resistant subclones, no relationships were found between the restored SN38 sensitivity and hypermethylation of the DAPK promoter, DAPK mRNA expression, DAPK protein expression and induction of DAPK protein after 5-aza-CdR treatment, unlike the strong suppression of 5-aza-CdR-induced DAPK protein expression in the cisplatin-resistant subclones. These findings indicate that reversibly methylated molecules, but not DAPK, may regulate SN38 resistance, and that demethylating agents can be strong sensitizing anticancer chemotherapeutic drugs for SN38-resistant cancers. PMID:22246465

  11. DNA methylation in human papillomavirus-infected cervical cells is elevated in high-grade squamous intraepithelial lesions and cancer

    PubMed Central

    Lee, Ki-Heon; So, Kyeong A; Hong, Sung Ran; Hwang, Chang-Sun; Kee, Mee-Kyung; Rhee, Jee Eun; Kang, Chun; Hur, Soo Young; Park, Jong Sup

    2016-01-01

    Objective DNA methylation has been shown to be a potential biomarker for early cancer detection. The aim of this study was to evaluate DNA methylation profiles according to liquid-based Pap (LBP) test results and to assess their diagnostic value in a Korean population. Methods A total of 205 patients with various Papanicolaou test results were enrolled to this study (negative, 26; atypical squamous cells of undetermined significance, 39; low grade squamous intraepithelial lesion, 44; high grade squamous intraepithelial lesion (HSIL), 48; and cancer, 48). DNA methylation analysis of four genes, ADCYAP1, PAX1, MAL, and CADM1, was performed on residual cervical cells from LBP samples using a quantitative bisulfite pyrosequencing method. To evaluate the diagnostic performance of the four methylated genes for cancer detection, receiver operating characteristic (ROC) curves were drawn. Sensitivities and specificities were also tested at cutoffs determined from the ROC curves. Results Cervical cancer cells showed dramatically increased methylation levels for the four genes analyzed. ADCYAP1 and PAX1 also trended toward elevated methylation levels in HSIL samples, although the levels were much lower than those in cancer cells. The sensitivities of methylated ADCYAP1, PAX1, MAL, and CADM1 for the detection of cancer were 79.2%, 75.0%, 70.8%, and 52.1%, and the specificities were 92.0%, 94.0%, 94.7%, and 94.0%, respectively. Methylated ADCYAP1 and PAX1 demonstrated relatively better discriminatory ability than did methylated MAL and CADM1 (area under the curves 0.911 and 0.916 vs. 0.854 and 0.756, respectively). Conclusion DNA methylation status, especially in the ADCYAP1 and PAX1 genes, showed relatively good specificity, ranging from 90% to 94%. The possible additive and complementary roles of DNA methylation testing with respect to conventional cervical cancer screening programs will need to be validated in prospective population-based studies. PMID:26768780

  12. Prevalence and impact on clinicopathological characteristics of human papillomavirus-16 DNA in cervical lymph node metastases of head and neck squamous cell carcinoma.

    PubMed

    Weiss, Daniel; Koopmann, Mario; Rudack, Claudia

    2011-06-01

    Human papillomavirus (HPV) is a basic risk factor for head and neck squamous cell carcinoma (HNSCC). Little knowledge exists about the impact of HPV on clinical diagnostic and therapy of patients with HNSCC. We evaluated the evidence of HPV16 in 131 retrospectively collected HNSCC and associated cervical lymph node metastases by HPV16 real-time polymerase chain reaction (PCR) and p16 immunohistochemistry and its impact on clinicopathological characteristics. HPV16-DNA and p16 overexpression were present in 27% of HNSCCs. All cervical lymph node metastases of HPV16-positive HNSCC showed HPV16-DNA. HPV16 was strongly associated with tumors arising from the oropharyngeal site (p < .000001), favorable outcome after standard therapy in univariate (p = .001) and multivariate (p = .0004) analysis, and cervical lymph node metastases before primary detection. HPV16-diagnostic in cervical lymph node metastases can predict the site of tumor origin in case of carcinoma of unknown primary (CUP) and favorable outcome and should, therefore, be included in routine diagnostic workup. Copyright © 2010 Wiley Periodicals, Inc.

  13. Comparison of self-collected vaginal, vulvar and urine samples with physician-collected cervical samples for human papillomavirus testing to detect high-grade squamous intraepithelial lesions

    PubMed Central

    Sellors, John W.; Lorincz, Attila T.; Mahony, James B.; Mielzynska, Iwona; Lytwyn, Alice; Roth, Paula; Howard, Michelle; Chong, Sylvia; Daya, Dean; Chapman, William; Chernesky, Max

    2000-01-01

    Background Certain types of human papillomavirus (HPV) in cervical samples are strongly associated with squamous intraepithelial lesions (SIL) and invasive cervical carcinoma. We determined and compared the test characteristics of testing for HPV with samples obtained by patients and with samples obtained by their physicians. Methods In a consecutive series of women referred to a colposcopy clinic at a teaching hospital because of abnormalities on cervical cytologic screening, 200 agreed to collect vulvar, vaginal and urine samples for HPV testing. The physician then collected cervical samples for HPV testing, and colposcopy, with biopsy as indicated, was performed. Presence of HPV was evaluated using the hybrid capture II assay (Digene Corp., Silver Spring, Md.) with a probe cocktail for 13 carcinogenic types. Cervical specimens were also tested for HPV by polymerase chain reaction and hybridization with type-specific probes. Cervical smears for cytologic examination were obtained from all women. Results High-grade lesions (high-grade squamous intraepithelial lesions [HSIL], equivalent to cervical intraepithelial neoplasia [CIN] grade 2 or 3, and adenocarcinoma) were found in 58 (29.0%) of the 200 women. Carcinogenic types of HPV were detected in the self-collected vaginal samples of 50 (86.2%) of these 58 women, in the self-collected vulvar samples of 36 (62.1%) and in the self-collected urine samples of 26 (44.8%). Carcinogenic types of HPV were detected in the cervical samples collected by physicians for 57 (98.3%) of these 58 women. The remaining 142 women (71.0%) had normal findings or low-grade squamous intraepithelial lesions (LSIL, CIN grade 1). Test results were negative or noncarcinogenic types of HPV were detected in the self-collected vaginal samples of 76 (53.5%) of these 142 women, in the self-collected vulvar samples of 89 (62.7%) and in the self-collected urine samples of 99 (69.7%). The sensitivity for self-collected samples ranged from 44.8% to

  14. Distribution of Cervical Lymph Node Metastases From Squamous Cell Carcinoma of the Oropharynx in the Era of Risk Stratification Using Human Papillomavirus and Smoking Status.

    PubMed

    Amsbaugh, Mark J; Yusuf, Mehran; Cash, Elizabeth; Silverman, Craig; Wilson, Elizabeth; Bumpous, Jeffrey; Potts, Kevin; Perez, Cesar; Bert, Robert; Redman, Rebecca; Dunlap, Neal

    2016-10-01

    To investigate the factors contributing to the clinical presentation of oropharyngeal squamous cell carcinoma (OPSCC) in the era of risk stratification using human papilloma virus (HPV) and smoking status. All patients with OPSCC presenting to our institutional multidisciplinary clinic from January 2009 to June 2015 were reviewed from a prospective database. The patients were grouped as being at low risk, intermediate risk, and high risk in the manner described by Ang et al. Variance in clinical presentation was examined using χ(2), Kruskal-Wallis, Mann-Whitney, and logistic regression analyses. The rates of HPV/p16 positivity (P<.001), never-smoking (P=.016), and cervical lymph node metastases (P=.023) were significantly higher for patients with OPSCC of the tonsil, base of tongue (BOT), or vallecula subsites when compared with pharyngeal wall or palate subsites. Low-risk patients with tonsil, base of tongue, or vallecula primary tumors presented with nodal stage N2a at a much higher than expected frequency (P=.007), and high-risk patients presented with tumor stage T4 at a much higher than expected frequency (P=.003). Patients with BOT primary tumors who were never-smokers were less likely to have clinically involved ipsilateral neck disease than were former smokers (odds ratio 1.8; P=.038). The distribution of cervical lymph node metastases was not associated with HPV/p16 positivity, risk group, or subsite. When these data were compared with those in historical series, no significant differences were seen in the patterns of cervical lymph node metastases for patients with OPSCC. For patients with OPSCC differences in HPV status, smoking history and anatomic subsite were associated with differences in clinical presentation but not with distribution of cervical lymph node metastases. Historical series describing the patterns of cervical lymph node metastases in patients with OPSCC remain clinically relevant. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Correlation of p16INK4a immunoexpression and human papillomavirus (HPV) detected by in-situ hybridization in cervical squamous neoplasia.

    PubMed

    Cheah, P L; Koh, C C; Nazarina, A R; Teoh, K H; Looi, L M

    2016-04-01

    Persistence and eventual integration of high-risk HPV (hrHPV) into the cervical cell is crucial to the progression of cervical neoplasia and it would be beneficial to morphologically identify this transformation in routine surgical pathology practice. Increased p16(INK4a) (p16) expression is a downstream event following HPV E7 binding to pRB. A study was conducted to assess the correlation between hrHPV detection using a commercial in-situ hybridization assay (Ventana INFORM HPV ISH) and p16 immunoexpression (CINtec Histology Kit) in cervical squamous intraepithelial lesions and squamous carcinoma. 27 formalin-fixed, paraffin-embedded cervical low-grade squamous intraepithelial lesions (LSIL), 21 high-grade squamous intraepithelial lesions (HSIL) and 51 squamous carcinoma (SCC) were interrogated. hrHPV was significantly more frequent in HSIL (76.2%) and SCC (88.2%) compared to LSIL(37.0%). p16 expression was similarly more frequent in HSIL (95.2%) and SCC (90.2%) compared to LSIL(3.7%). That the rates of hrHPV when compared with p16 expression were almost equivalent in HSIL and SCC while p16 was expressed in only 1 of the 10 LSIL with hrHPV, are expected considering the likelihood that transformation has occurred in HSIL and SCC but does not occur in majority of LSIL.

  16. Nanomechanical clues from morphologically normal cervical squamous cells could improve cervical cancer screening

    NASA Astrophysics Data System (ADS)

    Geng, Li; Feng, Jiantao; Sun, Quanmei; Liu, Jing; Hua, Wenda; Li, Jing; Ao, Zhuo; You, Ke; Guo, Yanli; Liao, Fulong; Zhang, Youyi; Guo, Hongyan; Han, Jinsong; Xiong, Guangwu; Zhang, Lufang; Han, Dong

    2015-09-01

    Applying an atomic force microscope, we performed a nanomechanical analysis of morphologically normal cervical squamous cells (MNSCs) which are commonly used in cervical screening. Results showed that nanomechanical parameters of MNSCs correlate well with cervical malignancy, and may have potential in cancer screening to provide early diagnosis.Applying an atomic force microscope, we performed a nanomechanical analysis of morphologically normal cervical squamous cells (MNSCs) which are commonly used in cervical screening. Results showed that nanomechanical parameters of MNSCs correlate well with cervical malignancy, and may have potential in cancer screening to provide early diagnosis. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr03662c

  17. Comparison of Linear Array and Line Blot Assay for Detection of Human Papillomavirus and Diagnosis of Cervical Precancer and Cancer in the Atypical Squamous Cell of Undetermined Significance and Low-Grade Squamous Intraepithelial Lesion Triage Study▿

    PubMed Central

    Castle, Philip E.; Gravitt, Patti E.; Solomon, Diane; Wheeler, Cosette M.; Schiffman, Mark

    2008-01-01

    We evaluated Linear Array (LA), a newly commercialized PGMY09/11 L1 consensus primer PCR test that detects 37 human papillomavirus (HPV) genotypes by reverse line blot hybridization, for the detection of individual HPV genotypes and carcinogenic HPV and its clinical performance for detecting 2-year cumulative cervical precancer and cancer using archived specimens from the Atypical Squamous Cell of Undetermined Significance (ASCUS) and Low-Grade Squamous Intraepithelial Lesion Triage Study. LA testing was conducted on enrollment specimens from women referred because of an ASCUS Pap test. To gauge the performance of the new test, the results were compared to those of its prototype predecessor assay, Line Blot Assay (LBA), restricted to paired results (n = 3,335). LA testing was done masked to LBA results and clinical outcomes. The results of LA and LBA testing were compared for detection of carcinogenic HPV and clinical outcomes of cervical precancer and cancer. Overall, 50% and 55% of the women tested positive for carcinogenic HPV by LBA and LA, respectively (P < 0.0001). The percent agreement for carcinogenic HPV detection was 88%, percent positive agreement was 80%, and kappa was 0.76 for detection of carcinogenic HPV by the two assays. There was a significant increase in detection by LA for most of the 37 HPV genotypes targeted by both assays, including for 13 of 14 carcinogenic HPV genotypes. LA detected more multiple-genotype infections for all HPV genotypes among HPV-positive women (P < 0.0001) and for carcinogenic HPV genotypes among carcinogenic-HPV-positive women (P < 0.0001). LA was more sensitive (92.3% versus 87.1%; P = 0.003) and less specific (48.2% versus 54.0%; P < 0.0001) than LBA for 2-year cumulative cervical precancer and cancer as diagnosed by the Pathology Quality Control Group. In conclusion, we found LA to be a promising assay for the detection of HPV genotypes and carcinogenic HPV, and it may be clinically useful for the detection of

  18. Comparison of linear array and line blot assay for detection of human papillomavirus and diagnosis of cervical precancer and cancer in the atypical squamous cell of undetermined significance and low-grade squamous intraepithelial lesion triage study.

    PubMed

    Castle, Philip E; Gravitt, Patti E; Solomon, Diane; Wheeler, Cosette M; Schiffman, Mark

    2008-01-01

    We evaluated Linear Array (LA), a newly commercialized PGMY09/11 L1 consensus primer PCR test that detects 37 human papillomavirus (HPV) genotypes by reverse line blot hybridization, for the detection of individual HPV genotypes and carcinogenic HPV and its clinical performance for detecting 2-year cumulative cervical precancer and cancer using archived specimens from the Atypical Squamous Cell of Undetermined Significance (ASCUS) and Low-Grade Squamous Intraepithelial Lesion Triage Study. LA testing was conducted on enrollment specimens from women referred because of an ASCUS Pap test. To gauge the performance of the new test, the results were compared to those of its prototype predecessor assay, Line Blot Assay (LBA), restricted to paired results (n = 3,335). LA testing was done masked to LBA results and clinical outcomes. The results of LA and LBA testing were compared for detection of carcinogenic HPV and clinical outcomes of cervical precancer and cancer. Overall, 50% and 55% of the women tested positive for carcinogenic HPV by LBA and LA, respectively (P < 0.0001). The percent agreement for carcinogenic HPV detection was 88%, percent positive agreement was 80%, and kappa was 0.76 for detection of carcinogenic HPV by the two assays. There was a significant increase in detection by LA for most of the 37 HPV genotypes targeted by both assays, including for 13 of 14 carcinogenic HPV genotypes. LA detected more multiple-genotype infections for all HPV genotypes among HPV-positive women (P < 0.0001) and for carcinogenic HPV genotypes among carcinogenic-HPV-positive women (P < 0.0001). LA was more sensitive (92.3% versus 87.1%; P = 0.003) and less specific (48.2% versus 54.0%; P < 0.0001) than LBA for 2-year cumulative cervical precancer and cancer as diagnosed by the Pathology Quality Control Group. In conclusion, we found LA to be a promising assay for the detection of HPV genotypes and carcinogenic HPV, and it may be clinically useful for the detection of

  19. EGFR Promoter Methylation, EGFR Mutation, and HPV Infection in Chinese Cervical Squamous Cell Carcinoma.

    PubMed

    Zhang, Wei; Jiang, Yinghao; Yu, Qingmiao; Qiang, Shaoying; Liang, Ping; Gao, Yane; Zhao, Xingye; Liu, Wenchao; Zhang, Ju

    2015-10-01

    Therapy strategy toward epidermal growth factor receptor (EGFR) inhibition in cervical cancer has been ongoing. EGFR promoter methylation status and EGFR tyrosine kinase inhibitor-sensitive mutations in cervical cancer may be significant for clinical outcome prediction using anti-EGFR treatment. In this study, EGFR tyrosine kinase inhibitor-sensitive mutations, EGFR exons 18, 19, and 21 mutations, were detected by sequencing in a total of 293 Chinese cervical squamous cell carcinoma tissue samples. EGFR promoter methylation status was detected by an EGFR asymmetric PCR and hybridization-fluorescence polarization assay and sequencing in 293 Chinese cervical squamous cell carcinoma tissue samples. High-risk human papillomavirus (HPV) genotypes in 293 Chinese cervical squamous cell carcinoma tissue samples were detected by an asymmetric GP5+/6+ PCR and hybridization-fluorescence polarization assay. No EGFR exons 18, 19, and 21 mutations were detected, EGFR promoter methylation status was identified in 98 samples, and HPV 16 infection was the first frequent HPV genotype. The methylated EGFR promoter was identified most frequently in cervical squamous cell carcinoma samples with HPV 16 infection (53.4%). Statistical significant difference of EGFR promoter methylation prevalence was found between HPV 16 and other HPV genotypes (P<0.01). This study suggested that there was no EGFR tyrosine kinase inhibitor-sensitive mutation in EGFR exons 18, 19, and 21 in Chinese cervical squamous cell carcinoma tissue samples. EGFR promoter methylation was common and it might be associated with HPV 16 infection in Chinese cervical squamous cell carcinoma. The results provided a novel understanding and an applicable pharmacogenomic tool for individualized management of cervical cancer patients.

  20. Coexistence of placental site nodule and cervical squamous carcinoma in a 72-year-old woman.

    PubMed

    Luna, Darling Valverde; Dulcey, Isabel; Nogales, Francisco F

    2013-05-01

    We report a unique case of the coexistence of cervical cancer and placental site nodule (PSN) in a 72-year-old multiparous woman presenting with vaginal bleeding. She had undergone tubal sterilization 30 years before. On admission, she had profuse vaginal bleeding, and a bulky cervical mass was seen on vaginal examination. Histology revealed the coexistence of a moderately differentiated invasive squamous cell carcinoma with a PSN in its stroma. Its immunohistochemistry revealed characteristic phenotypes for both lesions--the squamous carcinoma was strongly positive for p16. The intermediate trophoblasts of the PSN showed a diffuse positivity for CAM 5.2, human placental lactogen, CD10, and α-inhibin and, focally, for human chorionic gonadotropin. This is the first report on the coexistence of these 2 lesions in an elderly postmenopausal patient and demonstrates that PSN can be found after the menopause as an unexpected lesion in this age group, mimicking various cervical malignancies.

  1. Effects of docetaxel in combination with radiation on human head and neck cancer cells (ZMK-1) and cervical squamous cell carcinoma cells (CaSki ).

    PubMed

    Pradier, O; Rave-Fränk, M; Lehmann, J; Lücke, E; Boghun, O; Hess, C F; Schmidberger, H

    2001-03-15

    The purpose of this study was to determine, as we did for paclitaxel, the cytotoxic and radiosensitizing potential of docetaxel in human head and neck cancer cells (ZMK-1), and in cervical squamous cell carcinoma cells (CaSki). ZMK-1 cells were incubated with docetaxel for 3, 9 or 24 hr before irradiation and 24 hr after irradiation. CaSki cells were incubated with docetaxel 24 hr before and after irradiation. For ZMK-1 cells, the docetaxel concentrations (0.7, 0.7 and 0.35 nM) were determined to obtain approximately equivalent cell survival at the different incubation times (3, 9 and 24 hr, respectively). For CaSki cells, the necessary concentration of docetaxel was 0.07 nM. Radiation doses were given from 0 to 7 Gy. Cell survival was measured by a standard clonogenic assay after a 9-day incubation. Flow cytometry was used to measure the capacity of docetaxel to accumulate cells in the G2/M phase of the cell cycle. We observed a weak accumulation of cells in the G2/M phase for the ZMK-1 cells and a pronounced accumulation for CaSki cells. For docetaxel incubation before irradiation, the isoeffect enhancement ratios for ZMK-1 cells determined at the 37% survival level were 1.18, 2.01, and 2.40 for pre-incubation at 3, 9 and 24 hr, respectively; for CaSki cells the ratio was 1.44. For a docetaxel incubation of 24 hr after irradiation, the isoeffect enhancement ratios determined at the 37% survival level were 1.54 and 1.17 for the ZMK-1, and CaSki cells, respectively. A radiosensitizing effect of docetaxel could be demonstrated unambiguously in the two cell lines used. In contrast to our previously published results with paclitaxel, docetaxel seems to be a better radiosensitizer than paclitaxel.

  2. SIRT1 overexpression in cervical squamous intraepithelial lesions and invasive squamous cell carcinoma.

    PubMed

    Velez-Perez, Anneliese; Wang, Xiaohong I; Li, Min; Zhang, Songlin

    2017-01-01

    Invasive squamous cell carcinoma (SCC) of the cervix involves the progression of premalignant cervical intraepithelial neoplasia (CIN) and is associated with persistent human papillomavirus infection. Most CINs will regress, and the challenge is to identify the lesions likely to progress to invasive cancer. We evaluated Sirtuin 1 (SIRT1) expression in nonneoplastic cervix, CINs, and SCCs as a potential biomarker to predict disease progression. A total of 101 cases were selected including 29 CIN 1s, 32 CIN 2s, 16 CIN 3s, 2 microinvasive SCCs, and 22 invasive SCCs. Cervical nonneoplastic squamous epithelium showed weak positivity of SIRT1 in the basal layer. SIRT1 cytoplasmic overexpression was found in 13.8% of CIN 1s (4/29), 40.6% of CIN 2s (13/32), and 50% of CIN 3s (8/16), and it was statistically significant between CIN 1 and CIN 2/3 lesions (P=.01). All 24 cases of invasive and microinvasive SCC showed SIRT1 overexpression, with 25% (6/24) showing cytoplasmic staining only, 4.2% (1/24) showing nuclear staining only, and 70.8% (17/24) showing both nuclear and cytoplasmic staining. From CIN 1 to SCC, SIRT1 expression showed steady and statistically significant increase (CIN 1 versus CIN 2-3, P=.01; CIN 2-3 versus SCC, P=.0001). Thus, SIRT1 may serve as a potential biomarker for predicting the progression of CIN to invasive SCC. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. The Association of High Risk Human Papillomaviruses in Patients With Cervical Cancer: An Evidence Based Study on Patients With Squamous Cell Dysplasia or Carcinoma for Evaluation of 23 Human Papilloma Virus Genotypes

    PubMed Central

    Piroozmand, Ahmad; Mostafavi Zadeh, Seyed Mostafa; Madani, Azita; Soleimani, Reza; Nedaeinia, Reza; Niakan, Mohammad; Avan, Amir; Manian, Mostafa; Moradi, Mohammad; Eftekhar, Zahra

    2016-01-01

    Background Cervical cancer is one of the leading causes of cancer-related death in females. Human papilloma virus (HPV) is the major risk factor of cervical cancer. Objectives The aim of the current study was to explore the frequency and role of 23 different HPVs in patients with cervical cancer. Materials and Methods Overall, 117 formalin-fix and paraffin-embedded (FFPE) tissues from cervical cancer patients with squamous cell carcinoma (SCC) or dysplasia were collected from Mirza-Kochakkhan-Jangali hospital, Tehran, Iran during year 2013, to investigate the presence of HPV- HPV- 67, 68, 6, 11, 13, 16, 17, 30, 69, 39, 40, 42, 64, 66 and 51 to 59 genotypes. Results The Pap smear report illustrated the presence of malignancy in 71 cases, while 11 cases had no evidence of malignancy. Among the patients, 26 cases had sexually transmitted disease with relative frequency of 0.58. Infection with papilloma virus was observed in 83.6% of SCC patients and 45% of the dysplasia group. The most prevalent HPV genotypes were 18 with 31.62% and 16 with 27.35% of cases. Moreover the relative frequencies of HPV-33, -6, -58, -52, -35 and -51, genotypes were 15.38, 7.69, 5.98, 5.12 and 3.41%, respectively. Among the different genotypes of HPV, 31 had the lowest and 16 had the highest relative frequency. Conclusions Our findings demonstrate that HPV-16 and -18 have a higher prevalence in our population than 31 and 51. Further investigations are required to evaluate the role of these genotypes in a larger multicenter setting for establishing their values for early detection of patients, which is useful for screening and vaccination programs of cancerous and precancerous lesions of cervical cancer. PMID:27279992

  4. Revised terminology for cervical histopathology and its implications for management of high-grade squamous intraepithelial lesions of the cervix.

    PubMed

    Waxman, Alan G; Chelmow, David; Darragh, Teresa M; Lawson, Herschel; Moscicki, Anna-Barbara

    2012-12-01

    In March 2012, the College of American Pathologists and American Society for Colposcopy and Cervical Pathology, in collaboration with 35 stakeholder organizations, convened a consensus conference called the Lower Anogenital Squamous Terminology (LAST) Project. The recommendations of this project include using a uniform, two-tiered terminology to describe the histology of human papillomavirus-associated squamous disease across all anogenital tract tissues: vulva, vagina, cervix, penis, perianus, and anus. The recommended terminology is "low-grade" or "high-grade squamous intraepithelial lesion (SIL)." This terminology is familiar to clinicians, because it parallels the terminology of the Bethesda System cytologic reports. Biopsy results using SIL terminology may be further qualified using "intraepithelial neoplasia" (IN) terminology in parentheses. Laboratory p16 tissue immunostaining is recommended to better classify histopathology lesions that morphologically would earlier have been diagnosed as IN 2. p16 is also recommended for differentiating between high-grade squamous intraepithelial lesions and benign mimics. The LAST Project recommendations potentially affect the application of current guidelines for managing cervical squamous intraepithelial lesions. The authors offer interim guidance for managing cervical lesions diagnosed using this new terminology with special attention paid to managing young women with cervical high-grade squamous intraepithelial lesions on biopsy. Clinicians should be aware of the LAST Project recommendations, which include important changes from prior terminology.

  5. Revised Terminology for Cervical Histopathology and Its Implications for Management of High-Grade Squamous Intraepithelial Lesions of the Cervix

    PubMed Central

    Waxman, Alan G.; Chelmow, David; Darragh, Teresa M.; Lawson, Herschel; Moscicki, Anna-Barbara

    2014-01-01

    In March 2012, the College of American Pathologists and American Society for Colposcopy and Cervical Pathology, in collaboration with 35 stakeholder organizations, convened a consensus conference called the Lower Anogenital Squamous Terminology (LAST) Project. The recommendations of this project include using a uniform, two-tiered terminology to describe the histology of human papillomavirus-associated squamous disease across all anogenital tract tissues: vulva, vagina, cervix, penis, perianus, and anus. The recommended terminology is “low-grade” or “high-grade squamous intraepithelial lesion (SIL).” This terminology is familiar to clinicians, because it parallels the terminology of the Bethesda System cytologic reports. Biopsy results using SIL terminology may be further qualified using “intraepithelial neoplasia” (IN) terminology in parentheses. Laboratory p16 tissue immunostaining is recommended to better classify histopathology lesions that morphologically would earlier have been diagnosed as IN 2. p16 is also recommended for differentiating between high-grade squamous intraepithelial lesions and benign mimics. The LAST Project recommendations potentially affect the application of current guidelines for managing cervical squamous intraepithelial lesions. The authors offer interim guidance for managing cervical lesions diagnosed using this new terminology with special attention paid to managing young women with cervical high-grade squamous intraepithelial lesions on biopsy. Clinicians should be aware of the LAST Project recommendations, which include important changes from prior terminology. PMID:23168774

  6. Feature quantification and abnormal detection on cervical squamous epithelial cells.

    PubMed

    Zhao, Mingzhu; Chen, Lei; Bian, Linjie; Zhang, Jianhua; Yao, Chunyan; Zhang, Jianwei

    2015-01-01

    Feature analysis and classification detection of abnormal cells from images for pathological analysis are an important issue for the realization of computer assisted disease diagnosis. This paper studies a method for cervical squamous epithelial cells. Based on cervical cytological classification standard and expert diagnostic experience, expressive descriptors are extracted according to morphology, color, and texture features of cervical scales epithelial cells. Further, quantificational descriptors related to cytopathology are derived as well, including morphological difference degree, cell hyperkeratosis, and deeply stained degree. The relationship between quantified value and pathological feature can be established by these descriptors. Finally, an effective method is proposed for detecting abnormal cells based on feature quantification. Integrated with clinical experience, the method can realize fast abnormal cell detection and preliminary cell classification.

  7. Establishment of an animal model of spontaneous cervical lymph node metastasis of laryngeal squamous cell carcinoma and obtaining laryngocarcinoma cells with high metastatic potential.

    PubMed

    Chen, L W; Wang, J L; Zhang, L Y; Yang, S M; Li, C S; Yu, N; Zhao W, J D; Zhao, L D; Li, K; Liu, M B; Zhai, S Q

    2013-01-01

    To establish an animal model of spontaneous cervical lymph node metastasis of laryngeal squamous cell carcinoma and obtain laryngocarcinoma cells with high metastatic potential, laryngeal squamous cell carcinoma cell line HEP-2 in logarithmic phase were inoculated under the lingual margin mucosa of nude mice. HEP-2 cells metastasized to the cervical lymph nodes were isolated, cultured, and re-inoculated under the lingual margin mucosa of nude mice twice. The tumor formation in the tongue and in the cervical lymph nodes was confirmed by pathological examination. Carcinoma cells' ability of invasion and migration was detected by transwell assay. Human specific Alu sequences were detected by PCR, which indicated that the tumor cells originated from human laryngeal squamous cell carcinoma cell line HEP-2. Finally, an animal model of spontaneous lymph node metastasis of laryngeal squamous cell carcinoma was successfully established. Laryngeal squamous cell carcinoma cells with high metastatic potential to lymph nodes were obtained through repeated inoculations. .

  8. Human papilloma virus and squamous cell carcinoma of the anus.

    PubMed

    Gami, Bhavna; Kubba, Faris; Ziprin, Paul

    2014-01-01

    The incidence of anal cancer is increasing. In the UK, the incidence is estimated at approximately 1.5 per 100,000. Most of this increase is attributed to certain at-risk populations. Persons who are human immunodeficiency virus (HIV)-positive and men who have sex with men (MSM), Organ transplant recipients, women with a history of cervical cancer, human papilloma virus (HPV), or cervical intraepithelial neoplasia (CIN) are known to have a greater risk for anal cancer. This paper will focus on HPV as a risk factor for anal intraepithelial neoplasia (AIN) and discusses the etiology, anatomy, pathogenesis, management of squamous cell carcinoma (SCC) of the anus.

  9. Hypoxia-Inducible Erythropoietin Signaling in Squamous Dysplasia and Squamous Cell Carcinoma of the Uterine Cervix and Its Potential Role in Cervical Carcinogenesis and Tumor Progression

    PubMed Central

    Acs, Geza; Zhang, Paul J.; McGrath, Cindy M.; Acs, Peter; McBroom, John; Mohyeldin, Ahmed; Liu, Suzhen; Lu, Huasheng; Verma, Ajay

    2003-01-01

    Tissue hypoxia is a characteristic property of cervical cancers that makes tumors resistant to chemo- and radiation therapy. Erythropoietin (Epo) is a hypoxia-inducible stimulator of erythropoiesis. Acting via its receptor (EpoR), Epo up-regulates bcl-2 and inhibits apoptosis of erythroid cells and rescues neurons from hypoxic damage. In addition to human papillomavirus infection, increased bcl-2 expression and decreased apoptosis are thought to play a role in the progression of cervical neoplasia. Using reverse transcriptase-polymerase chain reaction and Western blotting we showed that HeLa and SiHa cervical carcinoma cells and human cervical carcinomas express EpoR, and that hypoxia enhances EpoR expression. Exogenous Epo stimulated tyrosine phosphorylation and inhibited the cytotoxic effect of cisplatin in HeLa cervical carcinoma cells. Using immunohistochemistry, we examined the expression of Epo, EpoR, p16, hypoxia-inducible factor (HIF)-1α, and bcl-2 in benign and dysplastic cervical squamous epithelia and invasive squamous cell carcinomas (ISCCs). EpoR expression in benign epithelia was confined to the basal cell layers, whereas in dysplasias it increasingly appeared in more superficial cell layers and showed a significant correlation with severity of dysplasia. Diffuse EpoR expression was found in all ISCCs. Expression of Epo and HIF-1α was increased in dysplasias compared to benign epithelia. Focal Epo and HIF-1α expression was seen near necrotic areas in ISCCs, and showed correlation in their spatial distribution. Significant correlation was found between expression of EpoR, and p16 and bcl-2 in benign and dysplastic squamous epithelia. Our results suggest that increased expression of Epo and EpoR may play a significant role in cervical carcinogenesis and tumor progression. Hypoxia-inducible Epo signaling may play a significant role in the aggressive behavior and treatment resistance of hypoxic cervical cancers. PMID:12759237

  10. Expression of CDC42 in cervical squamous cell carcinoma and its correlation with clinicopathologic characteristics

    PubMed Central

    Ma, Ding; Cheng, Yuan; Zhang, Youyi; Guo, Yanli

    2013-01-01

    Objective The high expression of cell division cycle 42 protein (CDC42) may be involved in the occurrence and progression of several tumors. However, the expression and function of CDC42 in cervical squamous cell carcinoma remains unclear. This study aimed to investigate the expression of CDC42 in cervical squamous cell carcinoma and its correlation with clinicopathologic characteristics. Methods The expression of CDC42 in 162 cervical squamous cell carcinoma tissue samples and 33 normal cervical tissue samples was investigated by immunohistochemistry. The CDC42 mRNA expression was detected by reverse transcription-polymerase chain reaction (RT-PCR). Results The cervical squamous cell carcinoma group showed a significantly higher CDC42 positive rate, compared to the normal cervical tissues (P<0.05). Furthermore, the tissues of stage II-IV carcinoma patients showed higher CDC42 expression levels compared to stage I patients (P=0.05). In addition, the expression of CDC42 was not correlated to age of patients, differentiation degree of cancer cells, or lymph node metastasis (P>0.05). Furthermore, compare with normal cervical tissues, the CDC42 mRNA expression in cervical cancer had no significant difference. Conclusions CDC42 was up-regulated at protein level, but not mRNA level, in cervical squamous cell carcinoma. The high expression of CDC42 was correlated to the clinical stage of the patients, indicating that CDC42 might contribute to the progression of cervical squamous cell carcinoma. PMID:24385692

  11. UHRF1 gene silencing inhibits cell proliferation and promotes cell apoptosis in human cervical squamous cell carcinoma CaSki cells.

    PubMed

    Ge, Ting-Ting; Yang, Meng; Chen, Zhuo; Lou, Ge; Gu, Tao

    2016-07-19

    Up-regulation of UHRF1 has been observed in a variety of cancers and appears to serve as an independent prognostic factor. To explore the effect of UHRF1 gene silencing on apoptosis and proliferation of cervical squamous cell carcinoma (CSCC) CaSki cells. This study consisted of 47 CSCC tissues and 40 normal cervical tissues. The CaSki cells were assigned into Blank group (CaSki cells not transfected), NC group (CaSki cells transfected with control siRNA), and UHRF1 Silence group (CaSki cells transfected with UHRF1 siRNA). qRT-PCR and Western blot were used for UHRF1 mRNA and protein expressions, CKK-8 assay for cell proliferation, flow cytometry for cell cycle and apoptosis, Western blot for expressions of apoptosis-related proteins. Nude mice tumor transplant experiment was performed. UHRF1 exhibited higher mRNA and protein expressions in the CSCC tissues than normal cervical tissues (both P < 0.05). The cell proliferation ability in the UHRF1 Silence group was reduced when compared with the Blank group and the NC group, the cells at S-G2M stage in the UHRF1 Silence group were dropped when compared with the Blank group and the NC group (P < 0.05), while the cells at G0/G1 stage were elevated (P < 0.05), and the proportion of Annexin V positive cells in the UHRF1 Silence group was increased in comparison with the Blank group and the NC group (P < 0.05). Nude mice tumor transplant experiment indicated that the growth rate and weight of tumor in the Blank group and NC group was higher and heavier than the UHRF1 Silence group (P < 0.05). UHRF1 showed a high expression in CSCC and UHRF1 silencing can reduce proliferation and enhance apoptosis of the CaSki cells.

  12. Acrokeratosis Paraneoplastica Associated with Cervical Squamous Cell Carcinoma

    PubMed Central

    Daveluy, Steven D.; Joiner, Michael C.; Hurst, Newton; Bishop, Michael; Miller, Steven R.

    2016-01-01

    Background. Acrokeratosis paraneoplastica, or Bazex syndrome, is a paraneoplastic syndrome characterized by cutaneous psoriasiform lesions with associated acral erythema and scale, as well as nail changes, including onycholysis and ungual dystrophy. Its most advanced, severe form involves the trunk, elbows, and knees. It is typically associated with upper aerodigestive tract malignancies in males. Rare cases associated with gynecological cancers have been reported, including uterine adenocarcinoma, as well as ovarian and vulvar squamous cell carcinomas. Cutaneous manifestations often precede cancer diagnosis. In most reported cases, skin changes resolve when the underlying malignancy is adequately treated. Main Observations. We present the case of a 56-year-old female diagnosed with acrokeratosis paraneoplastica following the discovery of FIGO stage IIB cervical squamous cell carcinoma (SCC). Scaling, hyperpigmentation, xerosis, and fissuring were noted on the patient's hands, feet, legs, arms, and lower back. Pitting was noted on her fingernails. Her cervical cancer was successfully treated with chemoradiotherapy, after which her cutaneous lesions persisted for two months before resolving. Conclusions. The presentation of acrokeratosis paraneoplastica in this context is atypical. Reports of associations with gynecological cancers, as in our patient's case, are exceedingly rare. PMID:28101384

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

    PubMed Central

    de Abreu, André LP; Malaguti, Natália; Souza, Raquel P; Uchimura, Nelson S; Ferreira, Érika C; Pereira, Monalisa W; Carvalho, Maria DB; Pelloso, Sandra M; Bonini, Marcelo G; Gimenes, Fabrícia; Consolaro, Marcia EL

    2016-01-01

    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. PMID:27429850

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

    PubMed

    de Abreu, André Lp; Malaguti, Natália; Souza, Raquel P; Uchimura, Nelson S; Ferreira, Érika C; Pereira, Monalisa W; Carvalho, Maria Db; Pelloso, Sandra M; Bonini, Marcelo G; Gimenes, Fabrícia; Consolaro, Marcia El

    2016-01-01

    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.

  15. Comparative analysis of HPV16 gene expression profiles in cervical and in oropharyngeal squamous cell carcinoma

    PubMed Central

    Cerasuolo, Andrea; Annunziata, Clorinda; Tortora, Marianna; Starita, Noemy; Stellato, Giovanni; Greggi, Stefano; Maglione, Maria Grazia; Ionna, Franco; Losito, Simona; Botti, Gerardo; Buonaguro, Luigi; Buonaguro, Franco M.; Tornesello, Maria Lina

    2017-01-01

    Human papillomavirus type 16 (HPV16) is the major cause of cervical cancer and of a fraction of oropharyngeal carcinoma. Few studies compared the viral expression profiles in the two types of tumor. We analyzed HPV genotypes and viral load as well as early (E2/E4, E5, E6, E6*I, E6*II, E7) and late (L1 and L2) gene expression of HPV16 in cervical and oropharyngeal cancer biopsies. The study included 28 cervical squamous cell carcinoma (SCC) and ten oropharyngeal SCC, along with pair-matched non-tumor tissues, as well as four oropharynx dysplastic tissues and 112 cervical intraepithelial neoplasia biopsies. Viral load was found higher in cervical SCC (<1 to 694 copies/cell) and CIN (<1 to 43 copies/cell) compared to oropharyngeal SCC (<1 to 4 copies/cell). HPV16 E2/E4 and E5 as well as L1 and L2 mRNA levels were low in cervical SCC and CIN and undetectable in oropharynx cases. The HPV16 E6 and E7 mRNAs were consistently high in cervical SCC and low in oropharyngeal SCC. The analysis of HPV16 E6 mRNA expression pattern showed statistically significant higher levels of E6*I versus E6*II isoform in cervical SCC (p = 0.002) and a slightly higher expression of E6*I versus E6*II in oropharyngeal cases. In conclusion, the HPV16 E5, E6, E6*I, E6*II and E7 mRNA levels were more abundant in cervical SCC compared to oropharyngeal SCC suggesting different carcinogenic mechanisms in the two types of HPV-related cancers. PMID:28423662

  16. Comparative analysis of HPV16 gene expression profiles in cervical and in oropharyngeal squamous cell carcinoma.

    PubMed

    Cerasuolo, Andrea; Annunziata, Clorinda; Tortora, Marianna; Starita, Noemy; Stellato, Giovanni; Greggi, Stefano; Maglione, Maria Grazia; Ionna, Franco; Losito, Simona; Botti, Gerardo; Buonaguro, Luigi; Buonaguro, Franco M; Tornesello, Maria Lina

    2017-05-23

    Human papillomavirus type 16 (HPV16) is the major cause of cervical cancer and of a fraction of oropharyngeal carcinoma. Few studies compared the viral expression profiles in the two types of tumor. We analyzed HPV genotypes and viral load as well as early (E2/E4, E5, E6, E6*I, E6*II, E7) and late (L1 and L2) gene expression of HPV16 in cervical and oropharyngeal cancer biopsies. The study included 28 cervical squamous cell carcinoma (SCC) and ten oropharyngeal SCC, along with pair-matched non-tumor tissues, as well as four oropharynx dysplastic tissues and 112 cervical intraepithelial neoplasia biopsies. Viral load was found higher in cervical SCC (<1 to 694 copies/cell) and CIN (<1 to 43 copies/cell) compared to oropharyngeal SCC (<1 to 4 copies/cell). HPV16 E2/E4 and E5 as well as L1 and L2 mRNA levels were low in cervical SCC and CIN and undetectable in oropharynx cases. The HPV16 E6 and E7 mRNAs were consistently high in cervical SCC and low in oropharyngeal SCC. The analysis of HPV16 E6 mRNA expression pattern showed statistically significant higher levels of E6*I versus E6*II isoform in cervical SCC (p = 0.002) and a slightly higher expression of E6*I versus E6*II in oropharyngeal cases. In conclusion, the HPV16 E5, E6, E6*I, E6*II and E7 mRNA levels were more abundant in cervical SCC compared to oropharyngeal SCC suggesting different carcinogenic mechanisms in the two types of HPV-related cancers.

  17. Clinical Utility of Molecular Biomarkers in Cervical Squamous Intraepithelial Lesions in a Young Adult Population

    PubMed Central

    Spiryda, Lisa Beth; Whitaker, Kara M.; Messersmith, Amy; Banister, Carolyn E.; Creek, Kim E.; Pirisi-Creek, Lucia A.

    2015-01-01

    Objective Although human papillomavirus (HPV) infection is necessary for cervical squamous intraepithelial lesion (SIL/CIN) and cancer to develop, exposure to HPV is not predictive of which women will develop cervical squamous intraepithelial lesion and cancer. This study examines mRNA expression of several potential biomarkers in exfoliated cervical cells collected from college age women. Methods Freshman female students were recruited into the Carolina Women’s Care Study (CWCS) which was designed to prospectively evaluate factors that contribute to persistent HPV infections. One component of this study was to extract mRNA from exfoliated cervical cells. In this study, mRNA expression of FZD, GDF15, IL1β and N-cadherin was assessed through real-time PCR. Statistical analysis was performed with a Student’s t-test; all results were standardized with GAPDH. Results Fifty samples were selected that reflected the demographics of the CWCS participants. IL1β mRNA expression was 9.4-fold higher in cervical cells from women with abnormal Pap tests (p=0.0018); LSIL had 12.7-fold higher expression than negatives (p=0.0011). FZD mRNA expression was 5.7-fold higher in CIN2 as compared to CIN1 (p=0.0041) and 8.5-fold higher compared to cytology/pathology-negative (p=0.0014). Other differences in mRNA expression showed trends but not reaching statistical significance for each condition. Conclusions It appears that several biomarkers involved in the cytokine/inflammatory pathway (IL1 β), cell adhesion pathway (N-cadherin), growth factors (GDF-15), WNT signaling pathway (FZD) may be potential biomarkers in conjunction with the Pap test and HPV that help predict which women are at highest risk for developing CIN3 and cervical cancer. PMID:26579841

  18. Clinical Utility of Molecular Biomarkers in Cervical Squamous Intraepithelial Lesions in a Young Adult Population.

    PubMed

    Spiryda, Lisa Beth; Whitaker, Kara M; Messersmith, Amy; Banister, Carolyn E; Creek, Kim E; Pirisi-Creek, Lucia A

    2016-01-01

    Although human papillomavirus (HPV) infection is necessary for cervical squamous intraepithelial lesion (SIL/CIN) and cancer to develop, exposure to HPV is not predictive of which women will develop SIL/CIN and cancer. This study examines mRNA expression of several potential biomarkers in exfoliated cervical cells collected from college-aged women. Freshman female students were recruited into the Carolina Women's Care Study, which was designed to prospectively evaluate factors that contribute to persistent HPV infections. One component of this study was to extract mRNA from exfoliated cervical cells. In this study, mRNA expression of Frizzled (FZD), growth differentiating factor 15, interleukin 1 beta (IL1β), and N-cadherin was assessed through real-time polymerase chain reaction. Statistical analysis was performed with a Student t test; all results were standardized with glyceraldehyde 3-phosphate dehydrogenase. Fifty samples were selected that reflected the demographics of the Carolina Women's Care Study participants. IL1β mRNA expression was 9.4-fold higher in cervical cells from women with abnormal Pap tests (p = .0018); low-grade squamous intraepithelial lesion had 12.7-fold higher expression than negatives (p = .0011). The FZD mRNA expression was 5.7-fold higher in CIN 2 as compared with CIN 1 (p = .0041) and 8.5-fold higher compared with cytology/pathology negative (p = .0014). Other differences in mRNA expression showed trends but not reaching statistical significance for each condition. It seems that several biomarkers involved in the cytokine/inflammatory pathway (IL1β), cell adhesion pathway (N-cadherin), growth factor (growth differentiating factor 15), and Wingless (WNT) signaling pathway (FZD) may be potential biomarkers in conjunction with the Pap test and HPV that help predict which women are at highest risk for developing CIN 3 and cervical cancer.

  19. Meta-analysis of type-specific human papillomavirus prevalence in Iranian women with normal cytology, precancerous cervical lesions and invasive cervical cancer: Implications for screening and vaccination.

    PubMed

    Jalilvand, Somayeh; Shoja, Zabihollah; Nourijelyani, Keramat; Tohidi, Hamid Reza; Hamkar, Rasool

    2015-02-01

    To predict the impact of current vaccines on cervical cancer and for the improvement of screening programs, regional data on distribution of human papillomavirus (HPV) types in women with or without cervical cancer is crucial. The present meta-analysis intend to comprehensively evaluate the HPV burden in women with invasive cervical cancer, high-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 2 and 3), low-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 1), atypical squamous cells of undetermined significance and normal cytology, as these data will help decision making in regards with screening programs and HPV vaccination in Iran. To determine the HPV prevalence and type distribution in Iranian women with or without cervical cancer, 20 published studies were included in this meta-analysis. In total, 713, 124, 104, 60, and 2577 women invasive cervical cancer, high-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 2 and 3), low-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 1), atypical squamous cells of undetermined significance and normal were reviewed, respectively. Overall HPV prevalence in women with invasive cervical cancer, high-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 2 and 3), low-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 1), atypical squamous cells of undetermined significance and normal cytology were 77.4%, 71.8%, 65.3%, 61.7%, and 8.4%, respectively. The six most common types were HPV 16, 18, 6/11, 31, and 33; among them HPV 16 was the most frequent type in all five different groups. According to this study, it was estimated that HPV vaccines could have a great impact on prevention of cervical cancer in Iran. In conclusion, this meta-analysis highlights the necessity of introducing vaccination program in Iran.

  20. High-grade cervical squamous intraepithelial lesion during pregnancy.

    PubMed

    Murta, Eddie Fernando Candido; de Souza, Flávio Henrique Caetano; de Souza, Maria Azniv Hazarabedian; Adad, Sheila Jorge

    2002-01-01

    An increasing incidence of high-grade squamous intraepithelial lesion (HSIL) has been observed among young women. Consequently, an increased number of cases are being discovered during pregnancy. We analyzed the clinical and therapeutic management of HSIL during pregnancy. A retrospective study was conducted from 1979 to 1998, and 58 registries of women with a cytological or histological diagnosis of HSIL during the pregnant-puerperal period were reviewed. Information obtained from medical records included age, gestational age at diagnosis, parity, age of first intercourse, number of sexual partners before pregnancy, tobacco use, cytologic and colposcopic findings, route of delivery, postpartum follow-up, and treatment. This information was compared with a non-pregnant control group with HSIL. The average age of pregnant women with HSIL was 27.9 +/- 5.2 years. The cytologic or histologic diagnosis of HSIL was made in the first trimester in 12 (20.7%) women and in the second trimester in 30 (51.7%) women. Average parity was 2.8 +/- 2 deliveries. Age of first intercourse ranged from 13 to 29 years (16.1 +/- 3.3). Thirty-two women (55.1%) had more than one sexual partner before pregnancy. Thirty-seven (63.8%) refereed tobacco use. According to the aforementioned aspects, no statistical difference was found in relation to control, except to cervical ectopia, which was more frequent in pregnant women (56.9% versus 42.6%). From the total of 58 pregnant women with cytologic or biopsy HSIL diagnosis, 53 had HSIL diagnosis made on cervical biopsy directed by colposcopy performed during the pregnancy; 44 (83%) of them were submitted to conservative management. HSIL was diagnosed by cervical biopsy in postpartum evaluation in 76% pregnant women with vaginal delivery and 78.6% women who underwent cesarean section. A conservative management of HSIL in pregnancy is proposed, with colposcopic evaluation during gestation and postpartum, regardless of route of delivery.

  1. p16 expression is not associated with human papillomavirus in urinary bladder squamous cell carcinoma.

    PubMed

    Alexander, Riley E; Hu, Yingchuan; Kum, Jennifer B; Montironi, Rodolfo; Lopez-Beltran, Antonio; Maclennan, Gregory T; Idrees, Muhammad T; Emerson, Robert E; Ulbright, Thomas M; Grignon, David G; Eble, John N; Cheng, Liang

    2012-11-01

    Squamous cell carcinoma of the urinary bladder is unusual and of unknown etiology. There is a well-established association between human papillomavirus (HPV) infection and the development of cervical and head/neck squamous cell carcinomas. However, the role of HPV in the pathogenesis of squamous cell carcinoma of the urinary bladder is uncertain. The purposes of this study were to investigate the possible role of HPV in the development of squamous cell carcinoma of the urinary bladder and to determine if p16 expression could serve as a surrogate marker for HPV in this malignancy. In all, 42 cases of squamous cell carcinoma of the urinary bladder and 27 cases of urothelial carcinoma with squamous differentiation were investigated. HPV infection was analyzed by both in situ hybridization at the DNA level and immunohistochemistry at the protein level. p16 protein expression was analyzed by immunohistochemistry. HPV DNA and protein were not detected in 42 cases of squamous cell carcinoma (0%, 0/42) or 27 cases of urothelial carcinoma with squamous differentiation (0%, 0/15). p16 expression was detected in 13 cases (31%, 13/42) of squamous cell carcinoma and 9 cases (33%, 9/27) of urothelial carcinoma with squamous differentiation. There was no correlation between p16 expression and the presence of HPV infection in squamous cell carcinoma of the bladder or urothelial carcinoma with squamous differentiation. Our data suggest that HPV does not play a role in the development of squamous cell carcinoma of the urinary bladder or urothelial carcinoma with squamous differentiation. p16 expression should not be used as a surrogate marker for evidence of HVP infection in either squamous cell carcinoma of the urinary bladder or urothelial carcinoma with squamous differentiation as neither HVP DNA nor protein is detectable in these neoplasms.

  2. TERT promoter hot spot mutations are frequent in Indian cervical and oral squamous cell carcinomas.

    PubMed

    Vinothkumar, Vilvanathan; Arunkumar, Ganesan; Revathidevi, Sundaramoorthy; Arun, Kanagaraj; Manikandan, Mayakannan; Rao, Arunagiri Kuha Deva Magendhra; Rajkumar, Kottayasamy Seenivasagam; Ajay, Chandrasekar; Rajaraman, Ramamurthy; Ramani, Rajendren; Murugan, Avaniyapuram Kannan; Munirajan, Arasambattu Kannan

    2016-06-01

    Squamous cell carcinoma (SCC) of the uterine cervix and oral cavity are most common cancers in India. Telomerase reverse transcriptase (TERT) overexpression is one of the hallmarks for cancer, and activation through promoter mutation C228T and C250T has been reported in variety of tumors and often shown to be associated with aggressive tumors. In the present study, we analyzed these two hot spot mutations in 181 primary tumors of the uterine cervix and oral cavity by direct DNA sequencing and correlated with patient's clinicopathological characteristics. We found relatively high frequency of TERT hot spot mutations in both cervical [21.4 % (30/140)] and oral [31.7 % (13/41)] squamous cell carcinomas. In cervical cancer, TERT promoter mutations were more prevalent (25 %) in human papilloma virus (HPV)-negative cases compared to HPV-positive cases (20.6 %), and both TERT promoter mutation and HPV infection were more commonly observed in advanced stage tumors (77 %). Similarly, the poor and moderately differentiated tumors of the uterine cervix had both the TERT hot spot mutations and HPV (16 and 18) at higher frequency (95.7 %). Interestingly, we observed eight homozygous mutations (six 228TT and two 250TT) only in cervical tumors, and all of them were found to be positive for high-risk HPV. To the best of our knowledge, this is the first study from India reporting high prevalence of TERT promoter mutations in primary tumors of the uterine cervix and oral cavity. Our results suggest that TERT reactivation through promoter mutation either alone or in association with the HPV oncogenes (E6 and E7) could play an important role in the carcinogenesis of cervical and oral cancers.

  3. Human papillomavirus genotype distribution in cervical intraepithelial neoplasia grade 2/3 and invasive cervical cancer in Japanese women.

    PubMed

    Azuma, Yukari; Kusumoto-Matsuo, Rika; Takeuchi, Fumihiko; Uenoyama, Asami; Kondo, Kazunari; Tsunoda, Hajime; Nagasaka, Kazunori; Kawana, Kei; Morisada, Tohru; Iwata, Takashi; Aoki, Daisuke; Kukimoto, Iwao

    2014-10-01

    Human papillomavirus vaccines are being introduced worldwide and are expected to reduce the incidence of cervical cancer. Here we report a cross-sectional study using a validated human papillomavirus genotyping method to reveal the human papillomavirus prevalence and genotype distribution in Japanese women with cervical intraepithelial neoplasia Grade 2/3 and invasive cervical cancer. Cervical exfoliated cells were collected from 647 patients with abnormal cervical histology (cervical intraepithelial neoplasia Grade 2, n = 164; cervical intraepithelial neoplasia Grade 3, n = 334; and invasive cervical cancer, n = 149), and subjected to the PGMY-PCR-based genotyping assay. The association between human papillomavirus infection and lesion severity was calculated using a prevalence ratio. Overall, the prevalence of human papillomavirus deoxyribonucleic acid was 96.3% in cervical intraepithelial neoplasia Grade 2, 98.8% in cervical intraepithelial neoplasia Grade 3 and 88.0% in invasive cervical cancer (97.8% in squamous cell carcinoma and 71.4% in adenocarcinoma). The three most prevalent types were as follows: human papillomavirus 16 (29.3%), human papillomavirus 52 (27.4%) and human papillomavirus 58 (22.0%) in cervical intraepithelial neoplasia Grade 2; human papillomavirus 16 (44.9%), human papillomavirus 52 (26.0%) and human papillomavirus 58 (17.4%) in cervical intraepithelial neoplasia Grade 3; and human papillomavirus 16 (47.7%), human papillomavirus 18 (23.5%) and human papillomavirus 52 (8.7%) in invasive cervical cancer. The prevalence ratio of human papillomavirus 16 was significantly higher in cervical intraepithelial neoplasia Grade 3 compared with cervical intraepithelial neoplasia Grade 2 (prevalence ratio, 1.62; 95% confidence interval, 1.26-2.13) and in squamous cell carcinoma compared with cervical intraepithelial neoplasia Grade 3 (prevalence ratio, 1.55; 95% confidence interval, 1.25-1.87). Multiple infections decreased from cervical

  4. [The detection of human papillomavirus 16, 18, 35 and 58 in cervical-uterine cancer and advanced degree of squamous intraepithelial lesions in Western Mexico: clinical-molecular correlation].

    PubMed

    Montoya-Fuentes, H; Suárez Rincón, A E; Ramírez-Muñoz, M P; Arévalo-Lagunas, I; Morán Moguel, M C; Gallegos Arreola, M P; Flores-Martínez, S E; Rosales Quintana, S; Sánchez Corona, J

    2001-04-01

    The purposes of this study were to estimate the infection frequency of Human Papilomavirus (HPV) and to identify the viral types in patients with diagnosis of uterine cervical cancer (UCC) and High Grade Squamous Intraepitelial lesions (HGSILs), and to correlate the molecular findings versus HPV infection suggestive clinical findings. Biopsies from 50 patients (37 HGSILs and 13 UCC) histopathologically diagnosed were studied. The presence of HPV were detected by means of the polymerase chain reaction (PCR) using consensus primers for types 6, 11, 16, 18, 31, 33, 35, and 58 among others, as well as specific primers for some of them. The frequencies for HPV 16, 18, 33, 35, and 58 in HGSIL samples were 24.3, 2.7, 0, 5.4 and 16.2% respectively. In UCC samples were 61.5, 7.7, 0, 0 and 15.4% with significative differences only for HPV 16. Clinical findings (histologic, colposcopic and histopathologic), showed deficient diagnostic accuracy in the identification of HPV 16 in HGSIL, wich resulted less frequent and there is a high frequency of HPV. These results are similar to those previously described in our country and the other populations, with the exception of HPV16 in HGSIL, wich resulted less frequent and there is a high frequency of HPV 58 in our region. When analyzing clinical features with the presence of HPV DNA, we conclude that these are insufficient to discard or establish the possibility of HPV infection in patients with HGSIL's and UUC.

  5. Therapeutic effects of antibiotic drug tigecycline against cervical squamous cell carcinoma by inhibiting Wnt/β-catenin signaling

    SciTech Connect

    Li, Hui; Jiao, Shun; Li, Xin; Banu, Hasina; Hamal, Shreejana; Wang, Xianrong

    2015-11-06

    Aberrant activation of the Wnt/β-catenin signaling pathway is common in human cervical cancers and has great potential therapeutic value. We show that tigecycline, a FDA-approved antibiotic drug, targets cervical squamous cell carcinoma through inhibiting Wnt/β-catenin signaling pathway. Tigecycline is effective in inducing apoptosis, inhibiting proliferation and anchorage-independent colony formation of Hela cells. The inhibitory effects of tigecycline are further enhanced upon combination with paclitaxel, a most commonly used chemotherapeutic drug for cervical cancer. In a cervical xenograft model, tigecycline inhibits tumor growth as a single agent and its combination with paclitaxel significantly inhibits more tumor growth throughout the duration of treatment. We further show that tigecycline decreases level of both cytoplasmic and nuclear β-catenin and suppressed Wnt/β-catenin-mediated transcription through increasing levels of Axin 1 in Hela cells. In addition, stabilization or overexpression of β-catenin using pharmacological and genetic approaches abolished the effects of tigecycline in inhibiting proliferation and inducing apoptosis of Hela cells. Our study suggests that tigecycline is a useful addition to the treatment armamentarium for cervical cancer and targeting Wnt/β-catenin represents a potential therapeutic strategy in cervical cancer. - Highlights: • We repurposed the antibiotic drug tigecycline for cervical cancer treatment. • Tigecycline is effectively against cervical cancer cells in vitro and in vivo. • Combination of tigecycline and paclitaxel is synergistic in targeting Hela cells. • Tigecycline acts on Hela cells through inhibiting Wnt/β-catenin signaling.

  6. Human papillomavirus DNA in plasma of patients with HPV16 DNA-positive uterine cervical cancer.

    PubMed

    Shimada, Takako; Yamaguchi, Naohiro; Nishida, Noriyuki; Yamasaki, Kentaro; Miura, Kiyonori; Katamine, Shigeru; Masuzaki, Hideaki

    2010-05-01

    The squamous cell carcinoma antigen is considered the most accurate serologic tumor marker for uterine cervical carcinoma. However, serum squamous cell carcinoma antigen levels were found to correlate significantly with clinical severity of atopic dermatitis and chronic renal failure. The present study was conducted in patients with human papillomavirus 16 DNA-positive uterine cervical cancer to determine the plasma level of human papillomavirus 16 DNA and the diagnostic values of plasma human papillomavirus DNA in these patients. Forty-three human papillomavirus 16-positive patients with cervical intraepithelial neoplasia or uterine cervical squamous cell carcinoma were recruited in this study. The diagnosis was cervical cancer in 20 patients, high-grade squamous intraepithelial lesions in 21, low-grade squamous intraepithelial lesions in 1 and negative for intraepithelial lesion or malignancy in 3 patients. Before any treatment, blood samples were collected from all patients. For analysis of human papillomavirus DNA in plasma of patients with cervical cancer, quantitative polymerase chain reaction fluorescent assay for human papillomavirus 16 was performed using human papillomavirus 16 primers and SYBR Green dye using the LightCycler 480 SW1.5 apparatus. Plasma human papillomavirus 16 DNA was detected in only 30.0% of the patients with human papillomavirus 16-positive cervical cancer and in none of normal controls. The copy number of plasma human papillomavirus 16 DNA was higher in patients with invasive cancer than in those with cervical intraepithelial neoplasia (CIN3), micro-invasive cancer and in normal individuals. These results indicated that the plasma human papillomavirus DNA level could be potentially used as a marker of low-invasive cervical cancer tumors in patients with normal squamous cell carcinoma antigen levels before treatment.

  7. Home-Based or Clinic-Based Human Papillomavirus (HPV) Screening

    ClinicalTrials.gov

    2017-01-23

    Atypical Squamous Cell of Undetermined Significance; Cervical Carcinoma; Cervical Intraepithelial Neoplasia Grade 2/3; Health Status Unknown; Human Papillomavirus Infection; Low Grade Cervical Squamous Intraepithelial Neoplasia; Stage 0 Cervical Cancer

  8. Genotype Distribution of Human Papillomavirus among Women with Cervical Cytological Abnormalities or Invasive Squamous Cell Carcinoma in a High-Incidence Area of Esophageal Carcinoma in China

    PubMed Central

    Wang, Yuanyuan; Wang, Shaohong; Shen, Jinhui; Peng, Yanyan; Chen, Lechuan; Mai, Ruiqin

    2016-01-01

    Data of HPV genotype including 16 high-risk HPV (HR-HPV) and 4 low-risk HPV from 38,397 women with normal cytology, 1341 women with cervical cytology abnormalities, and 223 women with ISCC were retrospectively evaluated by a hospital-based study. The prevalence of high-risk HPV (HR-HPV) was 6.51%, 41.83%, and 96.86% in women with normal cytology, cervical cytology abnormalities, and ISCC, respectively. The three most common HPV types were HPV-52 (1.76%), HPV-16 (1.28%), and HPV-58 (0.97%) in women with normal cytology, whereas the most prevalent HPV type was HPV-16 (16.85%), followed by HPV-52 (9.55%) and HPV-58 (7.83%) in women with cervical cytology abnormalities. Specifically, HPV-16 had the highest frequency in ASC-H (24.16%, 36/149) and HSIL (35.71%, 110/308), while HPV-52 was the most common type in ASC-US (8.28%, 53/640) and LSIL (16.80%, 41/244). HPV-16 (75.78%), HPV18 (10.31%), and HPV58 (9.87%) were the most common types in women with ISCC. These data might contribute to increasing the knowledge of HPV epidemiology and providing the guide for vaccine selection for women in Shantou. PMID:27610364

  9. Detection of human papillomavirus in sanitary napkins: a new paradigm in cervical cancer screening.

    PubMed

    Tong, Tommy R; Chan, Olivia W H; Chow, Tat-Chong; Yu, Vivian; Leung, Kai-Man; To, Shui-Him

    2003-03-01

    Human papillomavirus was successfully detected by polymerase chain reaction (PCR) in menstrual blood or vaginal discharge collected in sanitary napkins in 100% of 17 women having koilocytosis, cervical intraepithelial neoplasia, or squamous carcinoma. We advocate this form of cervical cancer screening because of its high sensitivity and acceptance by patients. Copyright 2003 Wiley-Liss, Inc.

  10. Interactions Between High- and Low-Risk HPV Types Reduce the Risk of Squamous Cervical Cancer.

    PubMed

    Sundström, Karin; Ploner, Alexander; Arnheim-Dahlström, Lisen; Eloranta, Sandra; Palmgren, Juni; Adami, Hans-Olov; Ylitalo Helm, Nathalie; Sparén, Pär; Dillner, Joakim

    2015-10-01

    The clinical significance of co-infections with high-risk (HR) and low-risk (LR) human papillomavirus (HPV) in the etiology of cervical cancer is debated, as prospective evidence on this issue is limited. However, the question is of increasing relevance in relation to HPV-based cancer prevention. In two population-based nested case-control studies among women participating in cervical screening with baseline normal smears, we collected 4659 smears from women who later developed cancer in situ (CIS; n = 524) or squamous cervical cancer (SCC; n = 378) and individually matched control subjects who remained free of disease during study follow-up. The median follow-up until diagnosis was 6.4 to 7.8 years. All smears were tested for HPV. We used conditional logistic regression models with two-way interaction terms to estimate relative risks (RRs) for CIS and SCC, respectively. All statistical tests were two-sided. Compared with women who were infected with HRHPV only, women who were also infected with LRHPV had a lower risk for SCC (RR = 0.2, 95% confidence interval [CI] = 0.04 to 0.99, P = .049). This interaction was not shown for CIS (RR = 1.1, 95% CI = 0.4 to 3.6). Women who were positive for both HRHPV and LRHPV had, on average, a 4.8 year longer time to diagnosis of SCC than women who were positive for HRHPV only (P = .006). Results were highly robust in sensitivity analyses. Co-infection with LRHPV is associated with a lower risk of future invasive disease and longer time to diagnosis than infection with HRHPV alone. We propose that co-infection with LRHPV interferes with the rate of progression to invasive cervical cancer. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  11. Differential gene expression identified in Uigur women cervical squamous cell carcinoma by suppression subtractive hybridization.

    PubMed

    Pan, Z; Chen, S; Pan, X; Wang, Z; Han, H; Zheng, W; Wang, X; Li, F; Qu, S; Shao, R

    2010-01-01

    Cervical cancer is one of the most common gynecological cancers worldwide. Over the past decade, much progress has been made in understanding the genetic changes associated with the development and progression of cervical cancer. However, the precise mechanisms of cervical carcinogenesis in Uigur women remain unclear. To screen differential gene expression in squamous cell carcinoma (SCC) of the cervix in Uigur women, suppressive subtractive hybridization (SSH) was performed on the cervical squamous cell carcinoma and corresponding normal cervical tissues of a Uigur patient. Thus we were be able to find the genes that are related with cervical tumors of Uigur women. A total of 300 samples were subject to DNA sequencing analysis and 46 genes were found to express differentially in tumors compared with normal tissues. Of the 46 genes, 24 genes were up-regulated whereas 22 genes were down-regulated in cervical tumors. The expression profiles of 5 of the 46 genes were further confirmed in 15 other Uigur patients by semi-quantitative reverse-transcription polymerase chain reaction. Our results revealed that ACADVL, CEBPB, IFITM1 and DNAJC9 are involved in cervical carcinogenesis.

  12. Distribution and attribution of high-risk human papillomavirus genotypes in cervical precancerous lesions in China.

    PubMed

    Wang, Wenpeng; An, Jusheng; Song, Yan; Wang, Minjie; Huang, Manni; Wu, Lingying

    2017-07-01

    While human papillomavirus vaccine was recently approved by China Food and Drug Administration, mapping of high-risk human papillomavirus distribution and attribution in cervical precancerous lesions in China becomes critical in development of a high-risk human papillomavirus-based cervical cancer screening and prevention strategy. In total, 1016 patients with cervical precancerous lesions diagnosed in the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences were analyzed retrospectively, including 111 patients with low-grade squamous intraepithelial lesions and 905 patients with high-grade squamous intraepithelial lesions. HPV16, 58, 52, 33, and 31 were the most common high-risk human papillomavirus genotypes in order of decreasing frequency among high-risk human papillomavirus-positive high-grade squamous intraepithelial lesions; this differed from the high-risk human papillomavirus distribution in low-grade squamous intraepithelial lesions (HPV16, 52, 39, 56, and 58). The distribution of high-risk human papillomavirus genotypes in single-type infections for high-grade squamous intraepithelial lesions (HPV16, 58, 33, and 52) was similar to that in multiple-type infections (HPV16, 58, 52, and 33). By contrast, a more diverse distribution spectrum of high-risk human papillomavirus genotypes for low-grade squamous intraepithelial lesions was observed between single-type (HPV16, 52, 39, and 56) and multiple-type infection (HPV52, 68, 58, 59, 39 and 56). A previously published method was adopted to calculate the fractional proportion of individual high-risk human papillomavirus genotypes in multiple infections. For this proportional attribution, HPV16 (48.9%), 58 (10.0%), 33 (5.5%), and 52 (5.5%) were the most frequent among all high-grade squamous intraepithelial lesions, whereas HPV16 (13.2%), 52 (11.6%), 39 (9.5%), and 56 (7.6%) were the most frequent among all low-grade squamous intraepithelial lesions. Differences in high-risk human

  13. Detection of High-Risk Human Papillomaviruses in the Prevention of Cervical Cancer in India.

    PubMed

    Baskaran, Krishnan; Kumar, P Kranthi; Karunanithi, Santha; Sethupathy, Subramanian; Thamaraiselvi, B; Swaruparani, S

    2015-01-01

    Human papillomaviruses (HPVs) are small, non-enveloped, double-stranded DNA viruses that infect epithelial tissues. Specific genotypes of human papillomavirus are the single most common etiological agents of cervical intraepithelial lesions and cervical cancer. Cervical cancer usually arises at squamous metaplastic epithelium of transformation zone (TZ) of the cervix featuring infection with one or more oncogenic or high-risk HPV (HR- HPV) types. A hospital- based study in a rural set up was carried out to understand the association of HR-HPV with squamous intraepithelial lesions (SILs) and cervical cancer. In the present study, HR-HPV was detected in 65.7% of low-grade squamous intraepithelial lesions (LSILs), 84.6% of high-grade squamous intraepithelial lesions (HSILs) and 94% of cervical cancer as compared to 10.7% of controls. The association of HPV infection with SIL and cervical cancer was analyzed with Chi square test (p<0.001). The significant association found confirmed that detection of HR-HPV is a suitable candidate for early identification of cervical precancerous lesions and in the prevention of cervical cancer in India.

  14. Human papillomavirus detection by hybrid capture II and residual or recurrent high-grade squamous cervical intraepithelial neoplasia after large loop excision of the transformation zone (LLETZ).

    PubMed

    Sarian, Luís Otávio; Derchain, Sophie Françoise Mauricette; Pittal, Denise da Rocha; Andrade, Liliana Aparecida Angelo; Morais, Sirlei Siani; Figueiredo, Priscila Garcia

    2005-01-01

    The purpose of this study was to assess the association between highly-oncogenic types HPV DNA detection by Hybrid Capture II (HCII) and residual or recurrent high-grade cervical intraepithelial neoplasia (CIN 2 or 3) during the follow-up of women submitted to large loop excision of the transformation zone (LLETZ). In this cohort study, 94 women submitted to LLETZ because of CIN 2 or 3 between March 2001 and September 2002 were followed up twice yearly until September 2003. Follow-up visits consisted of an interview regarding clinical, social and demographic characteristics complemented with gynecological examination with specimen collection for Pap test and HCII and colposcopy. Eighty-one patients attended the first visit (mean 4.8 months, range 3-6) and 75 the second visit (mean 10.9 months, range 7-17 months). McNemar's test to assess the variation of HPV DNA detection following LLETZ, odds ratios (OR) to evaluate the correlation between HPV DNA positivity and residual/recurrent CIN during follow-up, and logistic regression to assess the risk of residual/recurrent CIN were used. There was a strong and significant reduction in HPV detection after LLETZ (P < 0.001). HPV DNA detection was correlated with residual/recurrent CIN at the first (OR = 103.4; 95% CI 5.5 to 1961.2) and second (OR = 12.7; 95% CI 1.1 to 345.5) follow-up visits. Multivariate analysis showed HPV persistence as a stand-alone risk factor for residual/recurrent CIN (OR = 50.3; 95% CI 3.8 to 663.1). High risk HPV DNA detection decreased substantially after CIN treatment with LLETZ, but HPV persistence was strongly correlated with residual/recurrent CIN.

  15. Differentially expressed proteins among normal cervix, cervical intraepithelial neoplasia and cervical squamous cell carcinoma.

    PubMed

    Zhao, Q; He, Y; Wang, X-L; Zhang, Y-X; Wu, Y-M

    2015-08-01

    To explore the differentially expressed proteins in normal cervix, cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma (CSCC) tissues by differential proteomics technique. Cervical tissues (including normal cervix, CIN and CSCC) were collected in Department of Gynecologic Oncology of Beijing Obstetrics and Gynecology Hospital. Two-dimensional fluorescence difference in gel electrophoresis (2-D DIGE) and DeCyder software were used to detect the differentially expressed proteins. Matrix-assisted laser desorption/ionization-time-of-flight tandem mass spectrometry (MALDI-TOF/TOF MS) was used to identify the differentially expressed proteins. Western blot (WB) and immunohistochemistry (IHC) were performed to validate the expressions of selected proteins among normal cervix, CIN and CSCC. 2-D DIGE images with high resolution and good repeatability were obtained. Forty-six differentially expressed proteins (27 up-regulated and 19 down-regulated) were differentially expressed among the normal cervix, CIN and CSCC. 26 proteins were successfully identified by MALDI-TOF/TOF MS. S100A9 (S100 calcium-binding protein A9) was the most significantly up-regulated protein. Eukaryotic elongation factor 1-alpha-1 (eEF1A1) was the most significantly down-regulated protein. Pyruvate kinase isozymes M2 (PKM2) was both up-regulated and down-regulated. The results of WB showed that with the increase in the severity of cervical lesions, the expression of S100A9 protein was significantly increased among the three groups (P = 0.010). The expression of eEF1A1 was reduced but without significant difference (P = 0.861). The expression of PKM2 was significantly reduced (P = 0.000). IHC showed that protein S100A9 was mainly expressed in the cytoplasm, and its positive expression rate was 20.0 % in normal cervix, 70.0 % in CIN and 100.0 % in CSCC, with a significant difference among them (P = 0.006). eEF1A1 was mainly expressed in the cell plasma, and its

  16. Human wings apart-like gene is specifically overexpressed in cervical cancer.

    PubMed

    Lu, Xiaoqin; Cui, Jinquan; Fu, Meizhou; Wang, Wuliang

    2016-07-01

    Cervical cancer is the third most commonly diagnosed cancer in women. The human wings apart-like (hWAPL) gene, which is 30,793 bp long and located on 10q23.2., is a human homologue of the WAPL gene in Drosophila melanogaster. hWAPL has the characteristics of an oncogene in uterine cervical cancer. The present study investigated the expression of the hWAPL gene in tissues, including 9 common cancers, consisting of cervical, gastric and lung cancers, liver, bladder, esophageal, endometrial, renal and rectal carcinomas, cervical intraepithelial neoplasia (CIN) and benign squamous epithelia. The immunohistochemical analysis was conducted using paraffin-embedded tissues obtained from 413 patients, consisting of 27 benign squamous epithelial tissue samples, and 47 cervical cancer, 30 cervical intraepithelial neoplasia (CIN)I, 33 CINII, 38 CINIII, 29 gastric cancer, 28 liver carcinoma, 26 bladder carcinoma, 35 esophageal carcinoma, 25 endometrial, 26 renal carcinoma, 36 rectal carcinoma and 33 lung cancer tissues. The expression of hWAPL mRNA was evaluated by reverse transcription-quantitative polymerase chain reaction in 8 benign squamous epithelia and 11 cervical cancer tissues. Compared to benign squamous epithelia and the 8 other cancers, hWAPL protein was significantly increased in cervical cancer (P<0.001). The expression of the hWAPL protein in cervical cancer and CINIII tissues was markedly increased compared to the expression in CINI and CINII tissues (P<0.001). Despite the significant difference in the staining scores (P<0.001), no significant difference was observed in the percentage of tissues expressing hWAPL (P=0.102) between cervical cancer and CINIII. The hWAPL gene may therefore be specifically overexpressed in cervical cancer. The overexpression of hWAPL may play an important role in occurrence and development of cervical cancer.

  17. Absorption spectra of adenocarcinoma and squamous cell carcinoma cervical tissues

    NASA Astrophysics Data System (ADS)

    Ivashko, Pavlo; Peresunko, Olexander; Zelinska, Natalia; Alonova, Marina

    2014-08-01

    We studied a methods of assessment of a connective tissue of cervix in terms of specific volume of fibrous component and an optical density of staining of connective tissue fibers in the stroma of squamous cancer and cervix adenocarcinoma. An absorption spectra of blood plasma of the patients suffering from squamous cancer and cervix adenocarcinoma both before the surgery and in postsurgical periods were obtained. Linear dichroism measurements transmittance in polarized light at different orientations of the polarization plane relative to the direction of the dominant orientation in the structure of the sample of biotissues of stroma of squamous cancer and cervix adenocarcinoma were carried. Results of the investigation of the tumor tissues showed that the magnitude of the linear dichroism Δ is insignificant in the researched spectral range λ=280-840 nm and specific regularities in its change observed short-wave ranges.

  18. Oral Rigosertib for Squamous Cell Carcinoma

    ClinicalTrials.gov

    2016-05-18

    Head and Neck Squamous Cell Carcinoma; Anal Squamous Cell Carcinoma; Lung Squamous Cell Carcinoma; Cervical Squamous Cell Carcinoma; Esophageal Squamous Cell Carcinoma; Skin Squamous Cell Carcinoma; Penile Squamous Cell Carcinoma

  19. A case of EMRC for basaloid squamous carcinoma of the cervical esophagus.

    PubMed

    Nakamura, Munetaka; Nishikawa, Jun; Suenaga, Shigeyuki; Okamoto, Takeshi; Okamoto, Fumiki; Miura, Osamu; Sakaida, Isao

    2012-08-16

    Basaloid squamous carcinoma (BSC) of the esophagus is a rare esophageal tumor. A 79-year-old man with a history of proximal gastrectomy for gastric adenocarcinoma in 2000 was followed-up by esophagogastroduodenoscopy (EGD) annually. In June 2010, EGD revealed a new protruding lesion in the cervical esophagus. The small lesion was approximately 5 mm in size. A biopsy specimen showed poorly differentiated squamous cell carcinoma. We performed endoscopic mucosal resection using a cap-fitted endoscope (EMRC). The histological diagnosis of the endoscopically resected specimen was BSC and the invasion depth was limited to the muscularis mucosae. Horizontal and vertical margins were negative. We report the case of superficial BSC in the cervical esophagus successfully resected by EMRC.

  20. Cytokeratin7 and cytokeratin19 expression in high grade cervical intraepithelial neoplasm and squamous cell carcinoma and their possible association in cervical carcinogenesis.

    PubMed

    Lee, Hojung; Lee, Hyekyung; Cho, Yong Kyun

    2017-02-17

    High risk human papillomavirus (HR HPV) infects cells at the squamocolumnar junction (SCJ) of the cervix, causing cancer. Cytokeratin (CK)7 is an SCJ marker, and stains cervical neoplasia. CK19 is a binding partner of CK7 and expressed in cervical cancer. Despite this possible association between CK7/CK19 and cervical cancer, not much is known about the mechanism of CK7/CK19 involvement in HR HPV-mediated cervical carcinogenesis. We analyzed the expression pattern of CK7, CK19, and p16 by using immunohistochemistry and HPV infection by in situ hybridization in 25 cases of high grade cervical intraepithelial neoplasia (CIN3) and in 30 cases of squamous cell carcinoma (SCC). CK19, p16, and HPV expression was positive in all CIN3 and SCC cases. CK7 expression was positive in all CIN3 cases and in 20/30 (66%) SCCs. Each protein showed diffuse or patchy staining with topographic distinction. Patchy staining of CK7 and episomal HPV DNA overlapped in the upper layer of CIN3 and central portion of an invasive nest in the SCC, whereas patchy CK19 staining and integrated HPV DNA were usually noted in the lower layer of CIN3 and the periphery of the SCC nest. The p16 staining pattern coincided with that of CK19 in a subset of SCC. These results suggest that CK7 may be more related with viral episomal replication and CK19 with viral integration, contributing to viral replication and malignant transformation in HR HPV infected cells. In addition, coordinate CK7/CK19 staining may be used as a valuable marker for predicting physical status of HR HPV and E7 oncoprotein level in cervical tumor.

  1. Human Papillomavirus and Cervical Cancer

    PubMed Central

    Burd, Eileen M.

    2003-01-01

    Of the many types of human papillomavirus (HPV), more than 30 infect the genital tract. The association between certain oncogenic (high-risk) strains of HPV and cervical cancer is well established. Although HPV is essential to the transformation of cervical epithelial cells, it is not sufficient, and a variety of cofactors and molecular events influence whether cervical cancer will develop. Early detection and treatment of precancerous lesions can prevent progression to cervical cancer. Identification of precancerous lesions has been primarily by cytologic screening of cervical cells. Cellular abnormalities, however, may be missed or may not be sufficiently distinct, and a portion of patients with borderline or mildly dyskaryotic cytomorphology will have higher-grade disease identified by subsequent colposcopy and biopsy. Sensitive and specific molecular techniques that detect HPV DNA and distinguish high-risk HPV types from low-risk HPV types have been introduced as an adjunct to cytology. Earlier detection of high-risk HPV types may improve triage, treatment, and follow-up in infected patients. Currently, the clearest role for HPV DNA testing is to improve diagnostic accuracy and limit unnecessary colposcopy in patients with borderline or mildly abnormal cytologic test results. PMID:12525422

  2. High Expression of KIF20A Is Associated with Poor Overall Survival and Tumor Progression in Early-Stage Cervical Squamous Cell Carcinoma

    PubMed Central

    Gu, Haifeng; Li, Min; Liu, Zhimin; Feng, Yanling; Zheng, Nianzhen; Xie, Chuanmiao; Zhang, Yanna

    2016-01-01

    Background The kinesin family member 20a (KIF20A) protein has been implicated in the development and progression of many human cancers; however, its precise function and role in cervical cancer remain largely unclear. This study aimed to investigate the expression profile and prognostic value of KIF20A in patients with early-stage cervical squamous cell carcinoma. Methods We examined the mRNA and protein levels of KIF20A in eight cervical cancer cell lines and eight paired cervical cancer samples, compared with normal cervical epithelial cells and adjacent normal cervical tissues, respectively. Immunohistochemistry was performed to detect the expression of KIF20A in paraffin-embedded specimens from 169 early-stage cervical squamous cell carcinoma patients. Statistical analyses were applied to analyze the association between KIF20A expression and clinical variables, as well with patient survival. Results The mRNA and protein expression levels of KIF20A were significantly elevated in cervical cancer cell lines and lesions compared with normal cells and corresponding normal tissues (P < 0.05). Immunohistochemistry analysis in 169 cervical cancer cases revealed that increased KIF20A expression was strongly associated with human papillomavirus (HPV) infection (P = 0.008), clinical stage (P = 0.001), tumor recurrence (P = 0.016), vital status (P < 0.001), the property of the surgical margin (P = 0.032), the lymphovascular space involvement (P = 0.014), and pelvic lymph node metastasis (P = 0.001). The overall survival and disease-free survival of patients with high levels of KIF20A expression were significantly poorer than those with low KIF20A expression. KIF20A was an independent survival prognostic factor, as evidenced by univariate and multivariate analysis. Conclusions Our results illustrate that elevated KIF20A expression correlates with HPV infection, clinical stage, tumor recurrence, lymphovascular space involvement, pelvic lymph node metastasis, and poor outcome

  3. Increased expression of sialic acid in cervical biopsies with squamous intraepithelial lesions.

    PubMed

    López-Morales, Dolores; Reyes-Leyva, Julio; Santos-López, Gerardo; Zenteno, Edgar; Vallejo-Ruiz, Verónica

    2010-11-22

    Altered sialylation has been observed during oncogenic transformation. Sialylated oligosaccharides of glycoproteins and glycolipids have been implicated in tumor progression and metastases. In the cervical cancer high levels of sialic acid have been reported in the patients serum, and an increased of total sialic acid concentration has been reported for the cervical neoplasia and cervical cancer. This study investigates the changes in expression and distribution of α2,3-linked sialic acid and α2,6- linked sialic acid in low and high squamous intraepithelial lesions and in normal tissue. Lectin histochemistry was used to examine the expression and distribution of sialic acid in different grades of cervical neoplasia. We applied Maackia amurensis lectin, which interacts with α2,3-linked sialic acid and Sambucus nigra lectin specific for α2,6-linked sialic acid. The histochemical analysis showed that α2,3-linked sialic acid and α2,6- linked sialic acid increased in intensity and distribution in concordance with the grade of squamous intraepithelial lesion (SIL). These results are in concordance with a previous study that reports increased RNAm levels of three sialyltransferases. These results show that the change in sialylation occurs before cancer development and may play an important role in cellular transformation. These findings provide the basis for more detailed studies of the possible role of cell surface glycoconjugates bearing sialic acid in the cellular cervix transformation.

  4. Increased expression of sialic acid in cervical biopsies with squamous intraepithelial lesions

    PubMed Central

    2010-01-01

    Background Altered sialylation has been observed during oncogenic transformation. Sialylated oligosaccharides of glycoproteins and glycolipids have been implicated in tumor progression and metastases. In the cervical cancer high levels of sialic acid have been reported in the patients serum, and an increased of total sialic acid concentration has been reported for the cervical neoplasia and cervical cancer. This study investigates the changes in expression and distribution of α2,3-linked sialic acid and α2,6- linked sialic acid in low and high squamous intraepithelial lesions and in normal tissue. Methods Lectin histochemistry was used to examine the expression and distribution of sialic acid in different grades of cervical neoplasia. We applied Maackia amurensis lectin, which interacts with α2,3-linked sialic acid and Sambucus nigra lectin specific for α2,6-linked sialic acid. Results The histochemical analysis showed that α2,3-linked sialic acid and α2,6- linked sialic acid increased in intensity and distribution in concordance with the grade of squamous intraepithelial lesion (SIL). These results are in concordance with a previous study that reports increased RNAm levels of three sialyltransferases. Conclusions These results show that the change in sialylation occurs before cancer development and may play an important role in cellular transformation. These findings provide the basis for more detailed studies of the possible role of cell surface glycoconjugates bearing sialic acid in the cellular cervix transformation. PMID:21092209

  5. Prognostic Significance of Cytokeratin 19 and Squamous Cell Cancer Antigen in Histologically Negative Sentinel Lymph Nodes of Cervical Squamous Cell Carcinoma.

    PubMed

    Ren, Jie; Zhou, Zun-Lun; Xu, Shu; Yang, Ying-Jie

    2016-11-01

    The aim of the study was to evaluate the prognostic value of positive cytokeratin 19 (CK19) and squamous cell cancer antigen (SCCAg) expression in histologically negative sentinel lymph nodes after surgery for cervical squamous cell carcinoma. Immunohistochemistry was performed to detect the expression of CK19 and SCCAg using polyclonal antibody on 149 pair of formalin-fixed, paraffin-embedded cervical squamous cell carcinoma and histologically negative sentinel lymph node tissue samples, and results were compared with data from the prospectively registry of cervical squamous cell carcinoma by univariate and multivariate logistic regression model focusing specifically on recurrence. The survival was assessed by the Kaplan-Meier method and proportional hazards model. Cytokeratin 19 and SCCAg expression in histologically negative sentinel lymph nodes were documented in 15.4% (n = 23) and 20.8% (n = 31) patients and were associated with a higher incidence of tumor progression and poorer disease-free survival (DFS, P < 0.05). Multivariate logistic regression analysis demonstrated that CK19 (P = 0.001) and SCCAg (P = 0.001) expression in histologically negative sentinel lymph nodes, International Federation of Gynecology and Obstetrics staging (P = 0.000), and cervical stroma infiltration depth (P = 0.005) were independent predictive factors for recurrence. The proportional hazards model identified CK19 (P = 0.001) and SCCAg (P = 0.005) expression in histologically negative sentinel lymph nodes, International Federation of Gynecology and Obstetrics staging (P = 0.003), and cervical stroma infiltration depth (P = 0.005), as independently related to DFS. Using subgroup analysis, we found that the CK19+/SCCAg + subgroup has the poorest prognosis, whereas the CK19-/SCCAg - subgroup has the best prognosis (P = 0.000). Immunohistochemical assessment of both CK19 and SCCAg status in histologically negative sentinel lymph nodes may be a valuable approach for predicting

  6. Cervical Human Papillomavirus (HPV) Infection in South African Women: Implications for HPV Screening and Vaccine Strategies▿

    PubMed Central

    Allan, Bruce; Marais, Dianne J.; Hoffman, Margaret; Shapiro, Samuel; Williamson, Anna-Lise

    2008-01-01

    The prevalence of cervical human papillomavirus (HPV) in South African women (n = 1,073) increased from 20.4% (173/848) in women with normal cytology to 41.7% (48/115) in women with atypical squamous cells of undetermined significance, 70.2% (40/57) in women with low-grade squamous intraepithelial lesions, and 83% (44/53) in women with high-grade squamous intraepithelial lesions (HSILs). HPV types 16 and 35 were the dominant types in women with HSILs but not in women in the other categories. PMID:17977997

  7. The three most common human papillomavirus oncogenic types and their integration state in Thai women with cervical precancerous lesions and carcinomas.

    PubMed

    Aromseree, Sirinart; Chaiwongkot, Arkom; Ekalaksananan, Tipaya; Kongyingyoes, Bunkerd; Patarapadungkit, Natcha; Pientong, Chamsai

    2014-11-01

    To understand the potential role in cervical cancer development of the three most common high-risk human papillomavirus (HR-HPVs) in Thai women, HPV genotypes and viral genome statuses in different cervical lesions were investigated. Cervical tissues consisting of no cervical intraepithelial neoplasia (84 cases), grade I cervical intraepithelial neoplasia (176 cases), grade II-III cervical intraepithelial neoplasia (91 cases), and squamous cell carcinoma (66 cases) were subjected for HPV genotyping by polymerase chain reaction (PCR) and reverse line blot hybridization assay and for HPV genome status determination by amplification of papillomavirus oncogene transcripts (APOT) assay. HPV prevalence was 28.6% in no cervical intraepithelial neoplasia, 40.3% in grade I cervical intraepithelial neoplasia, 70.3% in grade II-III cervical intraepithelial neoplasia and 86.4% in squamous cell carcinoma cases. The three most common HR-HPV types were HPV 16, 58, and 18 which were distributed in all cervical lesions. HPV physical statuses could be investigated in 4 no cervical intraepithelial neoplasias, 2 grade I cervical intraepithelial neoplasias, 28 grade II-III cervical intraepithelial neoplasias and 31 squamous cell carcinomas. The integrated-derived transcripts were found 3.6% in grade II-III cervical intraepithelial neoplasia and 48.4% in squamous cell carcinoma, whereas no viral genome integration was found in the group of no cervical intraepithelial neoplasia or grade I cervical intraepithelial neoplasia samples. The frequencies of HR-HPV integration in squamous cell carcinoma were found 40%, 100%, 20% of HPV 16, 18, and 58. This study indicates the oncogenic potential ability of the three most common HR-HPVs associated with cervical cancer progression. © 2014 Wiley Periodicals, Inc.

  8. SU-E-P-18: Intensity-Modulated Radiation Therapy for Cervical Esophageal Squamous Cell Carcinoma

    SciTech Connect

    Bai, W; Qiao, X; Zhou, Z; Song, Y; Zhang, R; Zhen, C

    2015-06-15

    Purpose: To retrospectively analyze the outcomes and prognostic factors of cervical esophageal squamous cell carcinoma (SCC) treated with intensity modulated radiation therapy (IMRT). Methods: Thirty-seven patients with cervical esophageal SCC treated with IMRT were analyzed retrospectively. They received 54–66 Gy in 27–32 fractions. Nineteen patients received concurrent (n=12) or sequential (n=7) platinum-based two drugs chemoradiotherapy. Overall survival (OS), local control rates (LCR) and prognostic factors were evaluated. Acute toxicities and patterns of first failures were observed. Results: The median follow-up was 46 months for alive patients. The l-, 3-, 4- and 5-year OS of the all patients were 83.8%, 59.1%, 47.5% and 32.6% respectively. The median survival time was 46 months. The l-, 3-,4- and 5-year LCR were 82.9%, 63.0%, 54.5% and 54.5%, respectively. Univariate and Multivariate analysis all showed that size of GTV was an independent prognostic factor (p=0.033, p=0.039). There were no patients with Grade 3 acute radiation esophagitis and Grade 2–4 acute pneumonitis. The local failure accounted for 70.0% of all treatment-related failures. Conclusion: IMRT is safe and effective in the treatment of cervical esophageal squamous cell carcinoma. Size of GTV is an independent prognostic factor. Local failure still remains the main reason of treatment failures. The authors declare no conflicts of interest in preparing this article.

  9. Differential role of gene hypermethylation in adenocarcinomas, squamous cell carcinomas and cervical intraepithelial lesions of the uterine cervix.

    PubMed

    Blanco-Luquin, Idoia; Guarch, Rosa; Ojer, Amaya; Pérez-Janices, Noemí; Martín-Sánchez, Esperanza; Maria-Ruiz, Sergio; Monreal-Santesteban, Iñaki; Blanco-Fernandez, Laura; Pernaut-Leza, Eduardo; Escors, David; Guerrero-Setas, David

    2015-09-01

    Cervical cancer is the third most common cancer in women worldwide. The hypermethylation of P16, TSLC-1 and TSP-1 genes was analyzed in squamous cell carcinomas (SCC), cervical intraepithelial lesions (CIN) and adenocarcinomas (ADC) of the uterine cervix (total 181 lesions). Additionally human papillomavirus (HPV) type, EPB41L3, RASSF1 and RASSF2 hypermethylation were tested in ADC and the results were compared with those obtained previously by our group in SCC. P16, TSLC-1 and TSP-1 hypermethylation was more frequent in SCCs than in CINs. These percentages and the corresponding ones for EPB41L3, RASSF1 and RASSF2 genes were also higher in SCCs than in ADCs, except for P16. The presence of HPV in ADCs was lower than reported previously in SCC and CIN. Patients with RASSF1A hypermethylation showed significantly longer disease-free survival (P = 0.015) and overall survival periods (P = 0.009) in ADC patients. To our knowledge, this is the first description of the EPB41L3 and RASSF2 hypermethylation in ADCs. These results suggest that the involvement of DNA hypermethylation in cervical cancer varies depending on the histological type, which might contribute to explaining the different prognosis of patients with these types of tumors.

  10. Prostitution, condom use, and invasive squamous cell cervical cancer in Thailand.

    PubMed

    Thomas, D B; Ray, R M; Pardthaisong, T; Chutivongse, S; Koetsawang, S; Silpisornkosol, S; Virutamasen, P; Christopherson, W M; Melnick, J L; Meirik, O; Farley, T M; Riotton, G

    1996-04-15

    Cervical cancer is probably caused by a sexually transmitted agent. A case-control study was conducted in three hospitals in Thailand to investigate further the role of male sexual behavior, particularly regarding sexual contacts with prostitutes, in the development of this disease. Data were obtained from interviews with 225 married women with invasive squamous cell cervical carcinoma and 791 hospitalized controls, all of whom reported having only one sexual partner, and from interviews with their husbands. Risk of cervical cancer was strongly related to the women's husbands having visited prostitutes without using a condom when the husbands were less than 30 years old. A strong increasing trend in risk in relation to decreasing frequency of the husbands' condom use with prostitutes was observed, and a weaker increasing trend in risk with husbands' estimated lifetime total number of visits to prostitutes was found. The average latent period between the women's likely initial exposure to a sexually transmitted oncogenic agent and her diagnosis of invasive cervical cancer was about a quarter of a century. Regular use of condoms by customers of prostitutes could reduce the number of invasive cervical cancer cases in the general population of Thailand by at least one fourth.

  11. Evaluating Nuclear Membrane Irregularity for the Classification of Cervical Squamous Epithelial Cells

    PubMed Central

    Tang, Jing Rui; Mat Isa, Nor Ashidi; Ch’ng, Ewe Seng

    2016-01-01

    Pap test involves searching of morphological changes in cervical squamous epithelial cells by pathologists or cytotechnologists to identify potential cancerous cells in the cervix. Nuclear membrane irregularity is one of the morphological changes of malignancy. This paper proposes two novel techniques for the evaluation of nuclear membrane irregularity. The first technique, namely, penalty-driven smoothing analysis, introduces different penalty values for nuclear membrane contour with different degrees of irregularity. The second technique, which can be subdivided into mean- or median-type residual-based analysis, computes the number of points of nuclear membrane contour that deviates from the mean or median of the nuclear membrane contour. Performance of the proposed techniques was compared to three state-of-the-art techniques, namely, radial asymmetric, shape factor, and rim difference. Friedman and post hoc tests using Holm, Shaffer, and Bergmann procedures returned significant differences for all the three classes, i.e., negative for intraepithelial lesion or malignancy (NILM) versus low grade squamous intraepithelial lesion (LSIL), NILM versus high grade squamous intraepithelial lesion (HSIL), and LSIL versus HSIL when the span value equaled 3 was employed with linear penalty function. When span values equaled 5, 7, and 9, NILM versus LSIL and HSIL showed significant differences regardless of the penalty functions. In addition, the results of penalty-driven smoothing analysis were comparable with those of other state-of-the-art techniques. Residual-based analysis returned significant differences for the comparison among the three diagnostic classes. Findings of this study proved the significance of nuclear membrane irregularity as one of the features to differentiate the different diagnostic classes of cervical squamous epithelial cells. PMID:27741266

  12. Evaluating Nuclear Membrane Irregularity for the Classification of Cervical Squamous Epithelial Cells.

    PubMed

    Tang, Jing Rui; Mat Isa, Nor Ashidi; Ch'ng, Ewe Seng

    2016-01-01

    Pap test involves searching of morphological changes in cervical squamous epithelial cells by pathologists or cytotechnologists to identify potential cancerous cells in the cervix. Nuclear membrane irregularity is one of the morphological changes of malignancy. This paper proposes two novel techniques for the evaluation of nuclear membrane irregularity. The first technique, namely, penalty-driven smoothing analysis, introduces different penalty values for nuclear membrane contour with different degrees of irregularity. The second technique, which can be subdivided into mean- or median-type residual-based analysis, computes the number of points of nuclear membrane contour that deviates from the mean or median of the nuclear membrane contour. Performance of the proposed techniques was compared to three state-of-the-art techniques, namely, radial asymmetric, shape factor, and rim difference. Friedman and post hoc tests using Holm, Shaffer, and Bergmann procedures returned significant differences for all the three classes, i.e., negative for intraepithelial lesion or malignancy (NILM) versus low grade squamous intraepithelial lesion (LSIL), NILM versus high grade squamous intraepithelial lesion (HSIL), and LSIL versus HSIL when the span value equaled 3 was employed with linear penalty function. When span values equaled 5, 7, and 9, NILM versus LSIL and HSIL showed significant differences regardless of the penalty functions. In addition, the results of penalty-driven smoothing analysis were comparable with those of other state-of-the-art techniques. Residual-based analysis returned significant differences for the comparison among the three diagnostic classes. Findings of this study proved the significance of nuclear membrane irregularity as one of the features to differentiate the different diagnostic classes of cervical squamous epithelial cells.

  13. Requirement for Estrogen Receptor Alpha in a Mouse Model for Human Papillomavirus-Associated Cervical Cancer

    PubMed Central

    Chung, Sang-Hyuk; Wiedmeyer, Kerri; Shai, Anny; Korach, Kenneth S.; Lambert, Paul F.

    2008-01-01

    The majority of human cervical cancers are associated with the high-risk human papillomaviruses (HPVs), which encode the potent E6 and E7 oncogenes. Upon prolonged treatment with physiological levels of exogenous estrogen, K14E7 transgenic mice expressing HPV-16 E7 oncoprotein in their squamous epithelia succumb to uterine cervical cancer. Furthermore, prolonged withdrawal of exogenous estrogen results in complete or partial regression of tumors in this mouse model. In the current study we investigated whether estrogen receptor alpha (ERα) is required for the development of cervical cancer in K14E7 transgenic mice. We demonstrate that exogenous estrogen fails to promote either dysplasia or cervical cancer in K14E7/ERα−/− mice despite the continued presence of the presumed cervical cancer precursor cell type, reserve cells, and evidence for E7 expression therein. We also observed that cervical cancers in our mouse models are strictly associated with atypical squamous metaplasia (ASM), which is believed to be the precursor for cervical cancer in women. Consistently, E7 and exogenous estrogen failed to promote ASM in the absence of ERα. We conclude that ERα plays a crucial role at an early stage of cervical carcinogenesis in this mouse model. PMID:19047174

  14. Requirement for estrogen receptor alpha in a mouse model for human papillomavirus-associated cervical cancer.

    PubMed

    Chung, Sang-Hyuk; Wiedmeyer, Kerri; Shai, Anny; Korach, Kenneth S; Lambert, Paul F

    2008-12-01

    The majority of human cervical cancers are associated with the high-risk human papillomaviruses (HPV), which encode the potent E6 and E7 oncogenes. On prolonged treatment with physiologic levels of exogenous estrogen, K14E7 transgenic mice expressing HPV-16 E7 oncoprotein in their squamous epithelia succumb to uterine cervical cancer. Furthermore, prolonged withdrawal of exogenous estrogen results in complete or partial regression of tumors in this mouse model. In the current study, we investigated whether estrogen receptor alpha (ERalpha) is required for the development of cervical cancer in K14E7 transgenic mice. We show that exogenous estrogen fails to promote either dysplasia or cervical cancer in K14E7/ERalpha-/- mice despite the continued presence of the presumed cervical cancer precursor cell type, reserve cells, and evidence for E7 expression therein. We also observed that cervical cancers in our mouse models are strictly associated with atypical squamous metaplasia (ASM), which is believed to be the precursor for cervical cancer in women. Consistently, E7 and exogenous estrogen failed to promote ASM in the absence of ERalpha. We conclude that ERalpha plays a crucial role at an early stage of cervical carcinogenesis in this mouse model.

  15. Distribution of human papillomavirus genotypes in cervical lesions

    PubMed Central

    Ma, Li; Cong, Xiao; Shi, Mai; Wang, Xiu-Hong; Liu, Hai-Yan; Bian, Mei-Lu

    2017-01-01

    The aims of the present study were to investigate the distribution of human papillomavirus (HPV) genotypes in cervical lesions, and the association between different HPV genotypes and cervical lesions. Between January 2013 and June 2014, the HPV type determinations of nucleic acid by use of fluorescence polymerase chain reaction (PCR) method of 15,192 outpatients in China-Japan Friendship Hospital were performed and the infection status was analyzed. The results showed that: i) 2,366 Cases were HPV positive and 12,826 cases were HPV negative, the overall infection rate was 15.57% (2,366/15,192), in which a single genotype of HPV infection rate was 11.63% (1,767/15,192), and multiple genotypes of HPV infection rate was 3.94% (599/15,192); ii) HPV16, HPV52 and HPV58 infections were the most common HPV genotypes, the infection rates were 3.95% (600/15,192), 2.86% (435/15,192) and 2.67% (406/15,192), respectively; and iii) According to the gold standard of histopathological analysis via hematoxylin-eosin staining, HPV16, HPV52 and HPV58 accounted for 58.80% (154/267) of all CIN2 or above squamous epithelial lesions. Furthermore, three cases with pathological changes of the cervical severe glandular epithelium were all HPV18 infection. The difference was statistically significant (χ2=60.74, P<0.001). Single HPV subtype infection was primarily associated with HPV16, HPV52 and HPV58. In conclusion, HPV type detection had a may be important in screening of cervical lesions as a difference in pathogenic ability was noted among different HPV genotypes. As cervical cancer is an infectious disease, HPV testing may help detect more precancerous lesions, thus reducing the morbidity and mortality of cervical cancer. HPV16, HPV52 and HPV58 were associated with severe cervical squamous epithelial lesions; HPV18 was associated with cervical severe glandular cell pathological changes, although it was not the most common HPV genotype in China. When positive, a clinical cervical

  16. Veliparib, Topotecan Hydrochloride, and Filgrastim or Pegfilgrastim in Treating Patients With Persistent or Recurrent Cervical Cancer

    ClinicalTrials.gov

    2016-12-07

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma; Recurrent Cervical Carcinoma; Stage III Cervical Cancer; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer

  17. Analysis of cytosine-adenine repeats in P1 promoter region of IGF-1 gene in peripheral blood cells and cervical tissue samples of females with cervical intraepithelial lesions and squamous cervical cancer.

    PubMed

    Kwasniewski, Wojciech; Gozdzicka-Jozefiak, Anna; Kotarska, Maria; Polak, Grzegorz; Barczynski, Bartlomiej; Broniarczyk, Justyna; Nowak, Witold; Wolun-Cholewa, Maria; Kwasniewska, Anna; Kotarski, Jan

    2015-02-01

    High oncogenic risk human papillomaviruses (HPVs) are closely associated with cancer of the cervix. However, HPV infection alone may not be sufficient to cause cervical cancer, and other factors or cofactors may have a cumulative effect on the risk of progression from cervical HPV infection to cancer. The present study investigates the cytosine‑adenine (CA) repeat polymorphism in the P1 promoter region of the insulin‑like growth factor‑1 (IGF‑1) gene among cervical precancerous and cancer patients and healthy control females. The association between these polymorphisms, tissue and blood serum levels of IGF‑1, and cervical cancer risk and progression is evaluated. The material for analysis consisted of blood cells and postoperative tissues from patients diagnosed with low‑grade squamous intraepithelial lesions (L‑SILs), high‑grade squamous intraepithelial lesions (H‑SILs) and invasive cervical cancer (ICC). A polymerase chain reaction amplification and the sequencing of DNA were used for the identification of (CA)n repeats in the IGF‑1 P1 region and detection of HPV DNA. The blood serum concentration of IGF was determined by enzyme‑linked immunosorbent assay. The identification of the IGF‑1 protein in the cervical tissues was performed by immunohistochemical analysis. The range of the length of the CA repeats in the study DNA was 11 to 21. However, the most common allele length and genotype in the control and study patients from serum and tissues was 19 CA repeats and a homozygous genotype of CA19/19. Statistically significant differences in the concentration of IGF‑1 in the blood serum were observed between H‑SILs and controls, only (p=0.047). However, the concentration of IGF‑1 in the group of females with CA19/19, CA19<19 and CA19>19 was significantly higher in the group of patients with H‑SIL (P=0.041) and ICC (P=0.048) in comparison with the control group. An association was detected between CA repeat length <19 and/or >19, IGF

  18. Analysis of cytosine-adenine repeats in P1 promoter region of IGF-1 gene in peripheral blood cells and cervical tissue samples of females with cervical intraepithelial lesions and squamous cervical cancer

    PubMed Central

    KWASNIEWSKI, WOJCIECH; GOZDZICKA-JOZEFIAK, ANNA; KOTARSKA, MARIA; POLAK, GRZEGORZ; BARCZYNSKI, BARTLOMIEJ; BRONIARCZYK, JUSTYNA; NOWAK, WITOLD; WOLUN-CHOLEWA, MARIA; KWASNIEWSKA, ANNA; KOTARSKI, JAN

    2015-01-01

    High oncogenic risk human papillomaviruses (HPVs) are closely associated with cancer of the cervix. However, HPV infection alone may not be sufficient to cause cervical cancer, and other factors or cofactors may have a cumulative effect on the risk of progression from cervical HPV infection to cancer. The present study investigates the cytosine-adenine (CA) repeat polymorphism in the P1 promoter region of the insulin-like growth factor-1 (IGF-1) gene among cervical precancerous and cancer patients and healthy control females. The association between these polymorphisms, tissue and blood serum levels of IGF-1, and cervical cancer risk and progression is evaluated. The material for analysis consisted of blood cells and postoperative tissues from patients diagnosed with low-grade squamous intraepithelial lesions (L-SILs), high-grade squamous intraepithelial lesions (H-SILs) and invasive cervical cancer (ICC). A polymerase chain reaction amplification and the sequencing of DNA were used for the identification of (CA)n repeats in the IGF-1 P1 region and detection of HPV DNA. The blood serum concentration of IGF was determined by enzyme-linked immunosorbent assay. The identification of the IGF-1 protein in the cervical tissues was performed by immunohistochemical analysis. The range of the length of the CA repeats in the study DNA was 11 to 21. However, the most common allele length and genotype in the control and study patients from serum and tissues was 19 CA repeats and a homozygous genotype of CA19/19. Statistically significant differences in the concentration of IGF-1 in the blood serum were observed between H-SILs and controls, only (p=0.047). However, the concentration of IGF-1 in the group of females with CA19/19, CA19<19 and CA19>19 was significantly higher in the group of patients with H-SIL (P=0.041) and ICC (P=0.048) in comparison with the control group. An association was detected between CA repeat length <19 and/or >19, IGF concentration in blood serum and

  19. Oncostatin M receptor is a novel therapeutic target in cervical squamous cell carcinoma

    PubMed Central

    Caffarel, Maria M; Coleman, Nicholas

    2014-01-01

    Cervical carcinoma is the second most common cause of cancer deaths in women worldwide. Treatments have not changed for decades and survival rates for advanced disease remain low. An exciting new molecular target for the treatment of cervical squamous cell carcinoma (SCC), and possibly for SCCs at other anatomical sites, is the oncostatin M receptor (OSMR). This cell surface cytokine receptor is commonly copy number gained and overexpressed in advanced cervical SCC, changes that are associated with significantly worse clinical outcomes. OSMR overexpression in cervical SCC cells results in enhanced responsiveness to the major ligand oncostatin M (OSM), which induces several pro-malignant effects, including a pro-angiogenic phenotype and increased cell migration and invasiveness. OSMR is a strong candidate for antibody-mediated inhibition, a strategy that has had a major impact on haematological malignancies and various solid tumours such as HER2-positive breast cancers. © 2013 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. PMID:24659184

  20. Characterization of Single-Nucleotide Polymorphisms in the Tumor Necrosis Factor α Promoter Region and in Lymphotoxin α in Squamous Intraepithelial Lesions, Precursors of Cervical Cancer1

    PubMed Central

    Nieves-Ramirez, Miriam Enriqueta; Partida-Rodriguez, Oswaldo; Alegre-Crespo, Pedro Eduardo; Tapia-Lugo, Maria del Carmen; Perez-Rodriguez, Martha Esthela

    2011-01-01

    Development of cervical cancer is a long process of abnormal cancerous cell growth in the cervix and is primarily the result of infection with specific high-risk types of human papillomavirus (HPV). The cytokines tumor necrosis factor α (TNFα) and lymphotoxin α (LTA) have an important role in all stages of cervical cancer and have the ability to induce the regression or promote the development of human tumors. Biologically important single-nucleotide polymorphisms (SNPs) occur within the TNFα and LTA genes. Therefore, the purpose of this study was to investigate the SNPs in the TNFα promoter region (-163, -238, -244, -308, -376, -857, -863, and -1031) and in the first intron of LTA (+252) in women with precursor lesions of cervical cancer. Overall, we studied 396 women from Mexico City. A total of 191 patients with HPV infection and precursor cervical lesions were subdivided in two groups: those with low-grade squamous intraepithelial lesions (n = 132) and those with high-grade squamous intraepithelial lesions (n = 59). Women (n = 205) negative for HPV and without cervical lesions were also included in the study. DNA was extracted from peripheral white blood cells and from cervical samples, and detection of biallelic polymorphisms of TNFα and LTA was performed using the polymerase chain reaction-sequence-specific oligonucleotide probe and restriction fragment length polymorphism techniques, respectively. We demonstrated that risk is associated with the genotype G/A (odds ratio = 2.48) and that protection is associated with the genotype G/G of SNP TNFα -376 (odds ratio = 0.37). PMID:22190997

  1. Epidemiology of Cervical Squamous Intraepithelial Lesions in HIV Infected Women in Kenya: a cross-Sectional Study.

    PubMed

    Memiah, Peter; Makokha, Violet; Mbuthia, Wangeci; Kiiru, Grace Wanjiku; Agbor, Solomon; Odhiambo, Francesca; Ojoo, Sylvia; Mbizo, Justice; Muhula, Samuel; Mahasi, Gabriel; Biadgilign, Sibhatu

    2015-03-01

    Cervical cancer is the second most common cancer among women worldwide. Infection with the human immunodeficiency virus (HIV) and its related immunosuppression are associated with an increased risk of prevalent, incident, and persistent squamous intraepithelial lesions (SILs) of the cervix. The objective of the study was to describe the prevalence and predictors of high-risk HPV and cervical cancer to support the need for strengthening cervical cancer screening programs for HIV infected women in Kenya. A cross sectional study was conducted in a hospital in Central Kenya, Kiambu district. The study population constituted of HIV positive women attending the ART treatment clinic. A total of 715 HIV positive women initiated on Antiretroviral Therapy (ART) were enrolled in this study. About 359 (52.1%) were less than 40 years of age and 644 (90.3%) of the patients were widowed. About 642 (92.6%) of the HIV infected women were in follow-up period of ≥ 1 year. The outcome/prognosis of the patients undergoing ICC was 3 cured, 5 good and 4 poor respectively. In a multivariable ordinal logistic regression analysis showed that for a one-unit decrease of CD4, we expect 1.23 log odds of increasing the severity of cervical cancer (B = 1.23, P < 0.0 15), given that all of the other variables in the model are held constant. In conclusion screening of all HIV infected women, who are under HIV care and treatment, enrolling patients on HAART with higher CD4 counts is recommended to see the net effect of HAART response.

  2. [Human papillomavirus: a vaccine against cervical carcinoma uterine].

    PubMed

    Franceschi, Silvia

    2002-01-01

    Human papillomavirus (HPV) has been identified in fewer than 20 years as the central cause of cervical carcinoma and one of the most powerful known human carcinogens. At least 20 different types of HPV have been associated with relative risks of approximately 100 for both squamous-cell carcinoma and the rarer adenocarcinoma of the cervix uteri. Cytologic screening programs have contributed to the decline of cervical cancer mortality in Europe and the United States. Long-term screening programs remain, however, outside the reach of the poorest countries, where 80% of deaths for cervical carcinoma occurs. More than 20 different types of prophylactic and/or therapeutic vaccines against HPV are being evaluated in clinical or preclinical studies. One such type, a prophylactic vaccine based on the marked immunogenicity and safety of the empty viral capsid, will start being evaluated in 2002 in 3 phase-III randomized studies, mostly in the United States and Latin America. The International Agency for Research on Cancer and World Health Organization are planning, in parallel with the studies above, a double blind randomized phase IV study of approximately 40,000 adolescent and young women in Asia. Such study, which should include a cluster randomization (by village of birth); a comparison with another vaccine (rather than with placebo); and, possibly, the inclusion of adolescents and young adults of male sex. Such trial may accelerate by many years the availability of an anti-HPV vaccine among populations at highest risk for cervical carcinoma.

  3. The Association between HIV Infection, Antiretroviral Therapy and Cervical Squamous Intraepithelial Lesions in South Western Nigerian Women

    PubMed Central

    Ezechi, Oliver Chukwujekwu; Pettersson, Karen Odberg; Okolo, Clement Abu; Ujah, Innocent Achaya O.; Ostergren, Per Olof

    2014-01-01

    Introduction Findings from studies that evaluated the effect of antiretroviral drug use on the development of cervical squamous intraepithelial lesion differed in their conclusions. This study investigated the association between HIV infection, antiretroviral drug use and cervical squamous intraepithelial lesion in a high HIV and cervical cancer burden setting- Nigeria. Methods A cross sectional study among 1140 women of known HIV status enrolled in a randomised study to determine the test characteristics of visual inspection in detecting cytology diagnosed squamous intraepithelial lesion. Multivariate analysis was used to determine the association between HIV infection, antiretroviral drug use and the twin outcome variables of cervical squamous intraepithelial lesion (SIL) and High grade squamous intraepithelial lesion (HSIL) while controlling for confounders. Results Prevalence of cervical squamous intraepithelial lesion was 8.5%, with a higher prevalence of 14.3% in HIV positive compared to 3.3% in HIV negative women (aOR: 5.4; 95% CI: 2.9–8.8). Not using antiretroviral drugs was found to be associated with an increased risk of SIL (aOR: 2.1; 95% CI: 1.4–3.5) and HSIL (aOR: 2.6; 95% CI: 1.1–6.4). Participants who had a CD4 cell count <200 cells/mm3, were also found to be at increased risk for SIL (aOR: 1.9; 95% CI: 1.1–5.9) and HSIL (aOR: 5.7; 95% CI: 1.1–7.2). Conclusion HIV infection and severe immunosuppression were found to be associated with increased risk of cervical squamous intraepithelial lesion but not viral load. For the first time, in the West African sub-region with specific HIV type and strains, we established the protective effect of antiretroviral drug use against the development of SIL. Integration of cervical cancer screening programme into HIV services and early initiation of antiretroviral drug in HIV positive women especially those with severe immune-suppression could therefore prove to be useful in preventing and controlling

  4. Human papillomavirus infections among women with cervical lesions and cervical cancer in Eastern China: genotype-specific prevalence and attribution.

    PubMed

    Zhang, Lei; Bi, Qingqing; Deng, Hua; Xu, Jing; Chen, Juan; Zhang, Meilian; Mu, Xiaofeng

    2017-01-31

    Cervical cancer and its precursor, high-grade cervical intraepithelial neoplasia (CIN2/3), are associated with persistent high-risk human papillomavirus (HPV) infection. HPV genotype prevalence varies with severity of cervical lesions, patient age and geographical location. The aim of this study was to investigate HPV genotypes prevalence and attribution according to the severity of cervical lesions among Chinese women. A 4-year surveillance study was performed. A total of 1664 female patients were included and their cervical histological diagnosis consisted of cervical intraepithelial neoplasia grade 1 (CIN1, 376 cases), grade 2 (CIN2, 408 cases), grade 3 (CIN3, 336 cases) and invasive cervical cancers (ICC, 544 cases). HPV genotypes prevalence and attribution to cervical lesions were calculated and analyzed. The 95% confidence interval (CI) for proportion was also calculated. HPV positivity rates increased directly with cervical lesions severity (72.4% for CIN1, 81.4% for CIN2, 88.1% for CIN3 and 90.4% for ICC). Infections with multiple HPV types were inversely related to cervical lesions severity. HPV16, 52, 31, 33 and 58 were the most prevalent genotypes in ICC. 49.1% of squamous cell carcinoma, 65.1% of adenocarcinoma and 12.0-43.3% of cervical intraepithelial neoplasia could be attributed to vaccine-covered high-risk genotypes (HPV16/18). Inclusion of HPV52 and HPV31 in future vaccines would provide the highest marginal benefit in protection for individuals residing in this region. These findings provide information about HPV genotypes in this region which may be important to target with future vaccination and screening programs.

  5. Human papillomavirus and cervical cancer.

    PubMed

    Crosbie, Emma J; Einstein, Mark H; Franceschi, Silvia; Kitchener, Henry C

    2013-09-07

    Cervical cancer is caused by human papillomavirus infection. Most human papillomavirus infection is harmless and clears spontaneously but persistent infection with high-risk human papillomavirus (especially type 16) can cause cancer of the cervix, vulva, vagina, anus, penis, and oropharynx. The virus exclusively infects epithelium and produces new viral particles only in fully mature epithelial cells. Human papillomavirus disrupts normal cell-cycle control, promoting uncontrolled cell division and the accumulation of genetic damage. Two effective prophylactic vaccines composed of human papillomavirus type 16 and 18, and human papillomavirus type 16, 18, 6, and 11 virus-like particles have been introduced in many developed countries as a primary prevention strategy. Human papillomavirus testing is clinically valuable for secondary prevention in triaging low-grade cytology and as a test of cure after treatment. More sensitive than cytology, primary screening by human papillomavirus testing could enable screening intervals to be extended. If these prevention strategies can be implemented in developing countries, many thousands of lives could be saved.

  6. Detection, genotyping and quantitation of multiple hpv infections in south African women with cervical squamous cell carcinoma.

    PubMed

    Lebelo, Ramokone L; Bogers, Johannes J; Thys, Sofie; Depuydt, Christophe; Benoy, Ina; Selabe, S Gloria; Bida, Meshack N; Mphahlele, M Jeffrey

    2015-09-01

    In Africa, data is limited on quantitation of human papillomavirus (HPV) types in women with multiple infections. This study applied a real time PCR (qPCR) assay for detection, genotyping and quantitation of multiple HPV infections in 90 tissue blocks of South African women with cervical squamous cell carcinoma. One sample with multiple HPV types was subjected to laser micro-dissection and qPCR. Four samples were negative for β-globin and these were excluded from the analysis. The HPV DNA positivity rate was 93.0% (80/86). All 80 positives showed the presence of HR HPV types; HPV 68 was the only type negative in all the samples. Overall, HPV 16 was positive in most of the samples (88.8%), followed by HPV 56 (28.7%), HPV 18 (20.0%) and HPV 39 (18.7%). More than half of the samples (65.0%) had multiple infections. HPV 16 was present in majority of single (85.7%) and multiple infections (90.4%). HPV 16 showed higher viral loads in 70.3% of the HPV 16 co-infected samples. In one multiple infected sample laser micro-dissection and qPCR identified HPV 18 with higher viral load as the most likely cause of the invasive lesion. There is large number of multiple HPV infections in South African women with cervical squamous cell carcinoma. HPV 16 is the most frequently detected type and often presents with higher viral load, suggesting it could be responsible for pathogenesis of the lesions in the majority of cases.

  7. Pre-vaccination prevalence of infections with 25 non-high-risk human papillomavirus types among 1,000 Slovenian women in cervical cancer screening.

    PubMed

    Učakar, Veronika; Poljak, Mario; Oštrbenk, Anja; Klavs, Irena

    2014-10-01

    Cervical infections with non-high-risk human papillomavirus (non-HR-HPV) types have been associated with genital warts and a fraction of atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesions. The pre-vaccination prevalence of cervical infections with 25 non-HR-HPV types has been estimated, regardless of and without the coexistence of infection with HR-HPV types among Slovenian women 20-64 years old in cervical cancer screening, overall and according to age and cytology result. One thousand cervical specimens selected randomly from 4,455 specimens collected in 2010 in the Slovenian HPV prevalence survey were tested with Linear Array HPV Genotyping Test. Prevalence of cervical infections with any of the 25 non-HR-HPV types was 10.0% (95% CI: 8.1-11.9%) and with exclusively non-HR-HPV types 4.5% (95% CI: 3.2-5.8%). Prevalence of infections with any non-HR-HPV types among women with normal cytology was 8.8%, with atypical squamous cells of undetermined significance 30.4%, with low-grade squamous intraepithelial lesions 60.0%, and with high-grade squamous intraepithelial lesions 7.7%. Non-HR-HPV types without coexisting HR-HPV types were found in 4.0% of women with normal cytology, 26.1% with atypical squamous cells of undetermined significance, 6.7% with low-grade squamous intraepithelial lesions, and none with high-grade squamous intraepithelial lesion. Non-HR-HPV type cervical infections without coexisting HR-HPV infections were common among Slovenian women in cervical cancer screening with atypical squamous cells of undetermined significance, while rare in those with low-grade squamous intraepithelial lesions or worse. J. Med. Virol. 86: 1772-1779, 2014. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.

  8. Association of Casp3 microRNA Target Site (1049216) SNP With the Risk and Progress of Cervical Squamous Cell Carcinoma.

    PubMed

    Guo, Xin; Dong, Zhiming; Yamada, Sohsuke; Li, Yuanyuan; Guo, Yanli; Shen, Supeng; Liang, Jia; Tanimoto, Akihide; Guo, Wei

    2017-02-01

    In the present study, we investigated the relationship between the single-nucleotide polymorphism (SNP) of caspase-3 rs1049216 (C > T), a miRNA target site, and the risk and progression of cervical cancer. Using polymerase chain reaction-restriction fragment length polymorphism, we evaluated the genotype and distribution of caspase-3 rs1049216 in 515 patients with cervical squamous cell cancer and 415 controls. In additional experiments, we transfected luciferase reporter plasmids carrying T or C allele and/or miRNA mimics into the human cervical cell lines (HeLa and C-33A) to analyze its roles in the regulation of caspase-3 expression. By immunohistochemistry, the protein level of caspase-3 expression was examined in tumor tissues from 515 patients with cervical squamous cell cancer. We found that the TT genotype of caspase-3 rs1049216 conferred a significantly decreased risk of cervical cancer (adjusted odds ratio, 0.35; 95% confidence interval, 0.154-0.581) and may be associated with the progression of this cancer. Although the expression of caspase-3 in the TT genotype was higher than that in CC/CT genotype in peripheral blood mononuclear cells and tumor tissues. Additional luciferase analysis showed that the rs1049216 variant T allele was associated with significantly higher luciferase activity, compared with the C allele in the transfected cells, and when cotransfected with miRNAs, miRNA-181a could downregulate the luciferase activity in the cells that transfected the construct containing C allele, compared with T allele, which had not happened in the presence of other miRNAs selected. These data indicate that through upregulating the expression of caspase-3, the TT genotype of caspase-3 rs1049216 can be associated with not only the risk of cervical cancer but also the progression of this cancer.

  9. Human papillomavirus cervical infection and associated risk factors in a region of Argentina with a high incidence of cervical carcinoma.

    PubMed Central

    Tonon, S A; Picconi, M A; Zinovich, J B; Liotta, D J; Bos, P D; Galuppo, J A; Alonio, L V; Ferreras, J A; Teyssié, A R

    1999-01-01

    OBJECTIVE: To assess the prevalence and potential risk factors associated with human papillomavirus (HPV) cervical infection among women residing in a region of northeastern Argentina with a high incidence of cervical cancer. METHODS: A case-control study of 330 women participating in a cervical cytological screening program conducted in Posadas city, Misiones, Argentina, from February 1997 to November 1998 was carried out. Standardized questionnaires were administered, and clinical examination including colposcopy was performed. Fresh endocervical specimens for HPV DNA detection by generic polymerase chain reaction were collected and the products typed by dot-blot hybridization. RESULTS: Human papillomavirus DNA was found in 61% of samples analyzed (185/301). Samples with normal cytology had a 43% infection rate (85/199), while those classified as low-grade squamous intraepithelial lesion, high-grade squamous intraepithelial lesion, and invasive cervical carcinoma had an infection rate of 96% (53/55), 100% (29/29), and 100% (18/18), respectively. Human papillomavirus typing showed a 64% (118/185) prevalence of type 16 among all the infected population analyzed; type 16 was detected among 49% (42/85) of infected samples with normal cytology and in an average of 74% (74/100) with abnormal cytology. Sexual behavior, residence in southern Paraguay, and history of a previous sexually transmitted diseases were the main risk factors associated with high-grade cervical lesions. CONCLUSIONS: An elevated prevalence of HPV infection was detected in this population, which also has a high incidence of cervical cancer. The broad distribution of high-risk HPV type 16 in women with normal cytology and colposcopy suggests that viral infection is an important determinant of regional cancer incidence. PMID:10524669

  10. ZEB1 promotes the progression and metastasis of cervical squamous cell carcinoma via the promotion of epithelial-mesenchymal transition

    PubMed Central

    Ma, Yihui; Zheng, Xiangyu; Zhou, Jun; Zhang, Ying; Chen, Kuisheng

    2015-01-01

    Objective: The process of epithelial-mesenchymal transition (EMT) clearly contributes to cancer metastasis. The aim of this study was to investigate the expression of the EMT-related transcription repressor ZEB1 and the expression of EMT-associated markers (E-cadherin, β-catenin and N-cadherin) in cervical squamous cell carcinoma. In addition, the role of ZEB1 and these EMT-associated markers in the progression and metastasis of cervical squamous cell carcinoma was explored. Methods: The expression of ZEB1, E-cadherin, β-catenin and N-cadherin was evaluated in 81 specimens of cervical squamous cell carcinoma by immunohistochemistry; the clinicopathological significance of these markers was then analyzed. Results: 1) Of the 81 samples, 37 cases (45.7%) were positive for ZEB1, and nuclear expression of ZEB1 in tumor cells was positively associated with the differentiation status of the tumor tissue (P < 0.05), vascular invasion (P < 0.05) and lymph node metastasis (P < 0.05). 2) The loss of E-cadherin and β-catenin expression in tumor cells and the acquisition of N-cadherin expression were positively associated with the differentiation status of the tumor tissue (P < 0.05) and with the occurrence of vascular invasion (P < 0.05). 3) A significant negative correlation was observed between ZEB1 and E-cadherin expression (Spearman = -0.636, P < 0.05) and between ZEB1 and β-catenin expression (Spearman = -0.417, P < 0.05). Moreover, a significant positive correlation was observed between ZEB1 and N-cadherin expression (Spearman = 0.557, P < 0.05). Conclusions: These results emphasize the role of EMT in cervical squamous cell carcinoma. The upregulation of ZEB1 is associated with the abnormal expression of E-cadherin, β-catenin and N-cadherin, which might promote the progression and metastasis of cervical squamous cell carcinoma. PMID:26617850

  11. Human papilloma virus and cervical preinvasive disease

    PubMed Central

    Bari, M; Iancu, G; Popa, F

    2009-01-01

    Cervical cancer lesions represent a major threat to the health of the women worldwide. Human Papillomavirus (HPV) is responsible for 99.7% of cervical cancer cases, the infectious etiology giving the possibility of preventing cervical cancer by vaccination. The most aggressive HPV types are 16 and 18, which cause about 70% of cases of invasive cancer. The vaccination is recommended to the girls aged 11–12. The diagnosis and the treatment of cervical preinvasive disease allow the doctor to prevent the development of the invasive disease. PMID:20108750

  12. Increased expression of the retinoic acid-metabolizing enzyme CYP26A1 during the progression of cervical squamous neoplasia and head and neck cancer.

    PubMed

    Osanai, Makoto; Lee, Gang-Hong

    2014-10-07

    Retinoic acid (RA) is a critical regulator of cell differentiation, proliferation, and apoptosis in various cell types. Recently, the RA-metabolizing enzyme CYP26A1 (cytochrome P450, family 26, subfamily A, polypeptide 1) has been shown to have an oncogenic function in breast carcinogenesis. However, the relevance of elevated CYP26A1 expression in human cancers remains to be clarified. We immunohistochemically examined the expression of CYP26A1 in cervical squamous cell carcinoma (SCC) and its precursors, including low- and high-grade squamous intraepithelial lesions (LSIL and HSIL, respectively), as well as head and neck cancer (HNC). The association between CYP26A1 expression and a number of clinicopathological parameters was also evaluated. CYP26A1 was not expressed in normal cervical epithelium. CYP26A1 expression was present in LSIL but limited to basal and parabasal cells. HSIL cases exhibited strong nuclear expression of CYP26A1 and mixed cytoplasmic expression patterns with widely distributed expression toward the epithelial surface. Importantly, strong cytoplasmic staining of CYP26A1 was observed in 19 of 50 (38%) patients with cervical SCC. Elevated expression of CYP26A1 was significantly associated with younger age (<50 years) and lymph node involvement (pN). Similarly, CYP26A1 was not expressed in non-neoplastic tissues of the head and neck, but strong cytoplasmic staining of CYP26A1 was observed in 52 of 128 (41%) HNC cases. Such strong CYP26A1 expression was significantly associated with the primary tumor stage of carcinomas (pT) and the pathological tumor-node-metastasis (pTNM) stage in HNC. Our results indicated an elevated CYP26A1 expression in malignant and precancerous dysplastic lesions of the human cervix, which also increased with the progression of cervical squamous neoplasia. In addition, this report is the first to demonstrate the increased expression of CYP26A1 in HNC and its significant correlation with primary tumor growth. These data

  13. Prevalence of cervical neoplastic lesions and Human Papilloma Virus infection in Egypt: National Cervical Cancer Screening Project.

    PubMed

    el-All, Howayda S Abd; Refaat, Amany; Dandash, Khadiga

    2007-07-04

    Data from Egyptian studies provide widely varying estimates on the prevalence of pre-malignant and malignant cervical abnormalities and human papilloma virus (HPVs) infection. To define the prevalence and risk factors of pre-invasive and invasive cervical cancer (cacx), a community based full-scale cross sectional, household survey including 5453 women aged between 35 and 60 years was conducted. The study period was between February 2000 and December 2002. Initially, conventional Papanicolaou (Pap) smears were evaluated using the Bethesda system (TBS), followed by colposcopic guided biopsy (CGB) for all epithelial abnormalities (EA). In a third step, HPV was tested on all EA by in-situ hybridization (ISH) using first the broad spectrum HPV probe recognizing HPVs 6, 11, 16, 18, 30, 31, 35, 45, 51 and 52 followed by subtyping with probes 6/11, 16/18 and 31/33. Lastly, unequivocal cases were immunostained for herpes simplex type-2 (HSV-2), cytomegalovirus (CMV), and human immunodeficiency virus (HIV). EA representing 7.8% (424/5453), were categorized into atypical squamous cell of undetermined significance (ASCUS) (34.4%), atypical glandular cell of undetermined significance (AGCUS) (15.3%), combined ASCUS and AGCUS (3.1%), low grade squamous intraepithelial lesions (SIL) (41.0%), high grade SIL (5.2%) and invasive lesions (1%). CGB of EA (n = 281) showed non neoplastic lesions (12.8%), atypical squamous metaplasia (ASM) (19.2%), cervical intraepithelial neoplasia I (CIN) (44.4%), CIN II (4.4%), CINIII (2.8%), endocervical lesions (5.2%), combined squamous and endocervical lesions (10.0%), invasive squamous cell carcinoma (SCC) (0.02%) and extranodal marginal zone B cell lymphoma (MZBCL) (0.02%). The overall predictive value of cytology was 87% while the predictive value for high grade lesions was 80%. On histological basis, HPVs were present in 94.3% of squamous lesions while it was difficult to be identified in endocervical ones. ISH revealed positivity for pan HPV

  14. Human Papilloma Virus Associated Squamous Cell Carcinoma of the Head and Neck

    PubMed Central

    Ajila, Vidya; Shetty, Harish; Babu, Subhas; Shetty, Veena; Hegde, Shruthi

    2015-01-01

    Oral cancer is one of the commonest causes for mortality and morbidity with squamous cell carcinoma being the sixth most frequent malignant tumour worldwide. In addition to tobacco and alcohol, human papilloma virus (HPV) is associated with a proportion of head and neck cancers. As in cervical cancers, HPV types 16 and 18 are the cause of malignant transformation. HPV-positive cancers of head and neck have unique characteristics such as occurrence in a younger age group, distinct clinical and molecular features, and better prognosis as compared to HPV-negative carcinomas. They also possess the potential for prevention by using vaccination. The present review describes in detail the salient features of HPV associated oral squamous cell carcinoma (OSCC), its differences from HPV-negative OSCC, diagnostic features, and recent strategies in prevention and management. PMID:26483987

  15. Expression of the p16 and Ki67 in Cervical Squamous Intraepithelial Lesions and Cancer.

    PubMed

    Kanthiya, Kanjana; Khunnarong, Jakkapan; Tangjitgamol, Siriwan; Puripat, Napaporn; Tanvanich, Sujitra

    2016-01-01

    To evaluate the expression of p16 and Ki67 in cervical intraepithelial neoplasia (CIN) and cancer. We performed a immunohistochemical study of p16 and Ki67 in 243 cervical tissues 53 nondysplastic lesions, 106 CIN1, 61 CIN2/3 and 23 squamous cell carcinomas. The expression of p16 and Ki67 was interpreted independently by 2 researchers and the sensitivity and specificity to detect clinically significant lesions (≥ CIN2) were determined. The overall agreement results of positive or negative immunostaining of intrainter observer variability were 0.659 for p16 and 0.808 for Ki67. p16 expression was demonstrated in 91.3% of invasive carcinomas, 78.7% of CIN2/3, 10.4% of CIN1 and 9.4% of nondysplasic lesions. The corresponding Ki67 expression was: 100% of all invasive carcinomas, 75.4% of CIN2/3, 22.6% of CIN1, and 11.3% with nondysplasia. The expression was significantly different between CIN2/3 vs CIN1 for both p16 and Ki67 (pvalues <0.001 both), and cancer vs CIN2/3 for Ki67 (pvalue 0.008). The differences were not significant between CIN1 vs nondysplasia (pvalues 1.000 for p16 and 0.130 of Ki67), and cancer vs CIN2/3 for p16 (p value 0.219). The sensitivity and specificity to detect > CIN2 were 84.5% and 90.5% by p16 and 82.1% and 88.6% by Ki67. The rates for 16 and Ki67 expression were directly associated with the severity of cervical lesions. Significant differences in these markers expression may be useful in cases with equivocal histologic features among cervical intraepithelial lesions, but not between CIN1 and nondysplastic lesions. The two markers had high sensitivity and specificity in determining >CIN2.

  16. Identification of host transcriptional networks showing concentration-dependent regulation by HPV16 E6 and E7 proteins in basal cervical squamous epithelial cells

    PubMed Central

    Smith, Stephen P.; Scarpini, Cinzia G.; Groves, Ian J.; Odle, Richard I.; Coleman, Nicholas

    2016-01-01

    Development of cervical squamous cell carcinoma requires increased expression of the major high-risk human-papillomavirus (HPV) oncogenes E6 and E7 in basal cervical epithelial cells. We used a systems biology approach to identify host transcriptional networks in such cells and study the concentration-dependent changes produced by HPV16-E6 and -E7 oncoproteins. We investigated sample sets derived from the W12 model of cervical neoplastic progression, for which high quality phenotype/genotype data were available. We defined a gene co-expression matrix containing a small number of highly-connected hub nodes that controlled large numbers of downstream genes (regulons), indicating the scale-free nature of host gene co-expression in W12. We identified a small number of ‘master regulators’ for which downstream effector genes were significantly associated with protein levels of HPV16 E6 (n = 7) or HPV16 E7 (n = 5). We validated our data by depleting E6/E7 in relevant cells and by functional analysis of selected genes in vitro. We conclude that the network of transcriptional interactions in HPV16-infected basal-type cervical epithelium is regulated in a concentration-dependent manner by E6/E7, via a limited number of central master-regulators. These effects are likely to be significant in cervical carcinogenesis, where there is competitive selection of cells with elevated expression of virus oncoproteins. PMID:27457222

  17. Identification of host transcriptional networks showing concentration-dependent regulation by HPV16 E6 and E7 proteins in basal cervical squamous epithelial cells.

    PubMed

    Smith, Stephen P; Scarpini, Cinzia G; Groves, Ian J; Odle, Richard I; Coleman, Nicholas

    2016-07-26

    Development of cervical squamous cell carcinoma requires increased expression of the major high-risk human-papillomavirus (HPV) oncogenes E6 and E7 in basal cervical epithelial cells. We used a systems biology approach to identify host transcriptional networks in such cells and study the concentration-dependent changes produced by HPV16-E6 and -E7 oncoproteins. We investigated sample sets derived from the W12 model of cervical neoplastic progression, for which high quality phenotype/genotype data were available. We defined a gene co-expression matrix containing a small number of highly-connected hub nodes that controlled large numbers of downstream genes (regulons), indicating the scale-free nature of host gene co-expression in W12. We identified a small number of 'master regulators' for which downstream effector genes were significantly associated with protein levels of HPV16 E6 (n = 7) or HPV16 E7 (n = 5). We validated our data by depleting E6/E7 in relevant cells and by functional analysis of selected genes in vitro. We conclude that the network of transcriptional interactions in HPV16-infected basal-type cervical epithelium is regulated in a concentration-dependent manner by E6/E7, via a limited number of central master-regulators. These effects are likely to be significant in cervical carcinogenesis, where there is competitive selection of cells with elevated expression of virus oncoproteins.

  18. Retracted: Worst Pattern Of Invasion and occult cervical metastases for oral squamous carcinoma.

    PubMed

    Velosa, Claudia; Shi, Qiuying; Stevens, Todd M; Chiosea, Simion I; Purgina, Bibiana; Carroll, William; Rosenthal, Eben; Morlandt, Anthony; Loree, Thom; Brandwein-Weber, Margaret S

    2017-03-28

    The above article, published online in Wiley Online Library as the Version of Record on March 28, 2017 (doi 10.1002/hed.24754), has been retracted by agreement between the Editor-in-Chief, Ehab Y. Hanna, and Wiley Periodicals, Inc. The retraction has been agreed owing to a dispute as to authorship and inclusion of some data in the analysis. Velosa, C., Shi, Q., Stevens, T. M., Chiosea, S. I., Purgina, B., Carroll, W., Rosenthal, E., Morlandt, A., Loree, T. and Brandwein-Weber, M. S. (2017), Worst pattern of invasion and occult cervical metastases for oral squamous carcinoma. Head Neck. doi:10.1002/hed.24754. © 2017 Wiley Periodicals, Inc.

  19. Sexual and reproductive risk factors for invasive squamous cell cervical cancer.

    PubMed

    Brinton, L A; Hamman, R F; Huggins, G R; Lehman, H F; Levine, R S; Mallin, K; Fraumeni, J F

    1987-07-01

    A case-control study of 418 women with invasive squamous cell cervical cancer and 704 population controls enabled evaluation of risk factors for this relatively rare cancer. Consistent with an infectious etiology was a pronounced effect of multiple sexual partners, with those reporting 10 or more partners being at a significant threefold excess risk. Early first intercourse also was associated with some residual effect on risk, although the relationship was not linear, nor the explanation readily apparent. Those with multiple births were at significantly elevated risks, even after adjustment for sexual parameters. Menstrual and hygiene factors, including use of tampons, vaginal deodorants, and douching products, were not consistently related to risk. Histories of specific infections involving the genital tract were poor predictors of risk, since few women provided positive responses, but those with nonspecific diseases were at a significant twofold excess risk.

  20. Atezolizumab and Bevacizumab in Treating Patients With Recurrent, Persistent, or Metastatic Cervical Cancer

    ClinicalTrials.gov

    2017-09-28

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Recurrent Cervical Carcinoma; Stage IV Cervical Cancer; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer

  1. Bevacizumab, Radiation Therapy, and Cisplatin in Treating Patients With Previously Untreated Locally Advanced Cervical Cancer

    ClinicalTrials.gov

    2014-09-22

    Cervical Adenocarcinoma; Cervical Adenosquamous Cell Carcinoma; Cervical Squamous Cell Carcinoma; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer

  2. Prevalence of human papillomavirus genotypes among women with cervical lesions in the Shaanxi Province of China.

    PubMed

    Li, J; Wang, Y Y; Nan, X; Tian, X F; Yan, T; Wang, P; Yin, Y; Liu, Y; Yuan, R; Wang, G Q; Fu, Y L

    2016-03-31

    This study aimed to investigate human papilloma virus (HPV) genotypes among women with cervical lesions in Shaanxi Province, China, to obtain information regarding cervical lesion prevention and treatment. The study included 4508 HPV-positive subjects; cervical swab specimens were collected and tested for HPV infection status and HPV genotypes using polymerase chain reaction and reverse dot-blot hybridization. Women positive for HPV with cervical lesions, including chronic cervicitis, cervical intraepithelial neoplasia, and cervical squamous cell carcinoma (SCC), were examined; HPV-positive women with no cervical lesions were controls. Data were pooled and weighted estimates have been presented. For women with no cervical lesions and positive for one HPV genotype, HPV 52, 16, 58, 81, 33, and 56 were the most common; for multiple-HPV genotype infection, HPV 16, 52, 6, 18, 58, and 66 were the most common. Collectively, HPV 16, 58, 52, 18, 33, and 81 were the most common in women with cervical lesions. HPV 16 comprised 26.71% of single-genotype and 15.64% of multiple-genotype infections. The proportion of HPV-16-positive cases was 29.15%, which was the highest among all HPV genotypes (P < 0.01). Single-HPV genotype infection was the most common in cervical HPV infection (77.48%); infection with two HPV genotypes comprised 72.22% of multiple-genotype infections. The proportion of single-low-risk HPV genotype infections decreased with increase in cervical lesion severity; there were no single- or multiple-low-risk genotype HPV infections in cervical SCC patients. The proportion of multiple-genotype HPV infections with at least one high-risk genotype increased with cervical lesion severity.

  3. The Level of Squamous Cell Carcinoma Antigen and Lymph Node Metastasis in Locally Advanced Cervical Cancer.

    PubMed

    Lekskul, Navamol; Charakorn, Chuenkamon; Lertkhachonsuk, Arb-Aroon; Rattanasiri, Sasivimol; Israngura Na Ayudhya, Nathpong

    2015-01-01

    This study aimed to determine the utility and a cut-off level of serum squamous cell carcinoma antigen (SCC-Ag) to predict lymph node metastasis in locally advanced cervical cancer cases. We also investigated the correlation between SCC-Ag level and lymph node status. From June 2009 to June 2014, 232 patients with cervical cancer stage IB2-IVA, who were treated at Ramathibodi Hospital, were recruited. Receiver operating characteristic (ROC) curves were used to identify the best cut-off point of SCC-Ag level to predict lymph node metastasis. Quantile regression was performed to evaluate the correlation between SCC-Ag levels and pelvic lymph node metastasis, paraaortic lymph node metastasis, and parametrial involvement as well as tumor size. Pelvic lymph node metastasis and paraaortic lymph node metastasis were diagnosed in 46.6% and 20.1% of the patients, respectively. The median SCC-Ag level was 6 ng/mL (range, 0.5 to 464.6 ng/ mL). The areas under ROC curves between SCC-Ag level and pelvic lymph node metastasis, paraaotic lymph node metastasis, parametrial involvements were low. SCC-Ag level was significantly correlated with paraaortic lymph node status (p=0.045) but not with pelvic lymph node status and parametrial involvement. SCC-Ag level was also related to the tumor diameter (p<0.05). SCC-Ag level is not a good predictor for pelvic and paraaortic lymph node metastasis. However, it is still beneficial to assess the tumor burden of squamous cell carcinoma of the cervix.

  4. Effect of human papillomavirus vaccination on cervical cancer screening in Alberta

    PubMed Central

    Kim, Jong; Bell, Christopher; Sun, Maggie; Kliewer, Gordon; Xu, Linan; McInerney, Maria; Svenson, Lawrence W.; Yang, Huiming

    2016-01-01

    Background: A school-based program with quadrivalent human papillomavirus (HPV) vaccination was implemented in Alberta in 2008. We assessed the impact of this program on Pap test cytology results using databases of province-wide vaccination and cervical cancer screening. Methods: We conducted a nested case–control study involving a cohort of women in Alberta born between 1994 and 1997 who had at least 1 Pap test between 2012 and 2015. Women with negative cytology results were controls. Women with low-grade (atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion) and high-grade (atypical squamous cells, cannot rule out a high-grade lesion; or high-grade squamous intraepithelial lesion) cervical abnormalities were cases. Exposure status was assigned according to records of HPV vaccination. Odds ratios (ORs) for abnormal cytology results by vaccination status were adjusted for neighbourhood income, laboratory service, rural versus urban residency, and age. Results: The total study population was 10 204. Adjusting for age, vaccinated women had a higher screening rate than unvaccinated women (13.0% v. 11.4%, p < 0.001). Among women who received full vaccination (≥ 3 doses), the adjusted OR for cervical abnormalities was 0.72 (95% confidence interval [CI] 0.63–0.82). For high-grade lesions, the adjusted OR was 0.50 (95% CI 0.30–0.85). With 2-dose HPV vaccination, the adjusted OR for cervical abnormalities was 1.08 (95% CI 0.84–1.38). Interpretation: Quadrivalent HPV vaccination significantly reduced high-grade cervical abnormalities but required 3 doses. Vaccination against HPV was associated with screening uptake. Population-based vaccination and screening programs should work together to optimize cervical cancer prevention. PMID:27378467

  5. Primary Squamous Cell Carcinoma of the Upper Genital Tract: Utility of p16INK4a Expression and HPV DNA Status in its Differential Diagnosis from Extended Cervical Squamous Cell Carcinoma

    PubMed Central

    Yoo, Su Hyun; Son, Eun-Mi; Sung, Chang Okh

    2013-01-01

    Background Primary squamous cell carcinoma (SCC) of the upper genital tract, including the endometrium, fallopian tubes, and ovaries, is extremely rare. It must be distinguished from the mucosal extension of primary cervical SCC because determination of the primary tumor site is important for tumor staging. However, patients with SCC of the fallopian tubes or ovarian surface have often undergone prior hysterectomy with inadequate examination of the cervix, making it difficult to determine the primary site. Methods We compared histologic findings, p16INK4a expression, and human papillomavirus (HPV) DNA status in four patients with primary SCC of the upper genital tract and five patients with primary cervical SCC extending to the mucosa of the upper genital tract. Results All five SCCs of cervical origin showed strong expression of p16INK4a, whereas all four SCCs of the upper genital tract were negative, although one showed weak focal staining. Three of the five cervical SCCs were positive for HPV16 DNA, whereas all four primary SCCs of the upper genital tract were negative for HPV DNA. Conclusions Although a thorough histological examination is important, immunonegativity for p16INK4a and negative for HPV DNA may be useful adjuncts in determining primary SCCs of the upper genital tract. PMID:24421848

  6. Cervical nodal metastases in squamous cell carcinoma of the head and neck: what to expect.

    PubMed

    Mukherji, S K; Armao, D; Joshi, V M

    2001-11-01

    The treatment and management of malignancies of the head and neck is directly altered by the presence of metastatic cervical adenopathy. The treatment of nodal metastases in squamous cell carcinoma of the head and neck (HNSCCA) is determined by the lymphatic drainage of the upper aerodigestive tract. The lymphatic drainage is site-specific and occurs in a predictable manner. The purpose of this text is to provide an overview of the normal routes of lymphatic drainage in the head and neck and correlate this with the current nodal classification system. The specific aims of this manuscript are to 1) illustrate the expected lymphatic drainage patterns of HNSCCA arising in the different subsites (nasopharynx, oropharynx, oral cavity, larynx, and hypopharynx) and 2) review the expected frequency of metastases within nodal groups for HNSCCA that arise in these locations. An understanding of the topographical distribution and incidence of cervical lymph node metastases plays an integral role in the physical examination and radiological evaluation of patients with HNSCCA. For the neuroradiologist, this information may increases the ability to identify those nodal groups at risk for metastatic involvement. Copyright 2001 John Wiley & Sons, Inc. Head Neck 23: 995-1005, 2001.

  7. Early determination of uterine cervical squamous cell carcinoma radioresponse identifies high- and low-response tumors

    SciTech Connect

    Ohara, Kiyoshi . E-mail: ki-ohara@md.tsukuba.ac.jp; Oki, Akinori; Tanaka, Yumiko Oishi; Onishi, Kayoko; Fukumitsu, Nobuyoshi; Hashimoto, Takayuki; Satoh, Toyomi; Tsunoda, Hajime; Hata, Masaharu; Sugahara, Shinji; Tokuuye, Koichi; Akine, Yasuyuki; Yoshikawa, Hiroyuki

    2006-03-15

    Purpose: To investigate whether early-assessed radioresponse of tumors corresponds with late-assessed radioresponse, which is associated with local disease control in radiotherapy (RT) for cervical cancer. Methods and Materials: This prospective study included 12 patients with cervical squamous cell carcinoma treated by RT with or without concurrent cisplatin. Tumor volume was estimated by scheduled magnetic resonance imaging before (preRT), 3 to 4 weeks after (early assessment), and 6 to 7 weeks after (late assessment) RT initiation. Radioresponse was assessed with tumor shrinkage curves based on these volumes. Radioresponse for each tumor was calculated as the slope (day{sup -1}) of the shrinkage curve by fitting to an exponential equation. Results: Early-assessed radioresponse ranged from 0.001 to 0.106 day{sup -1} (median, 0.021 day{sup -1}) and late-assessed radioresponse from 0.009 to 0.091 day{sup -1} (median, 0.021 day{sup -1}), with no significant difference between them (p = 0.1191). The early-assessed radioresponse correlated with the late-assessed radioresponse (R {sup 2} = 0.714, p = 0.0005). Conclusions: Correspondence between early- and late-assessed radioresponse in a series of tumors showing a wide range of radioresponse was not particularly close overall. However, early assessment of radioresponsiveness did seem to be useful for characterizing those tumors with high or low radioresponsiveness.

  8. Oral contraceptives, human papillomavirus and cervical cancer.

    PubMed

    La Vecchia, Carlo; Boccia, Stefania

    2014-03-01

    Oncogenic human papillomavirus is the key determinant of cervical cancer, but other risk factors interact with it to define individual risk. Among these, there is oral contraceptive (OC) use. A quantitative review of the link between OCs and cervical cancer was performed. Long-term (>5 year) current or recent OC use has been related to an about two-fold excess risk of cervical cancer. Such an excess risk, however, levels off after stopping use, and approaches unity 10 or more years after stopping. The public health implications of OC use for cervical cancer are limited. In any case, such implications are greater in middle-income and low-income countries, as well as in central and eastern Europe and Latin America, where cervical cancer screening and control remain inadequate.

  9. Human papillomavirus genotypes in cervical intraepithelial neoplasia grade 3.

    PubMed

    Castle, Philip E; Schiffman, Mark; Wheeler, Cosette M; Wentzensen, Nicolas; Gravitt, Patti E

    2010-07-01

    There are few large case series describing the human papillomavirus (HPV) genotypes found in women diagnosed with rigorously reviewed cervical intraepithelial neoplasia grade 3 (CIN3), cervical precancer. The Atypical Squamous Cells of Undetermined Significance (ASCUS) and Low-Grade Squamous Intraepithelial Lesion (LSIL) Triage Study (ALTS) was a clinical trial to evaluate the best management strategies for women with equivocal (ASCUS) or mildly abnormal (LSIL) Pap tests. During enrollment and the 2-year follow-up, 608 women had a histopathologic diagnosis of CIN3 and PCR-based HPV genotyping results on cervical specimens. The genotyping results were ranked hierarchically according to cancer risk: HPV16 > other carcinogenic HPV > noncarcinogenic HPV > PCR negative. Among the 608 women diagnosed with CIN3, 601 (98.8%) cases were positive for any HPV genotype and 95.4% for any carcinogenic HPV. HPV16 (59.9%), HPV31 (18.1%), HPV52 (14.8%), HPV51 (14.0%), and HPV18 (13.2%) were the five most common HPV genotypes detected. Younger age, consensus histologic confirmation, smoking, and multiparity increased the likelihood of testing HPV 16 positive. Specifically, HPV16-positive CIN3 occurred at a younger age than CIN3 positive for other carcinogenic HPV genotypes (median of 23.5 years versus 25 years, respectively; P = 0.0003, Kruskal-Wallis). HPV16-positive CIN3 was more commonly diagnosed in younger women (versus older women), with consensus diagnosis (versus some disagreement between reviewers), and in smokers (versus nonsmokers), and was less commonly diagnosed in multiparous women compared CIN3 positive for other carcinogenic HPV genotypes. In populations vaccinated against HPV16 (and HPV18), the median age of CIN3 in women with ASCUS and LSIL cytology should shift to older ages, possibly permitting later age at first screening.

  10. Human Papillomavirus Vaccination and Cervical Cytology Outcomes Among Urban Low-Income Minority Females.

    PubMed

    Hofstetter, Annika M; Ompad, Danielle C; Stockwell, Melissa S; Rosenthal, Susan L; Soren, Karen

    2016-05-01

    The quadrivalent human papillomavirus (HPV) vaccine was licensed for use in 9- through 26-year-old females in 2006. Postlicensure studies in Australia, Denmark, and Canada have demonstrated vaccine effectiveness against abnormal cervical cytology results. However, there are limited data describing postlicensure effectiveness in the United States, particularly among minority females at higher risk for HPV infection and cervical cancer. To examine the effect of HPV vaccination on abnormal cervical cytology results among minority females. Retrospective cohort study conducted between January 2007 and January 2014 at 16 academically affiliated community clinics serving a low-income minority population. Included in this study was a population-based sample of 16 266 females aged 11 through 20 years as of January 1, 2007, who received care at a participating clinic on or after that date. Human papillomavirus vaccination, stratified by the number of doses. Cervical cytology abnormality following either HPV vaccination or, if unvaccinated, the first missed opportunity for HPV vaccination after January 1, 2007. Abnormalities were defined as atypical glandular cells, atypical squamous cells of undetermined significance, atypical squamous cells, cannot exclude a high-grade squamous intraepithelial lesion, low-grade squamous intraepithelial lesions, or high-grade squamous intraepithelial lesions. There were 4127 female patients who initiated quadrivalent HPV vaccination or had their first missed HPV vaccination opportunity from 11 through 20 years of age and underwent subsequent cervical cytology screening. The patients were primarily Spanish speaking (n = 2297; 58.3%) and publicly insured (n = 3801; 92.1%). The detection rate for an abnormal cervical cytology result during the observation period was lower among vaccinated (≥1 dose) (79.1 per 1000 person-years) vs unvaccinated (125.7 per 1000 person-years) females. The risk for an abnormal cervical cytology result

  11. Human papillomavirus (HPV) and oropharyngeal squamous cell carcinoma.

    PubMed

    Dalianis, Tina

    2014-12-01

    Numerous reports in recent decades have shown that, in addition to smoking and alcohol, human papillomavirus (HPV) is also associated with the development of oropharyngeal squamous cell carcinoma (OPSCC), predominantly in the tonsils and base of the tongue. In 2007, the International Agency on Research against Cancer (IARC) therefore declared HPV to be a risk factor for OPSCC and noted that 80% of those affected are men. In addition, patients with HPV-positive OPSCC, in particular never-smokers, have a much better clinical response to therapy than patients with HPV-negative OPSCC and other head and neck cancers. Most patients with HPV-positive OPSCC may thus not need the increasingly intensive chemo-radiotherapy currently administered today to most patients with head neck cancers and associated with many adverse effects. Furthermore, an increase in the incidence of OPSCC has been observed in many western countries, accompanied by a rise in the proportion of HPV-positive tumors. Patients with HPV-positive OPSCC, like those with cervical cancer, more often have an earlier sexual debut and have more sexual partners. It has therefore been proposed that the increased incidence of OPSCC observed might be due to an epidemic of sexually transmitted HPV. The important issues today regarding this growing cohort of patients with HPV-positive OPSCC are therefore individualized treatment and prevention. More specifically, selected HPV-positive OPSCC patients with biomarkers of good prognosis might be included in randomized trials with less intensive treatment. HPV vaccination should also be considered for boys, in addition to the current recommendations for immunization of girls.

  12. Induction of Human Squamous Cell-Type Carcinomas by Arsenic

    PubMed Central

    Martinez, Victor D.; Becker-Santos, Daiana D.; Vucic, Emily A.; Lam, Stephen; Lam, Wan L.

    2011-01-01

    Arsenic is a potent human carcinogen. Around one hundred million people worldwide have potentially been exposed to this metalloid at concentrations considered unsafe. Exposure occurs generally through drinking water from natural geological sources, making it difficult to control this contamination. Arsenic biotransformation is suspected to have a role in arsenic-related health effects ranging from acute toxicities to development of malignancies associated with chronic exposure. It has been demonstrated that arsenic exhibits preference for induction of squamous cell carcinomas in the human, especially skin and lung cancer. Interestingly, keratins emerge as a relevant factor in this arsenic-related squamous cell-type preference. Additionally, both genomic and epigenomic alterations have been associated with arsenic-driven neoplastic process. Some of these aberrations, as well as changes in other factors such as keratins, could explain the association between arsenic and squamous cell carcinomas in humans. PMID:22175027

  13. Cervical lymph node metastases and T1 squamous cell carcinoma of the lips.

    PubMed

    Bon-Mardion, N; De Raucourt, D; Babin, E; Rame, J P; Dehesdin, D; Choussy, O

    2015-01-01

    The occurrence of cervical lymph node metastasis is a major prognostic factor for head and neck squamous cell carcinoma (SCC) of the lip. This study focuses on patients with T1 stage tumours,in order to describe the prevalence of metastatic lymphadenopathies. A multicenter retrospective study was performed in three tertiary care referral centers and included 59 patients surgically treated for T1 stage SCC of the lips from January 1996 to December 2006. This surgical treatment concerned the tumour, with cervical neck dissection when lymph node metastasis was suspected. Cervical lymph node metastasis was found and histologically proven in 7 patients (11.9% of the cases, pN+ group; 95% confidence interval, 3.6 to 20.2%) during follow-up, never at the time of diagnosis. Metastasis appeared 13.3 ± 7.9 months (min. 5.3 months, max. 29.1 months) after the initial treatment and involved the IB level in all cases. Tumour progression was significantly longer in the pN+ group compared to patients with no lymph node metastases (sN-group). The pN+ group also had a significantly higher proportion of poorly or moderately differentiated tumours, and a significant decrease in overall survival, disease-free survival, and disease-specific survival. Lymph node metastasis occurs in roughly 12% of T1 stage SCC of the lips, and the management of neck lymph node areas is necessary. A randomized trial is needed to determine the proportion of occult lymph node metastases in T1N0 patients and the impact of this therapeutic procedure on survival.

  14. Galectin-1, -3 and -9 Expression and Clinical Significance in Squamous Cervical Cancer.

    PubMed

    Punt, Simone; Thijssen, Victor L; Vrolijk, Johannes; de Kroon, Cornelis D; Gorter, Arko; Jordanova, Ekaterina S

    2015-01-01

    Galectins are proteins that bind β-galactoside sugars and provide a new type of potential biomarkers and therapeutic targets in cancer. Galectin-1, -3 and -9 have become the focus of different research groups, but their expression and function in cervical cancer is still unclear. The aim of this study was to determine the phenotype of galectin-1, -3 and -9 expressing cells and the association with clinico-pathological parameters in cervical cancer. Galectin expression was scored in tumor cells, tumor epithelium infiltrating immune cells and stromal cells in squamous cervical cancer (n = 160). Correlations with clinico-pathological parameters and survival were studied according to the REMARK recommendations. We additionally investigated whether the galectins were expressed by tumor cells, fibroblasts, macrophages and T cells. Galectin-1 and -9 were both expressed by tumor cells in 11% of samples, while 84% expressed galectin-3. Strong galectin-1 expression by tumor cells was an independent predictor for poor survival (hazard ratio: 8.02, p = 0.001) and correlated with increased tumor invasion (p = 0.032) and receiving post-operative radiotherapy (p = 0.020). Weak and positive tumor cell galectin-3 expression were correlated with increased and decreased tumor invasion, respectively (p = 0.012). Tumor cell expression of galectin-9 showed a trend toward improved survival (p = 0.087). The predominant immune cell type expressing galectin-1, -3 and -9 were CD163+ macrophages. Galectin-1 and -3 were expressed by a minor population of T cells. Galectin-1 was mainly expressed by fibroblasts in the tumor stroma. To conclude, while tumor cell expression of galectin-9 seemed to represent a beneficial response, galectin-1 expression might be used as a marker for a more aggressive anti-cancer treatment.

  15. Galectin-1, -3 and -9 Expression and Clinical Significance in Squamous Cervical Cancer

    PubMed Central

    Punt, Simone; Thijssen, Victor L.; Vrolijk, Johannes; de Kroon, Cornelis D.; Gorter, Arko; Jordanova, Ekaterina S.

    2015-01-01

    Galectins are proteins that bind β-galactoside sugars and provide a new type of potential biomarkers and therapeutic targets in cancer. Galectin-1, -3 and -9 have become the focus of different research groups, but their expression and function in cervical cancer is still unclear. The aim of this study was to determine the phenotype of galectin-1, -3 and -9 expressing cells and the association with clinico-pathological parameters in cervical cancer. Galectin expression was scored in tumor cells, tumor epithelium infiltrating immune cells and stromal cells in squamous cervical cancer (n = 160). Correlations with clinico-pathological parameters and survival were studied according to the REMARK recommendations. We additionally investigated whether the galectins were expressed by tumor cells, fibroblasts, macrophages and T cells. Galectin-1 and -9 were both expressed by tumor cells in 11% of samples, while 84% expressed galectin-3. Strong galectin-1 expression by tumor cells was an independent predictor for poor survival (hazard ratio: 8.02, p = 0.001) and correlated with increased tumor invasion (p = 0.032) and receiving post-operative radiotherapy (p = 0.020). Weak and positive tumor cell galectin-3 expression were correlated with increased and decreased tumor invasion, respectively (p = 0.012). Tumor cell expression of galectin-9 showed a trend toward improved survival (p = 0.087). The predominant immune cell type expressing galectin-1, -3 and -9 were CD163+ macrophages. Galectin-1 and -3 were expressed by a minor population of T cells. Galectin-1 was mainly expressed by fibroblasts in the tumor stroma. To conclude, while tumor cell expression of galectin-9 seemed to represent a beneficial response, galectin-1 expression might be used as a marker for a more aggressive anti-cancer treatment. PMID:26066796

  16. Human papillomavirus and cervical cancer.

    PubMed

    Crook, T; Farthing, A

    Cervical cancer is the fifth most common cancer worldwide, and is second only to breast cancer as the leading cause of cancer deaths in women. Half a million cases are diagnosed annually with the highest rates in developing countries.

  17. The Prevalence of Human Papillomavirus in Cervical Cancer in Iran.

    PubMed

    Mortazavi, SH; Zali, MR; Raoufi, M; Nadji, M; Kowsarian, P; Nowroozi, A

    2002-01-01

    Background: The human papiloma virus (HPV), which is sexually transmitted, and most commonly causes genital warts, has been linked to cervical intraepithelial neoplasia and invasive carcinoma. Of ninety plus types of HPV, HPV-16 is the most prevalent in cervical cancer, followed by HPV-18, and HPV-33. As HPV's implication has not been assessed in the Middle East the main focus of this retrospective study was to determine the prevalence of HPV -16,18, and 33 in cases of cervical cancer from Iran. Material and Methods: This retrospective study covered 100 patients with uterine cervical carcinomas who were referred to two referral centers for cancer in Tehran-Iran. Pathological blocks were collected for these cases and initial review of the blocks showed poor specimens in 18 cases, which left 82 cases for the study. These samples were histologically examined to verify the presence and the type of carcinoma. The next step was in situ hybridzation for the detection of HPV common DNA. In Situ hybridization was preformed on all samples. Finally, Polymerase Chain Reaction (PCR) was preformed for the HPV types 16, 18, and 33. PCR amplification of exon 5 of the p53 gene was used as an internal control for the integrity of DNA. Takara PCR Human papilloma Detection method was used which includes primer for HPV 16, 18, and 33. Three primers were used alone, or in combination, in order to increase the sensitivity of the detection. Results: The majority of tumors were squamous cell carcinomas (87%). The rest were adenosquamous carcinoma and adenocarcinomas. None of the 82 different cervical carcinoma tissue samples were found to be positive by in situ hybridization. In the PCR samples, amplification of DNA was observed for 69 tumor specimens. In the remainning13 cases, the DNA in fixed tissue was degraded, as verified by the absence of an internal control band (p53). Out of the total 69 tumors (85.5%) with adequate DNA contained HPV band on PCR. The majority (73.9%) of HPV

  18. Radiological detection of extracapsular spread in head and neck squamous cell carcinoma (HNSCC) cervical metastases.

    PubMed

    Url, C; Schartinger, V H; Riechelmann, H; Glückert, R; Maier, H; Trumpp, M; Widmann, G

    2013-10-01

    Extracapsular spread of cervical lymph nodes deteriorates the prognosis of patients with head and neck squamous cell carcinoma. Postoperative radiochemotherapy is superior to postoperative radiotherapy alone in patients with histologically proven extracapsular spread. If extracapsular spread can be detected preoperatively, patients may favor primary radiochemotherapy instead of primary surgery plus postoperative radiochemotherapy. Computed tomography (CT) scans of nodal positive head and neck squamous cell carcinoma patients treated between 2008 and 2010 with comprehensive neck dissection as part of first line surgical treatment were retrospectively scanned for extracapsular spread by two blinded radiologists. If a positive lymph node was identified by the pathologist, CT scans were assessed for extracapsular spread retrospectively. CT criteria for Extracapsular spread were apparent fat and soft tissue infiltration or infiltration of sternocleidomastoid muscle, internal jugular vein or carotid artery. Radiologic judgment was compared with histological evidence of extracapsular spread and specificity and sensitivity of CT detection was calculated. Forty-nine patients with histologically proven positive lymph nodes (pN+) were included. Extracapsular spread was histologically proven in 17 cases; the number of all affected lymph nodes was not listed. Radiologist 1 found extracapsular spread in CT scans of 15/49 patients and radiologist 2 in 16/49 patients (Cohen's kappa=0.86; p<0.01). Sensitivity of radiologic extracapsular spread detection was 73% (95% confidential index (CI): 44.0-89.7%) and specificity 91% (75.0-98.0%). Extracapsular spread depicted on computed tomography using strict criteria has high specificity. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  19. Atypical squamous cells of undetermined significance: Bethesda classification and association with Human Papillomavirus.

    PubMed

    Barcelos, Ana Cristina Macêdo; Michelin, Márcia Antoniazi; Adad, Sheila Jorge; Murta, Eddie Fernando Candido

    2011-01-01

    To analyze patients with atypical squamous cells of undetermined significance (ASCUS) through a cytology review and the presence of microbiological agents, with consideration of colposcopy and semiannual tracking. 103 women with ASCUS were reviewed and reclassified: normal/inflammatory, ASCUS, low-grade squamous intraepithelial lesion (LSIL), or high-grade squamous intraepithelial lesion (HSIL). If ASCUS confirmed, it was subclassified in reactive or neoplastic ASCUS, ASC-US, or ASC-H; and Regione Emilia Romagna Screening Protocol. Patients underwent a colposcopic examination, and test for Candida sp., bacterial vaginosis, Trichomonas vaginalis, and human papillomavirus (HPV) were performed. Upon review, ASCUS was diagnosis in 70/103 (67.9%), being 38 (54.2%) reactive ASCUS and 32 (45.71%) neoplastic ASCUS; 62 (88.5%) ASC-US and 8 (11.41%) ASC-H. ASCUS (Regione Protocol), respectively 1-5: 15 (21.4%), 19 (27.1%), 3 (27.1%), 16 (22.8%), and 1 (1.4%). A higher number of cases of cervical intraepithelial neoplasia (CIN) II/III in the biopsies of patients with ASC-H compared to ASC-US (P = .0021). High-risk HPV test and presence of CIN II/III are more frequent in ASC-H than ASC-US (P = .031). ASC-H is associated with clinically significant disease. High-risk HPV-positive status in the triage for colposcopy of patients with ASC-US is associated with increased of CIN.

  20. Virology and molecular pathogenesis of HPV (human papillomavirus)-associated oropharyngeal squamous cell carcinoma.

    PubMed

    Miller, Daniel L; Puricelli, Michael D; Stack, M Sharon

    2012-04-15

    The current literature fully supports HPV (human papillomavirus)-associated OPSCC (oropharyngeal squamous cell carcinoma) as a unique clinical entity. It affects an unambiguous patient population with defined risk factors, has a genetic expression pattern more similar to cervical squamous cell carcinoma than non-HPV-associated HNSCC (head and neck squamous cell carcinoma), and may warrant divergent clinical management compared with HNSCC associated with traditional risk factors. However, a detailed understanding of the molecular mechanisms driving these differences and the ability to exploit this knowledge to improve clinical management of OPSCC has not yet come to fruition. The present review summarizes the aetiology of HPV-positive (HPV+) OPSCC and provides a detailed overview of HPV virology and molecular pathogenesis relevant to infection of oropharyngeal tissues. Methods of detection and differential gene expression analyses are also summarized. Future research into mechanisms that mediate tropism of HPV to oropharyngeal tissues, improved detection strategies and the pathophysiological significance of altered gene and microRNA expression profiles is warranted.

  1. [Prognostic analysis of cervical lymph node metastasis in patients with thoracic esophageal squamous cell carcinoma].

    PubMed

    Chen, Junqiang; Zhu, Kunshou; Zheng, Xiongwei; Chen, Mingqiang; Lin, Yu; Pan, Caizhu; Pan, Jianji

    2014-08-01

    To analyze the prognostic factors of cervical lymph node metastasis (CLN) in thoracic esophageal squamous cell carcinoma (TESCC), and to probe and verify the esophageal carcinoma staging of the 7th edition of American Joint Committee on Cancer (AJCC) TNM staging system. A total of 1 715 TESCC patients underwent radical esophagectomy plus three-field lymph node dissection at Fujian Provincial Cancer Hospital between January 1993 and March 2007. 547 patients had pathological metastasis of CLN, and 296 patients received surgery only (S group) and 251 patients received postoperative radiotherapy (S+R group). The prognostic factors were analyzed and the pattern of recurrence and metastases was studied according to the esophageal carcinoma staging criteria of the 7th edition of AJCC TNM staging system. The metastasis rate of CLN was 31.9% for the entire group, 44.2%, 31.5% and 14.4% for the upper, middle and lower TESCC, respectively (P < 0.001). The 5-year overall survival rate of the patients with metastatic CLN was 27.7%, and the median overall survival time was 27.5 months. The 5-year survival rate was 21.3% in the S group and 34.2% in the S+R group, and the median survival time was 21.9 months in the S group and 35.4 months in the S+R group (P < 0.001). Multivariate analysis showed that gender, lesion length in X-ray, N stage, AJCC stage and treatment modality were independent prognostic factors of CLN metastasis in TESCC. Independent prognostic factors for S group included the primary tumor site, pT stage, N stage and AJCC stage, and N stage was an independent prognostic factor for the S+R group. TESCC with CLN metastasis have a better prognosis after surgery. It supports that cervical lymph nodes belong to regional lymph nodes classified in the 7th edition of AJCC TNM staging system.

  2. Potential impact of mTOR inhibitors on cervical squamous cell carcinoma: A systematic review

    PubMed Central

    Assad, Daniele Xavier; Elias, Silvia Taveira; Melo, Andréia Cristina; Ferreira, Carlos Gil; De Luca Canto, Graziela; Guerra, Eliete Neves Silva

    2016-01-01

    The aim of the present systematic review was to analyze the potential impact of mammalian target of rapamycin (mTOR) inhibitors on the treatment of cervical squamous cell carcinoma (CSCC). A systematic literature search was conducted in PubMed, PMC, Scopus, Cochrane Library, LILACS, Web of Science, Google Scholar and ScienceDirect on January 19, 2015, without time and language restrictions. Studies that evaluated women of any age with CSCC and who received mTOR inhibitors alone or in association with other treatments were considered. Randomized and non-randomized clinical trials were included, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist was followed. Selected studies were methodologically appraised according to the Grades of Recommendation, Assessment, Development and Evaluation method to assess the quality of evidence. Of 642 identified citations, 43 studies were fully reviewed; however, only 3 studies met the inclusion criteria and were used for qualitative analysis. Of these, two studies were phase 1 and one was a phase 2 clinical trial. The studies included were not conclusive with regard to the association between mTOR inhibitor treatment and cervical cancer. The main analysis of secondary endpoints revealed that individuals treated with other drugs in association with mTOR inhibitors achieved partial responses (15.4–33.3%) or stable disease (17.6–28%). Treatment with mTOR inhibitors in general was well tolerated in patients with metastatic disease. The predominant toxicities were grade 1 and 2. The phase 1 trials included in this review demonstrated that mTOR inhibitor treatments are feasible and safe. However, the currently available evidence is insufficient to determine the effect of mTOR inhibitors on CSCC, and further investigation in high-quality, randomized clinical trials is required. PMID:27895779

  3. Diagnostic and Treatment Reproducibility of Cervical Intraepithelial Neoplasia / Squamous Intraepithelial Lesion and Factors Affecting the Diagnosis.

    PubMed

    Sağlam, Arzu; Usubütün, Alp; Dolgun, Anıl; Mutter, George L; Salman, M Coşkun; Kurtulan, Olcay; Akyol, Aytekin; Özkan, Eylem Akar; Baykara, Sema; Bülbül, Dilek; Calay, Zerrin; Eren, Funda; Gümürdülü, Derya; Haberal, Nihan; Ilvan, Şennur; Karaveli, Şeyda; Koyuncuoğlu, Meral; Müezzinoğlu, Bahar; Müftüoğlu, Kamil Hakan; Özen, Özlem; Özdemir, Necmettin; Peştereli, Elif; Ulukuş, Çağnur; Zekioğlu, Osman

    2017-01-01

    Inter-observer differences in the diagnosis of HPV related cervical lesions are problematic and response of gynecologists to these diagnostic entities is non-standardized. This study evaluated the diagnostic reproducibility of "cervical intraepithelial neoplasia" (CIN) and "squamous intraepithelial lesion" (SIL) diagnoses. 19 pathologists evaluated 66 cases once using H&E slides and once with immunohistochemical studies (p16, Ki-67 and Pro-ExC). Management response to diagnoses was evaluated amongst 12 gynecologists. Pathologists and gynecologists were also given a questionnaire about how additional information like smear results and age modify diagnosis and management. We show moderate interobserver diagnostic reproducibility amongst pathologists. The overall kappa value was 0.50 and 0.59 using the CIN and SIL classifications respectively. Impact of immunohistochemical evaluation on interpretation of cases differed and there was lack of statistically significant improvement of interobserver diagnostic reproducibility with the addition of immunohistochemistry. We saw that choice of treatment methods amongst gynecologists varied and overall concordance was only fair to moderate. The CIN2 diagnostic category was seen to have the lowest percentage agreement amongst both pathologists and gynecologists. We showed that pathologists had diagnostic "styles" and gynecologists had management "styles". In summary each pathologist had different diagnostic tendencies which were affected not only by histopathology and marker studies, but also by the patient management tendencies of the gynecologist that the pathologist worked with. The two-tiered modified Bethesda system improved diagnostic agreement. We concluded that immunohistochemistry should be used only to resolve problems in select cases and not for every case.

  4. Association of Schistosoma haematobium and human papillomavirus in cervical cancer: a case report.

    PubMed

    Savardekar, Lalita S; Balaiah, Donta; Mali, Bapurao N

    2010-01-01

    The association between Schistosoma haematobium and cervical cancer has been reported for a long time. However, recently human papillomavirus, a cofactor in the genesis of cervical cancer, has been confirmed. A case of squamous intraepithelial lesion after S haematobium infection is presented, and the relation between schistosomiasis, human papillomavirus and squamous intraepithelial lesion, with long-term follow-up by Papanicolaou smear, is discussed. A 33-year-old, normal, healthy woman with a history of Copper intrauterine device (IUD) use for 3.9 years presented for her annual contraceptive follow-up. Her Pap smear revealed inflammation with a S haematobium egg. She was followed up with Pap smears for 4 years. Retrospective contraceptive history revealed use ofa copper IUD on 5 occasions with a total duration of 13 years and 1 month. Similarly, annual follow-up of Pap smears for the past 13 years showed mild inflammation with bacterial vaginitis and monilial infection. Subsequent smears showed an Actinomyces-like organism and then human papillomavirus infection with atypical squamous cells of undetermined significance followed by human papillomavirus-associated low/high grade squamous intraepithelial lesion. Caution is required while screening routine Pap smears. Apart from nuclear abnormalities, one can observe unusual findings. Long-term followup by Pap smear following detection of S haematobium revealed that in the absence of human papillomavirus, S haematobium alone is not the causative agent for the abnormal proliferation of squamous epithelium of the cervix. Genital Schistosomia acts as a cofactor by traumatizing the genital epithelium or immune suppression to favor human papillomavirus infection.

  5. CEACAM1 in Cervical Cancer and Precursor Lesions: Association With Human Papillomavirus Infection

    PubMed Central

    Albarran-Somoza, Benibelks; Franco-Topete, Ramon; Delgado-Rizo, Vidal; Cerda-Camacho, Felipe; Acosta-Jimenez, Lourdes; Lopez-Botet, Miguel; Daneri-Navarro, Adrian

    2006-01-01

    Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is an adhesion molecule expressed in a wide variety of tissues including epithelial cells, leukocytes, and tumors that may establish both homotypic and heterotypic interactions. The aim of this work was to study the protein expression pattern of CEACAM1 in cervical cancer and precursor lesions in the context of human papillomavirus (HPV) infection. We used immunohistochemistry to analyze CEACAM1 expression in formalin-fixed, paraffin-embedded cervical tissues from 15 healthy women, 15 patients with low-grade squamous intraepithelial lesions (SIL), 15 patients with high-grade SIL, and 15 patients with squamous carcinomas. HPV types were identified by PCR. CEACAM1 was either undetectable (13/15) or low (2/15) in normal cervical tissues. By contrast, CEACAM1 expression was increased in high-grade SIL (10 samples staining intermediate/high and 4 samples staining low) as compared with low-grade SIL with undetectable (n=3) or low (n= 12) expression. CEACAM1 expression was undetectable or low in cervical carcinoma. Our results suggest that CEACAM1 may be an interesting progression marker in SIL and cervical cancer, in particular due to reported immunoregulatory properties. PMID:16924126

  6. Anatomic Invasive Depth Predicts Delayed Cervical Lymph Node Metastasis of Tongue Squamous Cell Carcinoma.

    PubMed

    Mitani, Sohei; Tomioka, Toshifumi; Hayashi, Ryuichi; Ugumori, Toru; Hato, Naohito; Fujii, Satoshi

    2016-07-01

    Delayed cervical lymph node metastasis (CLNM) is the most negative prognostic factor of tongue squamous cell carcinoma (SCC). This study analyzed the relationship between clinicopathologic factors, including anatomic invasive depth (AID), and CLNM. A total of 212 patients with clinically node-negative (cN0) tongue SCC who had undergone partial glossectomy through the mouth were eligible for this retrospective study. The deepest portions where tongue SCC cells invaded as determined by microscopic analyses were classified into 5 categories, including epithelial and submucosal tissue, lateral extrinsic tongue muscle (ETM), intrinsic tongue muscles (ITM), paralingual and sublingual spaces, and medial ETM according to AID. We examined the relationship between clinicopathologic factors including AID and delayed CLNM. Multivariate analysis demonstrated that AID was an independent predictive factor for delayed CLNM (P=0.0022; odds ratio=7.1). Deeper invasion than ITM, including ITM, paralingual and sublingual spaces, and medial ETM, had high sensitivity and negative predictive value for delayed CLNM (94.4% and 95.7%, respectively). Precise elucidation of AID may be useful for the preoperative decision for performing elective neck dissection. None of 11 patients in whom the deepest portion where tumor invaded to lateral ETM (according to AID) showed delayed CLNM, although tongue SCC T4a tumor is defined by the presence of invasion of cancer cells to ETM. Tumors with invasion to lateral ETM might have to be excluded from the pathologic T4a category.

  7. Immunoexpression of HPV 16/18 E6 and E7 oncoproteins in high-grade cervical squamous intraepithelial lesions in HIV-positive women.

    PubMed

    Rodrigues, L C; Speck, N M de Gois; Focchi, G R de Azevedo; Schimidt, M A; Marques, R M; Ribalta, J C Lascasas

    2016-02-19

    The aim of this study was to assess the immunoexpression of human papillomavirus genotypes 16 and 18 (E6 and E7) oncoproteins in cervical high-grade squamous intraepithelial lesions (HSIL) of human immunodeficiency virus (HIV)-positive women. These results were also compared to the persistence and/or recurrence of lesions after loop electrosurgical excision procedure. Cervical samples from 158 patients were divided into three groups according to the presence or absence of HSIL in women who were or were not HIV-positive. By using the tissue microarray technique, immunohistochemistry was performed to analyze the expression of HPV 16/18 E6 and E7 oncoproteins. Cervical samples from 95 HIV-positive women and 63 HIV-negative women were studied. A statistically significant difference was found in the immunoexpression of E6 and E7 oncoproteins in samples from HIV-positive women with HSIL and that of women with non-neoplastic tissue (P < 0.001). There was also a statistically significant correlation between the immunoexpression of E6 (P = 0.012) and E7 (P < 0.001) oncoproteins in lesion persistence among HIV-positive women. Within the limitations of this study, the immunoexpression of HPV 16/18 E6 and E7 oncoproteins may have prognostic value regarding lesion persistence in HIV-positive women.

  8. Human papillomavirus and human immunodeficiency virus infections: relation with cervical dysplasia-neoplasia in African women.

    PubMed

    La Ruche, G; You, B; Mensah-Ado, I; Bergeron, C; Montcho, C; Ramon, R; Touré-Coulibaly, K; Welffens-Ekra, C; Dabis, F; Orth, G

    1998-05-18

    Our study assessed the factors associated with cervical squamous intra-epithelial lesions (SILs) and invasive cervical cancer, with special attention to human immunodeficiency virus (HIV) and human papillomavirus (HPV) infections. Women from 3 outpatient gynecology clinics of Abidjan, Côte d'Ivoire, were screened for cervical abnormalities: 151 women with low-grade SILs and 151 controls, 60 with high-grade SILs and 240 controls, and 13 with invasive cancer and 65 controls were enrolled in 3 case-control studies. Controls were chosen at random among the women without lesions, with a frequency matching for age and center. We used the PCR method for the detection of cervical HPV DNA and the restriction fragment length polymorphism analysis for HPV typing. HIV antibody testing and CD4 cell count were performed. In multivariate analyses, factors associated with cervical lesions were: for low-grade SILs, HPV positivity, HIV-1 seropositivity and parity >3; for high-grade SILs, HPV positivity, chewing tobacco, HIV-1 seropositivity and illiteracy, and for invasive cancer, HPV positivity only. We found a diversity of HPV types associated with SILs. In HIV-1-infected women, SILs occurred at an early stage of HIV disease. Women infected with both HIV-1 and HPV were at much higher risk of SILs than women infected with each of these 2 viruses separately. Invasive cancer was linked to HIV-2 infection in univariate analysis only. Our results suggest that the relation of SILs with HIV-1 infection is mainly explained by HPV infection and that HIV-1-infected African women may not often reach the invasive stage of cervical cancer.

  9. Tissue transglutaminase mediates the pro-malignant effects of oncostatin M receptor over-expression in cervical squamous cell carcinoma

    PubMed Central

    Caffarel, Maria M; Chattopadhyay, Anasuya; Araujo, Angela M; Bauer, Julien; Scarpini, Cinzia G; Coleman, Nicholas

    2013-01-01

    Oncostatin M receptor (OSMR) is commonly over-expressed in advanced cervical squamous cell carcinoma (SCC), producing a significantly worse clinical outcome. Cervical SCC cells that over-express OSMR show enhanced responsiveness to the major ligand OSM, which induces multiple pro-malignant effects, including increased cell migration and invasiveness. Here, we show that tissue transglutaminase (TGM2) is an important mediator of the ligand-dependent phenotypic effects of OSMR over-expression in SCC cells. TGM2 expression correlated with disease progression and with OSMR levels in clinical samples of cervical and oral SCC. TGM2 depletion in cervical SCC cells abrogated OSM-induced migration on fibronectin-coated surfaces and invasiveness through extracellular matrix, while ectopic expression of TGM2 increased cell motility and invasiveness. Confocal microscopy and co-immunoprecipitation assays showed that TGM2 interacted with integrin–α5β1 in the presence of fibronectin in cervical SCC cells, with OSM treatment strengthening the interaction. Importantly, integrin–α5β1 and fibronectin were also over-expressed in cervical and oral SCC, where levels correlated with those of OSMR and TGM2. This combined tissue and in vitro study demonstrates for the first time that stimulation of over-expressed OSMR in cervical SCC cells activates TGM2/integrin-α5β1 interactions and induces pro-malignant changes. We conclude that an OSMR/TGM2/integrin-α5β1/fibronectin pathway is of biological significance in cervical SCC and a candidate for therapeutic targeting. Copyright © 2013 Pathological Society of Great Britain and Ireland. © 2013 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. PMID:23765377

  10. Size of cervical lymph node and metastasis in squamous cell carcinoma of the oral tongue and floor of mouth.

    PubMed

    Jarungroongruangchai, Weerawut; Charoenpitakchai, Mongkol; Silpeeyodom, Tawatchai; Pruksapong, Chatchai; Burusapat, Chairat

    2014-02-01

    Squamous cell carcinoma (SCC) of the oral tongue and floor of mouth are the most common head and neck cancers. Regional metastasis of SCC is most likely found at the cervical lymph node. Size and characteristics of pathologically suspicious lymph nodes are related to the aggressiveness of the primary tumor: The objective of this study is to analyze the conrrelation between sizes of cervical node and metastasis in SCC of oral tongue and floor of mouth. Retrospective review was conducted firom the patient's charts between January 2008 and December 2012. Clinical, histopathology and surgical records were reviewed. Cervical lymph nodes ofSCC of oral tongue and floor of mouth were reviewed and divided into four groups depending on their size (1-5 mm, 6-9 mm, 10-30 mm and more than 30 am,). A p-value <0.05 was considered statistically significant. 196 patients with SCC of the oral cavity were recorded. Sixteen patients ofSCC of the oral tongue and 15patients of SCC of the floor of mouth underwent neck dissection (641 cervical nodes). Most ofthe patients were diagnosed with stage 3 (41.94%). Extracapsular extension was found in 72.15% of SCC of oral tongue and 73.33 % of SCC ofthe floor of mouth. Size of cervical lymph nodes less than 10 mm was found to be metastasis at 9.27% and 10.82% of SCC of oral tongue and floor of mouth, respectively. Cervical node metastasis can be found in SCC of the oral tongue and floor ofmouth with clinlically negative node andsize of cervical node less than 10 mm. Here in, size of cervical node less than 10 mm was still important due to the chance for metastasis especially high grade tumors, advanced stage cancer and lymphovascular invasion.

  11. Cervical human papillomavirus infection in Mexican women with systemic lupus erythematosus or rheumatoid arthritis.

    PubMed

    Rojo-Contreras, W; Olivas-Flores, E M; Gamez-Nava, J I; Montoya-Fuentes, H; Trujillo-Hernandez, B; Trujillo, X; Suarez-Rincon, A E; Baltazar-Rodriguez, L M; Sanchez-Hernandez, J; Ramirez-Flores, M; Vazquez-Salcedo, J; Rojo-Contreras, J; Morales-Romero, J; Gonzalez-Lopez, L

    2012-04-01

    Cervical human papillomavirus (HPV+) infection is associated with an increased risk of cervical dysplasia. Although the frequency of HPV+ in systemic lupus erythematosus (SLE) has been investigated in some races its prevalence in Hispanic women is still unknown. This cross-sectional study evaluated the prevalence of cervical HPV+ in Mexican women with SLE (n = 34) or rheumatoid arthritis (RA) (n = 43) and in healthy controls (n = 146). These women were interviewed about risk factors for sexually transmitted infections and cervical cytology analysis was performed. HPV+ viral types were identified using PCR: HPV+ was observed in 14.7% of SLE, 27.9% of RA and 30.8% of controls. High-risk HPV types were observed in 11.7% of women with SLE, 27.9% of women with RA, and in 26% of the controls. High-risk viral types 58, 35 and 18 were the most frequently identified in SLE. Two women with SLE had a high-grade squamous intraepithelial lesion and one had cervical cancer. An association was observed between methotrexate utilization, longer duration of therapy with prednisone, and HPV+ in RA or SLE. Thus, there is a high prevalence of cervical HPV infection in Mexican women with SLE or RA, and physicians must be vigilant in preventing the development of cervical dysplasia.

  12. Human papillomavirus type 16 DNA in periungual squamous cell carcinomas

    SciTech Connect

    Moy, R.L.; Eliezri, Y.D.; Bennett, R.G. ); Nuovo, G.J.; Siverstein, S. Columbia Univ., New York, NY ); Zitelli, J.A. )

    1989-05-12

    Ten squamous cell carcinomas (in situ or invasive) of the fingernail region were analyzed for the presence of DNA sequences homologous to human papilloma-virus (HPV) by dot blot hybridization. In most patients, the lesions were verrucae of long-term duration that were refractory to conventional treatment methods. Eight of the lesions contained HPV DNA sequences, and in six of these the sequences were related to HPV 16 as deduced from low-stringency nucleic acid hybridization followed by low- and high-stringency washes. Furthermore, the restriction endonuclease digestion pattern of DNA isolated from four of these lesions was diagnostic of episomal HPV 16. The high-frequency association of HPV 16 with periungual squamous cell carcinoma is similar to that reported for HPV 16 with squamous cell carcinomas on mucous membranes at other sites, notably the genital tract. The findings suggest that HPV 16 may play an important role in the development of squamous cell carcinomas of the finger, most notably those lesions that are chronic and located in the periungual area.

  13. Transcriptome sequencing demonstrates that human papillomavirus is not active in cutaneous squamous cell carcinoma.

    PubMed

    Arron, Sarah T; Ruby, J Graham; Dybbro, Eric; Ganem, Don; Derisi, Joseph L

    2011-08-01

    β-Human papillomavirus (β-HPV) DNA is present in some cutaneous squamous cell carcinomas (cuSCCs), but no mechanism of carcinogenesis has been determined. We used ultra-high-throughput sequencing of the cancer transcriptome to assess whether papillomavirus transcripts are present in these cancers. In all, 67 cuSCC samples were assayed for β-HPV DNA by PCR, and viral loads were measured with type-specific quantitative PCR. A total of 31 SCCs were selected for whole transcriptome sequencing. Transcriptome libraries were prepared in parallel from the HPV18-positive HeLa cervical cancer cell line and HPV16-positive primary cervical and periungual SCCs. Of the tumors, 30% (20/67) were positive for β-HPV DNA, but there was no difference in β-HPV viral load between tumor and normal tissue (P=0.310). Immunosuppression and age were significantly associated with higher viral load (P=0.016 for immunosuppression; P=0.0004 for age). Transcriptome sequencing failed to identify papillomavirus expression in any of the skin tumors. In contrast, HPV16 and HPV18 mRNA transcripts were readily identified in primary cervical and periungual cancers and HeLa cells. These data demonstrate that papillomavirus mRNA expression is not a factor in the maintenance of cuSCCs.

  14. Human papillomavirus DNA and mRNA prevalence and association with cervical cytological abnormalities in the Irish HIV population.

    PubMed

    Loy, Aisling; McInerney, Jamie; Pilkington, Loretto; Keegan, Helen; Delamere, Sandra; Martin, Cara M; Sheils, Orla; O'Leary, John J; Mulcahy, Fiona

    2015-10-01

    The complex interplay between HIV and human papillomavirus and its link to cervical dysplasia is poorly understood. This is the first study to assess the prevalence of oncogenic human papillomavirus mRNA in HIV-positive women, its relationship to HIV and its potential use in the triage of cervical cancer screening in HIV-positive women. In this cross-sectional study, we included 321 HIV-positive women. In all, 28.7% had abnormal cervical cytology, 51.1% were human papillomavirus DNA-positive and 21.8% tested positive for human papillomavirus mRNA. Women with a CD4 count of <200 × 10(6)/L were more likely to test positive for human papillomavirus DNA and mRNA. Virally suppressed women were less likely to be human papillomavirus DNA-positive; however, the same did not hold true for human papillomavirus mRNA. We found the human papillomavirus mRNA screening to be more specific when screening for low-grade squamous intraepithelial lesion and high-grade squamous intraepithelial lesion than human papillomavirus DNA at 84.53% compared to 57.36%. However, the sensitivity was less at 51.59% versus 91.07% for human papillomavirus DNA. It may be possible in the future to use human papillomavirus mRNA/DNA testing within a triage algorithm for the screening and management of cervical cancer in the HIV-positive patient. © The Author(s) 2015.

  15. A reusable localized surface plasmon resonance biosensor for quantitative detection of serum squamous cell carcinoma antigen in cervical cancer patients based on silver nanoparticles array

    PubMed Central

    Zhao, Qianying; Duan, Ruiqi; Yuan, Jialing; Quan, Yi; Yang, Huan; Xi, Mingrong

    2014-01-01

    Squamous cell carcinoma antigen (SCCa), as a tumor biomarker, plays an important role in adjuvant diagnosis, treatment evaluation, and prognosis prediction for cervical cancer patients. Localized surface plasmon resonance (LSPR) technique based on noble metal nanoparticles bypasses the disadvantages of traditional testing strategies, in terms of free-labeling, short assay time, good sensitivity, and selectivity. Herein, we develop a novel and reusable LSPR biosensor for the detection of SCCa. First, a triangle-shaped silver nanoparticle array was fabricated using the nanosphere lithography method. Next, we investigated and verified the feasibility of amino coupling method using 11-mercaptoundecanoic acid (MUA) to form a functionalized chip surface with monoclonal anti-SCCa antibodies on the silver nanoparticles for distinct detection of SCCa. Different concentrations of SCCa were successfully tested in both buffer and human serum by the ultrasensitive and specific LSPR system, with a linear quantitative detection range of 0.1–1,000 pM under optimal conditions. With appropriate regeneration solution, for example 50 mM glycine-HCl (pH 2.0), the LSPR biosensor featured effective fabrication reproducibility, which reduced both production cost and testing time. Our study represents the first application of the LSPR biosensor in cervical cancer, and demonstrates that the rapid, simple, and reusable nanochip can serve as a potential alternative for clinical serological diagnosis of SCCa in cervical cancer patients. PMID:24591830

  16. A reusable localized surface plasmon resonance biosensor for quantitative detection of serum squamous cell carcinoma antigen in cervical cancer patients based on silver nanoparticles array.

    PubMed

    Zhao, Qianying; Duan, Ruiqi; Yuan, Jialing; Quan, Yi; Yang, Huan; Xi, Mingrong

    2014-01-01

    Squamous cell carcinoma antigen (SCCa), as a tumor biomarker, plays an important role in adjuvant diagnosis, treatment evaluation, and prognosis prediction for cervical cancer patients. Localized surface plasmon resonance (LSPR) technique based on noble metal nanoparticles bypasses the disadvantages of traditional testing strategies, in terms of free-labeling, short assay time, good sensitivity, and selectivity. Herein, we develop a novel and reusable LSPR biosensor for the detection of SCCa. First, a triangle-shaped silver nanoparticle array was fabricated using the nanosphere lithography method. Next, we investigated and verified the feasibility of amino coupling method using 11-mercaptoundecanoic acid (MUA) to form a functionalized chip surface with monoclonal anti-SCCa antibodies on the silver nanoparticles for distinct detection of SCCa. Different concentrations of SCCa were successfully tested in both buffer and human serum by the ultrasensitive and specific LSPR system, with a linear quantitative detection range of 0.1-1,000 pM under optimal conditions. With appropriate regeneration solution, for example 50 mM glycine-HCl (pH 2.0), the LSPR biosensor featured effective fabrication reproducibility, which reduced both production cost and testing time. Our study represents the first application of the LSPR biosensor in cervical cancer, and demonstrates that the rapid, simple, and reusable nanochip can serve as a potential alternative for clinical serological diagnosis of SCCa in cervical cancer patients.

  17. Combination of external beam radiotherapy and Californium (Cf)-252 neutron intracavity brachytherapy is more effective in control of cervical squamous cell carcinoma than that of cervical adenocarcinoma.

    PubMed

    Xiong, Yanli; Liu, Jia; Chen, Shu; Zhou, Qian; Xu, Wenjing; Tang, Chen; Chen, Yonghong; Yang, Mei; Lei, Xin

    2015-09-01

    The objective of this study was to compare the effect of combined external beam radiotherapy (EBRT) and Californium (Cf)-252 neutron intracavity brachytherapy (ICBT) on cervical squamous versus adenocarcinoma. A total of 106 patients with stage IB-IIIB cervical cancer were accrued between January 2005 and May 2011 and divided into squamous cell carcinoma (SCC) and adenocarcinoma (AC) as a pair with 53 patients in each group according to tumor size, stage, age, and hemoglobin level using matched-pair design. The whole pelvic EBRT was performed with 2 Gy/fraction, 4 fractions/week. The total dose was 48-54 Gy (the center of whole pelvic field was blocked by 4 cm in width after 20-36 Gy). Cf-252 neutron ICBT was delivered with 11 and 12 Gy-eq/f with the total dose at point A of 44 and 48 Gy-eq for SCC and AC patients, respectively. The mean follow-up time was 43 months. The 5-year LC, OS, DFS, LAC rates, and mean survival time were 66.0, 56.6, 52.8.0, 17.0%, and 76.4 ± 6.2 months, respectively, for AC patients, whereas they were 81.1, 69.8, 67.9, 11.3%, and 93.3 ± 4.3 months, respectively, for SCC patients. Furthermore, the early treatment toxicity was mild in both groups, the late treatment complications were mainly radiation-induced proctitis and cystitis, and there were no grade 3 or higher complications. Although the combination of Cf-252 neutron ICBT and EBRT was effective in both histology types of cervical cancer, a more aggressive strategy is needed to control cervical AC.

  18. Human papillomavirus prevalence among women with cervical intraepithelial neoplasia III and invasive cervical cancer from Goiânia, Brazil.

    PubMed

    Rabelo-Santos, S H; Zeferino, L; Villa, L L; Sobrinho, J P; Amaral, R G; Magalhães, A V

    2003-03-01

    This study estimated the prevalence and distribution of human papillomavirus (HPV) types among women with cervical intraepithelial neoplasia (CIN) grade III and invasive cervical cancer from Goi s (Brazil Central Region). Seventy-four cases were analyzed and consisted of 18 CIN III, 48 squamous cell carcinomas, 4 adenocarcinomas, 1 adenosquamous carcinoma and 3 undifferentiated carcinomas. HPV-DNA sequences were examined in formalin-fixed and paraffin-embedded tissues using primers from L1 region GP5+/GP6+. Polymerase chain reaction products were typed with dot blot hybridization using probes for HPV 16, 18, 31, 33, 45, 54, 6/11, 42/43/44, 51/52, 56/58. The prevalence of HPV was estimated to be 76% (56/74). HPV 16 was the most frequently found type, followed by HPV 33, 18 and 31. The prevalence of untyped HPV was 6%; 79% percent of the squamous cell carcinoma cases and 61% percent of the CIN III were positive for HPV and the prevalence rate of HPV types was the same for the total number of cases. According to other studies, HPV type 16 is the most prevalent virus in all Brazilian regions, but there is variation regarding to other types. Type 18 is the second most prevalent HPV in North, Southeast and South Brazil regions and types 31 and 33 are the second most prevalent HPV in Northeast and Central Brazil, respectively.

  19. Prevalence and risk factors of cervical squamous intraepithelial lesions among HIV-infected women in Dar es Salaam, Tanzania.

    PubMed

    Liu, Enju; McCree, Renicha; Mtisi, Expeditho; Fawzi, Wafaie W; Aris, Eric; Lema, Irene A; Hertzmark, Ellen; Chalamilla, Guerino; Li, Nan; Vermund, Sten H; Spiegelman, Donna

    2016-03-01

    To determine the prevalence and predictors of cervical squamous intraepithelial lesions (SIL) among HIV-infected women in Tanzania, a cross-sectional study was conducted among HIV-infected women at HIV care and treatment clinics. A Papanicolaou (Pap) smear was used as a screening tool for detection of cervical SIL. From December 2006 to August 2009, 1365 HIV-infected women received cervical screening. The median age was 35 (interquartile range [IQR]: 30-42) years, and the median CD4 + cell count was 164 (IQR: 80-257) cells/mm(3). The prevalence of cervical SIL was 8.7% (119/1365). In multivariate analysis, older age (≥50 versus 30-<40 years: prevalence ratio [PR], 2.36; 95% confidence interval [CI], 1.45-3.84, p for trend = 0.001), lower CD4 + cell counts (<100 versus ≥200 cells/mm(3): PR, 1.55; 95% CI, 1.01-2.36, p for trend = 0.03) and cervical inflammation (PR, 1.73; 95% CI, 1.16-2.60, p = 0.008) were associated with an increased risk of cervical SIL. Women with advanced WHO HIV disease stage (IV versus I/II: PR, 3.45; 95% CI, 1.35-8.85, p for trend = 0.01) had an increased risk for high-grade SIL. In resource-limited settings where it is not feasible to provide cervical cancer prevention services to all HIV-infected women, greater efforts should focus on scaling-up services among those who are older than 50 years, with lower CD4 cell counts and advanced HIV disease stage. © The Author(s) 2015.

  20. Human Papillomavirus Genotype Distribution in Invasive Cervical Cancer in Pakistan.

    PubMed

    Loya, Asif; Serrano, Beatriz; Rasheed, Farah; Tous, Sara; Hassan, Mariam; Clavero, Omar; Raza, Muhammad; De Sanjosé, Silvia; Bosch, F Xavier; Alemany, Laia

    2016-07-30

    Few studies have assessed the burden of human papillomavirus (HPV) infection in Pakistan. We aim to provide specific information on HPV-type distribution in invasive cervical cancer (ICC) in the country. A total of 280 formalin-fixed paraffin-embedded tissue blocks were consecutively selected from Shaukat Khanum Memorial Cancer Hospital and Research Centre (Lahore, Pakistan). HPV-DNA was detected by SPF10 broad-spectrum PCR followed by DNA enzyme immunoassay and genotyping by LiPA25. HPV-DNA prevalence was 87.5% (95%CI: 83.0-91.1), with 96.1% of cases histologically classified as squamous cell carcinoma. Most of the HPV-DNA positive cases presented single infections (95.9%). HPV16 was the most common type followed by HPV18 and 45. Among HPV-DNA positive, a significantly higher contribution of HPV16/18 was detected in Pakistan (78.4%; 72.7-83.3), compared to Asia (71.6%; 69.9-73.4) and worldwide (70.8%; 69.9-71.8) and a lower contribution of HPVs31/33/45/52/58 (11.1%; 7.9-15.7 vs. 19.8%; 18.3-21.3 and 18.5%; 17.7-19.3). HPV18 or HPV45 positive ICC cases were significantly younger than cases infected by HPV16 (mean age: 43.3, 44.4, 50.5 years, respectively). A routine cervical cancer screening and HPV vaccination program does not yet exist in Pakistan; however, the country could benefit from national integrated efforts for cervical cancer prevention and control. Calculated estimations based on our results show that current HPV vaccine could potentially prevent new ICC cases.

  1. Human Papillomavirus Genotype Distribution in Invasive Cervical Cancer in Pakistan

    PubMed Central

    Loya, Asif; Serrano, Beatriz; Rasheed, Farah; Tous, Sara; Hassan, Mariam; Clavero, Omar; Raza, Muhammad; De Sanjosé, Silvia; Bosch, F. Xavier; Alemany, Laia

    2016-01-01

    Few studies have assessed the burden of human papillomavirus (HPV) infection in Pakistan. We aim to provide specific information on HPV-type distribution in invasive cervical cancer (ICC) in the country. A total of 280 formalin-fixed paraffin-embedded tissue blocks were consecutively selected from Shaukat Khanum Memorial Cancer Hospital and Research Centre (Lahore, Pakistan). HPV-DNA was detected by SPF10 broad-spectrum PCR followed by DNA enzyme immunoassay and genotyping by LiPA25. HPV-DNA prevalence was 87.5% (95%CI: 83.0–91.1), with 96.1% of cases histologically classified as squamous cell carcinoma. Most of the HPV-DNA positive cases presented single infections (95.9%). HPV16 was the most common type followed by HPV18 and 45. Among HPV-DNA positive, a significantly higher contribution of HPV16/18 was detected in Pakistan (78.4%; 72.7–83.3), compared to Asia (71.6%; 69.9–73.4) and worldwide (70.8%; 69.9–71.8) and a lower contribution of HPVs31/33/45/52/58 (11.1%; 7.9–15.7 vs. 19.8%; 18.3–21.3 and 18.5%; 17.7–19.3). HPV18 or HPV45 positive ICC cases were significantly younger than cases infected by HPV16 (mean age: 43.3, 44.4, 50.5 years, respectively). A routine cervical cancer screening and HPV vaccination program does not yet exist in Pakistan; however, the country could benefit from national integrated efforts for cervical cancer prevention and control. Calculated estimations based on our results show that current HPV vaccine could potentially prevent new ICC cases. PMID:27483322

  2. Prevalence of cervical human papillomavirus (HPV) infection in Vanuatu.

    PubMed

    Aruhuri, Bernadette; Tarivonda, Len; Tenet, Vanessa; Sinha, Rohit; Snijders, Peter J F; Clifford, Gary; Pang, James; McAdam, Margaret; Meijer, Chris J L M; Frazer, Ian H; Franceschi, Silvia

    2012-05-01

    To provide information on human papillomavirus (HPV) prevalence and the distribution of individual HPV types in Pacific Islands, we conducted a population-based survey in Vanuatu, South Pacific. Nine hundred and eighty-seven women between 18 and 64 years of age were included. GP5(+)/6(+)-mediated PCR assay was used for HPV testing. The prevalence of 44 HPV types was 28.4% corresponding to an age (world)-standardized prevalence of 25.0% [95% confidence interval (CI), 21.9%-28.0%]. The prevalence of high-risk (HR) HPV types was 21.7% (age-standardized prevalence of 19.2%; 95% CI, 16.4%-22.0%). Among 840 women with adequate cytologic results, 13.6% showed cervical abnormalities, including 3.6% with high-grade squamous intraepithelial lesions (HSIL) and 0.8% with invasive cervical carcinoma. HPV prevalence declined from 46.1% in women aged ≤21 to 15.3% in those ≥45 years. Being single was significantly associated with HPV positivity. HR HPV findings by PCR assay and hybrid capture 2 (HC2; conducted in Vanuatu) were moderately correlated (κ test = 0.59). The positive predictive values of HR HPV positivity for HSIL or worse were 27.6% for PCR and 35.2% for HC2 among women aged ≥30. Nearly half of screening-positive women could not be reevaluated mainly on account of the difficulty to trace back women. The availability of a rapid HPV testing method that allows see-and-treat approaches at the same visit would be, therefore, essential. On account of their high cumulative burden of cervical lesions, also women older than 40 years should be included in at least the first screening round in unscreened populations.

  3. Aurora-A affects radiosenstivity in cervical squamous cell carcinoma and predicts poor prognosis

    PubMed Central

    Ma, Yuhua; Yang, Jie; Wang, Ruozheng; Zhang, Zegao; Qi, Xiaoli; Liu, Chunhua; Ma, Miaomiao

    2017-01-01

    Background Definitive radiation therapy (RT) (with or without cisplatin-based chemotherapy) is one of the most effective treatments for cervical squamous cell carcinoma (CSCC), but efficacy is limited due to resistance. In the present study, we investigated the relationship between the expression of Aurora kinase A (Aurora-A, AURKA)and response to RT in patients with CSCC. Methods The expression of Aurora-A in biopsy specimens of untreated primary tumors in 129 Uyghur patients with CSCC was investigated immunohistochemically. Primary treatment in these patients was definitive radical RT, which consisted of pelvic RT plus brachytherapy (total point A dose:70–85 Gy) (with or without cisplatin-based chemotherapy). The prognostic value of tumoral Aurora-A expression and patients’ clinical outcomes were evaluated. Results Aurora-A expression was significantly associated with lymph node metastasis (P<0.001), large tumor size (P<0.001), low hemoglobin (Hb) level (P=0.011) and recurrence (P<0.001), but not other clinicopathological factors. Definitive RT was unfavorable in patients with high Aurora-A expression (P < 0.001). In 129 enrolled patients, lymph node metastasis, large tumor size, low Hb level, and AURKA overexpression were prognostic factors for both recurrent free survival (RFS) and overall survival (OS) in univariate analysis. However, only high AURKA expression was an adverse independent risk factor for both RFS (hazard ratio, 3.953; 95% CI, 1.473-10.638; P = 0.006) and OS (hazard ratio 9.091; 95%CI 2.597-32.258; P<0.001) in multivariate analyses. Conclusions Aurora-A may serve as a predictive biomarker of radiation response and a therapeutic target to reverse radiation therapy resistance. PMID:28404933

  4. Cervical metastasis in squamous cell carcinoma of the hard palate and maxillary alveolus.

    PubMed

    Koshkareva, Yekaterina; Liu, Jeffrey C; Lango, Miriam; Galloway, Thomas; Gaughan, John P; Ridge, John A

    2016-01-01

    We conducted a retrospective study to determine the incidence and treatment outcomes of neck metastases in patients with squamous cell carcinoma (SCC) of the hard palate and/or maxillary alveolus after surgical excision of the primary tumor. We also sought to identify any risk factors for recurrence. Our study population was made up of 20 patients-9 men and 11 women, aged 46 to 88 years (mean: 72.6)-who had undergone excision of an SCC of the hard palate and/or maxillary alveolus at a tertiary care cancer center over a 7-year period. Half of all patients were former tobacco users. Of the 20 tumors, 10 involved the maxillary alveolus, 4 involved the hard palate, and 6 involved both sites. Three patients were clinically categorized as T1, 9 as T2, 6 as T3, and 2 as T4; pathologically, 8 tumors were categorized as T4a. In addition to maxillectomy, a neck dissection was performed in 7 patients-4 therapeutically and 3 electively. Eight of 20 patients experienced a recurrence: 4 local, 6 regional, and 2 distant (several patients had a recurrence at more than one site). Univariate analysis identified perineural invasion (p = 0.04) as a statistically significant risk factor for recurrence. Of 14 patients with a clinicopathologically negative neck, 5 (36%) developed a cervical recurrence, and 4 of them died of their disease. An advanced stage (T4 vs.

  5. ADXS11-001 High Dose HPV+ Cervical Cancer

    ClinicalTrials.gov

    2016-06-17

    Effects of Immunotherapy; Metastatic/Recurrent Cervical Cancer; Cervical Adenocarcinoma; Cervical Adenosquamous Cell Carcinoma; Cervical Squamous Cell Carcinoma; Cervical Small Cell Carcinoma; Stage III Cervical Cancer; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer

  6. The Combined Influence of Oral Contraceptives and Human Papillomavirus Virus on Cutaneous Squamous Cell Carcinoma

    PubMed Central

    Efird, Jimmy T.; Toland, Amanda E.; Lea, C. Suzanne; Phillips, Christopher J.

    2011-01-01

    The vast majority of cutaneous squamous cell carcinoma (CSCC) will occur in those with fair complexion, tendency to burn, and high ultraviolet radiation (UVR) exposure. Organ transplant recipients also are an important population at great risk for CSCC. An association has been reported between oral contraceptive (OC) use, human papillomavirus virus (HPV) and cervical cancer, and there could be a similar association for CSCC. The cutaneous HPV β-E6 protein, a close cousin of the transformative E6 protein underlying anogenital cancers, has been shown to inhibit apoptosis in response to UVR damage and stimulate morphologic transformation in rodent fibroblast cell lines. Furthermore, OC use has been shown to enhance HPV transcription and may contribute to CSCC risk through this pathway. PMID:21499554

  7. Cutaneous Squamous Cell Carcinoma and Human Papillomavirus: Is There An Association?

    PubMed Central

    Aldabagh, Bishr; Angeles, Jorge Gil C.; Cardones, Adela R.; Arron, Sarah T.

    2012-01-01

    Background The role of human papillomavirus (HPV) in the induction and maintenance of cervical, anogenital, and some oropharyngeal carcinomas is well recognized. However, its role in cutaneous squamous cell carcinoma (SCC) remains to be elucidated. HPV is thought to act as a possible co-carcinogen in the development of SCC. Objective To review the literature assessing the correlation and possible causation of HPV and cutaneous SCC in the immunocompetent and immunocompromised populations. Methods We reviewed HPV sampling and detection methods, epidemiologic studies examining HPV carriage in immunocompetent and immunosuppressed individuals, and evidence asserting an association between HPV and cutaneous SCC. Results Although an abundant body of evidence points toward a link between HPV and cutaneous SCC, many studies indicate otherwise. Recent studies have focused on viral activity in addition to DNA presence. Conclusion The possibility exists that HPV may play a role in the induction but not maintenance of cutaneous SCC. PMID:22928516

  8. An animal model of buccal mucosa cancer and cervical lymph node metastasis induced by U14 squamous cell carcinoma cells.

    PubMed

    Zhao, Xin; Pang, Liang; Qian, Yu; Wang, Qiang; Li, Yong; Wu, Mingyi; Ouyang, Zilan; Gao, Zhi; Qiu, Lihua

    2013-04-01

    The buccal mucosa is the site with the highest risk of contracting a malignancy in habitual betel quid chewers who expose the buccal mucosa to high doses of carcinogens. Of all oral cancers, those of the buccal mucosa are associated with the poorest prognoses. Therefore, it would be helpful to have an animal model to evaluate new treatment modalities for buccal mucosa cancer. In the present study, we evaluated whether the imprinting control region (ICR) mouse animal model could be employed as a cancer model for buccal mucosa cancer. Sixty male ICR mice were randomly divided into two groups, a normal group (n=10) and a cancer-induced group (n=50). Each mouse in the cancer group was inoculated with 0.05 ml U14 cancer cell suspension (1×10(7)/ml) on the buccal mucosa. Histological staining and gene expression assays revealed that neck lymph node metastasis animal models were established. After 20 days, the cheek tumor formation rate of the ICR mice reached 100%. Furthermore, the neck lymph node metastasis rate was 53%. We identified that U14 cells produce strong metastasis in ICR mice. Metastasis of the tumor to the lymph node began with carcinoma metastasis encroaching on the marginal sinus. Then it infiltrated to the cortex and medulla and the infiltration continued until the normal lymph node structure was completely damaged. This animal model may be employed in medical research on buccal mucosa cancer and cervical lymph node metastasis. In conclusion, our findings indicate that U14 cell-induced mouse buccal mucosa cancer may be a potential cancer model for human buccal mucosa squamous cell carcinoma.

  9. Gene Expression Changes in Cervical Squamous Cell Carcinoma After Initiation of Chemoradiation and Correlation With Clinical Outcome

    SciTech Connect

    Klopp, Ann H.; Jhingran, Anuja Ramdas, Latha; Story, Michael D.; Broadus, Russell R.; Lu, Karen H.; Eifel, Patricia J.; Buchholz, Thomas A.

    2008-05-01

    Purpose: The purpose of this study was to investigate early gene expression changes after chemoradiation in a human solid tumor, allowing identification of chemoradiation-induced gene expression changes in the tumor as well as the tumor microenvironment. In addition we aimed to identify a gene expression profile that was associated with clinical outcome. Methods and Materials: Microarray experiments were performed on cervical cancer specimens obtained before and 48 h after chemoradiation from 12 patients with Stage IB2 to IIIB squamous cell carcinoma of the cervix treated between April 2001 and August 2002. Results: A total of 262 genes were identified that were significantly changed after chemoradiation. Genes involved in DNA repair were identified including DDB2, ERCC4, GADD45A, and XPC. In addition, significantly regulated cell-to-cell signaling pathways included insulin-like growth factor-1 (IGF-1), interferon, and vascular endothelial growth factor signaling. At a median follow-up of 41 months, 5 of 12 patients had experienced either local or distant failure. Supervised clustering analysis identified a 58-gene set from the pretreatment samples that were differentially expressed between patients with and without recurrence. Genes involved in integrin signaling and apoptosis pathways were identified in this gene set. Immortalization-upregulated protein (IMUP), IGF-2, and ARHD had particularly marked differences in expression between patients with and without recurrence. Conclusions: Genetic profiling identified genes regulated by chemoradiation including DNA damage and cell-to-cell signaling pathways. Genes associated with recurrence were identified that will require validation in an independent patient data set to determine whether the 58-gene set associated with clinical outcome could be useful as a prognostic assay.

  10. Histopathologic extent of cervical intraepithelial neoplasia 3 lesions in the atypical squamous cells of undetermined significance low-grade squamous intraepithelial lesion triage study: implications for subject safety and lead-time bias.

    PubMed

    Sherman, Mark E; Wang, Sophia S; Tarone, Robert; Rich, Laurie; Schiffman, Mark

    2003-04-01

    Cervical intraepithelial neoplasia 3 (CIN3) is the precursor of mostsquamous carcinomas and serves as a surrogate end point. However, small CIN3 lesions are rarely associated with concurrent invasion. We hypothesized that aggressive follow-up for cytology of atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) leads predominantly to detection of smaller CIN3 lesions than those usually associated with cancer. We assessed this hypothesis in a masked histopathologic review of 330 CIN3 lesions in the ASCUS LSILTriage Study, focusing on ASCUS referrals. ASCUS referrals underwent randomized management [colposcopy for repeat cytology of high-grade squamous intraepithelial lesion (HSIL), colposcopy for oncogenic human papillomavirus (HPV) detection or repeat HSIL, or immediate colposcopy]; then all were followed with repeat cytology for 2 years, followed by colposcopy and aggressive treatment. We assessed all CIN3 lesions qualitatively and measured 39 of them. CIN3 lesions were overwhelmingly small. Compared with enrollment, lesions found at follow-up or exit involved fewer tissue fragments (P < 0.01) and showed less diffuse gland involvement (P = 0.03). CIN3 lesions found postenrollment after HPV testing involved the fewest tissue fragments [versus immediate colposcopy (P = 0.04) or repeat cytology of HSIL (P = 0.02)], and none showed diffuse gland involvement. The median distal-proximal length was 6.5 mm (median replacement of total epithelium = 5%) in the 39 measured cases. We conclude that CIN3 lesions underlying ASCUS or LSIL generally lack features associated with invasion, particularly if managed using HPV testing, suggesting that aggressive management leads to early detection of CIN3 but probably prevents relatively few cancers in screened populations.

  11. Radiation Therapy and Cisplatin With or Without Epoetin Alfa in Treating Patients With Cervical Cancer and Anemia

    ClinicalTrials.gov

    2014-12-29

    Anemia; Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma; Drug Toxicity; Radiation Toxicity; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer

  12. A model and nomogram to predict tumor site origin for squamous cell cancer confined to cervical lymph nodes.

    PubMed

    Ali, Arif N; Switchenko, Jeffrey M; Kim, Sungjin; Kowalski, Jeanne; El-Deiry, Mark W; Beitler, Jonathan J

    2014-11-15

    The current study was conducted to develop a multifactorial statistical model to predict the specific head and neck (H&N) tumor site origin in cases of squamous cell carcinoma confined to the cervical lymph nodes ("unknown primaries"). The Surveillance, Epidemiology, and End Results (SEER) database was analyzed for patients with an H&N tumor site who were diagnosed between 2004 and 2011. The SEER patients were identified according to their H&N primary tumor site and clinically positive cervical lymph node levels at the time of presentation. The SEER patient data set was randomly divided into 2 data sets for the purposes of internal split-sample validation. The effects of cervical lymph node levels, age, race, and sex on H&N primary tumor site were examined using univariate and multivariate analyses. Multivariate logistic regression models and an associated set of nomograms were developed based on relevant factors to provide probabilities of tumor site origin. Analysis of the SEER database identified 20,011 patients with H&N disease with both site-level and lymph node-level data. Sex, race, age, and lymph node levels were associated with primary H&N tumor site (nasopharynx, hypopharynx, oropharynx, and larynx) in the multivariate models. Internal validation techniques affirmed the accuracy of these models on separate data. The incorporation of epidemiologic and lymph node data into a predictive model has the potential to provide valuable guidance to clinicians in the treatment of patients with squamous cell carcinoma confined to the cervical lymph nodes. © 2014 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

  13. Increased Ki-67 proliferative index and absence of P16INK4 in CIN-HPV related pathogenic pathways different from cervical squamous intraepithelial lesion.

    PubMed

    Kuo, K-T; Chang, H-C; Hsiao, C-H; Lin, M-C

    2006-07-01

    It is generally assumed that similar pathways are involved in human papillomavirus (HPV) induced pathogenesis of cervical squamous intraepithelial lesions (SILs) and cancers and a subset of conjunctival intraepithelial neoplasm (CIN)-that the malignancies or pre-cancerous lesions arise through HPV oncoproteins E6 and E7, which disrupt the pathways of p53 and the product of the retinoblastoma (Rb) gene and, in turn, increase the protein product of gene p16INK4 through the mechanism of positive feedback. Several cell cycle molecules are detected to test this hypothesis. Nine cases of CIN and eight non-CIN cases were analysed for the expression of Ki-67, pRb, p53, and p16INK4 via immunohistochemistry. Nine cases of cervical high grade squamous intraepithelial lesion (HSIL), and 10 cases of cervical low grade squamous intraepithelial lesion (LSIL) were included for stain control of p16INK4a, and comparison of p16INK4a expression to CIN cases. A nested polymerase chain reaction and a genechip HPV typing were used to detect HPV infection and types in the CIN and non-CIN samples HPV positivity was demonstrated in all of the CIN lesions but in none of the non-CIN lesions. The Ki-67 proliferative index (Ki-67 PI) was statistically higher in the CIN group than the non-CIN group; however, there were no differences of expression of pRb and p53 between the two groups and no expression of p16INK4 in all cases. All nine cases of HSIL, and seven out of 10 cases of LSIL used for stain control were immunoreactive for p16INK4a. There were statistically significant differences in overexpression of p16INK4a between the CINs and SILs The Ki-67 proliferative index may be a sensitive marker for CIN lesions and these results, with significant differences in overexpression of p16INK4a between CINs and SILs, may provide new evidence that HPV related mucosal dysplasia in different anatomical locations may lead to dissimilar molecular pathways.

  14. Human papillomavirus induced transformation in cervical and head and neck cancers.

    PubMed

    Adams, Allie K; Wise-Draper, Trisha M; Wells, Susanne I

    2014-09-15

    Human papillomavirus (HPV) is one of the most widely publicized and researched pathogenic DNA viruses. For decades, HPV research has focused on transforming viral activities in cervical cancer. During the past 15 years, however, HPV has also emerged as a major etiological agent in cancers of the head and neck, in particular squamous cell carcinoma. Even with significant strides achieved towards the screening and treatment of cervical cancer, and preventive vaccines, cervical cancer remains the leading cause of cancer-associated deaths for women in developing countries. Furthermore, routine screens are not available for those at risk of head and neck cancer. The current expectation is that HPV vaccination will prevent not only cervical, but also head and neck cancers. In order to determine if previous cervical cancer models for HPV infection and transformation are directly applicable to head and neck cancer, clinical and molecular disease aspects must be carefully compared. In this review, we briefly discuss the cervical and head and neck cancer literature to highlight clinical and genomic commonalities. Differences in prognosis, staging and treatment, as well as comparisons of mutational profiles, viral integration patterns, and alterations in gene expression will be addressed.

  15. Human Papillomavirus Induced Transformation in Cervical and Head and Neck Cancers

    PubMed Central

    Adams, Allie K.; Wise-Draper, Trisha M.; Wells, Susanne I.

    2014-01-01

    Human papillomavirus (HPV) is one of the most widely publicized and researched pathogenic DNA viruses. For decades, HPV research has focused on transforming viral activities in cervical cancer. During the past 15 years, however, HPV has also emerged as a major etiological agent in cancers of the head and neck, in particular squamous cell carcinoma. Even with significant strides achieved towards the screening and treatment of cervical cancer, and preventive vaccines, cervical cancer remains the leading cause of cancer-associated deaths for women in developing countries. Furthermore, routine screens are not available for those at risk of head and neck cancer. The current expectation is that HPV vaccination will prevent not only cervical, but also head and neck cancers. In order to determine if previous cervical cancer models for HPV infection and transformation are directly applicable to head and neck cancer, clinical and molecular disease aspects must be carefully compared. In this review, we briefly discuss the cervical and head and neck cancer literature to highlight clinical and genomic commonalities. Differences in prognosis, staging and treatment, as well as comparisons of mutational profiles, viral integration patterns, and alterations in gene expression will be addressed. PMID:25226287

  16. Immunohistochemical detection of the X-linked inhibitor of apoptosis protein (XIAP) in cervical squamous intraepithelial neoplasia and squamous carcinoma.

    PubMed

    Burstein, David E; Idrees, Muhammad T; Li, Gon; Wu, Maoxin; Kalir, Tamara

    2008-04-01

    Premalignant and invasive squamous lesions of the uterine cervix were surveyed for the immunohistochemical detectability of the X-linked inhibitor of apoptosis protein (XIAP), believed to be the most potent of a novel group of proteins designated inhibitor of apoptosis proteins (IAPs). IAPs bind and prevent the activation of apoptosis-mediating caspases. Recent cancer biologic studies have implicated IAPs in therapeutic resistance and tumor aggressiveness. XIAP in particular is considered a highly promising target for drug discovery. Forty-four formalin-fixed and paraffin-embedded archival tissue sections were deparaffinized; subjected to citrate-based antigen retrieval; and immunostained with anti-XIAP monoclonal antibody (clone 48, BD Biosciences, San Jose, Calif) diluted 1:250, 4 degrees C x 72 hours; and developed using EnVision-Plus (Dako, Carpinteria, Calif) and diaminobenzidine as chromagen. Particulate or heterogeneous cytoplasmic staining was considered positive. Normal squamous epithelium was XIAP-positive in 7 of 34 cases (20.6%). Preinvasive intraepithelial lesions were positively stained in 54.5% of cases. Nineteen of 22 invasive squamous carcinomas were positive (86.4%). The intensity and extensiveness of XIAP immunostaining varied among individual cases, but trended upward with loss of tumor differentiation: 8 of 9 cases with strong staining were poorly differentiated carcinomas. The present study suggests the characteristic link between poor tumor differentiation and more aggressive clinical behavior could in some malignancies be based upon the concomitant induction of XIAP. Induction of XIAP appears to occur in a subset of intraepithelial lesions; in others, XIAP is detected only upon progression to invasive carcinoma. Detection of enhanced XIAP expression may also pinpoint those lesions that might benefit from pharmacologic disruption of XIAP's actions.

  17. Developmental biomechanics of the human cervical spine.

    PubMed

    Nuckley, David J; Linders, David R; Ching, Randal P

    2013-04-05

    Head and neck injuries, the leading cause of death for children in the U.S., are difficult to diagnose, treat, and prevent because of a critical void in our understanding of the biomechanical response of the immature cervical spine. The objective of this study was to investigate the functional and failure biomechanics of the cervical spine across multiple axes of loading throughout maturation. A correlational study design was used to examine the relationships governing spinal maturation and biomechanical flexibility curves and tolerance data using a cadaver human in vitro model. Eleven human cadaver cervical spines from across the developmental spectrum (2-28 years) were dissected into segments (C1-C2, C3-C5, and C6-C7) for biomechanical testing. Non-destructive flexibility tests were performed in tension, compression, flexion, extension, lateral bending, and axial rotation. After measuring their intact biomechanical responses, each segment group was failed in different modes to measure the tissue tolerance in tension (C1-C2), compression (C3-C5), and extension (C5-C6). Classical injury patterns were observed in all of the specimens tested. Both the functional (p<0.014) and failure (p<0.0001) mechanics exhibited significant relationships with age. Nonlinear flexibility curves described the functional response of the cervical spine throughout maturation and elucidated age, spinal level, and mode of loading specificity. These data support our understanding of the child cervical spine from a developmental perspective and facilitate the generation of injury prevention or management schema for the mitigation of child spine injuries and their deleterious effects.

  18. Radiation Therapy Plus Cisplatin and Gemcitabine in Treating Patients With Cervical Cancer

    ClinicalTrials.gov

    2014-12-23

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer

  19. Atypical Squamous Cells of Undetermined Significance: Bethesda Classification and Association with Human Papillomavirus

    PubMed Central

    Barcelos, Ana Cristina Macêdo; Michelin, Márcia Antoniazi; Adad, Sheila Jorge; Murta, Eddie Fernando Candido

    2011-01-01

    Introduction. To analyze patients with atypical squamous cells of undetermined significance (ASCUS) through a cytology review and the presence of microbiological agents, with consideration of colposcopy and semiannual tracking. Methods. 103 women with ASCUS were reviewed and reclassified: normal/inflammatory, ASCUS, low-grade squamous intraepithelial lesion (LSIL), or high-grade squamous intraepithelial lesion (HSIL). If ASCUS confirmed, it was subclassified in reactive or neoplastic ASCUS, ASC-US, or ASC-H; and Regione Emilia Romagna Screening Protocol. Patients underwent a colposcopic examination, and test for Candida sp., bacterial vaginosis, Trichomonas vaginalis, and human papillomavirus (HPV) were performed. Results. Upon review, ASCUS was diagnosis in 70/103 (67.9%), being 38 (54.2%) reactive ASCUS and 32 (45.71%) neoplastic ASCUS; 62 (88.5%) ASC-US and 8 (11.41%) ASC-H. ASCUS (Regione Protocol), respectively 1-5: 15 (21.4%), 19 (27.1%), 3 (27.1%), 16 (22.8%), and 1 (1.4%). A higher number of cases of cervical intraepithelial neoplasia (CIN) II/III in the biopsies of patients with ASC-H compared to ASC-US (P = .0021). High-risk HPV test and presence of CIN II/III are more frequent in ASC-H than ASC-US (P = .031). Conclusions. ASC-H is associated with clinically significant disease. High-risk HPV-positive status in the triage for colposcopy of patients with ASC-US is associated with increased of CIN. PMID:21760701

  20. Human papillomavirus-specific genotypes in cervical lesions of women referred for smears with atypical glandular cells or adenocarcinoma in situ.

    PubMed

    Rabelo-Santos, Silvia Helena; Derchain, Sophie Françoise Mauricette; Villa, Luísa Lina; Costa, Maria Cecília; Sarian, Luis Otávio Zanatta; do Amaral Westin, Maria Cristina; Kornegay, Janet; Zeferino, Luiz Carlos

    2009-05-01

    This study was designed to analyze whether specific human papillomavirus (HPV) genotypes may predict histologic outcomes in women with glandular abnormalities in their cervical smears. Of the 160 women included, 111 were diagnosed with atypical glandular cells, 35 had both atypical glandular cells and high-grade squamous intraepithelial lesions, whereas 14 women had AIS, in 1 case associated with high-grade squamous intraepithelial lesions. All women underwent colposcopic examinations and biopsy was performed in 129/160 (80.6%). Thirty-one women (19.3%) were considered negative for neoplasia and scheduled for follow-up. All specimens were tested for 27 HPV genotypes by Roche's polymerase chain reaction-reverse line blot assay. Histologic diagnoses were either cervical intraepithelial neoplasia or invasive carcinoma in 75 (58%) women, and negative for neoplasia in 54 (42%). The overall prevalence of HPV was 43%. HPV 16 was the most prevalent type followed by HPV 18. HPV 16 was significantly associated with squamous and glandular neoplasia and HPV 18 with glandular neoplasia. In women with cervical intraepithelial neoplasia 2 or 3, 11 different HPV genotypes were found, whereas in those who had invasive glandular or invasive carcinoma HPV 16 and HPV 18 were found predominantly. The detection of HPV 16 in women with glandular abnormalities in cervical smears did not help differentiating squamous from glandular lesions. However, the detection of HPV 53 in abnormal smears can predict squamous neoplasia, whereas HPV 18 can predict glandular neoplasia as histologic diagnoses.

  1. Biphenotypic human papillomavirus-associated head and neck squamous cell carcinoma: a report of two cases.

    PubMed

    Pitiyage, Gayani; Lei, Mary; Guererro Urbano, Teresa; Odell, Edward; Thavaraj, Selvam

    2015-07-11

    Human papillomavirus-associated oropharyngeal squamous cell carcinoma is now recognised as a subtype of head and neck cancer with distinct clinical, molecular and histological characteristics. The majority of these carcinomas are of non-keratinising squamous type but there is a growing number of histomorphologic variants of this disease. Here we describe the clinical, histomorphologic and immunophenotypic features of two cases of human papillomavirus-associated oropharyngeal squamous cell carcinoma demonstrating a clearly delineated biphasic differentiated and undifferentiated phenotype.

  2. Prevalence of Human Papillomavirus Genotypes Among Women With High-Grade Cervical Lesions in Beijing, China.

    PubMed

    Xiao, Meizhu; Xu, Qiuxiang; Li, Hongyan; Gao, Huiqiao; Bie, Yachun; Zhang, Zhenyu

    2016-01-01

    The aim of the study is to investigate the prevalence of high-risk human papillomavirus (hr-HPV) genotypes among Han women with high-grade cervical lesions in Beijing, China.Cervical cell specimens from patients with histopathologically confirmed cervical lesions at 7 hospitals in Beijing were examined with a validated HPV kit for 13 hr-HPV genotypes during the study period. The patients were divided into a low-grade cervical lesions group (cervical intraepithelial neoplasia grade 1, CIN1) and a high-grade cervical lesions group (CIN2+, including cervical intraepithelial neoplasia grade 2, CIN2; cervical intraepithelial neoplasia grade 3, CIN3; squamous cervical cancer, SCC; and adenocarcinoma of the cervix, ACC) based on the histopathology results.A total of 2817 eligible patients were enrolled, including 610 cases identified as CIN1 and 2207 as CIN2+. The hr-HPV positive rates in the CIN1 and CIN2+ groups were 78.2% (477/610) and 93.3% (2060/2207), respectively. The most frequently detected genotypes were HPV16, 58, 52 and18 in the CIN1 group and HPV16, 58, 33, and 52 in the CIN2+ group, in descending order of prevalence. In addition, the prevalence of HPV18 among the patients with ACC was 28.6% (14/49), significantly >7.2% (54/752) prevalence among the SCC patients (P < 0.001). Additionally, significantly more women in the CIN2+ group had multiple infections compared with those in the CIN1 group (38.1% and 24.9%, respectively; P < 0.001). However, as the cervical lesion grade increased, the prevalence of multiple hr-HPV infections gradually deceased to 44.2% in the CIN2 patients, 36.7% in the CIN3 patients, and 35.3% in the cervical cancer (CC) patients, which included SCC and ACC patients. In cases of multiple hr-HPV infections in the CIN2+ group, double infections accounted for ∼76.6%, and HPV16+58, HPV16+52, and HPV16+18 were the most common combinations, in descending order. The most frequent combination for triple infections was HPV16+58+31, with

  3. Human Papillomavirus and Head and Neck Squamous Cell Carcinoma

    PubMed Central

    Hennessey, P.T.; Westra, W.H.; Califano, J.A.

    2009-01-01

    Over the past 20 years, high-risk human papillomavirus (HPV) infection has been established as a risk factor for developing head and neck squamous cell carcinoma, independent of tobacco and alcohol use. In particular, HPV is strongly associated with the development of oropharyngeal cancer and a small minority of oral cavity cancers. In this review, we summarize what is currently known about the biology of HPV, the mechanisms by which it effects malignant transformation, and the potential impact of HPV status on the clinical management of persons with head and neck cancer. PMID:19407148

  4. Special AT-rich sequence-binding protein 1: a novel biomarker predicting cervical squamous cell carcinoma prognosis and lymph node metastasis.

    PubMed

    Wang, Shuxiang; Wang, Le; Zhang, Yu; Liu, Yunduo; Meng, Fanling; Ma, Jingquan; Shang, Pan; Gao, Ya; Huang, Qi; Chen, Xiuwei

    2015-09-01

    Special AT-rich sequence-binding protein 1 is aberrantly expressed in various malignant tumors. However, the expression and function of special AT-rich sequence-binding protein 1 in cervical squamous cell carcinoma have not been reported. The objective of this study was to investigate the clinical significance of special AT-rich sequence-binding protein 1 in cervical squamous cell carcinoma. In this study, we investigated the expression of special AT-rich sequence-binding protein 1 through immunohistochemistry in 25 normal cervix specimens and 167 cervical squamous cell carcinomas and analyzed its association with various clinicopathologic parameters, including patient outcome. Special AT-rich sequence-binding protein 1 protein was detected in 58 (34.7%) out of 167 patients and was highly related to International Federation of Gynecology and Obstetrics stage, histologic grade, lymph node metastasis, vascular-lymphatic invasion and recurrence of cervical squamous cell carcinoma. Patients with positive special AT-rich sequence-binding protein 1 expression had significantly lower overall survival and disease-free survival compared with patients with negative expression of special AT-rich sequence-binding protein 1 (P = 0.001 and P < 0.001, respectively). A multivariate Cox regression analysis revealed that special AT-rich sequence-binding protein 1 was an independent prognostic marker for both disease-free survival and overall survival of cervical squamous cell carcinoma patients (P = 0.038 and P = 0.010, respectively). A multivariate logistic regression analysis showed that special AT-rich sequence-binding protein 1 expression was strongly associated with lymph node metastasis (odds ratio = 2.497; P = 0.032). Sensitivity and specificity of special AT-rich sequence-binding protein 1 for lymph node metastasis were 61.0 and 73.8%, respectively. These results showed that special AT-rich sequence-binding protein 1 expression was associated with tumor progression

  5. Human Papillomavirus 18 Genetic Variation and Cervical Cancer Risk Worldwide

    PubMed Central

    Chen, Alyce A.; Gheit, Tarik; Franceschi, Silvia

    2015-01-01

    ABSTRACT Human papillomavirus 18 (HPV18) is the second most carcinogenic HPV type, after HPV16, and it accounts for approximately 12% of squamous cell carcinoma (SCC) as well as 37% of adenocarcinoma (ADC) of the cervix worldwide. We aimed to evaluate the worldwide diversity and carcinogenicity of HPV18 genetic variants by sequencing the entire long control region (LCR) and the E6 open reading frame of 711 HPV18-positive cervical samples from 39 countries, taking advantage of the International Agency for Research on Cancer biobank. A total of 209 unique HPV18 sequence variants were identified that formed three phylogenetic lineages (A, B, and C). A and B lineages each divided into four sublineages, including a newly identified candidate B4 sublineage. The distribution of lineages varied by geographical region, with B and C lineages found principally in Africa. HPV18 (sub)lineages were compared between 453 cancer cases and 236 controls, as well as between 81 ADC and 160 matched SCC cases. In region-stratified analyses, there were no significant differences in the distribution of HPV18 variant lineages between cervical cancer cases and controls or between ADC and SCC. In conclusion, our findings do not support the role of HPV18 (sub)lineages for discriminating cancer risk or explaining why HPV18 is more strongly linked with ADC than SCC. IMPORTANCE This is the largest and most geographically/ethnically diverse study of the genetic variation of HPV18 to date, providing a comprehensive reference for phylogenetic classification of HPV18 sublineages for epidemiological and biological studies. PMID:26269181

  6. γH2Ax Expression as a Potential Biomarker Differentiating between Low and High Grade Cervical Squamous Intraepithelial Lesions (SIL) and High Risk HPV Related SIL

    PubMed Central

    Kefala, Maria; Kottaridi, Christine; Spathis, Aris; Gouloumi, Alina-Roxani; Pouliakis, Abraham; Pappas, Asimakis; Sioulas, Vasileios; Chrelias, Charalambos; Karakitsos, Petros; Panayiotides, Ioannis

    2017-01-01

    Background γH2AX is a protein biomarker for double-stranded DNA breakage; its expression was studied in cervical squamous intraepithelial lesions and carcinomas. Methods Immunostaining for phospho-γH2AX was performed in sections from histologically confirmed cervical SIL and carcinomas, as well as from normal cervices used as controls. In total, 275 cases were included in the study: 112 low grade SIL (LGSIL), 99 high grade SIL (HGSIL), 24 squamous cell carcinoma (SCC), 12 adenocarcinoma and 28 cervical specimens with no essential lesions. Correlation of histological grading, high risk vs. low risk HPV virus presence, activated vs. non-activated status (by high risk HPV mRNA expression) and γH2AX expression in both basal and surface segments of the squamous epithelium was performed. Results Gradual increase of both basal and surface γH2AX expression was noted up from normal cervices to LGSIL harboring a low risk HPV type, to LGSIL harboring a high risk virus at a non-activated state (p<0.05). Thereafter, both basal and surface γH2AX expression dropped in LGSIL harboring a high risk virus at an activated state and in HGSIL. Conclusions γH2AX could serve as a potential biomarker discriminating between LGSIL and HGSIL, as well as between LGSIL harboring high risk HPV at an activated state. PMID:28118377

  7. Human Papillomavirus Genotype Distribution among Thai Women with High-Grade Cervical Intraepithelial Lesions and Invasive Cervical Cancer: a Literature Review.

    PubMed

    Kietpeerakool, Chumnan; Kleebkaow, Pilaiwan; Srisomboon, Jatupol

    2015-01-01

    Infection with high-risk human papillomavirus (HR-HPV) is an essential cause of cervical cancer. Because of substantial geographical variation in the HPV genotype distribution, data regarding HPV type-specific prevalence for a particular country are mandatory for providing baseline information to estimate effectiveness of currently implemented HPV-based cervical cancer prevention. Accordingly, this review was conducted to evaluate the HR-HPV genotype distribution among Thai women with precancerous cervical lesions i.e. cervical intraepithelial neoplasia grade 2-3 (CIN 2-3), adenocarcinoma in situ (AIS), and invasive cervical cancer by reviewing the available literature. The prevalence of HR-HPV infection among Thai women with CIN 2-3 ranged from 64.8% to 90.1% and the three most common genotypes were HPV 16 (38.5%), HPV 58 (20.0%), and HPV 18 (5.5%). There were high squamous cell carcinoma/CIN 2-3 prevalence ratios in women with CIN 2-3 infected with HPV 33 and HPV 58 (1.40 and 1.38, respectively), emphasizing the importance of these subtypes in the risk of progression to invasive cancer among Thai women. Data regarding the prevalence and genotype distribution of HR-HPV in Thai women with AIS remain unavailable. Interesting findings about the distribution of HPV genotype in cervical cancer among Thai women include: (1) a relatively high prevalence of HPV 52 and HPV 58 in invasive squamous cell carcinoma; (2) the prevalence of HPV 18-related adenocarcinoma is almost double thepreviously reported prevalence, and (3) 75% of neuroendocrine carcinomas are HPV18-positive when taking into account both single and multiple infections.

  8. Human papillomavirus and the long-term risk of cervical neoplasia.

    PubMed

    van der Graaf, Yolanda; Molijn, Anco; Doornewaard, Heleen; Quint, Wim; van Doorn, Leen-Jan; van den Tweel, Jan

    2002-07-15

    The risk of cervical neoplasia for women with normal Papanicolaou smears was calculated for those whose smears were human papillomavirus (HPV) positive and those whose smears were HPV negative. Data on 347 cases and controls were analyzed in a population-based, nested case-control study. Cases (n = 77) were women who participated in the Utrecht screening program (1976-1984) in the Netherlands and who developed cervical intraepithelial neoplasia 3 or microinvasive or invasive squamous cervical cancer after having a negative smear (1980-1986). Controls (n = 270) were matched on age (+/-5 years) and follow-up period. DNA was isolated from the Papanicolaou smears and was tested for the presence of HPV DNA by using the ultrasensitive broad-spectrum, general short-fragment polymerase chain reaction. HPV was found in 55 (71%) of the baseline smears of the 77 cases and in 31 (11%) of those of the 270 controls. The age-adjusted odds ratios for developing cervical intraepithelial neoplasia or microinvasive or invasive cervical cancer were 19.2 (95 percent confidence interval (CI): 10.3, 35.7) for HPV positivity in general, 5.4 (95% CI: 1.5, 19.5) for infection with low-risk HPV genotypes, 24.0 (95% CI: 12.4, 46.4) for high-risk HPV genotypes, and 104.8 (95% CI: 29.5, 372.7) for HPV type 16.

  9. Human papillomavirus-mediated carcinogenesis and HPV-associated oral and oropharyngeal squamous cell carcinoma. Part 2: Human papillomavirus associated oral and oropharyngeal squamous cell carcinoma.

    PubMed

    Feller, Liviu; Wood, Neil H; Khammissa, Razia A G; Lemmer, Johan

    2010-07-15

    Human papillomavirus (HPV) infection of the mouth and oropharynx can be acquired by a variety of sexual and social forms of transmission. HPV-16 genotype is present in many oral and oropharyngeal squamous cell carcinomata. It has an essential aetiologic role in the development of oropharyngeal squamous cell carcinoma in a subset of subjects who are typically younger, are more engaged with high-risk sexual behaviour, have higher HPV-16 serum antibody titer, use less tobacco and have better survival rates than in subjects with HPV-cytonegative oropharyngeal squamous cell carcinoma. In this subset of subjects the HPV-cytopositive carcinomatous cells have a distinct molecular profile. In contrast to HPV-cytopositive oropharyngeal squamous cell carcinoma, the causal association between HPV-16 and other high-risk HPV genotypes and squamous cell carcinoma of the oral mucosa is weak, and the nature of the association is unclear. It is likely that routine administration of HPV vaccination against high-risk HPV genotypes before the start of sexual activity will bring about a reduction in the incidence of HPV-mediated oral and oropharyngeal squamous cell carcinoma. This article focuses on aspects of HPV infection of the mouth and the oropharynx with emphasis on the link between HPV and squamous cell carcinoma, and on the limitations of the available diagnostic tests in identifying a cause-and-effect relationship of HPV with squamous cell carcinoma of the mouth and oropharynx.

  10. Cellular systems for studying human oral squamous cell carcinomas.

    PubMed

    Patel, Vyomesh; Iglesias-Bartolome, Ramiro; Siegele, Bradford; Marsh, Christina A; Leelahavanichkul, Kantima; Molinolo, Alfredo A; Gutkind, J Silvio

    2011-01-01

    The human oral squamous epithelium plays an important role in maintaining a barrier function against mechanical, physical, and pathological injury. However, the self-renewing cells residing on the basement membrane of the epithelium can give rise to oral squamous cell carcinomas (OSCC), now the sixth most common cancer in the developed world, which is still associated with poor prognosis. This is due, in part, to the limited availability of well-defined culture systems for studying oral epithelial cell biology, which could advance our understanding of the molecular basis of OSCC. Here, we describe methods to successfully isolate large cultures of human oral epithelial cells and fibroblasts from small pieces of donor tissues for use in techniques such as three-dimensional cultures and animal grafts to validate genes suspected of playing a role in OSCC development and progression. Finally, the use of isolated oral epithelial cells in generating iPS cells is discussed which holds promise in the field of oral regenerative medicine.

  11. Squamous cell carcinoma of the cervix: a cytology-histology-human papillomavirus correlation in clinical practice.

    PubMed

    Miller, Ross A; Waters, Lindsay L; Mody, Dina R; Tams, Kimberlee C

    2015-06-01

    Cervical cancer mortality has declined by 74% in the United States since the implementation of the Papanicolaou (Pap) test. Nevertheless, more than 12,000 US women annually develop cervical cancer, and squamous cell carcinoma (SqCa) remains the predominant cervical malignancy. To evaluate screening techniques used in the detection of SqCa of the cervix and provide insights regarding which technique(s) is (are) most efficacious in our study population. We retrospectively reviewed all available cytologic, human papillomavirus (HPV), and histologic malignancy burden data from patients diagnosed with SqCa. The clinical data were collected from 2 geographically and socioeconomically diverse hospital systems. Cases in which identified patients had a Pap test with a negative result/unsatisfactory specimen within 5 years of SqCa tissue diagnosis were considered Pap test screening failures. Cases in which patients were diagnosed with HPV-negative SqCa were considered HPV screening failures. Eighty-eight cases (patients' ages ranging from 19 to 73 years) were identified. Of those, cytologic history was available for 64 cases present in our electronic medical history record. Three cases were cytology screening failures (one being an unsatisfactory specimen) and 3 cases were HPV screening failures (one being the cytologic unsatisfactory case). Although measuring sensitivity in practice has limitations, we calculated the SqCa detection sensitivity at 95.3% by Pap test alone and 97% when HPV DNA testing was incorporated. Our results highlight the necessity of combining Pap and HPV testing. Although the number of cases identified is relatively small, our data suggest detection failures will decrease as the practice of combining HPV and Pap testing increases.

  12. Fine-needle aspiration of cervical lymph nodes yields adequate materials for accurate HPV testing in metastatic head and neck squamous cell carcinomas.

    PubMed

    Hou, Yanjun; Chaudhary, Shweta; Shen, Rulong; Li, Zaibo

    2016-10-01

    High-risk Human papillomavirus (HR-HPV)-associated head and neck squamous cell carcinoma (HNSCC) is a distinct epidemiologic and pathologic disease. The data of HR-HPV testing on fine-needle aspiration (FNA) materials of cervical lymph nodes in patients with metastatic HNSCC are limited. We retrospectively reviewed metastatic HNSCC cases with cervical lymph node FNAs which were tested for p16 immunohistochemistry (IHC) and HR-HPV DNA in situ hybridization (ISH). Of the 87 cases studied, the overall adequacy rate of cell block material was 86% for HR-HPV ISH, 93% for p16 IHC, 84% for both and 95% for either one. Pathologist-performed FNAs showed significantly higher percentage of satisfactory specimens for p16 and HR-HPV tests than clinician-performed FNAs. Of the 73 cases adequate for both p16 IHC and HR-HPV ISH, the concordant rate between p16 and HR-HPV results was 78%. P16 positivity had sensitivity of 90% and specificity of 75% to predict primary oropharyngeal HNSCC, while HR-HPV test showed a similar high sensitivity (91%) but a better specificity (94%). FNAs of cervical lymph nodes yield adequate materials for reliable HR-HPV testing in metastatic HNSCCs and should be incorporated into routine pathologic evaluation for these patients. The high concordance between p16 IHC and HR-HPV ISH suggests p16 IHC may serve as a surrogate for HR-HPV ISH in metastatic HNSCC cases with oropharyngeal origin and is helpful to pinpoint primary tumor site. Diagn. Cytopathol. 2016;44:792-798. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  13. Cetuximab, Cisplatin, and Radiation Therapy in Treating Patients With Stage IB, Stage II, Stage III, or Stage IVA Cervical Cancer

    ClinicalTrials.gov

    2014-12-29

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer

  14. Cisplatin and Radiation Therapy Followed by Paclitaxel and Carboplatin in Treating Patients With Stage IB-IVA Cervical Cancer

    ClinicalTrials.gov

    2017-05-03

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage IIIA Cervical Cancer; Stage IIIB Cervical Cancer; Stage IVA Cervical Cancer

  15. Clinical significance of CK7, HPV-L1, and koilocytosis for patients with cervical low-grade squamous intraepithelial lesions: a retrospective analysis.

    PubMed

    Cao, Lanqing; Sun, Ping-Li; Yao, Min; Chen, Shifan; Gao, Hongwen

    2017-07-01

    Most cervical low-grade squamous intraepithelial lesions (LSILs) do not progress to high-grade squamous intraepithelial lesions (HSILs); however, reliable biomarkers that predict LSIL progression are lacking. We investigated the association of cytokeratin 7 (CK7), human papillomavirus-L1 capsid protein (HPV-L1), and koilocytosis with clinical outcomes of patients with LSIL. CK7, HPV-L1, Ki67, and p16-INK4A expression was determined in 72 cervical LSIL and 28 HSIL biopsy samples; koilocytosis was evaluated by reviewing biopsy slides. Fifty patients with LSIL received follow-up. CK7, HPV-L1, and koilocytosis were detected in 48.6%, 44.4%, and 52.0% of LSIL tissues and in 78.6%, 10.7%, and 64.3% of HSIL tissues, respectively. Lesion grade was correlated directly with CK7 expression (P=.007) and inversely with HPV-L1 expression (P=.004). CK7 expression in LSILs was correlated inversely with HPV-L1 expression and directly with p16-INK4A and Ki67 status. Furthermore, koilocytosis was significantly associated with HPV-L1 and p16-INK4A expression. Progression to cervical intraepithelial lesions of grades ≥2 occurred in 34% of cases. CK7 negativity and HPV-L1 positivity were significantly associated with lower HSIL progression rates. HPV-L1-positive and CK7-negative LSILs showed significantly lower progression rates compared with HPV-L1-negative and CK7-positive LSILs (6.3% v-positive cases showed a significantly lower progression rate (17.6%) compared with nonkoilocytic and HPV-L1-negative cases (50%). CK7-negative, HPV-L1-positive, and koilocytic LSILs showed a progression rate of 7.7%. Koilocytosis and p16-INK4A were not significantly associated with clinical outcomes. Hence, evaluating HPV-L1, CK7, and koilocytosis profiles combined may be more reliable for LSIL prognostication. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Comparison of Cervical Spine Anatomy in Calves, Pigs and Humans.

    PubMed

    Sheng, Sun-Ren; Xu, Hua-Zi; Wang, Yong-Li; Zhu, Qing-An; Mao, Fang-Min; Lin, Yan; Wang, Xiang-Yang

    2016-01-01

    Animals are commonly used to model the human spine for in vitro and in vivo experiments. Many studies have investigated similarities and differences between animals and humans in the lumbar and thoracic vertebrae. However, a quantitative anatomic comparison of calf, pig, and human cervical spines has not been reported. To compare fundamental structural similarities and differences in vertebral bodies from the cervical spines of commonly used experimental animal models and humans. Anatomical morphometric analysis was performed on cervical vertebra specimens harvested from humans and two common large animals (i.e., calves and pigs). Multiple morphometric parameters were directly measured from cervical spine specimens of twelve pigs, twelve calves and twelve human adult cadavers. The following anatomical parameters were measured: vertebral body width (VBW), vertebral body depth (VBD), vertebral body height (VBH), spinal canal width (SCW), spinal canal depth (SCD), pedicle width (PW), pedicle depth (PD), pedicle inclination (PI), dens width (DW), dens depth (DD), total vertebral width (TVW), and total vertebral depth (TVD). The atlantoaxial (C1-2) joint in pigs is similar to that in humans and could serve as a human substitute. The pig cervical spine is highly similar to the human cervical spine, except for two large transverse processes in the anterior regions ofC4-C6. The width and depth of the calf odontoid process were larger than those in humans. VBW and VBD of calf cervical vertebrae were larger than those in humans, but the spinal canal was smaller. Calf C7 was relatively similar to human C7, thus, it may be a good substitute. Pig cervical vertebrae were more suitable human substitutions than calf cervical vertebrae, especially with respect to C1, C2, and C7. The biomechanical properties of nerve vascular anatomy and various segment functions in pig and calf cervical vertebrae must be considered when selecting an animal model for research on the spine.

  17. Difference in prevalence of human papillomavirus genotypes in cytomorphologically normal cervical smears is associated with a history of cervical intraepithelial neoplasia.

    PubMed

    Van Den Brule, A J; Walboomers, J M; Du Maine, M; Kenemans, P; Meijer, C J

    1991-05-30

    The prevalence of human papillomavirus (HPV) genotypes was investigated by the polymerase chain reaction (PCR) method in cytologically normal and abnormal cervical scrapes obtained from asymptomatic women (n = 1,346), participating in a triennial screening program for cervical cancer, and from a gynecological outpatient population (n = 593). In the symptom-free population oncogenic HPV types 16, 18, 31 and 33 were present in 1.5% of cytologically normal scrapes, while the overall HPV prevalence rate was 3.5%. Significantly, higher HPV prevalence rates of 7% (oncogenic HPV; p less than 0.01) and 14% (all HPV; p less than 0.01), respectively, were found in cytologically normal scrapes of the gynecologic outpatient population. It appeared that in this outpatient group 78% of the smears containing HPV 16 and 18 were associated with a history of cervical pathology, i.e. cervical intraepithelial neoplasia grade I to III. In smears with mild and severe dysplasia and smears suspected of carcinoma in situ from both populations, the overall HPV prevalence was 70%, 84% and 100%, respectively. In all squamous-cell carcinomas of the cervix (n = 50) HPV was detected. Frequencies of HPV 16 and 18 increased from 41% in mild dysplasia to 94% in cervical carcinomas. Since a low prevalence of HPV was found in cytomorphologically normal cervices of women without a clinicopathological history, the findings in this study suggest that HPV detection in population-based screening programs for cervical neoplasia can be an important tool in identifying women who are at risk of developing dysplasia and cervical cancer.

  18. Multiple Human Papillomavirus Infections with High Viral Loads Are Associated with Cervical Lesions but Do Not Differentiate Grades of Cervical Abnormalities

    PubMed Central

    Depuydt, Christophe; Benoy, Ina; Bogers, Johannes; Antoine, Jerome; Arbyn, Marc; Pawlita, Michael

    2013-01-01

    Multiple human papillomavirus (HPV) genotypes often coexist within cervical epithelia and are frequently detected together in smears of different grades of cervical neoplasia. Describing the association between multiple infections and cervical disease is important in generating hypotheses regarding its pathogenesis. We analyzed the prevalence of multiple HPV infections and their attribution to cervical disease in a screening population of 999 consecutive BD SurePath liquid-based cervical cytology samples enriched with atypical squamous cells of undetermined significance (ASCUS) (n = 100), low-grade squamous intraepithelial lesions (LSIL) (n = 100), and high-grade squamous intraepithelial lesions (HSIL) (n = 97). HPV genotyping was performed only on cytology specimens using a broad-spectrum GP5+/6+-PCR/multiplex HPV genotyping (BSGP5+/6+-PCR/MPG) assay that detects and quantifies 51 HPV genotypes and 3 subtypes. Using a recently defined high viral load cutoff, the quantitative data were scored as high or low viral load. In the 36-month follow-up, 79 histologically confirmed cervical intraepithelial neoplasia grade 2 or greater (CIN2+) cases were identified. In the screening population, there was a trend of having more multiple infections at a younger age. Multiple HPV infections were common. Multiple HPV types were most prevalent in LSIL (75.9% of HPV positives), followed by HSIL (65.5%), ASCUS (64.6%), and negative for intraepithelial lesion or malignancy (NILM) (36.8%). On average, 3.2 and 2.5 HPV types were detected per LSIL and HSIL sample, respectively. Multiple HPV types with high viral loads were most prevalent in LSIL (62.6% of high viral load positives), followed by HSIL (51.9%), ASCUS (40.7%), and NILM (19.3%). Patients with multiple high viral loads showed a 4- to 6-fold-higher risk of having cervical precancerous cytological lesions than did patients with single high viral loads. Compared to NILM, multiple infections, especially with multiple high viral

  19. Comparison of absorption spectra of adenocarcinoma and squamous cell carcinoma cervical tissue

    NASA Astrophysics Data System (ADS)

    Peresunko, O. P.; Zelinska, N. V.; Prydij, O. G.; Zymnyakov, D. A.; Ushakova, O. V.

    2013-12-01

    We studied a methods of assessment of a connective tissue of cervix in terms of specific volume of fibrous component and an optical density of staining of connective tissue fibers in the stroma of squamous cancer and cervix adenocarcinoma. An absorption spectra of blood plasma of the patients suffering from squamous cancer and cervix adenocarcinoma both before the surgery and in postsurgical periods were obtained. Linear dichroism measurements transmittance in polarized light at different orientations of the polarization plane relative to the direction of the dominant orientation in the structure of the sample of biotissues of stroma of squamous cancer and cervix adenocarcinoma were carried. Results of the investigation of the tumor tissues showed that the magnitude of the linear dichroism Δ is insignificant in the researched spectral range λ=280-840 nm and specific regularities in its change observed short-wave ranges.

  20. Cervical level IIb metastases in squamous cell carcinoma of the oral cavity: a systematic review and meta-analysis.

    PubMed

    Kou, Yurong; Zhao, Tengfei; Huang, Shaohui; Liu, Jie; Duan, Weiyi; Wang, Yunjing; Wang, Zechen; Li, Delong; Ning, Chunliu; Sun, Changfu

    2017-01-01

    The aim of this study was to clarify whether level IIb dissection should be performed or avoided in the treatment of oral squamous cell carcinoma by meta-analysis. Articles that were published before June 2017 were searched electronically in four databases (Web of Science, PubMed, Ovid and China National Knowledge Infrastructure) without any date or language restrictions by two independent reviewers. Abstracts and full-text papers which investigated the cervical metastases to level IIb from primary head and neck cancers and were deemed potentially relevant were screened. Data were analyzed using RevMan 5.3. Four hundred and fifty-five abstracts and 129 full-text papers were screened, and 22 studies were included in the analysis. Among the 2001 patients included, 112 patients had level IIb metastases, the pooled frequency of which was 6% (95% confidence interval [CI]: 4.0-7.0). Among the 400 patients with tongue squamous cell carcinoma from 12 studies, 37 patients had level IIb metastases, the pooled incidence of which was 7% (95% CI: 5.0-10.0). Metastases to level IIb always went together with level IIa, and only three patients were found to have isolated level IIb metastases without involving the other levels. Due to the low frequency of level IIb nodal metastases in oral squamous cell carcinoma patients and rare occurrence of isolated level IIb, level IIb dissection could be avoided when the primary lesions were in early stages (T1 and T2), with the exception of tongue cancer. It is recommended to dissect level IIb tongue cancers without considering the stages of primary lesions and the lymph nodes status. It is also suggested that level IIb dissection should be performed in patients preoperatively or intraoperatively found with multilevel neck metastasis, especially level IIa metastasis.

  1. Expression of P-Akt, NFkappaB and their correlation with human papillomavirus infection in cervical carcinoma.

    PubMed

    Du, C X; Wang, Y

    2012-01-01

    To investigate the expression of P-Akt and NFkappaB and their correlation with human papillomavirus (HPV) infection in cervical carcinoma. Expression of P-Akt and NFkappaB was detected by an immunohistochemical SP technique with HPV DNA detetion by PCR in 26 cases of cervical carcinoma tissues, 18 cases of cervical intraepithelial neoplasia tissues (CINI / n = 5, CINII / n = 3, CINIII / n = 10) and 19 cases of chronic cervicitis tissues. The different expressions of P-Akt and NFkappaB were compared in different pathological types of cervical carcinoma (cervical squamous cell carcinoma, cervical adenocarcinoma), different pathological grading (high, medium, poorly differentiated) and different clinical stage (FIGO I to IV). The relationships between P-Akt and NFkappaB, respectively, with HPV infection in cervical carcinoma were analyzed. The positive expression rate of P-Akt in chronic cervicitis tissues, CIN and cervical carcinoma tissues was 21.05%, 66.67%, and 92.31%, respectively. There was no obvious difference in the expression of P-Akt in cervical carcinoma in different pathological types or in pathological grading and no obvious difference in different clinical stages. The positive expression rate of NFkappaB in chronic cervicitis tissues, CIN and cervical carcinoma tissues was 10.52%, 72.22% and 96.15%, respectively; there was no statistically significant difference among the groups for different pathological types and there was no obvious difference in different pathological grading or different clinical stage. There was an obviously positive correlation between P-Akt and NFkappaB expression rate and degree of disease (r = 0.998, p < 0.05). Cervical carcinoma and CIN cases totaled 44; the positive expression rate of P-Akt was 87.55% in 32 cases of positive HPV-DNA of the 44 cases, and the positive expression rate of P-Akt was only 16.70% in 12 cases of negative HPV-DNA of the 44 cases. The positive expression rate of NFkappaB was obviously higher in the

  2. Epidemiology of cervical intraepithelial neoplasia: the role of human papillomavirus.

    PubMed

    Cox, J T

    1995-03-01

    The evidence implicating specific HPV types in the aetiology of cervical cancer is now strong enough to establish a causative role. HPV infection of the cervix affects the developing immature metaplastic cells of the transformation zone. Cervical neoplasia can be viewed as the interaction of high risk papillomavirus and immature metaplastic epithelium. Once maturity is reached, there is minimal risk of subsequent development of cervical squamous neoplasia. Exposure to HPV is an extremely common event, especially in young sexually active women. Yet, despite frequent HPV exposure at that phase of life in which the cervical transformation zone is at its most vulnerable, established expressed disease is relatively uncommon. Most studies in which the natural history of CIN is not altered by cervical biopsy reveal a progression rate from low to high grade CIN of less than one third. Where viral type is taken into account, however, the progression rate from normal but high risk HPV-infected cervical epithelium to CIN 2 or 3 is higher. Despite this, most cervical abnormalities will not transform into invasive cancer, even if left untreated. The variance between the high rate of HPV infection, the intermediate rate of CIN and the relatively low rate of cervical cancer establishes a stepwise gradient of disease of increasing severity with decreasing prevalence. In an immunocompetent host, HPV infection alone does not appear to be sufficient to induce the step from high grade CIN to invasion. Epidemiological studies indicating that HPV infection with oncogenic viral types is far more common than cervical neoplasia suggest the necessity of cofactors in cervical carcinogenesis. The long time-lag between initial infection and eventual malignant conversion suggests that random events may be necessary for such conversion, and the spontaneous regression of many primary lesions suggests that most patients are not exposed to these random events. Potential cofactors include cigarette

  3. Cisplatin and Radiation Therapy With or Without Tirapazamine in Treating Patients With Cervical Cancer

    ClinicalTrials.gov

    2014-06-18

    Cervical Adenocarcinoma; Cervical Adenosquamous Cell Carcinoma; Cervical Squamous Cell Carcinoma; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer

  4. [Human papillomavirus detection in cervical cancer prevention].

    PubMed

    Picconi, María Alejandra

    2013-01-01

    Cervical cancer (CC), which is strongly associated to high-risk human papillomavirus (hr-HPV) infection, continues being a significant health problem in Latin America. The use of conventional cytology to detect precancerous cervical lesions has had no major impact on reducing CC incidence and mortality rates, which are still high in the region. New screening tools to detect precancerous lesions became available, which provide great opportunities for CC prevention, as do highly efficacious HPV vaccines able to prevent nearly all lesions associated with HPV-16 and -18 when applied before viral exposure. Currently, hr-HPV testing represents an invaluable component of clinical guidelines for screening, management and treatment of CC and their precursor lesions. Many testing strategies have been developed that can detect a broad spectrum of hr-HPV types in a single assay; however, only a small subset of them has documented clinical performance for any of the standard HPV testing indications. HPV tests that have not been validated and lack proof of reliability, reproducibility and accuracy should not be used in clinical management. Once incorporated into the lab, it is essential to submit the whole procedure of HPV testing to continuous and rigorous quality assurance to avoid sub-optimal, potentially harmful practices. Recent progress and current status of these methods are discussed in this article.

  5. Human Papillomavirus and Epstein-Barr virus co-infection in Cervical Carcinoma in Algerian women

    PubMed Central

    2013-01-01

    Background Despite the fact that the implication of human papillomavirus (HPV) in the carcinogenesis and prognosis of cervical cancer is well established, the impact of a co-infection with high risk HPV (HR-HPV) and Epstein-Barr virus (EBV) is still not fully understood. Methods Fifty eight randomly selected cases of squamous cell carcinomas (SCC) of the uterine cervix, 14 normal cervices specimens, 21 CIN-2/3 and 16 CIN-1 cases were examined for EBV and HPV infections. Detection of HR-HPV specific sequences was carried out by PCR amplification using consensus primers of Manos and by Digene Hybrid Capture. The presence of EBV was revealed by amplifying a 660 bp specific EBV sequence of BALF1. mRNA expression of LMP-1 in one hand and protein levels of BARF-1, LMP-1 and EBNA-1 in the other hand were assessed by RT-PCR and immunoblotting and/or immunohischemistry respectively. Results HR-HPV infection was found in patients with SCC (88%), low-grade (75%) and high grade (95%) lesions compared to only 14% of normal cervix cases. However, 69%, 12.5%, 38.1%, and 14% of SCC, CIN-1, CIN-2/3 and normal cervix tissues, respectively, were EBV infected. The highest co-infection (HR-HPV and EBV) was found in squamous cell carcinoma cases (67%). The latter cases showed 27% and 29% expression of EBV BARF-1 and LMP-1 oncogenes respectively. Conclusion The high rate of HR-HPV and EBV co-infection in SCC suggests that EBV infection is incriminated in cervical cancer progression. This could be taken into account as bad prognosis in this type of cancer. However, the mode of action in dual infection in cervical oncogenesis needs further investigation. PMID:24252325

  6. Human Papillomavirus Genotype Distribution among Cervical Cancer Patients prior to Brazilian National HPV Immunization Program

    PubMed Central

    Martins, Luís Felipe L.; Pontes, Valéria B.; Corrêa, Flávia M.; Montenegro, Raquel C.; Pinto, Laine C.; Soares, Bruno M.; Vidal, João Paulo C. B.; Félix, Shayany P.; Bertoni, Neilane; Moreira, Miguel Angelo M.

    2017-01-01

    To evaluate the impact of HPV immunization and possible changes in virus type-specific prevalence associated with cervical cancer, it is important to obtain baseline information based on socioeconomic, educational, and environmental characteristics in human populations. We describe these characteristics and the type-specific HPV distribution in 1,183 women diagnosed with cervical cancer in two Brazilian healthcare institutions located at the Southeastern (Rio de Janeiro/RJ) and the Amazonian (Belém/PA) regions. Large differences were observed between women in these regions regarding economic, educational, and reproductive characteristics. The eight most frequent HPV types found in tumor samples were the following: 16, 18, 31, 33, 35, 45, 52, and 58. Some HPV types classified as unknown or low risk were found in tumor samples with single infections, HPV 83 in RJ and HPV 11, 61, and 69 in PA. The proportion of squamous cervical cancer was lower in RJ than in PA (76.3% versus 87.3%, p < 0.001). Adenocarcinoma was more frequent in RJ than in PA (13.5% versus 6.9%, p < 0.001). The frequency of HPV 16 in PA was higher in younger women (p < 0.05). The success of a cervical cancer control program should consider HPV types, local health system organization, and sociodemographic diversity of Brazilian regions. PMID:28512474

  7. The prognostic significance of beta human chorionic gonadotrophin and its metabolites in women with cervical carcinoma.

    PubMed Central

    Crawford, R A; Iles, R K; Carter, P G; Caldwell, C J; Shepherd, J H; Chard, T

    1998-01-01

    AIMS: To examine long term survival of women with primary and recurrent cervical carcinoma in relation to (1) excretion of beta-core (a urinary metabolite of beta human chorionic gonadotrophin (beta hCG)) and (2) beta hCG immunostaining of the tumours, to determine the suitability of these markers for assessing prognosis. METHODS: This was a prospective observational study undertaken in a gynaecological oncology centre: 57 women with primary cervical cancer and 42 with recurrent disease were recruited between January 1990 and September 1992. Kaplan-Meier survival analysis with the log rank test was used to assess survival differences with survival rate given per year of follow up. RESULTS: In primary disease, the four year survival for the beta-core negative group was 79%, compared with 14% for the beta-core positive group (p = 0.001). This was still significant for early stage disease or squamous lesions alone. In recurrent disease, beta-core positivity was not prognostically significant. Immunohistochemistry was of no prognostic significance in either group. CONCLUSIONS: beta-core excretion appears to be useful in assessing prognosis of primary cervical cancer but not of recurrent disease. A large prospective study of urinary beta-core in early stage cervical cancer is needed to determine whether it can be used as an index for modifying treatment. PMID:9930074

  8. Quantitative detection of molecular markers ProEx C (minichromosome maintenance protein 2 and topoisomerase IIa) and MIB-1 in liquid-based cervical squamous cell cytology.

    PubMed

    Beccati, Maria Donatella; Buriani, Carolina; Pedriali, Massimo; Rossi, Sonia; Nenci, Italo

    2008-06-25

    In this study, the authors conducted a comparative quantitative evaluation of the proliferation markers ProEx C (an aberrant S-phase induction marker, human papillomavirus E6-E7 correlated) and MIB-1 in squamous intraepithelial lesions (SIL) to identify a biomolecular profile informative for the diagnosis of high-grade SIL/cervical intraepithelial neoplasia 3 or greater that was complementary to the morphologic Papanicolaou (Pap) test ("biomolecular Pap test"). After the cytologic diagnosis, reflex immunocytochemistry was carried out on 76 unstained SurePath cell samples (20 routine samples that were negative for intraepithelial lesion or malignancy and 56 positive samples that were selected with matching histology). Both a morphometric analysis with a software imaging analysis system and a quantitative analysis of atypical squamous clusters were performed. The quantitative evaluation revealed an excellent, direct correlation between the 2 markers, although ProEx C was more selective and more informative for the progression of low- and moderate-grade lesions, because it only revealed cells in aberrant S-phase cell cycle. The quantitative morphometric analysis revealed the increased presence of atypical, positive clusters and the percentage of positive cells within, both paralleling the severity of the lesions. The threshold of a 3% ProEx C-positive nuclear area was useful for splitting lesions into groups with a low risk or high risk of progression. Both ProEx C and MIB-1 were valid proliferation markers in cytologic preparations, and nuclear positivity was quantified successfully by using computer-assisted analysis. The analysis of atypical clusters may be a valuable tool in the diagnosis of SIL. The presence of atypical clusters and their positivity for proliferation markers are good first-glance indicators of lesion grade. (c) 2008 American Cancer Society.

  9. Frequency of Human papillomavirus in women attending cervical cancer screening program in Chile.

    PubMed

    Brebi, Priscilla; Ili, Carmen Gloria; Andana, Alejandra; Menzel, Doris; Lopez, Jaime; Guzman, Pablo; Melo, Angelica; Buchegger, Kurt; Roa, Juan C

    2017-08-03

    Human papillomavirus (HPV) is the etiological factor for cervical cancer and its precursor lesions. The characterization of HPV genotypes in preneoplastic lesions and cervical cancer could establishes the effectiveness of vaccination plan in Chilean population. The aim of this study was to determine HPV frequency in a group of women including in a cervical screening program in the public health care system in Chile. We analyzed 985 cervical smears samples from women with different histological diagnosis, attending to public health care in Temuco-Chile between 2004 and 2012, to detect HPV genotypes, through PCR followed by reverse line blotting assay. HPV was found present in 80.8% (n = 796) of samples. Only a 5.6% of 985 samples were infected with a low-risk HPV, considering multiple infections. 10.5% (n = 8/76) of normal cervical epithelia, 83.5% (n = 208/249) and 87.6% (n = 557/636) of low and high grade squamous intraepithelial lesions, respectively, and 95.8% (n = 23/24) of squamous cervical carcinomas tested positive for HPV. HPV 16 was the most frequent genotype found (Overall 44.9%, n = 442/985; SCC: 62.5%, n = 15/24). A high variability of HPV types was also found in preneoplastic lesions, whereas there was a selection of genotypes in neoplasia. Also, there was a higher risk of infection with HPV 16 in women ≤26 years and 34-41 years old (p < 0.05), meanwhile infections with HPV 16 or HPV 18 have related with cancer development (p < 0.01). These data provide further information about the frequency of HPV genotypes in women with cervical lesions in Chile, and the introduction of new targeted vaccines against a wider spectrum of HPV is suggested.

  10. Cervical Spine Stiffness and Geometry of the Young Human Male

    DTIC Science & Technology

    1982-11-01

    vertebrae as compared with the cervical , thus, conferring greater mobility to the cervical spine ; c) The articular facet joint subtends, in sagittal section...AFAMRL- TR-80-138 V’o CERVICAL SPINE STIFFNESS AND GEOMETRY OF <P4 THE YOUNG HUMAN MALE Y. KING LIUQ Ph.D. K. W. KRIEGER, Ph.D. G. NJUS, M.S. K. UENO...t3 5-_3_ 4 TITLE and SubItle) 5 TYPE OF REPORT & PERIOD COVERED CERVICAL SPINE STIFFNESS AND GEOMETRY OF THE YOUNG HUM&N MALE s PER•OR,’NGO’G

  11. Inhibitory action of relaxin on human cervical smooth muscle.

    PubMed

    Norström, A; Bryman, I; Wiqvist, N; Sahni, S; Lindblom, B

    1984-09-01

    The influence of purified porcine relaxin on contractility of human cervical smooth muscle was investigated in vitro. Strips of cervical tissue were obtained by needle biopsy from pregnant and nonpregnant women and were mounted in a superfused organ chamber for isometric measurement of contractile activity. Relaxin (0.005-25 micrograms/ml) inhibited the spontaneous contractions in cervical strips from 18% of nonpregnant, 68% of early pregnant, and in 100% of term pregnant women. These results indicate that relaxin has an inhibitory action on cervical smooth muscle and that this effect is more constantly detected as pregnancy proceeds.

  12. Infracentimetric cervical lymph node metastasis in head and neck squamous cell carcinoma: Incidence and prognostic value.

    PubMed

    Pauzie, A; Gavid, M; Dumollard, J-M; Timoshenko, A; Peoc'h, M; Prades, J-M

    2016-11-01

    Supracentimetric cervical lymph node metastasis is classically a poor prognostic factor for locoregional recurrence and survival in head and neck cancer. Causality, however, is more controversial for infracentimetric cervical lymph node metastases. The objective of this study was to evaluate the incidence and prognostic value of infracentimetric lymph node metastasis. Two hundred and forty-three neck dissections from 150 head and neck cancer patients were analyzed. A single pathologist exhaustively inventoried the number and size of all adenopathies in the surgical specimen. Cervical lymph node metastases were infracentimetric in 38% of cases, with 72% extracapsular spread (versus 91% for supracentimetric adenopathies; P<0.01). Infracentimetric metastases were more often associated with other cervical lymph node metastases (mean 5.3 versus 3.9; P=0.14). Fifty three percent of specimens showed only supracentimetric metastases (versus 13% infracentimetric metastases; P<0.01). Disease-specific and failure-free survival were lower in case of infracentimetric metastasis, associated with supracentimetric metastasis or not, than in case of macrometastasis only. Infracentimetric cervical lymph node metastasis is a factor of poor prognosis, and may represent a different, more aggressive lymphatic process. We suggest complete neck dissection by the surgeon and meticulous analysis by the pathologist, the results of which guide complementary therapy. Close surveillance of recurrence is also recommended. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  13. Glycoprotein and Glycan in Tissue and Blood Samples of Patients With Stage IB-IVA Cervical Cancer Undergoing Surgery to Remove Pelvic and Abdominal Lymph Nodes

    ClinicalTrials.gov

    2016-10-26

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer

  14. Human papillomavirus types and recurrent cervical warts

    SciTech Connect

    Nuovo, G.J. ); Pedemonte, B.M. )

    1990-03-02

    The authors analyzed cervical intraepithelial neoplasias (CINs) detected after cryotherapy to determine if recurrence is associated with the same human papillomavirus (HPV) type found in the original lesion. Eight women had detectable HPV DNA in CINs that occurred after ablation of another CIN, and for each patient the HPV type in the pretreatment lesion was different from that in the CIN that appeared after cryotherapy. This compares with 12 women who had HPV detected in two or more CINs present at the same time, 11 of whom had the same HPv type noted. they concluded that although multiple, simultaneous CINs in a woman often contain the same HPV type, recurrent CINs that occur after cryotherapy contain an HPV type different from that present in the pretreatment lesion.

  15. Human Papillomavirus Types Distribution in Organised Cervical Cancer Screening in France

    PubMed Central

    Heard, Isabelle; Tondeur, Laura; Arowas, Laurence; Falguières, Michael; Demazoin, Marie-Christine; Favre, Michel

    2013-01-01

    Background Knowledge of prevalence rates and distribution of human papillomavirus (HPV) genotypes prior high HPV vaccine coverage is necessary to assess its expected impact on HPV ecology and on cervical lesions and cancers. Methods Residual specimens of cervical cytology (N = 6,538) were obtained from 16 sites participating in organised cervical cancer screening pilot programs throughout France, anonymised and tested for HPV DNA using the PapilloCheck® genotyping test. Samples were stratified according to age of women and cytological grades. Results The age-standardised prevalence rates of HPV 16 and/or 18 (with or without other high-risk types) was 47.2% (95% Confidence Interval, CI: 42.4–52.1) in high-grade squamous intraepithelial lesions (HSILs), 20.2% in low-grade SIL (95% CI: 16.7–23.7) and 3.9% (95% CI: 2.8–5.1) in normal cytology. Overall HR HPV were detected in 13.7% (95%I CI: 11.7–15.6) of normal cytology. In women below 30 years of age, 64% of HSILs were associated with HPV16 and/or 18. In our study population, HPV16 was the most commonly detected type in all cervical grades with prevalence rates ranking from 3.0% in normal cytology to 50.9% in HSILs. HPV16 was also detected in 54% (27/50) of invasive cervical cancers including 5 adenocarcinomas. Conclusion HPV16 was strongly associated with cervical precancer and cancer. The high prevalence rates of HPV16/18 infection among women below 30 years of age with HSILs suggests that the impact of vaccination would be primarily observed among young women. PMID:24244490

  16. Human papillomavirus genotypes distribution in 175 invasive cervical cancer cases from Brazil

    PubMed Central

    2013-01-01

    Background Invasive cervical cancer is the second most common malignant tumor affecting Brazilian women. Knowledge on Human Papillomavirus (HPV) genotypes in invasive cervical cancer cases is crucial to guide the introduction and further evaluate the impact of new preventive strategies based on HPV. We aimed to provide updated comprehensive data about the HPV types’ distribution in patients with invasive cervical cancer. Methods Fresh tumor tissue samples of histologically confirmed invasive cervical cancer were collected from 175 women attending two cancer reference hospitals from São Paulo State: ICESP and Hospital de Câncer de Barretos. HPV detection and genotyping were performed by the Linear Array HPV Genotyping Test (Roche Molecular Diagnostics, Pleasanton,USA). Results 170 out of 172 valid samples (99%) were HPV DNA positive. The most frequent types were HPV16 (77.6%), HPV18 (12.3%), HPV31 (8.8%), HPV33 (7.1%) and HPV35 (5.9%). Most infections (75%) were caused by individual HPV types. Women with adenocarcinoma were not younger than those with squamous cell carcinoma, as well, as women infected with HPV33 were older than those infected by other HPV types. Some differences between results obtained in the two hospitals were observed: higher overall prevalence of HPV16, absence of single infection by HPV31 and HPV45 was verified in HC-Barretos in comparison to ICESP patients. Conclusions To our knowledge, this is one of the largest studies made with fresh tumor tissues of invasive cervical cancer cases in Brazil. This study depicted a distinct HPV genotype distribution between two centers that may reflect the local epidemiology of HPV transmission among these populations. Due to the impact of these findings on cervical cancer preventive strategies, extension of this investigation to routine screening populations is warranted. PMID:23883423

  17. Gynecologic Cancer InterGroup (GCIG) consensus review for cervical adenocarcinoma.

    PubMed

    Fujiwara, Hiroyuki; Yokota, Harushige; Monk, Bradley; Treilleux, Isabelle; Devouassoux-Shisheboran, Mojgan; Davis, Alison; Kim, Jae-Weon; Mahner, Sven; Stany, Michael; Pignata, Sandro; Ray-Coquard, Isabelle; Fujiwara, Keiichi

    2014-11-01

    Cervical adenocarcinoma is known to be less common than squamous cell carcinoma of the cervix comprising approximately 25% of all cervical carcinomas. Differences in associated human papillomavirus types, patterns of spread, and prognosis call for treatments that are not always like those for squamous cancers. In this review, we report a consensus developed by the Gynecologic Cancer InterGroup surrounding cervical adenocarcinoma for epidemiology, pathology, treatment, and unanswered questions. Prospective clinical trials are needed to help develop treatment guidelines.

  18. [Presence of high risk human papilomaviruses (HPV) in the low grade cervical lesion].

    PubMed

    Iljazović, Ermina; Mustadenagić-Mujanović, Jasminka; Karasalihović, Zinaida; Cickusić, E; Avdić, S

    2006-01-01

    Low grade squamous intraepithelial lesion (LGSIL) and atypical squamous cells undetermined significance (ASCUS) are the most frequent verified cellular abnormalities. Their management are still highly controversial mostly caused by uncertainty about their histology and nature of originate. Detection of HPV DNA in the absence of cytological abnormalities can also indicate presence of high-grade cervical intraepithelial neoplasia (CIN). The aim of this study was to show the association of the benign cellular changes, ASCUS and LGSIL with oncogenic types of HPV and to prove the necessity of more intensive screening of this group of patients. Cytology and pathomorphology analyses were performed first. Identification of the presence of human papiloma virus was carried out by the Digene Hybride Capture II test for all patients. Identification of different HPV types for the particular number of patients was carried out by RFLP (Rsetriction Fragments Length of Polymorphism). Out of the 101 patients in the first group 92 (91,08%) were HPV positive, and 41, 58% had no cellular abnormalities, ASCUS or LGSIL. Out of 509 patients of the second group 26.92% were positive for HRHPV, and 78,97% of them had no cellular abnormalities, ASCUS or LGSIL. HPV 16 was detected in 27.36% (ASCUS/LGSIL) of low risk cervical lesion of the first examined period. The combination of smears with the detection of high risk HPV types increases the triage sensitivity especially at patients with mild.

  19. Human Papillomavirus types distribution among women with cervical preneoplastic, lesions and cancer in Luanda, Angola

    PubMed Central

    Damião, Paciência de Almeida; Oliveira-Silva, Michelle; Moreira, Miguel Ângelo; Poliakova, Natalia; de Lima, Maria Emilia RT; Chiovo, José; Nicol, Alcina Frederica

    2016-01-01

    Introduction Cervical cancer is the leading cause of cancer deaths among females in Angola and human papillomavirus (HPV) is the main risk factor for the development of pre-cancerous squamous intraepithelial lesions. The diversity and frequency of HPV types in Angola has yet to be reported. Aim To determine the frequency of HPV among women with squamous intraepithelial lesions from women in Luanda, Angola. Methods Study participants included women diagnosed with cytological abnormalities that voluntarily provided Pap smears (n = 64). Genomic DNA was extracted from the samples for use as templates in the PCR amplification of HPV sequences. PCR products were sequenced to determine HPV type. Results HPV DNA was detected in 71.9% (46/64) in the samples. A higher diversity of HPV types was found in the cytological lesions, such as ASCUS and LSIL (HPV16, 6, 18, 31, 58, 66, 70 and 82, in order of frequency) than that detected for HSIL and SSC (HPV16, 18, 6 and 33). The most prevalent HPV type were: HPV16, HPV6 and HPV18. Conclusion This is the first report on HPV type diversity and frequency in woman of Angola. The results suggest that large-scale studies across Africa would improve our understanding of interrelationship between HPV infections and cervical cancer. More directly, the identification of the HPV types most prevalent suggests that women in Angola would benefit from currently available HPV vaccines. PMID:28154623

  20. Variants of human papillomavirus types 16 and 18: histological findings in women referred for atypical glandular cells or adenocarcinoma in situ in cervical smear.

    PubMed

    Rabelo-Santos, Silvia Helena; Villa, Luísa Lina; Derchain, Sophie Françoise; Ferreira, Silvaneide; Sarian, Luis Otávio Zanatta; Angelo-Andrade, Liliana Aparecida Lucci; do Amaral Westin, Maria Cristina; Zeferino, Luiz Carlos

    2006-10-01

    Human papillomavirus (HPV) genotypes cannot fully explain the histological diagnosis of women with glandular abnormalities detected by cervical smear. Thus, this study was designed to analyze the distribution of HPV-16 and HPV-18 variants in women referred because of atypical glandular cells and adenocarcinoma in situ in their cervical smears and its association with histological results. Twenty-four women with HPV-16 and 6 with HPV-18, selected from 160 women with cervical smears suggestive of glandular abnormalities, were included. Histological results showed cervicitis (1 case), squamous neoplasia (18 cases), glandular neoplasia (7 cases), and glandular neoplasia associated with a squamous component (4 cases). Among the 24 cases presenting HPV-16, the European variant was detected in 15 (62%) and the Asian American in 9 (38%). Among the 15 cases associated with the European variant, 14 (93%) presented squamous neoplasia and 1 (7%) invasive adenocarcinoma. Asian-American HPV-16 variants were significantly associated with histological diagnosis of glandular neoplasia alone (odds ratio, 9.3 [1.4-60.2]) or associated with squamous neoplasia (odds ratio, 18.7 [1.5-232.3]). Adenocarcinomas were detected in 4 of 6 HPV-18-positive cases, being 2 cases had the European variant, 1 had the Asian Amerindian variant, and 1 had the African variant. The association of HPV-16 with squamous or glandular neoplasia is explained by its variants. In this study, squamous neoplasia was related to the European variant of HPV-16, whereas glandular neoplasia was related to the Asian-American variant. Glandular neoplasia is associated with HPV-18, but the results of our analysis of its variants were inconclusive.

  1. Increased expression of long non-coding RNA XIST predicts favorable prognosis of cervical squamous cell carcinoma subsequent to definitive chemoradiation therapy

    PubMed Central

    Kobayashi, Reiko; Miyagawa, Ryu; Yamashita, Hideomi; Morikawa, Teppei; Okuma, Kae; Fukayama, Masashi; Ohtomo, Kuni; Nakagawa, Keiichi

    2016-01-01

    The present retrospective study aimed to examine the association between the expression of long non-protein-coding RNAs (lncRNAs) and clinical prognosis in the pretreatment formalin-fixed, paraffin-embedded (FFPE) tissue samples of cervical squamous cell carcinoma patients that underwent platinum-based chemoradiation therapy. Between 2001 and 2013, 49 consecutive patients with squamous cell cervical carcinoma were selected for the present study (median follow-up period, 44.1 months). The patients possessed an International Federation of Gynecology and Obstetrics stage of IB1/IIA1 (with pelvic lymph node metastasis), IB2 or IIA2-IVA, and had been treated with definitive chemoradiation therapy. The pretreatment FFPE tumor biopsies of the patients obtained diagnosis were used for analysis. Total RNAs were extracted from the FFPE tumor tissues and reverse transcription-quantitative polymerase chain reaction was performed to examine the expression level of lncRNAs. The expression level of X inactive-specific transcript (XIST) demonstrated a significant association with the overall survival rate (P=0.014). The 4-year overall survival rates were 87.1 and 54.4% in the high and low XIST expression groups, respectively. Since the expression of XIST is associated with the overall survival rate, this lncRNA has the potential to become a predictor for the prognosis of cervical squamous cell carcinoma patients that are treated with chemoradiation therapy. Additional studies are required to investigate the underlying mechanisms of XIST that are associated with prognosis. PMID:27899965

  2. Polypeptide synthesis in columnar and squamous explants of human uterine cervix.

    PubMed

    Cowan, M E; Ward, K; Woodman, C B; Skinner, G R

    1982-10-01

    There were quantitative and qualitative differences in the in-vitro synthesis of 3 polypeptides between squamous and columnar epithelial explants of human cervix. One cross-linked keratin-like polypeptide of mol. wt 50,000 was synthesized and phosphorylated by squamous but not by columnar explants; a second cross-linked keratin-like polypeptide of mol. wt 52,000, which was present in larger amounts in squamous than columnar explants, was both glycosylated and phosphorylated during in-vitro explantation of squamous tissue; a third polypeptide of mol. wt 25,200 which was keratin-like but not cross-linked, was synthesized in squamous-tissue explants but in only 4% of columnar-tissue explants.

  3. Polypeptide synthesis in columnar and squamous explants of human uterine cervix.

    PubMed Central

    Cowan, M. E.; Ward, K.; Woodman, C. B.; Skinner, G. R.

    1982-01-01

    There were quantitative and qualitative differences in the in-vitro synthesis of 3 polypeptides between squamous and columnar epithelial explants of human cervix. One cross-linked keratin-like polypeptide of mol. wt 50,000 was synthesized and phosphorylated by squamous but not by columnar explants; a second cross-linked keratin-like polypeptide of mol. wt 52,000, which was present in larger amounts in squamous than columnar explants, was both glycosylated and phosphorylated during in-vitro explantation of squamous tissue; a third polypeptide of mol. wt 25,200 which was keratin-like but not cross-linked, was synthesized in squamous-tissue explants but in only 4% of columnar-tissue explants. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:6184064

  4. p16(INK4a) as a complementary marker of high-grade intraepithelial lesions of the uterine cervix. I: Experience with squamous lesions in 189 consecutive cervical biopsies.

    PubMed

    Dray, Michael; Russell, Peter; Dalrymple, Chris; Wallman, Neil; Angus, George; Leong, Adelyn; Carter, Jonathan; Cheerala, Bharathi

    2005-04-01

    To test the usefulness of p16(INK4a) immunostaining for improving the diagnostic accuracy of cervical punch biopsies referred to a routine laboratory setting during the investigation of women with abnormal Papanicolaou smears. A total of 188 consecutive and unselected colposcopically directed cervical biopsies and a single contemporaneous cervical polyp were accessioned prospectively over a 3-month period, step-serially sectioned and examined by H&E and immunostained for p16(INK4a). The clinical context, results of concurrent Papanicolaou smears/ThinPrep slides and Digene hybrid capture tests for high-risk human papillomavirus (HPV) subtypes, as well as follow-up cervical smears/ThinPrep, biopsies and loop excisions of transformation zones or cone biopsies were all correlated with the morphological and immunohistochemical findings. Seventy-seven biopsies (40.7%) displayed a high-grade squamous intraepithelial lesion (HGSIL; cervical intraepithelial neoplasia [CIN] 2-3), 27 (14.3%) showed a low grade squamous intraepithelial lesion (HPV +/- CIN1) and 85 (45%) showed a range of non-dysplastic (inflammatory or reactive) changes. Diffuse strong parabasal immunostaining for p16(INK4a), suggestive of integrated high-risk HPV DNA into the host genome, was observed in 81 biopsies (42.9%, including the cervical polyp) and correlated (>90%) with HGSIL in the H&E sections. Only one case revealed irreconcilable discordance between the histological features and this strong parabasal immunostaining pattern. Focal and weaker midzonal or superficial p16(INK4a) immunostaining, suggestive of episomal HPV infection, was noted in 19 biopsies (10%) and these biopsies exhibited a range of histological changes but predominantly low grade squamous intraepithelial lesion (LGSIL). No staining of the squamous epithelium was seen in 89 biopsies (47.1%). Again, only one case revealed irreconcilable discordance between the histological features and this negative immunostaining pattern. On

  5. Human Papillomavirus Testing in the Prevention of Cervical Cancer

    PubMed Central

    Wentzensen, Nicolas; Wacholder, Sholom; Kinney, Walter; Gage, Julia C.; Castle, Philip E.

    2011-01-01

    Strong evidence now supports the adoption of cervical cancer prevention strategies that explicitly focus on persistent infection with the causal agent, human papillomavirus (HPV). To inform an evidence-based transition to a new public health approach for cervical cancer screening, we summarize the natural history and cervical carcinogenicity of HPV and discuss the promise and uncertainties of currently available screening methods. New HPV infections acquired at any age are virtually always benign, but persistent infections with one of approximately 12 carcinogenic HPV types explain virtually all cases of cervical cancer. In the absence of an overtly persistent HPV infection, the risk of cervical cancer is extremely low. Thus, HPV test results predict the risk of cervical cancer and its precursors (cervical intraepithelial neoplasia grade 3) better and longer than cytological or colposcopic abnormalities, which are signs of HPV infection. The logical and inevitable move to HPV-based cervical cancer prevention strategies will require longer screening intervals that will disrupt current gynecologic and cytology laboratory practices built on frequent screening. A major challenge will be implementing programs that do not overtreat HPV-positive women who do not have obvious long-term persistence of HPV or treatable lesions at the time of initial evaluation. The greatest potential for reduction in cervical cancer rates from HPV screening is in low-resource regions that can implement infrequent rounds of low-cost HPV testing and treatment. PMID:21282563

  6. The different functions and clinical significances of caveolin-1 in human adenocarcinoma and squamous cell carcinoma

    PubMed Central

    Fu, Pin; Chen, Fuchun; Pan, Qi; Zhao, Xianda; Zhao, Chen; Cho, William Chi-Shing; Chen, Honglei

    2017-01-01

    Caveolin-1 (Cav-1), a major structural protein of caveolae, is an integral membrane protein which plays an important role in the progression of carcinoma. However, whether Cav-1 acts as a tumor promoter or a tumor suppressor still remains controversial. For example, the tumor-promoting function of Cav-1 has been found in renal cancer, prostate cancer, tongue squamous cell carcinoma (SCC), lung SCC and bladder SCC. In contrast, Cav-1 also plays an inhibitory role in esophagus adenocarcinoma, lung adenocarcinoma and cutaneous SCC. The role of Cav-1 is still controversial in thyroid cancer, hepatocellular carcinoma, gastric adenocarcinoma, colon adenocarcinoma, breast cancer, pancreas cancer, oral SCC, laryngeal SCC, head and neck SCC, esophageal SCC and cervical SCC. Besides, it has been reported that the loss of stromal Cav-1 might predict poor prognosis in breast cancer, gastric cancer, pancreas cancer, prostate cancer, oral SCC and esophageal SCC. However, the accumulation of stromal Cav-1 has been found to be promoted by the progression of tongue SCC. Taken together, Cav-1 seems playing a different role in different cancer subtypes even of the same organ, as well as acting differently in the same cancer subtype of different organs. Thus, we hereby explore the functions of Cav-1 in human adenocarcinoma and SCC from the perspective of clinical significances and pathogenesis. We envision that novel targets may come with the further investigation of Cav-1 in carcinogenesis. PMID:28243118

  7. Human papillomavirus among women with atypical squamous cells of undetermined significance in southern Brazil.

    PubMed

    Paesi, Suelen; Correa, Leonardo; Tregnago, Márcia Caldart; Mandelli, Jovana; Roesch-Ely, Mariana

    2015-01-01

    To determine the prevalence of atypical squamous cells of undetermined significance (ASCUS) and human papillomavirus (HPV) genotypes in a population in southern Brazil. In a retrospective cross-sectional study, the prevalence of ASCUS was determined among women aged 20-60 years who were referred to a private medical center in Caxias do Sul by a gynecologist for assessment of a cervical condition between January 1, 2010, and September 30, 2011. Histologic and cytologic samples were tested for HPV, and polymerase chain reaction (PCR) was used to genotype any HPV DNA identified. Among the 250 included women, 25 (10.0%) had ASCUS. HPV DNA was found in 15 (60.0%) women with ASCUS and 115 (51.1%) of the 225 without ASCUS. Viral typing showed that 7 (46.7%) HPV-positive women with ASCUS had multiple infections with up to five different genotypes. Both low- and high-risk HPV genotypes were found in ASCUS samples; the most prevalent genotypes were HPV6/HPV11 (affecting 10 [66.7%] women), HPV51 (6 [40.0%]), and HPV16 (6 [40.0%]). ASCUS is not an indication of HPV infection. HPV screening and genotyping would benefit women with ASCUS, because treatment can be planned according to risk of carcinogenesis. Copyright © 2014 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  8. Human papillomavirus infection in oral squamous cell carcinomas from Chilean patients.

    PubMed

    Reyes, Montserrat; Rojas-Alcayaga, Gonzalo; Pennacchiotti, Gina; Carrillo, Diego; Muñoz, Juan P; Peña, Nelson; Montes, Rodrigo; Lobos, Nelson; Aguayo, Francisco

    2015-08-01

    Human papillomavirus (HPV) is the causal agent of cervical, anogenital and a subset of oropharyngeal carcinomas. In addition, the role of HPV in oral carcinogenesis has been suggested, although the findings are inconclusive. In this study, using conventional polymerase chain reaction (PCR) and genotyping by specific PCR and DNA sequencing, we analyzed the HPV presence in 80 oral squamous cell carcinomas (OSCCs) from Chilean subjects. In addition, we determined the expression of p16, p53, pRb and Ki-67 using immunohistochemistry (IHC). The CDKN2A (p16) promoter methylation was evaluated using methylation-specific PCR (MSP). HPV sequences were found in 9/80 (11%) OSCCs. Non-statistically significant association with p53, pRb, Ki-67 and p16 levels were found (p=0.77; 0.29; 0.83; 0.21, respectively). HPV-16 and 18 were the most prevalent HPV genotypes in 8/9 (89%) OSCCs. In addition, CDKN2A (p16) was methylated in 39% of OSCCs. No association with HPV presence (p=0.917) was found. These results suggest that HPV positive OSCCs are entities that do not resemble the molecular alterations of HPV-associated tumors in a Chilean population. More studies are warranted to determine the role of HPV in OSCCs. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Human Papillomavirus Test for Triage of Japanese Women With Low-Grade Squamous Intraepithelial Lesions.

    PubMed

    Iwata, Takashi; Hasegawa, Toshihiko; Ochiai, Kazunori; Takizawa, Ken; Umezawa, Satoshi; Kuramoto, Hiroyuki; Ohmura, Mineo; Kubushiro, Kaneyuki; Arai, Hiroharu; Sakamoto, Masaru; Motoyama, Teiichi; Watanabe, Kayoko; Aoki, Daisuke

    2015-12-01

    We evaluated high-risk human papillomavirus (HR-HPV) DNA testing for high-grade cervical intraepithelial neoplasia (CIN) lesions by cobas HPV test and diagnostic HPV16/18 genotyping in Japanese women with low-grade squamous intraepithelial lesions. Of 357 patients, HR-HPV positivity prevalence was 75.6%, and 21.3% had grade 2 or higher CIN lesions (CIN2+), with the highest prevalence at 30 to 34 years. Negative predictive values of HR-HPV for CIN2+ in our patients were 93.1% (any age) and 94.9% (40-50 years). Absolute risk for CIN2+ in HR-HPV positive and HPV16/18 positive individuals was 25.9 and 35.1, respectively. Relative risk for CIN2+ lesions was 5.1 for HPV16/18 positive versus HR-HPV negative, and 3.8 for HR-HPV positive versus HR-HPV negative women. Predictive values of CIN2+ positive were higher for HPV16/18 positive women (any age) than 12 other HPV positive-genotypes, and highest (50%) at 40-50 years. The HPV16/18 genotyping might prevent women (>40 years) at risk of high-grade CIN lesions from undergoing unnecessary colposcopy/overtreatment of nonprogressive lesions. © The Author(s) 2015.

  10. Human papillomaviral load changes in low-grade squamous intraepithelial lesions of the uterine cervix

    PubMed Central

    Ho, C-M; Cheng, W-F; Chu, T-Y; Chen, C-A; Chuang, M-H; Chang, S-F; Hsieh, C-Y

    2006-01-01

    To better predict risk of progression of low-grade squamous intraepithelial lesions (LSILs) of the uterine cervix in women with human papillomavirus (HPV) infections, 294 baseline cervical specimens from women with LSILs were evaluated. Specimens were tested for HPV DNA using hybrid capture 2 (HC2) and PCR-reverse line blotting. 65 LSILs with HPV DNA types 16, 18, 52, or 58 were examined for physical status, E2/E6 ratio and viral load at two time points, along with patient age. Women with LSILs whose viral loads increased between baseline and 6 month follow-up had a 45% risk of developing HSIL (OR=7.6, 95% CI=1.9–29.4, P<0.01), as evaluated by real-time PCR and a 44% risk (OR=6.1, 95% CI=1.6–22.7, P<0.01), as evaluated by HC2. The two viral load measures correlated well (Person's coefficient, r=0.687, P<0.001). Such evaluations of viral load changes (increased or not increased) through repeat HPV DNA testing could predict progression of disease in LSIL cases of HPV types 16, 18, 52, and 58, which correlates to clinical implications. PMID:17060938

  11. Human papillomavirus false positive cytological diagnosis in low grade squamous intraepithelial lesion.

    PubMed

    Núñez-Troconis, José; Delgado, Mariela; González, Julia; Velásquez, Jesvy; Mindiola, Raimy; Whitby, Denise; Conde, Betty; Munroe, David J

    2009-12-01

    The purpose of this study was to investigate the number of Human Papillomavirus false positive cytological diagnosis in low grade squamous intraepithelial lesions (LSIL). Three hundred and two women who assisted to an Out-Patient Gynecologic Clinic in Maracaibo, Venezuela, were recruited for this study. Each patient had the Pap smear and a cervical swab for Hybrid Capture 2 (HC2). Three cytotechnologists reviewed the Pap smears and two pathologists rescreened all of them. The cytotechnologists reported 161 (53.3%) Pap smears negatives for intraepithelial lesion (IL) or malignancy, and 141 cases (46.7%) with epithelial abnormalities. They reported 46% of 302 patients with HPV infection in Pap smear slides. The pathologists found that 241 (79.8%) Pap smears were negatives for IL or malignancy and 61 (20.2%), with abnormal Pap smears. They found 14.6% HPV infection in all Pap smears (p<0.0001; 46% vs 14.6%). The HC2 study showed that 47 samples (15.6%) were positive for HPV. The study found that 114 Pap smears (False Positive: 85%) of 134 reported by the cytotechnologists and 24 (False Positive: 43%) of 56 cytologies reported by the pathologists as LSIL, were negative for HPV infection determined by HC2 (p<0.00003). The present study suggests that the cytotechnologists overdiagnosed cellular changes associated with HPV infection in the Pap smear, increasing the FP cytological diagnosis of LSIL.

  12. Human papillomavirus profile of women in Belize City, Belize: correlation with cervical cytopathologic findings.

    PubMed

    Cathro, Helen P; Loya, Theresa; Dominguez, Frederick; Howe, Susan L; Howell, Renee; Orndorff, Kyle; Moreno, Jessica; Mendez, Elena; Fung, Po Chu; Beer, Natalie L; Allen, Peter; Sosa, Alba M; Gurka, Kelly K; Stoler, Mark H; Frierson, Henry F

    2009-07-01

    Cervical carcinoma is the most common cancer among Belizean women; however, data regarding the frequency of human papillomavirus (HPV) genotypes and their association with cervical cancer are nonexistent. We therefore included HPV genotyping as part of a week-long cervical cancer screening campaign conducted in Belize City in 2007. Conventional Papanicolaou smears with Hybrid Capture (HC) 2 HPV testing were performed on 463 women. All HC2-positive samples were genotyped using a developmental GP5+/GP6+ polymerase chain reaction-coupled Luminex assay for 2 low-risk and 18 high-risk HPV types. The prevalence of high-risk HPV was 15.6% in the total population, 10.1% in those with normal cytologic findings, and 93.3% in women with a high-grade squamous intraepithelial lesion. Of patients with HPV infections, 35% had multiple types (5.4% of the total group). Of all women and of women with normal cytologic findings, 5.2% and 2.8%, respectively, had HPV16 or 18. For all women, HPV16, 18, 56, and 52 were present in decreasing order of frequency. HPV11 was present in only one patient, and none had HPV6. HPV16 was found in 47% of high-grade squamous epithelial lesions; however, no case of HSIL had HPV18 or 45. HPV35 and HPV58 were the next most common types in high-grade squamous intraepithelial lesion, each occurring in 20% of cases of high-grade squamous intraepithelial lesion, followed by HPV31 in 13.3%. Although women younger than 25 years old were underrepresented, these data suggest that the HPV profile of this cohort of Belizean women differs somewhat from that in the region. In addition, these data are of importance with regard to the development of HPV vaccines that will be used in less developed countries, where care should be taken not to implement vaccination at the cost of basic screening and diagnostic services.

  13. Human papillomavirus detection in head and neck squamous cell carcinoma.

    PubMed

    Vietía, Dayahindara; Liuzzi, Juan; Avila, Maira; De Guglielmo, Zoraya; Prado, Yrneh; Correnti, María

    2014-01-01

    Human Papillomavirus (HPV) has been associated with benign and malignant lesions in different epitheliums. The relationship between specific genotypes of high-risk HPV and some human cancers is well established. The aim of this work was to detect the HPV genotypes present in head and neck squamous cell carcinoma (HNSCC). We evaluated 71 samples of patients with histopathological diagnosis of HNSCC. The DNA extraction was conducted with the QIAGEN commercial kit. HPV detection and genotyping were performed by reverse hybridisation (INNO-LiPA) following the commercial specifications. The mean age of the patients evaluated was 60.7 ± 13.11 years. The distribution of the lesions included 25 (35.20%) cases of squamous cell carcinoma (SCC) of the oral cavity, 23 (32.39%) of larynx, 16 (22.50%) of the oropharynx, 4 (5.63%) of paranasal sinus, and 2 (2. 80%) cases of SCC of the nostril. Of the patients, 78.9% were males, and of these 76% were tobacco users and 67.6% were alcohol consumers. The viral DNA was detected in 67.6% of the samples. The oral cavity and the larynx were the highest HPV-positivity sites with 35.40% and 29.10% respectively. The most frequent genotype was 16 as single infection (18.70%), or in combination with another HPV types. In the oral cavity and larynx the genotypes 16 or the combination 6 and 51 were present in 11.76% and 14.28%, respectively; and in the oropharynx the most frequent genotype was 16 in 22.50% of the cases, and in the paranasal sinus 50% presented infection with HPV-6. We observed that tumours with most advanced size and stage presented greater HPV positivity. This study shows a high percentage of HPV positivity in SCC is mainly associated with high-risk HPV. It is important to highlight that viral infection, especially HPV-16, could be a risk factor in HNSCC progression.

  14. Human papillomavirus detection in head and neck squamous cell carcinoma

    PubMed Central

    Vietía, Dayahindara; Liuzzi, Juan; Ávila, Maira; De Guglielmo, Zoraya; Prado, Yrneh; Correnti, María

    2014-01-01

    Introduction Human Papillomavirus (HPV) has been associated with benign and malignant lesions in different epitheliums. The relationship between specific genotypes of high-risk HPV and some human cancers is well established. The aim of this work was to detect the HPV genotypes present in head and neck squamous cell carcinoma (HNSCC). Methods We evaluated 71 samples of patients with histopathological diagnosis of HNSCC. The DNA extraction was conducted with the QIAGEN commercial kit. HPV detection and genotyping were performed by reverse hybridisation (INNO-LiPA) following the commercial specifications. Results The mean age of the patients evaluated was 60.7 ± 13.11 years. The distribution of the lesions included 25 (35.20%) cases of squamous cell carcinoma (SCC) of the oral cavity, 23 (32.39%) of larynx, 16 (22.50%) of the oropharynx, 4 (5.63%) of paranasal sinus, and 2 (2. 80%) cases of SCC of the nostril. Of the patients, 78.9% were males, and of these 76% were tobacco users and 67.6% were alcohol consumers. The viral DNA was detected in 67.6% of the samples. The oral cavity and the larynx were the highest HPV-positivity sites with 35.40% and 29.10% respectively. The most frequent genotype was 16 as single infection (18.70%), or in combination with another HPV types. In the oral cavity and larynx the genotypes 16 or the combination 6 and 51 were present in 11.76% and 14.28%, respectively; and in the oropharynx the most frequent genotype was 16 in 22.50% of the cases, and in the paranasal sinus 50% presented infection with HPV-6. We observed that tumours with most advanced size and stage presented greater HPV positivity. Conclusions This study shows a high percentage of HPV positivity in SCC is mainly associated with high-risk HPV. It is important to highlight that viral infection, especially HPV-16, could be a risk factor in HNSCC progression. PMID:25374623

  15. Cervical lymph node metastases of squamous cell carcinoma from an unknown primary: outcomes and patterns of failure.

    PubMed

    Mistry, R C; Qureshi, S S; Talole, S D; Deshmukh, S

    2008-01-01

    Management of cervical lymph nodes metastases of squamous cell carcinoma (SCC) from primary of unknown origin (PUO) is contentious and there is insignificant data from India on this subject. To present experience of management of these patients treated with curative intent at a single institution. Retrospective study of patients treated between 1989-1994 in a tertiary referral cancer centre. Eighty-nine patients were evaluated in the study period and their survival compared with patients with common sites of primary in the head and neck with comparable node stage. Kaplan-Meier method. The clinical stage of the neck nodes at presentation was N1 in 11%, N2a in 28.5%, N2b in 22.5%, N3 in 35% and Nx in 3.4% patients. All patients underwent surgery and 70 patients received more than 40Gy postoperative radiotherapy. Twenty-nine (32.6%) patients had relapse of which 19 (21%) were in the neck. Postoperative radiotherapy did not influence the neck relapse (p=0.72). Primary was detected in 13 patients (14.6%) on subsequent follow up. The overall five and eight-years survival was 55% and 51% respectively. The overall five-year survival was better compared to patients with known primary with comparable node stage. Patients with cervical lymph nodes metastases of SCC from PUO have reasonable survival and low rate of development of subsequent primary when treated with surgery and radiotherapy. The overall survival is comparable to that of patients with known primary and hence an attempt at cure should always be made.

  16. Cervical Shedding of Human T Cell Lymphotropic Virus Type I Is Associated with Cervicitis

    PubMed Central

    Zunt, Joseph R.; Dezzutti, Charlene S.; Montano, Silvia M.; Thomas, Katherine K.; Alarcón, Jorge O. V.; Quijano, Eberth; Courtois, Barry N.; Sánchez, Jorge L.; Campos, Pablo; Gotuzzo, Eduardo; Guenthner, Patricia C.; Lal, Renu B.; Holmes, King K.

    2009-01-01

    Human T cell lymphotropic virus type I (HTLV-I) is sexually transmitted. The purpose of this study was to determine the prevalence and risk factors for cervical shedding of HTLV-I DNA among Peruvian sex workers. HTLV tax DNA was detected in cervical specimens from 43 (68%) of 63 HTLV-I–infected sex workers and in samples obtained during 113 (52%) of 216 clinic visits between 1993 and 1997. Detection of HTLV DNA was associated with the presence of ≥30 polymorphonuclear cells (PMNs) within cervical mucus per 100×microscopic field (odds ratio [OR], 4.3, 95% confidence interval [CI], 1.8–10.1) and with the presence of cervical secretions (OR, 2.0; 95% CI 1.2–3.4). Hormonal contraceptive use (OR 1.7; 95% CI, 0.8–3.6) and concomitant cervical infection by Chlamydia trachomatis (OR, 1.5; 95% CI, 0.3–4.3) or Neisseria gonorrhoeae (OR, 1.1; 95% CI, 0.6–3.7) were not significantly associated with HTLV-I shedding. Our results suggest that cervicitis may increase cervical HTLV-I shedding and the sexual transmission of this virus. PMID:12447745

  17. Cervical shedding of human T cell lymphotropic virus type I is associated with cervicitis.

    PubMed

    Zunt, Joseph R; Dezzutti, Charlene S; Montano, Silvia M; Thomas, Katherine K; Alarcón, Jorge O V; Quijano, Eberth; Courtois, Barry N; Sánchez, Jorge L; Campos, Pablo; Gotuzzo, Eduardo; Guenthner, Patricia C; Lal, Renu B; Holmes, King K

    2002-12-01

    Human T cell lymphotropic virus type I (HTLV-I) is sexually transmitted. The purpose of this study was to determine the prevalence and risk factors for cervical shedding of HTLV-I DNA among Peruvian sex workers. HTLV tax DNA was detected in cervical specimens from 43 (68%) of 63 HTLV-I-infected sex workers and in samples obtained during 113 (52%) of 216 clinic visits between 1993 and 1997. Detection of HTLV DNA was associated with the presence of > or =30 polymorphonuclear cells (PMNs) within cervical mucus per 100x microscopic field (odds ratio [OR], 4.3, 95% confidence interval [CI], 1.8-10.1) and with the presence of cervical secretions (OR, 2.0; 95% CI 1.2-3.4). Hormonal contraceptive use (OR 1.7; 95% CI, 0.8-3.6) and concomitant cervical infection by Chlamydia trachomatis (OR, 1.5; 95% CI, 0.3-4.3) or Neisseria gonorrhoeae (OR, 1.1; 95% CI, 0.6-3.7) were not significantly associated with HTLV-I shedding. Our results suggest that cervicitis may increase cervical HTLV-I shedding and the sexual transmission of this virus.

  18. Apoptosis in cervical squamous carcinoma: predictive value for survival following radiotherapy

    PubMed Central

    Paxton, J; Bolger, B; Armour, A; Symonds, R; Mao, J; Burnett, R

    2000-01-01

    Background—Apoptosis, or programmed cell death, can be induced by radiotherapy. The extent of apoptosis in a tumour before treatment may have important implications for response to radiotherapy and long term survival. Aim—To examine the extent of apoptosis in tumour tissue from patients with squamous carcinoma of the cervix before radiotherapy, and to correlate this with response to treatment and prognosis. Methods—The percentage of apoptotic cells was assessed in 146 carcinomas of the cervix from patients scheduled to receive radiotherapy. The CAS 200 static image analysis system was used to count the number of tumour nuclei per high power field, while the numbers of apoptotic cells in the same field were visualised simultaneously on the image analyser and recorded manually. Results—The median apoptotic level was 0.73%. Patients were divided into two groups around the median. There was no statistically significant difference in outcome between the two groups as determined by long term survival following radiotherapy. Conclusions—The CAS 200 static image analyser system can be used to assist in the rapid semiautomated assessment of apoptosis in conventionally prepared tissue. The results suggest that the apoptotic state of a tumour before treatment is of no value in predicting response to radiotherapy and subsequent prognosis. Tumour stage, size, and BrdU labelling index, as a measure of proliferation rate, remain the most important prognostic factors in terms of predicting local tumour control. Key Words: apoptosis • uterine cervix • squamous cell carcinoma PMID:10823138

  19. Synchronous metastatic squamous cell carcinoma to the colon and cervical lymph nodes from a carcinoma of unknown primary site: A case report.

    PubMed

    Ito, Homare; Miyakura, Yasuyuki; Tsukui, Hidenori; Naoi, Daishi; Tahara, Makiko; Morimoto, Mitsuaki; Koinuma, Koji; Horie, Hisanaga; Lefor, Alan Kawarai; Sata, Naohiro

    2016-05-12

    Metastatic squamous cell carcinoma (SCC) from an unknown primary site to the colon has not been reported previously. A 75-year-old woman presented with a mass in the left submandibular region. Biopsy revealed a Class V lesion, but the histologic type was undetermined. Surgical resection of the left submandibular gland with cervical lymph node dissection was performed. However, SCC was seen in the lymph nodes only, with no tumor in the submandibular gland. Three months after surgery, computed tomography revealed that the preoperatively diagnosed lesion in the transverse colon had grown considerably. A laparoscopic right hemicolectomy was performed. Histological examination showed features of SCC, similar to the findings in the cervical lymph nodes. We report a rare case of synchronous metastatic SCC to the colon and cervical lymph nodes from a carcinoma of unknown primary site. Published by Oxford University Press and JSCR Publishing Ltd. All rights reserved. © The Author 2016.

  20. Expression of HIF-2α and VEGF in Cervical Squamous Cell Carcinoma and Its Clinical Significance

    PubMed Central

    Zhang, Lixia; Chen, Qiang; Hu, Jing; Chen, Yue; Liu, Chenglong; Xu, Changshui

    2016-01-01

    CSCC is a systemic disease involving polygenic alteration and multiple steps, and HIF and VEGF are closely associated with tumorigenesis. Specimens surgically resected from 64 cases of CSCC and 22 cases of normal cervical tissue were selected randomly to detect the expression of HIF-2α and VEGF in CSCC for exploring their clinical significance; information regarding the age, lymph node metastasis, and FIGO staging were collected as well; expression of HIF-2α and VEGF was detected by qPCR and immunohistochemistry. We found that the expression of HIF-2α and VEGF mRNA in CSCC was significantly higher than that of normal cervical tissues and showed a positive correlation between them. The positive rates of HIF-2α and VEGF protein expression in CSCC and normal cervical tissues were 93.8% and 18.2%, respectively, with correlation between them. The expression of both HIF-2α and VEGF mRNA did not relate closely to age but the FIGO staging and lymph node metastasis. Compared with the counterpart control group, CSCC tissues with high FIGO staging and lymph node metastasis had a higher level of HIF-2α and VEGF mRNA expression. So, HIF-2α and VEGF were overexpressed in CSCC, which has a great clinical significance for its diagnosis. PMID:27413748

  1. Prevalence of human papillomavirus infection & cervical abnormalities in HIV-positive women in eastern India

    PubMed Central

    Chakravarty, Jaya; Chourasia, Ankita; Thakur, Minaxi; Singh, Abhishek Kumar; Sundar, Shyam; Agrawal, Nisha Rani

    2016-01-01

    Background & objectives: India has the third highest burden of HIV and highest number of cervical cancer in the world. A cross-sectional study was performed to determine the prevalence and types of human papillomavirus (HPV) infection, and the factors associated with HPV infection and abnormal cervical cytology in HIV-positive women attending the Antiretroviral Therapy (ART) Centre in a tertiary care hospital in eastern India. Methods: We screened 216 HIV- positive women with Papanicolau smear cytology and HPV testing. HPV DNA was detected by using consensus primers followed by sequencing. Results: Of the 216 HIV-positive women screened, 58 (26.85%) were HPV-positive; 56 (25.9%) were of high-risk (HR) HPV type. The most prevalent HPV type was HPV-16 (7.9%); non 16 and 18 HPV types were present in 17.6 per cent patients. Age ≤ 35 yr [(OR), 2.56 (1.26-5.19)], illiteracy [OR, 2.30 (1.19-4.46)], rural residence [OR, 3.99 (1.27-12.56)] and CD4 ≤350/μl [OR, 2.46 (1.26-4.83)] were associated with increased risk of acquisition of HPV. One hundred thirty nine (74.33%) patients had normal/ negative for intraepithelial lesions (NILM) cytology, three (1.60%) had atypical squamous cells of undetermined significance (ASCUS), 32 (17.11%) had low-grade squamous intraepithelial lesions (LSIL), 10 (5.35%) had high-grade squamous intraepithelial lesions (HSIL) and three (1.60%) had carcinoma cervix. WHO clinical Stage III and IV [OR, 2.83 (1.07-7.49)] and CD4 ≤350/μl [OR, 2.84 (1.30-6.20)] were risk factors for abnormal cytology. Interpretation &conclusions: Our study showed 26.85 per cent HPV positivity in HIV infected women in this region, with HPV-16 as the commonest genotype. Abnormal cervical cytology was seen in about 25 per cent women. Regular Pap smear screening as recommended by the National AIDS Control Organization will help in early detection of cervical abnormalities in HIV- positive women. PMID:26997018

  2. Prevalence of human papillomavirus infection & cervical abnormalities in HIV-positive women in eastern India.

    PubMed

    Chakravarty, Jaya; Chourasia, Ankita; Thakur, Minaxi; Singh, Abhishek Kumar; Sundar, Shyam; Agrawal, Nisha Rani

    2016-01-01

    India has the third highest burden of HIV and highest number of cervical cancer in the world. A cross-sectional study was performed to determine the prevalence and types of human papillomavirus (HPV) infection, and the factors associated with HPV infection and abnormal cervical cytology in HIV-positive women attending the Antiretroviral Therapy (ART) Centre in a tertiary care hospital in eastern India. We screened 216 HIV- positive women with Papanicolau smear cytology and HPV testing. HPV DNA was detected by using consensus primers followed by sequencing. Of the 216 HIV-positive women screened, 58 (26.85%) were HPV-positive; 56 (25.9%) were of high-risk (HR) HPV type. The most prevalent HPV type was HPV-16 (7.9%); non 16 and 18 HPV types were present in 17.6 per cent patients. Age ≤ 35 yr [(OR), 2.56 (1.26-5.19)], illiteracy [OR, 2.30 (1.19-4.46)], rural residence [OR, 3.99 (1.27-12.56)] and CD4 ≤ 350/µl [OR, 2.46 (1.26-4.83)] were associated with increased risk of acquisition of HPV. One hundred thirty nine (74.33%) patients had normal/ negative for intraepithelial lesions (NILM) cytology, three (1.60%) had atypical squamous cells of undetermined significance (ASCUS), 32 (17.11%) had low-grade squamous intraepithelial lesions (LSIL), 10 (5.35%) had high-grade squamous intraepithelial lesions (HSIL) and three (1.60%) had carcinoma cervix. WHO clinical Stage III and IV [OR, 2.83 (1.07-7.49)] and CD4 ≤ 350/µl [OR, 2.84 (1.30-6.20)] were risk factors for abnormal cytology. Our study showed 26.85 per cent HPV positivity in HIV infected women in this region, with HPV-16 as the commonest genotype. Abnormal cervical cytology was seen in about 25 per cent women. Regular Pap smear screening as recommended by the National AIDS Control Organization will help in early detection of cervical abnormalities in HIV- positive women.

  3. Identification of human papillomavirus in esophageal squamous papillomas

    PubMed Central

    Bohn, Olga L; Navarro, Leticia; Saldivar, Jesus; Sanchez-Sosa, Sergio

    2008-01-01

    AIM: To investigate the presence of human papillomavirus (HPV) in esophageal squamous papilloma (ESP) and determine p16, p53 and Ki67 expression in a Mexican cohort. METHODS: Nineteen cases diagnosed as ESP, corresponding to 18 patients were reviewed; nineteen cases of normal esophageal mucosa were used as negative controls. HPV detection was performed by amplified chromogenic in situ hybridization (ACISH) using a wide spectrum-cocktail probe and PCR. RESULTS: The average age at presentation was 46.3 years (range 28-72 years). Patients included four (22.22%) males and 14 (77.77%) females. The most frequent location was upper third (11 cases), followed by middle third (3 cases) and unknown site (5 cases). Immunohistochemistry (IHC) revealed basal and focal p53 expression in 17 cases (89%); p16 was expressed in eight cases (42.10%) and the Ki67 index ranged from 10% to 30%. HPV was detected in 14 out of 16 cases (87.5%) by ACISH: Twelve showed diffuse nuclear patterns and two showed granular patterns. HPV DNA was identified by PCR in 12 out of 14 cases (85.7%). Low-risk HPV types were detected in the most of the cases. CONCLUSION: This study provides identification of HPV infection in almost 80% of ESP using either ACISH or PCR; overall, all of these lesions show low expression of cell-cycle markers. We suggest ACISH as an alternative diagnostic tool for HPV detection in ESP. PMID:19084918

  4. Increased EGF receptors on human squamous carcinoma cell lines.

    PubMed Central

    Cowley, G. P.; Smith, J. A.; Gusterson, B. A.

    1986-01-01

    Characterisation and quantitation of epidermal growth factor receptors (EGFR) have been carried out on eight human squamous carcinoma cell lines and the results compared with those from simian virus transformed keratinocytes and normal keratinocytes grown under similar conditions. All cells tested possess both high and low affinity receptors with dissociation constants ranging from 2.4 X 10(-10) M to 5.4 X 10(-9) M. When epidermal growth factor (EGF) binds to its receptor it is internalised and degraded and the receptor is down regulated. Malignant cells and virally transformed cells possess 5-50 times more EGF receptors than normal keratinocytes and one cell line LICR-LON-HN-5 possesses up to 1.4 X 10(7) receptors per cell, which is the highest number yet reported for a cell line. These results are discussed in the context of recent data that suggest that the increased expression of EGF receptors in epidermoid malignancies may be an important component of the malignant phenotype in these tumours. PMID:2420349

  5. Human papillomavirus DNA in squamous cell carcinoma of the lung.

    PubMed Central

    Hirayasu, T; Iwamasa, T; Kamada, Y; Koyanagi, Y; Usuda, H; Genka, K

    1996-01-01

    AIM: To compare the incidence of squamous cell carcinoma (SCC) of the lung in Okinawa with that in Niigata on the mainland. METHODS: All patients presenting with SCC of the lung in Okinawa and Niigata in 1993 were included in the study. Diagnoses were confirmed by conventional histological examination of paraffin wax sections. Human papillomavirus (HPV) was detected by non-isotopic in situ hybridisation (NISH) and polymerase chain reaction (PCR) amplification with primers specific for the E6 and E7 regions of the HPV genome. PCR products were analysed by Southern and dot blotting. RESULTS: The incidence of well differentiated SCC of the lung was high in patients from Okinawa compared with moderately and poorly differentiated types, and compared with the incidence of SCC in patients from Niigata. This is despite similar patterns of age, sex (predominatly male), and smoking habit. More patients from Okinawa, however, were positive for HPV DNA by PCR (79%) and NISH (53%). Many patients haboured HPV types 6, 16, and 18. Only 30% of patients from Niigata were positive for HPV DNA by PCR and 20% by NISH. These patients all harboured one HPV type only. CONCLUSION: Surprisingly large numbers of patients from Okinawa were positive for HPV DNA. The detection of HPV DNA was strongly associated with well differentiated SCC. This was particularly true for HPV types 6 and 16. There was no correlation between either smoking and detection of HPV DNA, or smoking and histological differentiation. Images PMID:8943746

  6. Beneficial Effects of Human Papillomavirus Vaccine for Prevention of Cervical Abnormalities in Miyagi, Japan.

    PubMed

    Ozawa, Nobuyoshi; Ito, Kiyoshi; Tase, Toru; Metoki, Hirohito; Yaegashi, Nobuo

    2016-01-01

    Prevention of cervical cancer has been unsuccessful in Japan because of low rates of cancer screening and vaccination. The Vaccine Adverse Review Committee of the Japanese Government investigated 2,475 adverse events and reported 617 (6.9/100,000) severe cases and 176 (2.0/100,000) cases with chronic pain. The proactive recommendation for human papillomavirus (HPV) vaccination has been suspended since June 2013. In this study, we examined vaccination rate and incidence of abnormal cervical cytology in women aged 20 to 24 years attending cancer screening in Miyagi. Among the 3,272 women who underwent a health check in the fiscal year 2014 (April 2014-March 2015), 332 (10.2%) received a HPV vaccination. The HPV vaccination rates were 42.3%, 10%, 17.5%, 3.8% and 4.0% in women aged 20, 21, 22, 23 and 24 years, respectively. The rates of atypical squamous cells of undetermined significance (ASC-US) or worse were 2.41% (8/332) in women with HPV vaccination and 5.03% (148/2,940) in those without HPV vaccination, indicating a significant decrease in vaccinated women (p = 0.03). ASC-US cases were referred to HPV DNA tests. In addition, the rates of high grade squamous intraepithelial lesion (HSIL) or worse were 0.30% (1/332) in women with HPV vaccination and 0.82% (24/2,940) in those without HPV vaccination, showing the marginal decrease in women who were vaccinated (p = 0.3). Thus, this study indicates that HPV vaccination is associated with a reduction in the incidence of cervical abnormalities, suggesting a need for scientific discussion of reinstatement of proactive recommendation for HPV vaccine in Japan.

  7. [Human papillomavirus genotype distribution in cervical infections among woman in La Plata, Argentina].

    PubMed

    Abba, M C; Gomez, M A; Golijow, C D

    2003-01-01

    Genital infection with human papillomavirus (HPV) is one of the most common sexually transmitted viral diseases. High risk HPV are now considered the main etiologic agent of cancer of the uterine cervix and their high-grade precursor lesions. The aim of the present study was to investigate the endemic HPV-genotype spectrum in a population of women from the city of La Plata, Argentina. With this purpose, 718 cervical scrapes or biopsies corresponding to 152 normal samples (Pap I/II), 84 samples classified as atypical squamous cells of undetermined significance (ASCUS), 100 condyloma, 279 low-grade squamous intraepithelial lesions (LGSIL), 82 high-grade squamous intraepithelial lesions (HGSIL), and 21 squamous cell carcinomas (SCC) were studied. The detection of HPV-DNA was performed by nested polymerase chain reaction, using My 09/11 and Gp 05/06. The viral genotypes were analyzed by single-stranded conformation polymorphisms, employing low ionic strength solution (LIS-SSCP). The overall prevalence of HPV infection was 75% in the analyzed population, with a frequency of 46% for normal cervix, 69% for ASCUS, 86% for condyloma, 80% for LGSIL, 98% for HGSIL and 100% for SCC. The most prevalent viral types were HPV 16 (35%), followed by HPV 6/11 (27% each one), HPV 33 (6%) and HPV 18 (5%). HPV 16 was the most prevalent viral type among women with LGSIL, HGSIL and SCC, representing 33%, 50% and 67% of the genital infections, respectively. HPV 6 and 11 were the most frequent viral types among samples classified as Pap I/II, ASCUS and condyloma. Women between 21 and 30 year old showed the highest prevalence of HPV positivity, compraising the 32.2% of total infections.

  8. [Metastatic oropharyngeal squamous cell carcinoma in cervical lymph nodes associated to HPV infection type 16 and 45; clinical, morphological and molecular study of two cases].

    PubMed

    Soria-Céspedes, Danny; Canchola Aguilar, Guadalupe; Lara-Torres, César Octavio; Sánchez-Marle, Juan Felipe; Hernández-Peña, Roberto Enrique; Ortiz-Hidalgo, Carlos

    2013-01-01

    Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma has been identified as a distinct entity within squamous cell carcinoma of the head and neck. In contrast to carcinomas associated with alcohol and/or tobacco, this subtype occurs at younger age, with frequent absence of classic risk factors, correlation with oral sexual habits, strong predilection for the palatial tonsils and the base of the tongue (lingual tonsils), basaloid or lymphoepithelial differentiation, higher degree of radiosensitivity, and overall better survival. We report two cases of lymph node, metastatic, poorly differentiated squamous cell carcinoma that were positive by immunohistochemistry for p16 with detection of HPV-16 and HPV-45 by PCR.

  9. Evaluation of the level of progression of extracapsular spread for cervical lymph node metastasis in oral squamous cell carcinoma.

    PubMed

    Yamada, S; Yanamoto, S; Otani, S; Hasegawa, T; Miyakoshi, M; Minamikawa, T; Ohga, N; Kamata, T; Komori, T; Kitagawa, Y; Kurita, H; Umeda, M

    2016-02-01

    Only a few reports on the level of progression of extracapsular spread (ECS) have been published. The aim of this study was to evaluate the efficacy of the level of progression of ECS in identifying those patients with oral squamous cell carcinoma (OSCC) at a high risk of recurrence who would benefit most from the intensification of adjuvant therapy. The level of progression of ECS for cervical lymph node metastasis in OSCC was divided into three types (A-C), and their relationships with patient prognosis were examined. ECS was observed in 87 of 441 patients with OSCC. The recurrence rate in patients with type C, which was defined as macroscopic tumour invasion into perinodal fat or muscle tissue, was high (69.8%), with 13 cases of death due to distant metastasis. The 3-year disease-specific survival rate for patients with type C was 49.0% and these patients also had a significantly poorer prognosis (P<0.01). The results of the multivariate analysis suggested that the prognosis of ECS in OSCC patients was associated with the level of progression of ECS, especially type C (P<0.01). Overall, the results of this study suggest that the level of progression of ECS is a useful prognostic factor in OSCC patients. Copyright © 2015 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  10. [Matrix metalloproteinases 2 and 9, their endogenous regulators, and angiotensin-converting enzyme in cervical squamous cell carcinoma].

    PubMed

    Timoshenko, O S; Kugaevskaya, E V; Gureeva, T A; Zavalishina, L E; Andreeva, Yu Yu; Solovуeva, N I

    2015-01-01

    to investigate the specific features of the expression of matrix metalloproteinases 2 and 9 (MMP-2, MMP-9), tissue inhibitor of metalloptoteinase 2 (TIMP-2), urokinase-type plasminogen activator (uPA), and angiotensin-converting enzyme (ACE) in cervical squamous cell carcinoma (CSCC). The samples of tumor tissue and morphologically normal tissue adjacent to the tumor were investigated. Enzymatic assays applying specific substrates, as well as zymographic and immunohistochemical studies were used. The invasive potential of CSCC has been established to be substantially influenced by the increased expression of MMP-9 and uPA and by the decreased expression of TIMP-2, as well as to a lesser extent by a change in MMP-2 expression. MMP-9 may serve as a marker for invasive growth. Enhanced ACE activity in cancer confirms the involvement of this enzyme in tumor progression. The morphologically normal tissue adjacent to the tumor shows the substantial expression of MMP-2 and MMP-9 and in some cases the enhanced activity of uPA and ACE, which makes an additional contribution to the increased invasive potential of tumor. The findings are important in understanding the mechanisms of cancer progression and may affect therapeutic strategies for the patient.

  11. Persistent human papillomavirus infection as a predictor of cervical intraepithelial neoplasia.

    PubMed

    Schlecht, N F; Kulaga, S; Robitaille, J; Ferreira, S; Santos, M; Miyamura, R A; Duarte-Franco, E; Rohan, T E; Ferenczy, A; Villa, L L; Franco, E L

    2001-12-26

    Human papillomavirus (HPV) infection is believed to be the central cause of cervical cancer, although most of the epidemiological evidence has come from retrospective, case-control studies, which do not provide information on the dynamics of cumulative or persistent exposure to HPV infection. To assess the risks of cervical neoplasia related to prior persistent HPV infections. Longitudinal study of the natural history of HPV infection and cervical neoplasia in women residing in the city of São Paulo, Brazil, which was conducted between November 1993 and March 1997 and involved repeated measurements of HPV and lesions with follow-up until June 2000. A total of 1611 women with no cytological lesions at enrollment and HPV test results available from the first 2 visits. Cervical specimens taken for Papanicolaou cytology and HPV testing every 4 months in the first year and twice yearly thereafter. Incident cervical cancer precursor lesions ascertained by expert review of all cytology smears. The incidence rate of squamous intraepithelial lesions (SILs) was 0.73 per 1000 women-months (95% confidence interval [CI], 0.5-0.9) among women free of HPV at the 2 initial visits and 8.68 (95% CI, 2.3-15.1) among women with HPV type 16 or 18 infections persisting over both visits. Relative to those negative for HPV oncogenic types at both initial visits, the relative risk (RR) of incident SIL was 10.19 (95% CI, 5.9-17.6) for persistent infections with any known oncogenic HPV types. The equivalent RR of incident high-grade SIL was 11.67 (95% CI, 4.1-33.3). The RRs of lesions were considerably higher for persistent infections with HPV type 16 or 18. A strong relationship exists between persistent HPV infections and SIL incidence, particularly for HPV types 16 and 18.

  12. Extreme selection in humans against homeotic transformations of cervical vertebrae.

    PubMed

    Galis, Frietson; Van Dooren, Tom J M; Feuth, Johan D; Metz, Johan A J; Witkam, Andrea; Ruinard, Sebastiaan; Steigenga, Marc J; Wijnaendts, Liliane C D

    2006-12-01

    Why do all mammals, except for sloths and manatees, have exactly seven cervical vertebrae? In other vertebrates and other regions, the vertebral number varies considerably. We investigated whether natural selection constrains the number of cervical vertebrae in humans. To this end, we determined the incidence of cervical ribs and other homeotic vertebral changes in radiographs of deceased human fetuses and infants, and analyzed several existing datasets on the incidence in infants and adults. Our data show that homeotic transformations that change the number of cervical vertebrae are extremely common in humans, but are strongly selected against: almost all individuals die before reproduction. Selection is most probably indirect, caused by a strong coupling of such changes with major congenital abnormalities. Changes in the number of thoracic vertebrae appear to be subject to weaker selection, in good correspondence with the weaker evolutionary constraint on these numbers. Our analysis highlights the role of prenatal selection in the conservation of our common body plan.

  13. Correlation Among Six Biologic Factors (p53, p21{sup WAF1}, MIB-1, EGFR, HER2, and Bcl-2) and Clinical Outcomes After Curative Chemoradiation Therapy in Squamous Cell Cervical Cancer

    SciTech Connect

    Yamashita, Hideomi; Murakami, Naoya; Asari, Takao; Okuma, Kae; Ohtomo, Kuni; Nakagawa, Keiichi

    2009-07-15

    Purpose: The expressions of six cell-cycle-associated proteins were analyzed in cervical squamous cell carcinomas in correlation in a search for prognostic correlations in tumors treated with concurrent chemoradiation therapy (cCRT). Methods and Materials: The expressions of p53, p21/waf1/cip1, molecular immunology borstel-1 (MIB-1), epidermal growth factor receptor (EGFR), human epidermal growth factor receptor type 2 (HER2), and Bcl-2 were studied using an immunohistochemical method in 57 cases of cervical squamous cell carcinoma treated with cCRT. Patients received cCRT between 1998 and 2005. The mean patient age was 61 years (range, 27-82 years). The number of patients with Stage II, III, and IVA disease was 18, 29, and 10, respectively. Results: The number of patients with tumors positive for p53, p21/waf1/cip1, MIB-1, EGFR, HER2, and Bcl-2 was 26, 24, 49, 26, 13, and 11, respectively; no significant correlation was noted. The 5-year overall survival rates of HER2-positive and -negative patients was 76% vs. 44%, which was of borderline significance (p = 0.0675). No significant correlation was noted between overall survival and expressions of p53, p21/waf1/cip1, MIB-1, EGFR, and Bcl-2. No correlation was observed between local control and expression of any of the proteins. Conclusion: Expression of HER2 protein had a weak impact of borderline significance on overall survival in squamous cell carcinoma of the uterine cervix treated with cCRT. However, no clinical associations could be established for p53, p21/waf1/cip1, MIB-1, EGFR, and Bcl-2 protein expressions.

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

    PubMed Central

    2014-01-01

    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. PMID:24751127

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

    PubMed

    Resende, Leandro Santos de Araújo; Rabelo-Santos, Sílvia Helena; Sarian, Luís Otávio; Figueiredo Alves, Rosane Ribeiro; Ribeiro, Andréa Alves; Zeferino, Luiz Carlos; Derchain, Sophie

    2014-04-22

    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. 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. 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. 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.

  16. Human Papilloma Virus (HPV) Induced Head & Neck Squamous Cell Carcinoma: A Comprehensive Retrospect

    PubMed Central

    Nishat, Roquaiya; Ramachandra, Sujatha; Kumar, Harish; Bandyopadhyay, Alokenath

    2015-01-01

    Head and Neck Squamous Cell Carcinoma accounts for the sixth most common malignancy occurring worldwide with tobacco and alcohol being the two well established risk factors. In the recent years, substantial evidence has been obtained that Human Papilloma Virus (HPV) associated head and neck cancers are on the rise. This article provides an insight into the structure of HPV genome, molecular pathogenesis, detection methods and clinical implications of HPV positive Head and Neck Squamous Cell Carcinoma. PMID:26266234

  17. A continuous fiber distribution material model for human cervical tissue.

    PubMed

    Myers, Kristin M; Hendon, Christine P; Gan, Yu; Yao, Wang; Yoshida, Kyoko; Fernandez, Michael; Vink, Joy; Wapner, Ronald J

    2015-06-25

    The uterine cervix during pregnancy is the vital mechanical barrier which resists compressive and tensile loads generated from a growing fetus. Premature cervical remodeling and softening is hypothesized to result in the shortening of the cervix, which is known to increase a woman׳s risk of preterm birth. To understand the role of cervical material properties in preventing preterm birth, we derive a cervical material model based on previous mechanical, biochemical and histological experiments conducted on nonpregnant and pregnant human hysterectomy cervical tissue samples. In this study we present a three-dimensional fiber composite model that captures the equilibrium material behavior of the tissue in tension and compression. Cervical tissue is modeled as a fibrous composite material, where a single family of preferentially aligned and continuously distributed collagen fibers are embedded in a compressible neo-Hookean ground substance. The total stress in the collagen solid network is calculated by integrating the fiber stresses. The shape of the fiber distribution is described by an ellipsoid where semi-principal axis lengths are fit to optical coherence tomography measurements. The composite material model is fit to averaged mechanical testing data from uni-axial compression and tension experiments, and averaged material parameters are reported for nonpregnant and term pregnant human cervical tissue. The model is then evaluated by investigating the stress and strain state of a uniform thick-walled cylinder under a compressive stress with collagen fibers preferentially aligned in the circumferential direction. This material modeling framework for the equilibrium behavior of human cervical tissue serves as a basis to determine the role of preferentially-aligned cervical collagen fibers in preventing cervical deformation during pregnancy.

  18. Role of human papillomavirus in oropharyngeal squamous cell carcinoma: A review

    PubMed Central

    Woods, Robbie SR; O’Regan, Esther M; Kennedy, Susan; Martin, Cara; O’Leary, John J; Timon, Conrad

    2014-01-01

    Human papillomavirus (HPV) has been implicated in the pathogenesis of a subset of oropharyngeal squamous cell carcinoma. As a result, traditional paradigms in relation to the management of head and neck squamous cell carcinoma have been changing. Research into HPV-related oropharyngeal squamous cell carcinoma is rapidly expanding, however many molecular pathological and clinical aspects of the role of HPV remain uncertain and are the subject of ongoing investigation. A detailed search of the literature pertaining to HPV-related oropharyngeal squamous cell carcinoma was performed and information on the topic was gathered. In this article, we present an extensive review of the current literature on the role of HPV in oropharyngeal squamous cell carcinoma, particularly in relation to epidemiology, risk factors, carcinogenesis, biomarkers and clinical implications. HPV has been established as a causative agent in oropharyngeal squamous cell carcinoma and biologically active HPV can act as a prognosticator with better overall survival than HPV-negative tumours. A distinct group of younger patients with limited tobacco and alcohol exposure have emerged as characteristic of this HPV-related subset of squamous cell carcinoma of the head and neck. However, the exact molecular mechanisms of carcinogenesis are not completely understood and further studies are needed to assist development of optimal prevention and treatment modalities. PMID:24945004

  19. Molecular Detection and Typing of Human Papillomaviruses in Paraffin-Embedded Cervical Cancer and Pre-Cancer Tissue Specimens

    PubMed Central

    Mahmoodi, Pezhman; Motamedi, Hossein; Seyfi Abad Shapouri, Masoud Reza; Bahrami Shehni, Mahjabin; Kargar, Mohammad

    2016-01-01

    Background: Cervical cancer is one of the important reasons of mortality among females. Prevention, early diagnosis and immediate treatment can affect the rate of mortality in this cancer and several epidemiological studies have shown a strong relationship between human papilloma viruses (HPVs) and cervical cancer. Objectives: The present study was conducted to survey HPV infections in a women population with cervical cancer and cervical dysplasia/metaplasia in southwest of Iran. Materials and Methods: 72 paraffin-embedded cervical biopsies which had been previously archived from women with cervical cancer and cervical dysplasia were examined by polymerase chain reaction (PCR). Afterward, the detected HPV strains were typed by restriction fragment length polymorphism (RFLP) analysis of PCR amplicons. Results: 60 out of 72 samples had necessary requirements and HPV DNA was detected in 43.3% of these samples. Most HPV positive samples belonged to women aged from 48 to 63 years. On the other hand, HPV infection among patients with squamous cell carcinoma (SCC) was 48.78% and in women with dysplasia/metaplasia was 26.66%. The most prevalent type of the human papilloma virus was HPV16 (100%). Conclusions: Knowing the most prevalent type of the human papilloma viruses circulating in the population (HPV16) can be applied in the future screening and managing programs of this major disease and also in vaccination against the prevalent types of the virus. Meanwhile, it seems that more studies should be performed to determine the role of different risk factors involved in development of the disease, especially those related with social behaviors and traditions with respect to different areas. PMID:27366309

  20. Risk factors for cervical lymph node metastasis in superficial head and neck squamous cell carcinoma.

    PubMed

    Sasaki, Toru; Kishimoto, Seiji; Kawabata, Kazuyoshi; Sato, Yukiko; Tsuchida, Tomohiro

    2015-03-30

    The necessity of transoral surgery for head and neck carcinoma is increasing, but its indications for the treatment of superficial head and neck carcinomas have not yet been established. This study was intended to help establish the standard indications for transoral surgery and additional therapy in patients with superficial head and neck carcinoma. Sixty-two patients with 83 superficial head and neck carcinoma underwent transoral tumor resection at the Cancer Institute Hospital between June 2006 and September 2011. We measured the tumor size and thickness, examined the gross appearance, permeation of vessels, and droplet infiltration, and analyzed the correlations between each parameter. Sessile type of tumor on gross appearance showed a significantly higher incidence of thickness≥1000 µm than the other types. Tumor thickness≥1000 µm was associated with higher incidences of permeation of vessels, droplet infiltration, and cervical lymph node metastasis. In superficial head and neck carcinoma, if the endoscopic gross appearance is the sessile type, tumor thickness is likely to be ≥1000 µm and risk of cervical lymph node metastasis is increased.

  1. The Lower Anogenital Squamous Terminology Standardization Project for HPV-Associated Lesions: background and consensus recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology.

    PubMed

    Darragh, Teresa M; Colgan, Terence J; Cox, J Thomas; Heller, Debra S; Henry, Michael R; Luff, Ronald D; McCalmont, Timothy; Nayar, Ritu; Palefsky, Joel M; Stoler, Mark H; Wilkinson, Edward J; Zaino, Richard J; Wilbur, David C

    2012-07-01

    The terminology for human papillomavirus (HPV)-associated squamous lesions of the lower anogenital tract has a long history marked by disparate diagnostic terms derived from multiple specialties. It often does not reflect current knowledge of HPV biology and pathogenesis. A consensus process was convened to recommend terminology unified across lower anogenital sites. The goal was to create a histopathologic nomenclature system that reflects current knowledge of HPV biology, optimally uses available biomarkers, and facilitates clear communication across different medical specialties. The Lower Anogenital Squamous Terminology (LAST) Project was cosponsored by the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology and included 5 working groups; 3 work groups performed comprehensive literature reviews and developed draft recommendations. Another work group provided the historical background and the fifth will continue to foster implementation of the LAST recommendations. After an open comment period, the draft recommendations were presented at a consensus conference attended by LAST work group members, advisors, and representatives from 35 stakeholder organizations including professional societies and government agencies. Recommendations were finalized and voted on at the consensus meeting. The final, approved recommendations standardize biologically relevant histopathologic terminology for HPV-associated squamous intraepithelial lesions and superficially invasive squamous carcinomas across all lower anogenital tract sites and detail the appropriate use of specific biomarkers to clarify histologic interpretations and enhance diagnostic accuracy. A plan for disseminating and monitoring recommendation implementation in the practicing community was also developed. The implemented recommendations will facilitate communication between pathologists and their clinical colleagues and improve accuracy of histologic diagnosis with the

  2. The Lower Anogenital Squamous Terminology Standardization Project for HPV-Associated Lesions: background and consensus recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology.

    PubMed

    Darragh, Teresa M; Colgan, Terence J; Cox, J Thomas; Heller, Debra S; Henry, Michael R; Luff, Ronald D; McCalmont, Timothy; Nayar, Ritu; Palefsky, Joel M; Stoler, Mark H; Wilkinson, Edward J; Zaino, Richard J; Wilbur, David C

    2012-10-01

    The terminology for human papillomavirus(HPV)–associated squamous lesions of the lower anogenital tract has a long history marked by disparate diagnostic terms derived from multiple specialties. It often does not reflect current knowledge of HPV biology and pathogenesis. A consensus process was convened to recommend terminology unified across lower anogenital sites. The goal was to create a histopathologic nomenclature system that reflects current knowledge of HPV biology, optimally uses available biomarkers, and facilitates clear communication across different medical specialties. The Lower Anogenital Squamous Terminology (LAST) Project was co-sponsored by the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology and included 5 working groups; 3 work groups performed comprehensive literature reviews and developed draft recommendations. Another work group provided the historical background and the fifth will continue to foster implementation of the LAST recommendations. After an open comment period, the draft recommendations were presented at a consensus conference attended by LAST work group members, advisors, and representatives from 35 stakeholder organizations including professional societies and government agencies. Recommendations were finalized and voted on at the consensus meeting. The final, approved recommendations standardize biologically relevant histopathologic terminology for HPV-associated squamous intraepithelial lesions and superficially invasive squamous carcinomas across all lower anogenital tract sites and detail the appropriate use of specific biomarkers to clarify histologic interpretations and enhance diagnostic accuracy. A plan for disseminating and monitoring recommendation implementation in the practicing community was also developed. The implemented recommendations will facilitate communication between pathologists and their clinical colleagues and improve accuracy of histologic diagnosis with

  3. The Lower Anogenital Squamous Terminology Standardization project for HPV-associated lesions: background and consensus recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology.

    PubMed

    Darragh, Teresa M; Colgan, Terence J; Thomas Cox, J; Heller, Debra S; Henry, Michael R; Luff, Ronald D; McCalmont, Timothy; Nayar, Ritu; Palefsky, Joel M; Stoler, Mark H; Wilkinson, Edward J; Zaino, Richard J; Wilbur, David C

    2013-01-01

    The terminology for human papillomavirus (HPV)-associated squamous lesions of the lower anogenital tract has a long history marked by disparate diagnostic terms derived from multiple specialties. It often does not reflect current knowledge of HPV biology and pathogenesis. A consensus process was convened to recommend terminology unified across lower anogenital sites. The goal was to create a histopathologic nomenclature system that reflects current knowledge of HPV biology, optimally uses available biomarkers, and facilitates clear communication across different medical specialties. The Lower Anogenital Squamous Terminology (LAST) project was co-sponsored by the College of American Pathologists (CAP) and the American Society for Colposcopy and Cervical Pathology (ASCCP) and included 5 working groups; three work groups performed comprehensive literature reviews and developed draft recommendations. Another work group provided the historical background and the fifth will continue to foster implementation of the LAST recommendations. After an open comment period, the draft recommendations were presented at a consensus conference attended by LAST work group members, advisors and representatives from 35 stakeholder organizations including professional societies and government agencies. Recommendations were finalized and voted upon at the consensus meeting. The final approved recommendations standardize biologically-relevant histopathologic terminology for HPV-associated squamous intraepithelial lesions and superficially invasive squamous carcinomas across all lower anogenital tract sites and detail appropriate use of specific biomarkers to clarify histologic interpretations and enhance diagnostic accuracy. A plan for disseminating and monitoring recommendation implementation in the practicing community was also developed. The implemented recommendations will facilitate communication between pathologists and their clinical colleagues and improve accuracy of histologic

  4. Association of human papilloma virus with pterygia and ocular-surface squamous neoplasia

    PubMed Central

    Di Girolamo, N

    2012-01-01

    There are more microorganisms that colonize the human body than resident cells; some are commensal whereas others are pathogenic. Pathogenic microorganisms are sensed by the innate or adaptive immune system, an immune response is initiated, and the infection is often cleared. Some microorganisms have developed strategies to evade immune defenses, ensuring their long-term survival with potentially devastating consequences for the host. Approximately 18% of all cancers can be attributed to infective agents; the most common being Helicobacter pylori, Human papilloma virus (HPV) and Hepatitis B and C virus in causing stomach, cervical and liver carcinoma, respectively. This review focuses on whether HPV infection is necessary for initiating pterygia, a common benign condition and ocular-surface squamous neoplasia (OSSN), a rare disease with metastatic potential. The search engine PubMed was used to identify articles from the literature related to HPV and pterygium or conjunctival neoplasia. From 34 investigations that studied HPV in pterygia and OSSN, a prevalence rate of 18.6% (136/731) and 33.8% (144/426), respectively, was recorded. The variation in HPV prevalence (0–100%) for both disease groups may have arisen from study-design faults and the techniques used to identify the virus. Overall, the data suggest that HPV is not necessary for initiating either condition but may be a co-factor in susceptible hosts. Currently, over 60 million people worldwide have been immunized with HPV vaccines, but any effect on pterygium and OSSN development may not be known for some time as these lesions can evolve over decades or occur in older individuals. PMID:22134594

  5. Preoperative evaluation of cervical lymph nodes for metastasis in patients with oral squamous cell carcinoma: A comparative study of efficacy of palpation, ultrasonography and computed tomography

    PubMed Central

    Mishra, Niranjan; Rath, Krushna Chandra; Upadhyay, Upendra Nath; Raut, Subhrajit; Baig, Shadab Ali; Birmiwal, Krishna Gopal

    2016-01-01

    Introduction: Oral cancer is a major health threat in a country like India, where patients frequently present with advanced disease with regional dissemination to cervical lymph nodes. The management and prognosis depend on the status of cervical lymph nodes. Thus, it becomes imperative to diagnose and evaluate them preoperatively. Aim: This study aims to compare the efficacy of palpation, ultrasonography (USG) and computed tomography (CT) in the preoperative evaluation of cervical lymph node for metastasis in patients with oral squamous cell carcinoma. Settings: Department of Oral and Maxillofacial Surgery, SCB Dental College and Hospital, Cuttack, Odisha, India. Methodology: A total of thirty patients of either sex of age group 20–70 years, diagnosed with oral cancer were randomly selected for the study and subjected to palpation, USG and computer tomography followed by histopathology for confirmation. The results were evaluate statistically by sensitivity, specificity, positive predictive value, and negative predictive value and accuracy. Results: For level IA palpation, USG and CT were equally sensitive (100%) and specific (100%). Although palpation, USG and CT were equally sensitive (80%) for level IB, the specificity of palpation (70%) cervical lymph nodes in patients with oral squamous cell carcinoma. CT along with USG should be used for accurate preoperative evaluation of cervical lymph node. PMID:28356691

  6. Differentiating between endocervical glandular neoplasia and high grade squamous intraepithelial lesions in endocervical crypts: cytological features in ThinPrep and SurePath cervical cytology samples.

    PubMed

    Thiryayi, Sakinah A; Marshall, Janet; Rana, Durgesh N

    2009-05-01

    A recent audit at our institution revealed a higher number of cases diagnosed as endocervical glandular neoplasia on ThinPrep (TP) cervical cytology samples (9 cases) as opposed to SurePath (SP) (1 case), which on histology showed only high-grade cervical intraepithelial neoplasia (CIN) with endocervical crypt involvement (CI). We attempted to ascertain the reasons for this finding by reviewing the available slides of these cases, as well as slides of cases diagnosed as glandular neoplasia on cytology and histology; cases diagnosed as high-grade squamous intraepithelial lesions (HSIL) on cytology which had CIN with CI on histology and cases with mixed glandular and squamous abnormalities diagnosed both cytologically and histologically. Single neoplastic glandular cells and short pseudostratified strips were more prevalent in SP than TP with the cell clusters in glandular neoplasia 3-4 cells thick, in contrast to the dense crowded centre of cell groups in HSIL with CI. The cells at the periphery of groups can be misleading. Cases with HSIL and glandular neoplasia have a combination of the features of each entity in isolation. The diagnosis of glandular neoplasia remains challenging and conversion from conventional to liquid based cervical cytology requires a period of learning and adaptation, which can be facilitated by local audit and review of the cytology slides in cases with a cytology-histology mismatch. (c) 2009 Wiley-Liss, Inc.

  7. Human papillomavirus-related basaloid squamous cell carcinoma of the bladder associated with genital tract human papillomavirus infection.

    PubMed

    Ginori, Alessandro; Barone, Aurora; Santopietro, Rosa; Barbanti, Gabriele; Cecconi, Filippo; Tripodi, Sergio Antonio

    2015-02-01

    Basaloid squamous cell carcinoma is a biologically aggressive neoplasm mainly found in the head and neck region. Recently, four cases of basaloid squamous cell carcinoma of the bladder have been reported, and three of them occurred in patients with neurogenic bladder, repeated catheterizations and human papillomavirus infection of the urinary tract. To the best of our knowledge, none of the patients affected by basaloid squamous cell carcinoma of the bladder described in the literature had documented genital involvement by human papillomavirus. Herein, we describe the case of a woman with neurogenic bladder affected by basaloid squamous cell carcinoma of the bladder and by a concomitant genital tract human papillomavirus infection. © 2014 The Japanese Urological Association.

  8. Synchronous metastatic cutaneous squamous cell carcinoma and chronic lymphocytic leukaemia/small lymphocytic lymphoma in a cervical lymph node: Case report of an unusual event.

    PubMed

    Dos Santos, Harim-Tavares; Benevenuto, Bruno-Augusto; Filho, Edson-Robles-Castilla; Altemani, Albina

    2015-12-01

    The synchronous occurrence of two different neoplasias is an uncommon event, which may arise between tumors originating in the same organ or in cancer-to-cancer metastasis. We report a rare case of chronic lymphocytic leukaemia / small lymphocytic lymphoma associated with a cutaneous metastatic squamous cell carcinoma in a cervical lymph node. In the affected lymph node, it was observed an effacement of the normal architecture by neoplastic lymphocytes and it was noted the presence of neoplastic invasive epithelial islands. Immunohistochemical analysis demonstrated that lymphocytic proliferation was positive for CD20, CD5, CD23 and Kappa, and negative for CD3, CD10, Cyclin D1 and Lambda. The morphological and immunohistochemical profile lead to a phenotype of B-cell chronic lymphocytic leukaemia / small lymphocytic lymphoma. The epithelial cells were positive for CK5, thus rendering the diagnosis of synchronous metastatic cutaneous squamous cell carcinoma and chronic lymphocytic leukaemia/small lymphocytic lymphoma. Literature supports the poor prognosis in cases that present coexistence of squamous cell carcinoma and chronic lymphocytic leukaemia / small lymphocytic lymphoma. Thus, it is necessary to be aware about this unusual finding in order to provide specific treatment. Chronic lymphocytic leukaemia, small lymphocytic lymphoma, squamous cell carcinoma, metastasis.

  9. Impact of histological subtype on survival in patients with locally advanced cervical cancer that were treated with definitive radiotherapy: adenocarcinoma/adenosquamous carcinoma versus squamous cell carcinoma

    PubMed Central

    Kuroda, Hiromasa; Kimura, Tadashi

    2017-01-01

    Objective To compare the survival outcomes of patients with cervical squamous cell carcinoma (SCC) and adenocarcinoma/adenosquamous carcinoma (AC/ASC) among patients with locally advanced cervical cancer that were treated with definitive radiotherapy. Methods The baseline characteristics and outcome data of patients with locally advanced cervical cancer who were treated with definitive radiotherapy between November 1993 and February 2014 were collected and retrospectively reviewed. A Cox proportional hazards regression model was used to investigate the prognostic significance of AC/ASC histology. Results The patients with AC/ASC of the cervix exhibited significantly shorter overall survival (OS) (p=0.004) and progression-free survival (PFS) (p=0.002) than the patients with SCC of the cervix. Multivariate analysis showed that AC/ASC histology was an independent negative prognostic factor for PFS. Among the patients who displayed AC/ASC histology, larger tumor size, older age, and incomplete response to radiotherapy were found to be independent prognostic factors. PFS was inversely associated with the number of poor prognostic factors the patients exhibited (the estimated 1-year PFS rates; 100.0%, 77.8%, 42.8%, 0.0% for 0, 1, 2, 3 factors, respectively). Conclusion Locally advanced cervical cancer patients with AC/ASC histology experience significantly worse survival outcomes than those with SCC. Further clinical studies are warranted to develop a concurrent chemoradiotherapy (CCRT) protocol that is specifically tailored to locally advanced cervical AC/ASC. PMID:28028992

  10. Squamous cell carcinoma of the anterior tongue: is tumour thickness an indicator for cervical metastasis?

    PubMed

    Loganathan, P; Sayan, A; Hsu, D W K; Paraneetharan, S; Ilankovan, V

    2017-04-01

    The incidence of squamous cell carcinoma (SCC) of the tongue accounts for 90% of all malignancies affecting the oral cavity and oropharynx. The distribution between the anterior and posterior tongue is equal. Nodal metastasis is dependent on various factors including tumour thickness, site, size, differentiation, and perineural and perivascular invasion. There is increasing evidence of a close correlation between tumour thickness and metastasis. A retrospective study covering the 16-year period from 2000 to 2016 was performed. Eighty-one patients with anterior tongue SCC were included. The only primary treatment was surgery. All patients were T1/T2N0M0 stage. Sixty-five patients underwent local excision with simultaneous selective neck dissection; 29 of these patients were confirmed to have occult metastasis. Sixteen patients underwent local excision only as an initial treatment. Four of them subsequently developed neck metastasis within a 6- to 18-month period. The results of this study support recent publications associating tumour thickness with nodal disease. Therefore, it is postulated that prophylactic neck dissection should be considered when the tumour thickness of anterior tongue SCC exceeds 5mm, in order to prevent lymphatic spread and improve the survival rate.

  11. Analysis of gene status in cervical dysplastic lesions and squamous cell carcinoma using tissue microarrays.

    PubMed

    Costa, Carlota; Espinet, Blanca; Molina, Miguel A; Salgado, Rocio; Salido, Marta; Baró, Teresa; Fusté, Pere; Mancebo, Gemma; Carreras, Ramón; Solé, Francesc; Serrano, Sergi; Alameda, Francesc

    2009-07-01

    Cervical displasia are classified as CIN-I, CIN-II and CIN-III. It has been observed that in at least 60% of CIN-I and CIN-II, the pathology disappears spontaneously, while around 30% persist at 24 months, 10% progress to CIN-III and 1% develops as a SCC. The factors involved in the evolution of the pathology are not defined, although infection of HPV is a necessary condition, but not the only one. For this reason, the identification of genetic changes is an essential element for understanding the carcinogenic process. It can also serve as a helpful tool for identifying patients who may be susceptible to its evolution and treatment, from patients whose lesions could regress spontaneous and for whom periodic follow-ups would be enough. Fifty three cervical biopsies from patients with dysplasia and ISCC were included in the study. These biopsies were set into nine macroarrays. Eight genes and five proteins were examined in each samples (hTERT, PIK3CA, hTERC, MYC, CCND1, BCL2, ZNF217 and p16) by fluorescence in situ hybridization (FISH) and/or immunohistochemistry (IHC). The results reflected that the genetic alterations of PIK3CA, ZNF217 and CCND1 were associated with the evolution of normal tissue to CIN I, those of hTERC and ERBB with the evolution of LSIL to HSIL, those of hTERT and MYC with the evolution of CIN-II/CIN-III to ISCC, and those of BCL-2 with the inception of ISCC. With regards to proteins, the expression of MYC and CCND1 in the initial stages of the illness would help in the acquisition of the altered cellular phenotype.

  12. Genotype distribution of cervical human papillomavirus DNA in women with cervical lesions in Bioko, Equatorial Guinea

    PubMed Central

    García-Espinosa, Benjamín; Nieto-Bona, Ma Paz; Rueda, Sonsoles; Silva-Sánchez, Luís Fernando; Piernas-Morales, Ma Concepción; Carro-Campos, Patricia; Cortés-Lambea, Luís; Moro-Rodríguez, Ernesto

    2009-01-01

    Background The HVP vaccine is a useful tool for preventing cervical cancer. The purpose of this study is to determine the most frequent HPV genotypes in Equatorial Guinea in order to develop future vaccination strategies to apply in this country. Methods A campaign against cervical cancer was carried out in the area on a total of 1,680 women. 26 of the women, following cytological screening, were treated surgically with a loop electrosurgical excision procedure (LEEP). Cases were studied histologically and were genotyped from paraffin blocks by applying a commercial kit that recognized 35 HPV types. Results Cytological diagnoses included 17 HSIL, 1 LSIL, 5 ASC-H and 3 AGUS. Histological diagnosis resulted in 3 cases of microinvasive squamous cell carcinoma stage IA of FIGO, 9 CIN-3, 8 CIN-2, 2 CIN-1, 3 flat condylomas and mild dysplasia of the endocervical epithelium. Fifteen of twenty-five cases genotyped were positive for HPV (60%). HPV 16 and 33 were identified in four cases each, HPV 58 in two other cases, and HPV 18, 31, 52, and 82 in one case, with one HPV 16 and 58 coinfection. Conclusion The frequency of HPV types in the African area varies in comparison to other regions, particularly in Europe and USA. Vaccination against the five most common HPV types (16, 33, 58, 18, and 31) should be considered in the geographic region of West Africa and specifically in Equatorial Guinea. PMID:19740435

  13. Human papillomavirus prevalence in paired urine and cervical samples in women invited for cervical cancer screening.

    PubMed

    Burroni, Elena; Bonanni, Paolo; Sani, Cristina; Lastrucci, Vieri; Carozzi, Francesca; Iossa, Anna; Andersson, Karin Louise; Brandigi, Livia; Di Pierro, Carmelina; Confortini, Massimo; Levi, Miriam; Boccalini, Sara; Indiani, Laura; Sala, Antonino; Tanini, Tommaso; Bechini, Angela; Azzari, Chiara

    2015-03-01

    With the introduction of Human papillomavirus (HPV) vaccination in young girls in 2007, it is important to monitor HPV infections and epidemiological changes in this target population. The present study has evaluated the detection of human papillomavirus DNA in paired cervical and urine samples to understand if HPV testing in urine could be used as non-invasive method to monitor HPV status in young women. The study enrolled 216 twenty five-year-old women, resident in Florence and invited for the first time to the cervical cancer Screening Program within a project evaluating the impact of HPV vaccination. HPV genotyping was performed on 216 paired urine and cervical samples. The overall concordance between cervix and urine samples, investigated by HPV genotyping (INNO-LiPA HPV Genotyping Extra), was: 85.6% (184/215), 84.6% (182/215), 80% (172/215) when the same HPV, at least the same HR HPV and all HR HPV, respectively, were detected. HPV type specific concordance in paired urine and cervical samples was observed in 85.8% (175/204) of women with normal cytology and in seven out of nine women with abnormal cytology. Urine seems to be a suitable and reliable biological material for HPV DNA detection as evidenced by the high concordance with HPV detected in cervical samples. These results suggest that urine could be a good noninvasive tool to monitor HPV infection in vaccinated women.

  14. Accuracy of urinary human papillomavirus testing for the presence of cervical human papillomaviruses and higher grades of cervical intraepithelial neoplasia.

    PubMed

    Piyathilake, Chandrika J; Badiga, Suguna; Chambers, Michelle M; Brill, Ilene K; Matthews, Roland; Partridge, Edward E

    2016-09-15

    Although urine-based testing for human papillomavirus (HPV) is being explored as a practical approach for cervical cancer screening, whether the results differ by age, race, or indicators of excess body weight or in populations exposed to HPV vaccines has not been documented by previous studies. The purpose of this study was to determine the accuracy of urinary HPV testing for the presence of cervical HPVs and high-grade cervical intraepithelial lesions (grade 2 and 3 cervical intraepithelial neoplasia [CIN]) by the aforementioned population characteristics. The study population consisted of 502 women diagnosed with different grades of CIN. HPV testing was performed with paired urine and cervical cell DNA with the Roche Diagnostics Linear Array test. Agreement coefficient 1 and probabilities were calculated to determine the accuracy of urinary HPV testing for the presence of cervical HPVs and CIN lesions. Substantial to almost perfect agreement (0.66-0.83) was observed in the detection of any HPV genotype in urine specimens versus cervical specimens, regardless of the population characteristics. Although the positive predictive value for the detection of CIN lesions was relatively low, the negative predictive value for CIN-3 was high (≥90%) among women positive for any of the urinary or cervical high-risk human papillomavirus (HR-HPV) genotypes or HPV genotypes not included in currently available HPV vaccines. The results demonstrate that urinary HPV testing provides highly satisfactory results for excluding the possibility of any cervical HPV infections, including HPV types not included in vaccines and CIN lesions associated with any HR-HPV, regardless of a woman's age, race, or excess body weight. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2836-2844. © 2016 American Cancer Society. © 2016 American Cancer Society.

  15. The clinician's view: role of human papillomavirus testing in the American Society for Colposcopy and Cervical Pathology Guidelines for the management of abnormal cervical cytology and cervical cancer precursors.

    PubMed

    Cox, J Thomas

    2003-08-01

    The American Society for Colposcopy and Cervical Pathology (ASCCP) National Consensus Conference for the Management of Women With Cervical Cytological Abnormalities and Cervical Cancer Precursors was held on the National Institutes of Health campus in Bethesda, Md, September 6-8, 2001. The conference was attended by 121 representatives from 29 national organizations interested in cervical cancer screening issues. For the first time, guidelines for the management of women with abnormal cervical cytology, developed from evidence-based literature, were presented to delegates from the majority of organizations with interest in cervical cancer screening, voted on, and revised when necessary to achieve a majority two-thirds approval. This development of consensus-approved guidelines is likely to be considered one of the most important milestones to date in the management of women with abnormal cervical cytology. The timing of this Consensus Conference resulted from the convergence of many different factors, including new cytologic terminology developed at the Bethesda 2001 workshop and publication of the enrollment data from the National Cancer Institute's Atypical Squamous Cells of Undetermined Significance (ASC-US)/Low-Grade Squamous Intraepithelial Lesions (LSIL) Triage Study, otherwise known as ALTS. Additionally, new preliminary longitudinal ALTS data provided much of the information on the natural history of abnormal Papanicolaou tests and cervical intraepithelial neoplasia (CIN), as well as data on the performance of both new liquid-based cytology and human papillomavirus (HPV) DNA testing in the management of women following colposcopy. The result was a large database of new information that provided the foundation for the ASCCP Consensus Conference. This article covers only the recommendations of the ASCCP Guidelines that were based in large part on the results of the ALTS trial. Therefore, the focus is on the management of women with equivocal (ASC-US) and low

  16. Cervical neoplasia after diagnosis and follow-up of women with atypical squamous cells of undetermined significance.

    PubMed

    Murta, E F C; Da Silva, C S; Vieira, J B; Khabbaz, K M; Adad, S J

    2007-01-01

    Although the cytological finding of atypical squamous cells of undetermined significance (ASCUS) occurs in around 5% of women undergoing cytological screening, the clinical evolution is unknown. The objective of this study was to evaluate women with a diagnosis of ASCUS and compare the histological findings and clinical evolution over six and 12 months. 1244 patients with ASCUS (two diagnostic cytologists) were evaluated in this study with Pap Smears and colposcopy (biopsy if necessary) at the first visit, and thereafter at second and third visits (6 and 12 months after the first visit). Comparisons were made between cytological findings and histological diagnoses at every visit during the study and during evolution. At the first visit, 60.3% of the biopsied patients presented histological findings of CIN I, 17.46% CIN II/III and 6.3% invasive neoplasia. At the second visit, 48.3% of the biopsied patients presented CIN I, 24.1% CIN II/III and none invasive neoplasia. At the third visit, 68.9% of the biopsied patients presented CIN I, 13.8% CIN II/III and none invasive carcinoma. If we consider all visits, a total of 213 colposcopy-guided biopsies were performed, representing 17.1% of all the patients included. Of these, 164 (13.2%) presented a histological diagnosis of cervical intraepithelial neoplasia (CIN) and eight (0.6%) presented with invasive carcinoma. We conclude that CIN or invasive lesions frequently occur in women with a diagnosis of ASCUS. Immediate review of the thin sections, new cytological tests or colposcopy and rigorous follow-up should be considered when making a diagnosis of ASCUS.

  17. Co-expression of CD147 and GLUT-1 indicates radiation resistance and poor prognosis in cervical squamous cell carcinoma

    PubMed Central

    Huang, Xin-Qiong; Chen, Xiang; Xie, Xiao-Xue; Zhou, Qin; Li, Kai; Li, Shan; Shen, Liang-Fang; Su, Juan

    2014-01-01

    The aim of this study was to investigate the association of CD147 and GLUT-1, which play important roles in glycolysis in response to radiotherapy and clinical outcomes in patients with locally advanced cervical squamous cell carcinoma (LACSCC). The records of 132 female patients who received primary radiation therapy to treat LACSCC at FIGO stages IB-IVA were retrospectively reviewed. Forty-seven patients with PFS (progression-free survival) of less than 36 months were regarded as radiation-resistant. Eighty-five patients with PFS longer than 36 months were regarded as radiation-sensitive. Using pretreatment paraffin-embedded tissues, we evaluated CD147 and GLUT-1 expression by immunohistochemistry. Overexpression of CD147, GLUT-1, and CD147 and GLUT-1 combined were 44.7%, 52.9% and 36.5%, respectively, in the radiation-sensitive group, and 91.5%, 89.4% and 83.0%, respectively, in the radiation-resistant group. The 5-year progress free survival (PFS) rates in the CD147-low, CD147-high, GLUT-1-low, GLUT-1-high, CD147- and/or GLUT-1-low and CD147- and GLUT-1- dual high expression groups were 66.79%, 87.10%, 52.78%, 85.82%, 55.94%, 82.90% and 50.82%, respectively. CD147 and GLUT-1 co-expression, FIGO stage and tumor diameter were independent poor prognostic factors for patients with LACSCC in multivariate Cox regression analysis. Patients with high expression of CD147 alone, GLUT-1 alone or co-expression of CD147 and GLUT-1 showed greater resistance to radiotherapy and a shorter PFS than those with low expression. In particular, co-expression of CD147 and GLUT-1 can be considered as a negative independent prognostic factor. PMID:24817962

  18. Interobserver reproducibility of cervical lymph node measurements at CT in patients with head and neck squamous cell carcinoma.

    PubMed

    Chung, M S; Cheng, K L; Choi, Y J; Roh, J L; Lee, Y S; Lee, S S; Lee, J H; Baek, J H

    2016-12-01

    To determine the interobserver reproducibility of measuring cervical lymph nodes at computed tomography (CT) in patients with head and neck squamous cell carcinoma (HNSCC) and to investigate the influence of finding extracapsular spread (ECS) at CT on measurement reliability. The institutional review board approved the study protocol, and informed consent was obtained. A total of 146 patients with 224 suspicious lymph nodes underwent CT before treatment. Two observers independently measured the diameters (minimal axial, maximum axial, and maximum longitudinal diameter) and assessed the ECS using CT. The greatest diameter was defined as the largest among the three measured diameters. Interobserver variability was determined by the within-subject coefficient of variation, and interobserver agreement was determined by the intraclass correlation coefficient (ICC). The within-subject coefficients of variation were 7.8%, 7.6%, and 11.4% for the minimal axial, maximum axial, and greatest diameters, respectively. The ICC values for interobserver agreement were excellent for all diameter measurements (i.e., ICC >0.9). Minimum and maximum axial diameter measurements were statistically more reliable than the greatest diameter measurement (p=0.008 and p=0.0001, respectively). The presence of ECS on CT does not significantly affect the reliability of lymph node diameter measurements (p>0.05). Lymph node diameter measurement on CT is a highly reproducible and robust method. Additionally, imaging features of ECS do not affect reliability. Therefore, the measurement of lymph node diameter can be confidently performed in daily clinical practice or clinical trials. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  19. Role of difucosylated Lewis Y antigen in outcome of locally advanced cervical squamous cell carcinoma treated with cisplatin regimen.

    PubMed

    Leone, Julieta; Perez, Juan E; Dominguez, Maria E; Iturbe, Julian; Leone, José P; Mac Donnell, Maria C; Grosman, Gabriel; Vallejo, Carlos T; Leone, Bernardo A; Zwenger, Ariel O

    2016-07-30

    Several mechanisms are involved in the development of resistance to therapy in locally advanced cervical squamous cell carcinoma (LACSCC). Studies have shown that CD44 and Lewis Y antigen (LeY) form a complex that is associated with chemoresistance, tumor invasion and metastasis. We assessed the role of CD44 and LeY in the outcome of LACSCC patients treated with different chemotherapy regimens. 126 LACSCC patients at FIGO stages IIB-IVA were selected from the GOCS database: 74 patients included in 3 different prospective phase II trials in the neoadjuvant setting (vinorelbine, docetaxel, ifosfamide-vinorelbine-cisplatin) and 52 patients treated with standard radiochemotherapy based on cisplatin (RCBC). Clinical data at baseline, disease-free survival (DFS) and overall survival (OS) were recorded. Univariate and multivariate Cox models were employed. Median age was 45.6 years (range: 24.9-80.5). Sixty-three and 47 tumors were CD44+ and LeY+, respectively. Tumors with expansive growth showed higher grade (p = 0.0024), mitotic index (p = 0.0505), tumor necrosis (p = 0.0191), LeY+ (p = 0.0034) and CD44+/LeY+ coexpression (p = 0.0334). CD44+ cells were present in 91.3% of patients with local recurrence (p = 0.0317). Advanced stage was associated with LeY+ tumors. Patients treated with RCBC had worse DFS and OS when their tumors expressed LeY (p = 0.0083 and p = 0.0137, respectively). Pre-treatment hemoglobin level, FIGO stage and tumor response remained the most significant prognostic factors in Cox regression. In our cohort of LACSCC patients, the coexpression of CD44 and LeY was not associated with worse outcome. However, in the subgroup of patients receiving RCBC, LeY expression was correlated with shorter DFS and OS.

  20. Co-expression of CD147 and GLUT-1 indicates radiation resistance and poor prognosis in cervical squamous cell carcinoma.

    PubMed

    Huang, Xin-Qiong; Chen, Xiang; Xie, Xiao-Xue; Zhou, Qin; Li, Kai; Li, Shan; Shen, Liang-Fang; Su, Juan

    2014-01-01

    The aim of this study was to investigate the association of CD147 and GLUT-1, which play important roles in glycolysis in response to radiotherapy and clinical outcomes in patients with locally advanced cervical squamous cell carcinoma (LACSCC). The records of 132 female patients who received primary radiation therapy to treat LACSCC at FIGO stages IB-IVA were retrospectively reviewed. Forty-seven patients with PFS (progression-free survival) of less than 36 months were regarded as radiation-resistant. Eighty-five patients with PFS longer than 36 months were regarded as radiation-sensitive. Using pretreatment paraffin-embedded tissues, we evaluated CD147 and GLUT-1 expression by immunohistochemistry. Overexpression of CD147, GLUT-1, and CD147 and GLUT-1 combined were 44.7%, 52.9% and 36.5%, respectively, in the radiation-sensitive group, and 91.5%, 89.4% and 83.0%, respectively, in the radiation-resistant group. The 5-year progress free survival (PFS) rates in the CD147-low, CD147-high, GLUT-1-low, GLUT-1-high, CD147- and/or GLUT-1-low and CD147- and GLUT-1- dual high expression groups were 66.79%, 87.10%, 52.78%, 85.82%, 55.94%, 82.90% and 50.82%, respectively. CD147 and GLUT-1 co-expression, FIGO stage and tumor diameter were independent poor prognostic factors for patients with LACSCC in multivariate Cox regression analysis. Patients with high expression of CD147 alone, GLUT-1 alone or co-expression of CD147 and GLUT-1 showed greater resistance to radiotherapy and a shorter PFS than those with low expression. In particular, co-expression of CD147 and GLUT-1 can be considered as a negative independent prognostic factor.

  1. Previous cervical cytology and high-risk human papillomavirus testing in a cohort of patients with invasive cervical carcinoma in Shandong Province, China

    PubMed Central

    Wang, Xinguo; Peng, Dezhi; Bi, Chunrui; Jiang, Lingbo; Zhao, Dongman; Tian, Xinxin

    2017-01-01

    Background Currently, available data regarding previous cervical cytology and high-risk human papillomavirus (hrHPV) test results to detect invasive cervical cancer are limited and controversial in China. Therefore, this retrospective study in a population of Chinese women with invasive cervical carcinoma aimed to gain further insight into the roles of cytology and hrHPV testing in cervical cancer screening. Methods A total of 1214 cases with a histological diagnosis of invasive cervical cancer were retrieved from the Pathology Database of Jinan KingMed Diagnostics (JKD) over a 5-year period. Previous cytology and hrHPV test results of 469 patients carried out within the year before cancer diagnosis were documented. Results A higher percentage of patients who had undergone prior screening had micro-invasive cervical carcinoma than patients who had no prior screening (25.4% vs. 12.1%, P < 0.001). Of the 469 patients with available prior screening results, 170 had cytology alone, 161 had hrHPV testing alone, and 138 had both cytology and hrHPV testing. There was a significantly lower percentage of hrHPV-positive cases with adenocarcinoma than with squamous cell carcinoma (77.8% vs. 96.4%, P = 0.001). The hrHPV test showed a significantly higher sensitivity than cytology alone (94.4% vs. 85.3%, P = 0.006). The overall sensitivity of the combination of cytology and hrHPV testing (98.6%) was much higher than that of cytology alone (P < 0.001) but only marginally higher than that of hrHPV testing alone (P = 0.058). Conclusions The results revealed that prior cervical screening can detect a significantly larger number of micro-invasive cervical cancers. The hrHPV test can provide a more sensitive and efficient strategy than cytology alone. As the addition of cytology to hrHPV testing can only marginally increase the efficiency of the hrHPV test, hrHPV testing should be used as the primary screening approach, especially in the low-resource settings of China. PMID:28662160

  2. Prevalence of human papillomaviruses in patients with head and neck squamous cell carcinoma in Lithuania and Belarus.

    PubMed

    Gudleviciene, Zivile; Didziapetriene, Janina; Mackeviciene, Irina; Cicenas, Saulius; Smolyakova, Raisa; Zhukavetc, Aliaksandr; Zivile, Gudleviciene; Janina, Didziapetriene; Irina, Mackeviciene; Saulius, Cicenas; Raisa, Smolyakova; Aliaksandr, Zhukavetc

    2014-03-01

    Overall, head and neck sqamous cell carcinoma accounts for more than 550,000 cases annually worldwide. It is well known that human papillomavirus (HPV) is the main risk factor for cervical cancer development. As the incidence and the mortality of cervical cancer are closely related to the HPV prevalence, we hypothesized that there is the same association between HPV prevalence and head and neck squamous cell carcinoma. Therefore we performed the study aiming to compare the level of HPV infection and HPV type distribution between two groups of Lithuanian and Belarusian patients with head and neck sqamous cell carcinoma. One hundred ninety head and neck sqamous cell carcinoma patients were included in the study, 75 from Lithuania and 115 from Belarus. PCR was used for HPV detection and typing. The distribution of HPV infection among head and neck sqamous cell carcinoma patients was similar in the Lithuanian (20.0%) and Belarusian (18.3%) patient groups, however differences were found in the distribution of HPV types. © 2013 Wiley Periodicals, Inc.

  3. Papanicolau smear chances to be diagnostic for cervical squamous intraepithelial lesions (SIL) with or without detectable HPV DNA at in situ hybridization analysis.

    PubMed

    Sopracordevole, F; Cadorin, L; Muffato, G; De Benetti, L; Parin, A

    1993-01-01

    The Authors have correlated 39 cervical diagnostic biopsies for squamous intraepithelial lesions (SILs) with correspective Papanicolau smears (PS), with relation to the presence or the absence of HPV of oncogenic type (HPV-one) detected by in situ hybridization (ISH). Agreement between cytological and histological diagnosis was present in 14 of 16 cases with detectable HPV-one and only in 12 of 23 cases without detectable HPV-one at ISH. The importance of the HPV type in the SILs with relation to the diagnostic accuracy of Papanicolaou smears has been discussed.

  4. Testosterone-induced "Virilization" of Mesonephric Duct Remnants and Cervical Squamous Epithelium in Female-to-Male Transgenders: A Report of 3 Cases.

    PubMed

    Singh, Kamaljeet; Sung, C James; Lawrence, W Dwayne; Quddus, M Ruhul

    2016-08-26

    Mesonephric ducts regress in genotypic females, leaving behind few remnants. These vestigial structures are often recognized in the mesosalpinx and paracervical regions. We report here 3 cases of female-to-male transgenders who underwent hysterectomy following testosterone treatment. Both female and male genital structures were identified on histologic examination. Although the morphologic appearances of the specimens were unremarkable, histologically 1 case revealed a well-formed fallopian tube as well as an epididymis and 2 cases showed prostate glands to be present in the cervical squamous epithelium.

  5. High expression of TGF-β1 in the vaginal incisional margin predicts poor prognosis in patients with stage Ib-IIa cervical squamous cell carcinoma.

    PubMed

    Fan, Dong-Mei; Wang, Xin-Jun; He, Tao; Wang, Yan; Zhou, Dan; Kong, Guo-Qiang; Jiang, Tao; Zhang, Mei-Mei

    2012-04-01

    This study evaluated the relationship between altered cytoplasmic expression of TGF-β1 in tissues of the vaginal incisional margin and vaginal cancer recurrence in patients with stage Ib-IIa cervical squamous cell carcinoma (CSCC). This paper also discusses the prognostic value of TGF-β1 expression at these locations. We found that TGF-β1 expression in the vaginal margin had a close association with vaginal recurrence of stage Ib-IIa CSCC and was an independent prognostic marker of this disease.

  6. MRI and PET Imaging in Predicting Treatment Response in Patients With Stage IB-IVA Cervical Cancer

    ClinicalTrials.gov

    2017-06-27

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Cervical Undifferentiated Carcinoma; Recurrent Cervical Carcinoma; Stage IB2 Cervical Cancer; Stage II Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IIIA Cervical Cancer; Stage IIIB Cervical Cancer; Stage IVA Cervical Cancer

  7. Antibody levels against alpha-galactosyl epitopes in sera of patients with squamous intraepithelial lesions and early invasive cervical carcinoma.

    PubMed

    Tremont-Lukats, I W; Avila, J L; Hernández, D; Vásquez, J; Teixeira, G M; Rojas, M

    1997-02-01

    We measured serum levels of anti-Gal(alpha 1-->3)Gal and anti-Gal(alpha 1-->2)Gal antibodies in 89 and 91 women, respectively, by using ELISA. These patients had cervical intraepithelial neoplasia (CIN) grades 1 to 3 and early invasive cervical carcinoma (ICC). Our objective was to compare anti-alpha-galactosyl antibody levels among them and with those of normal controls. High levels of anti-Gal(alpha 1-->2)Gal antibodies were detected in 22% of patients (P = 0.006). The mean level was 1.6 times greater than that of controls, without difference among subgroups. Thirty percent of patients had abnormally high anti-Gal levels (P = 0.001). Mean levels were twofold greater than the mean control value. Subsets with human papillomavirus/CIN 1 and CIN 2-3 had high immunoreactivity (P = 0.004). Both antibodies showed a significant correlation (r = 0.53, P < 0.00001). We conclude that 22 to 30% of patients with CIN 1-3 showed significantly high levels of anti-alpha-galactosyl antibodies. This seroreactivity might be related to the abnormal expression of alpha-galactosyl residues at some point of the natural history of human papillomavirus infection of the uterine cervix, suggesting an active immune response by natural antibodies against this virus. Further studies are needed to determine whether anti-alpha-galactosyl antibodies confer protection in human papillomavirus infection.

  8. Immunohistochemical Expression of VEGF and Podoplanin in Uterine Cervical Squamous Intraepithelial Lesions

    PubMed Central

    Belfort-Mattos, Patrícia Napoli; Focchi, Gustavo Rubino de Azevedo; Ribalta, Julisa Chamorro Lascasas; Megale De Lima, Tatiana; Nogueira Carvalho, Carmen Regina; Kesselring Tso, Fernanda; De Góis Speck, Neila Maria

    2016-01-01

    VEGF and podoplanin (PDPN) have been identified as angiogenesis and/or lymphangiogenesis regulators and might be essential to restrict tumor growth, progression, and metastasis. In the present study, we evaluate the association between the expression of these markers and CIN grade. Immunohistochemistry was performed in 234 uterine cervical samples using conventional histologic sections or TMA with the monoclonal antibodies to VEGF (C-1 clone) and podoplanin (D2-40 clone). Positive-staining rates of VEGF in 191 CIN specimens were significantly associated with histological grade (P < 0.001). Negative and/or focal immunostaining for PDPN were more frequent in CIN 3 (P = 0.016). We found that patients with CIN 3 more frequently had strong and more diffuse staining for VEGF and diminished staining for PDPN (P = 0.018). Strong and more diffuse VEGF immunoexpressions in CIN 2 and CIN 3 were detected when compared to CIN 1. Negative and/or focal PDPN immunoexpression appear to be more frequent in CIN 3. Moderate to strong VEGF expression may be a tendency among patients with high-grade lesions and diminished PDPN expression. PMID:27313335

  9. Tumor budding correlates with occult cervical lymph node metastasis and poor prognosis in clinical early-stage tongue squamous cell carcinoma.

    PubMed

    Xie, Nan; Wang, Cheng; Liu, Xiqiang; Li, Ruyao; Hou, Jinsong; Chen, Xiaohua; Huang, Hongzhang

    2015-04-01

    Tumor budding has been suggested to be a prognostic factor in various human cancers. However, the prognostic value of tumor budding for early-stage (cT1/2N0) tongue squamous cell carcinoma remains inconclusive. This study analyzed the correlation of tumor budding with the clinicopathologic features, and its prognostic significance for cT1/2N0 stage tongue squamous cell carcinoma. One hundred and ninety-five patients with T1/2 stage tongue squamous cell carcinoma enrolled in the retrospective study. Tumor invasive depth, the intensity of tumor budding, and other clinicopathological features were reviewed. Overall survivals were evaluated by the Kaplan-Meier method. For multivariable analysis, Cox's proportional hazards regression models were performed. The frequency of tumor buds in tongue squamous cell carcinoma is about 85.6% in this study. The intensity of tumor budding showed strong correlations with occult lymph node metastasis (P < 0.05), local relapse (P < 0.01), worse invasive pattern (P < 0.01), and invasive depth (P < 0.05). The invasive depth was significantly associated with T classification (P < 0.01) and lymph node metastasis (P < 0.01). And both high intensity of tumor budding and deeper invasive depth correlated with reduced overall survival. Cox's regression models proved tumor budding to be an independent prognostic factor in clinical early-stage tongue squamous cell carcinoma. Tumor local relapses were also a predictor of tongue squamous cell carcinoma progression. Tumor budding is a frequent event in tongue squamous cell carcinoma. It independently predicted prognosis of patients with T1/2 stage tongue squamous cell carcinoma and may be used for routing pathological diagnosis and the decision of elective lymph node dissection. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. [Membrane type 1 matrix metalloproteinase (MT1-MMP) and the regulators of its activity as invasive factors in squamous cell cervical carcinomas].

    PubMed

    Timoshenko, O S; Gureeva, T A; Kugaevskaia, E V; Solov'eva, N I

    2014-01-01

    Membrane type 1 matrix metalloproteinase (MT1MMP) is one of matrix metalloproteinases (MMP), which play а key role in tumor invasion and metastasis. The aim of this study was to elucidate the peculiarities of expression of MT1MMP and endogenous regulators of its activity: the activator - furin and the inhibitor - TIMP-2, as invasive factors of squamous cell cervical carcinomas (SCC). The study was carried out using 11 specimens of SCC and 11 specimens of morphologically normal tissue adjacent to the tumor. It was shown that the increase of MT1-MMP and furin expression and low of TIMP-2 expression makes the main contribution to the destructive (invasive) potential of SCC. Moreover, substantial expression of MT1-MMP was registered in the specimens of morphologically normal adjoining to tumor tissue. This expression was found to make an additional contribution to the destructive potential of the cervical tumor.

  11. Human papillomavirus infection in HIV-1 infected women in Catalonia (Spain): implications for prevention of cervical cancer.

    PubMed

    Stuardo, Valeria; Agustí, Cristina; Godinez, José Manuel; Montoliu, Alexandra; Torné, Aureli; Tarrats, Antoni; Alcalde, Carmen; Martín, Dolores; Fernández-Montoli, Eulalia; Vanrell, Cristina; Solé, Josefa; Canet, Yolanda; Marqueta, José Manuel; Mohamed, Jadiyettu; Cuenca, Isabel; Lonca, Montserrat; Sirera, Guillem; Ferrer, Elena; Domingo, Pere; Lloveras, Belen; Miro, Josep María; De Sanjosé, Silvia; Casabona, Jordi

    2012-01-01

    High-risk human Papillomavirus infection is a necessary factor for cervical squamous intraepithelial lesions and invasive cervical cancer. In HIV-1-infected women, HPV infection is more prevalent and a higher risk of cervical cancer has been identified. We aimed to calculate the prevalence of infection by HR-HPV, determine the factors associated with this infection and abnormal cytology findings and to describe the history of cervical cancer screening in HIV-1-infected women. We enrolled 479 HIV-1-infected women from the PISCIS cohort. Each patient underwent a gynecological check-up, PAP smear, HPV AND Hybrid capture, HPV genotyping, and colposcopy and biopsy, if necessary. We applied questionnaires to obtain information on sociodemographic, behavioral, clinical, and cervical screening variables. We present a cross-sectional analysis. Median age was 42 years. The prevalence of HR-HPV infection was 33.2% and that of high-grade squamous intraepithelial lesions (HSIL) was 3.8%. The most common genotypes were 16(23%), 53(20.3%), and 52(16.2%). The factor associated with HR-HPV infection was age <30 years (odds ratio[OR],2.5; 95%confidence interval[CI],1.1-5.6). The factors associated with the presence of HSIL or low-grade squamous intraepithelial lesions (LSIL) were CD4T-lymphocyte count <200 cells/mm(3) versus >500 cells/mm(3) (OR,8.4; 95%CI,3.7-19.2), HIV-1 viral load >10,000 copies/mL versus <400 copies/mL (OR,2.1; 95%CI,1.0-4.4), and use of oral contraceptives (OR,2.0; 95%CI,1.0-3.9). Sixty percent of HIV-1-infected women had had one Pap smear within the last 2 years. The high prevalence of HPV infection and cervical lesions in the HIV-1-infected population in Catalonia, as well as the low coverage and frequency of screening in this group, means that better preventive efforts are necessary and should include vaccination against HPV, better accessibility to screening programs, training of health care professionals, and specific health education for HIV-1-infected

  12. Human Papillomavirus Infection in HIV-1 Infected Women in Catalonia (Spain): Implications for Prevention of Cervical Cancer

    PubMed Central

    Stuardo, Valeria; Agustí, Cristina; Godinez, José Manuel; Montoliu, Alexandra; Torné, Aureli; Tarrats, Antoni; Alcalde, Carmen; Martín, Dolores; Fernández-Montoli, Eulalia; Vanrell, Cristina; Solé, Josefa; Canet, Yolanda; Marqueta, José Manuel; Mohamed, Jadiyettu; Cuenca, Isabel; Lonca, Montserrat; Sirera, Guillem; Ferrer, Elena; Domingo, Pere; Lloveras, Belen; Miro, Josep María; De Sanjosé, Silvia; Casabona, Jordi

    2012-01-01

    Background High-risk human Papillomavirus infection is a necessary factor for cervical squamous intraepithelial lesions and invasive cervical cancer. In HIV-1-infected women, HPV infection is more prevalent and a higher risk of cervical cancer has been identified. We aimed to calculate the prevalence of infection by HR-HPV, determine the factors associated with this infection and abnormal cytology findings and to describe the history of cervical cancer screening in HIV-1-infected women. Methods We enrolled 479 HIV-1–infected women from the PISCIS cohort. Each patient underwent a gynecological check-up, PAP smear, HPV AND Hybrid capture, HPV genotyping, and colposcopy and biopsy, if necessary. We applied questionnaires to obtain information on sociodemographic, behavioral, clinical, and cervical screening variables. We present a cross-sectional analysis. Results Median age was 42 years. The prevalence of HR-HPV infection was 33.2% and that of high-grade squamous intraepithelial lesions (HSIL) was 3.8%. The most common genotypes were 16(23%), 53(20.3%), and 52(16.2%). The factor associated with HR-HPV infection was age <30 years (odds ratio[OR],2.5; 95%confidence interval[CI],1.1–5.6). The factors associated with the presence of HSIL or low-grade squamous intraepithelial lesions (LSIL) were CD4T-lymphocyte count <200cells/mm3 versus >500cells/mm3 (OR,8.4; 95%CI,3.7–19.2), HIV-1 viral load >10,000copies/mL versus <400copies/mL (OR,2.1; 95%CI,1.0–4.4), and use of oral contraceptives (OR,2.0; 95%CI,1.0–3.9). Sixty percent of HIV-1–infected women had had one Pap smear within the last 2 years. Conclusions The high prevalence of HPV infection and cervical lesions in the HIV-1–infected population in Catalonia, as well as the low coverage and frequency of screening in this group, means that better preventive efforts are necessary and should include vaccination against HPV, better accessibility to screening programs, training of health care professionals, and

  13. Prevalence characteristics of high-risk human papillomaviruses in women living in Shanghai with cervical precancerous lesions and cancer.

    PubMed

    Gu, Ying; Ma, Chenyun; Zou, Jue; Zhu, Yi; Yang, Rong; Xu, Yan; Zhang, Yu

    2016-04-26

    A complete understanding of the natural history of infection with high-risk human papillomaviruses (HPVs) in cervical cancer requires data from regional and ethnic studies. The prevalence of high-risk HPVs was evaluated retrospectively in 2040 patients with cervicitis, 239 with cervical intraepithelial neoplasia grade 1 (CIN1), 242 with CIN2/3, and 42 patients with invasive squamous cell carcinoma (SCC) based on data from patients who visited our hospital between May 2013 and May 2015. The rates of high-risk HPV infection in patients with cervicitis, CIN1, CIN2/3, and invasive SCC were 40.8%, 74.9%, 70.2%, and 83.3%, respectively. The three most dominant HPV genotypes were HPV16, 58, and 52. HPV16 and HPV58 positivity in cervicitis, CIN1, CIN2/3, and SCC patients were 20.9% and 16.4%, 19.0% and 20.1%, 44.1% and 23.5%, and 60.0% and 31.4%, respectively. Compared to cervicitis, the odds ratios (ORs) for CIN2/3 in HPV16- and HPV58-positive patients were 2.99 (95% confidence interval [CI]: 1.32-4.33) and 1.56 (1.11-3.21), respectively; for SCC, the corresponding values were 5.68 (2.31-7.893) and 2.33 (1.41-3.87). Further identifying of carcinogenic HPVs and a fully aware of regional differences in HPV genotype distribution are tasks of top priority for cervical cancer control and prevention.

  14. Phase Ib Study of BKM120 With Cisplatin and XRT in High Risk Locally Advanced Squamous Cell Cancer of Head and Neck

    ClinicalTrials.gov

    2017-05-19

    Carcinoma, Squamous Cell of Head and Neck; HPV Positive Oropharyngeal Squamous Cell Carcinoma; Hypopharyngeal Cancer; Early Invasive Cervical Squamous Cell Carcinoma; Carcinoma of Larynx; Cancer of Nasopharynx

  15. Prevalence of human papillomavirus in the cervical epithelium of Mexican women: meta-analysis

    PubMed Central

    2012-01-01

    Background Human Papillomavirus (HPV) in cervical epithelium has been identified as the main etiological factor in the developing of Cervical Cancer (CC), which has recently become a public health problem in Mexico. This finding has allowed for the development of vaccines that help prevent this infection. In the present study, we aimed to determine the prevalence and HPV type-distribution in Mexican women with CC, high-grade squamous intraepithelial lesion (HSIL), low-grade squamous intraepithelial lesion (LSIL), and Normal cytology (N) to estimate the impact of the HPV vaccines. Methods The PubMed database was used to identify and review all articles that reported data on HPV prevalence in CC, precursor lesions, and normal cytology of Mexican women. Results A total of 8,706 samples of the tissues of Mexican women were stratified according to diagnosis as follows: 499 for CC; 364 for HSIL; 1,425 for LSIL, and 6,418 for N. According to the results, the most prevalent genotypes are the following: HPV16 (63.1%), -18 (8.6%), -58, and −31 (5%) for CC; HPV-16 (28.3%), 58 (12.6%), 18 (7.4%), and 33 (6.5%) for HSIL; HPV-16 (13.1%), 33 (7.4%), 18 (4.2%), and 58 (2.6%) for LSIL, and HPV-16 (3.4%), 33 (2.1%), 18, and 58 (1.2%) for N. Conclusions Taken together, genotypes 58 and 31 (10%) are more common than type 18 (8.6%) in CC. Therefore, the inclusion of these two genotypes in a second-generation vaccine would provide optimal prevention of CC in Mexico. PMID:23199368

  16. Detection of Human Papillomavirus in Chronic Cervicitis, Cervical Adenocarcinoma, Intraepithelial Neoplasia and Squamus Cell Carcinoma

    PubMed Central

    Mirzaie-Kashani, Elahe; Bouzari, Majid; Talebi, Ardeshir; Arbabzadeh-Zavareh, Farahnaz

    2014-01-01

    Background: Cervical cancer is the second most common cancer in women worldwide. Recent studies show that human papillomavirus (HPV) DNA is present in all cervical carcinomas and in some cervicitis cases, with some geographical variation in viral subtypes. Therefore determination of the presence of HPV in the general population of each region can help reveal the role of these viruses in tumors. Objectives: This study aimed to estimate the frequency of infection with HPV in cervicitis, cervical adenocarcinoma, intraepithelial neoplasia and squamus cell carcinoma samples from the Isfahan Province, Iran. Patients and Methods: One hundred and twenty two formalin fixed paraffin embedded tissue samples of crevicitis cases and different cervix tumors including cervical intraepithelial neoplasia (CIN) (I, II, III), squamus cell carcinoma (SCC) and adenocarcinoma were collected from histopathological files of Al-Zahra Hospital in Isfahan. Data about histopathological changes were collected by reexamination of the hematoxylin and eosin stained sections. DNA was extracted and subjected to Nested PCR using consensus primers, MY09/MY11 and GP5+/GP6+, designed for amplification of a conserved region of the genome coding for L1 protein. Results: In total 74.5% of the tested samples were positive for HPV. Amongst the tested tumors 8 out of 20 (40%) of CIN (I, II, III), 5 out of 21 (23.8%) of adenocarcinoma cases and 78 out of 79 chronic cervicitis cases were positive for HPV. Conclusions: The rate of different carcinomas and also the rate of HPV infection in each case were lower than other reports from different countries. This could be correlated with the social behavior of women in the area, where they mostly have only one partner throughout their life, and also the rate of smoking behavior of women in the studied population. On the other hand the rate of HPV infection in chronic cervicitis cases was much higher than cases reported by previous studies. This necessitates more

  17. [Importance of immunohistochemical studies in the diagnosis and the prognostic evaluation of cervical intraepithelial neoplasia and invasive squamous cell carcinoma of the uterine cervix. Review].

    PubMed

    García-Tamayo, Jorge; Molina, Julia; Blasco-Olaetxea, Eduardo

    2009-06-01

    Immunohistochemical studies in cervical intraepithelial neoplasia and cervical carcinoma are evaluated in this review. A variety of proteins like p53, bcl2, C-Myc, Ki 67, Cyclines, P16 INK4a, p21, p27, beta-catenin, Wnt and MCM, have been related to the development of cervical neoplasia and human papilloma virus infection. It is described how transcriptional factors of genes induce loss of heterozygosity, numerical chromosome abnormality and inactivation of gene products or the partial loss of some membrane glycoproteins induced by oncogenic human papillomaviruses (HPV).

  18. [Detection of multiple human papillomavirus infection in cervical specimens by flow fluorescent hybridization].

    PubMed

    Chen, Qing-yun; Bian, Mei-lu; Zhang, Xiao-yan; Ou, Hua; Ma, Li

    2009-04-07

    To explore the clinical significance of detection of multiple human papillomavirus infection in cervical lesions detected by flow fluorescent hybridization technology with Luminex multi-analytic profiling (xMAP). Cervical exfoliated cell specimens were collected from 301 randomly selected women accepting opportunistic screening for cervical lesions with the cytological results and hybrid capture 2 (HC-2) assay>or=atypical squamous cells of uncertain significance (ASC-US), 48 with the pathological diagnosis>or=cervical intraepithelial neoplasia (CIN)2 (case group) and 253 with normal histological result or only inflammation (control group), aged (34+/-9) (21-59). The samples were tested with xMAP technology with blind method. The coincidence of the xMAP and HC-2 was assessed. The HPV genotype, multiple HPV infection rate, and their relationships to the patients' clinical-pathological features were analyzed. The rates of sensitivity, specificity, and accuracy of xMAP technology to detect>or=CIN2 cervical lesions were 80.49%, 80.00%, and 80.07% respectively. The positive and negative predictive values were 47.06% and 96.30% respectively. The Kappa Index for agreement between xMAP technology and HC-2 was 0.56. The prevalence rate of high-risk HPV infection was 28.24% (85/301). The prevalence rate of multiple HPV infection was 11.30% (34/301), significantly lower than that of single type high-risk HPV infection (16.94%, P<0.05). The proportion of multiple HPV infection in total positive HPV results was 35.05% (34/97). The proportion of duplex and treble HPV infection were 29.90% (29/97) and 5.15% (5/97) respectively. The multiple HPV infection rate of the case group was 37.50% (18/48), significantly higher than that of the control group (6.32%, 16/253, P<0.01). The common duplex HPV infection modes were 16+51/58 (n=4), 51/58+52/59 (n=4), 11+16 (n=3), and 11+52/59 (n=3), 18+52/59 (n=3). The common treble HPV infection modes were 11+16+52/59, 16+18+31, 16+18+52/59, 31

  19. The role of human papillomavirus in squamous carcinoma of the head and neck.

    PubMed

    Li, Guojun; Sturgis, Erich M

    2006-03-01

    Human papillomavirus type-16 infection is associated with a significant portion of squamous carcinoma of the head and neck, particularly for the oropharynx and for those lacking the other risk factors of tobacco and alcohol. The link between human papillomavirus type-16 and carcinoma of the oropharynx is based on the identification of human papillomavirus type-16 in oropharyngeal tumors and the association of human papillomavirus type-16 with the risk of oropharyngeal cancer estimated in case-control epidemiologic studies. This review highlights the molecular mechanism of human papillomavirus carcinogenesis and the association of human papillomavirus type-16 as a risk factor for squamous cell carcinoma of the oropharynx as well as recent research efforts utilizing human papillomavirus as a biomarker of clinical outcomes.

  20. Associations of P16INK4a promoter hypermethylation with squamous intra-epithelial lesion, cervical cancer and their clinicopathological features: a meta-analysis

    PubMed Central

    Cui, Ning-hua; Zhang, Shuai; Wang, Chen; Zheng, Fang

    2017-01-01

    To assess the associations of P16INK4a methylation status with low-grade squamous intra-epithelial lesion (LSIL), high-grade squamous intra-epithelial lesion (HSIL), cervical cancer (CC) and their clinicopathological features, a meta-analysis with 29 eligible studies was conducted. Pooled odds ratios (ORs) with their 95% confidence intervals (CIs) were estimated to assess the strength of the associations. Heterogeneity, sensitivity of pooled results and publication bias were also evaluated. Overall, there was an increasing trend of P16INK4a hypermethylation rates among LSIL (21.4%), HSIL (30.9%) and CC (35.0%) specimens. P16INK4a hypermethylation was significantly associated with the increased risk of LSIL, HSIL and CC, with the pooled ORs of 3.26 (95% CI: 1.86-5.71), 5.80 (95% CI: 3.80-8.84) and 12.17 (95% CI: 5.86-25.27), respectively. A significant association was also found between P16INK4a hypermethylation and smoking habit (OR = 3.88, 95% CI: 2.13-7.08). Taken together, meta-analysis results support P16INK4a hypermethylation as an epigenetic marker for the progression of cervical carcinogenesis. PMID:27669738

  1. Virology and Molecular Pathogenesis of Human Papillomavirus (HPV)-Associated Oropharyngeal Squamous Cell Carcinoma

    PubMed Central

    Miller, Daniel L.; Puricelli, Michael D.; Stack, M. Sharon

    2012-01-01

    Current literature fully supports HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) as a unique clinical entity. It affects an unambiguous patient population with defined risk factors, has a genetic expression pattern more similar to cervical squamous cell carcinoma than non-HPV-associated head and neck squamous cell carcinoma (HNSCC), and may warrant divergent clinical management compared to HNSCC associated with traditional risk factors. However, a detailed understanding of the molecular mechanisms driving these differences and the ability to exploit this knowledge to improve clinical management of OPSCC has not yet come to fruition. This review summarizes the etiology of HPV positive (HPV+) OPSCC and provides a detailed overview of HPV virology and molecular pathogenesis relevant to infection of oropharyngeal tissues. Methods of detection and differential gene expression analyses are also summarized. Future research into mechanisms that mediate tropism of HPV to oropharyngeal tissues, improved detection strategies, and the pathophysiologic significance of altered gene and microRNA expression profiles is warranted. PMID:22452816

  2. [Prevalence of human papillomavirus infection in squamous cell carcinoma of the oral cavity, oropharynx and larynx].

    PubMed

    Villagómez-Ortíz, Vicente José; Paz-Delgadillo, Diana Estela; Marino-Martínez, Iván; Ceseñas-Falcón, Luis Ángel; Sandoval-de la Fuente, Anabel; Reyes-Escobedo, Alfonso

    2016-01-01

    Cancer of the head and neck comprises a group of neoplasms that share a similar anatomical origin. Most originate from the epithelium of the aerodigestive tract and 90% correspond to squamous cell carcinoma. In the last 15 years, an increase in the incidence of squamous cell carcinoma induced by human papillomavirus (HPV) has been seen, mainly types 16 and 18, which are the most frequent found in cancers of the oral cavity and oropharynx, and types 6 and 11 in laryngeal cancer. There are reports in the literature that show HPV as the leading cause of oropharyngeal squamous cell carcinoma. Determine the prevalence of infection with high-risk HPV in patients diagnosed with squamous cell carcinoma of the oral cavity, oropharynx and larynx. An observational, cross-sectional, descriptive, unblinded study was performed. Prevalence of HPV infection was determined by polymerase chain reaction (PCR) in DNA samples from tumour tissue of patients with squamous cell carcinoma of the oral cavity, oropharynx and larynx. Typing was subsequently performed in HPV positive samples in order to detect types 18, 16, 11 and 6, using custom primers. A total of 45 patients were included. The association between laryngeal squamous cell carcinoma and HPV was established in two patients, which represented an overall prevalence of 4.4% in our population, and 10% for laringeal tumours. There is a low prevalence of HPV infection in squamous cell carcinoma of the oral cavity, oropharynx and larynx, in our population. Prospective studies on younger patients could provide more information. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

  3. Epidemiology of human papillomavirus infections: new options for cervical cancer prevention.

    PubMed

    Bosch, F Xavier

    2003-01-01

    In the last two decades, the cervical cancer puzzle has become a coherent description that includes the identification of human papillomavirus (HPV) as the sexually transmitted etiologic agent and the characterization of the major determinants of HPV acquisition. Triage studies have consistently shown that HPV testing is more sensitive that repeated cytology in identifying underlying high-grade lesions in women with atypical squamous cells of undetermined significance (ASCUS). Studies that reflect primary screening conditions have shown that the sensitivity of HPV tests is higher than standard cytology in detecting high-grade lesions whereas the specificity is similar only in women aged 30-35 and above. HPV vaccines have an intrinsic attraction as a preventive strategy in populations with limited resources. However, vaccines designed to widespread use are still in development and testing phases. Time is ripe for exploring in depth the clinical implications of current achievements and to devise novel strategies for the prevention of cervical cancer. This paper is available too at: http://www.insp.mx/salud/index.html.

  4. Isolation of a novel human papillomavirus (type 51) from a cervical condyloma

    SciTech Connect

    Nuovo, G.J.; Crum, C.P.; Levine, R.U.; Silverstein, S.J. ); De Villiers, E.M. )

    1988-04-01

    The authors cloned the DNA from a novel human papillomavirus (HPV) present in a cervical condyloma. When DNA from this isolate was hybridized at high stringency with HPV types 1 through 50 (HPV-1 through HPV-50), it showed weak homology with HPV-6 and -16 and stronger homology with HPV-26. A detailed restriction endonuclease map was prepared which showed marked differences from the maps for other HPVs that have been isolated from the female genital tract. Reassociation kinetic analysis revealed that HPV-26 and this new isolate were less than 10% homologous; hence, the new isolate is a noel strain of HPV. The approximate positions of the open reading frames of the new strain were surmised by hybridization with probes derived from individual open reading frames of HPV-16. In an analysis of 175 genital biopsies from patients with abnormal Papanicolaou smears, sequences hybridizing under highly stringent conditions to probes from this novel HPV type were found in 4.2, 6.1, and 2.4% of biopsies containing normal squamous epithelium, condylomata, and intraepithelial neoplasia, respectively. In addition, sequences homologous to probes from this novel isolate were detected in one of five cervical carcinomas examined.

  5. Impact of human papillomavirus (HPV) 16 and 18 vaccination on prevalent infections and rates of cervical lesions after excisional treatment.

    PubMed

    Hildesheim, Allan; Gonzalez, Paula; Kreimer, Aimee R; Wacholder, Sholom; Schussler, John; Rodriguez, Ana C; Porras, Carolina; Schiffman, Mark; Sidawy, Mary; Schiller, John T; Lowy, Douglas R; Herrero, Rolando

    2016-08-01

    Human papillomavirus vaccines prevent human papillomavirus infection and cervical precancers. The impact of vaccinating women with a current infection or after treatment for an human papillomavirus-associated lesion is not fully understood. To determine whether human papillomavirus-16/18 vaccination influences the outcome of infections present at vaccination and the rate of infection and disease after treatment of lesions. We included 1711 women (18-25 years) with carcinogenic human papillomavirus infection and 311 women of similar age who underwent treatment for cervical precancer and who participated in a community-based trial of the AS04-adjuvanted human papillomavirus-16/18 virus-like particle vaccine. Participants were randomized (human papillomavirus or hepatitis A vaccine) and offered 3 vaccinations over 6 months. Follow-up included annual visits (more frequently if clinically indicated), referral to colposcopy of high-grade and persistent low-grade lesions, treatment by loop electrosurgical excisional procedure when clinically indicated, and cytologic and virologic follow-up after treatment. Among women with human papillomavirus infection at the time of vaccination, we considered type-specific viral clearance, and development of cytologic (squamous intraepithelial lesions) and histologic (cervical intraepithelial neoplasia) lesions. Among treated women, we considered single-time and persistent human papillomavirus infection, squamous intraepithelial lesions, and cervical intraepithelial neoplasia 2 or greater. Outcomes associated with infections absent before treatment also were evaluated. Infection-level analyses were performed and vaccine efficacy estimated. Median follow-up was 56.7 months (women with human papillomavirus infection) and 27.3 months (treated women). There was no evidence of vaccine efficacy to increase clearance of human papillomavirus infections or decrease incidence of cytologic/histologic abnormalities associated with human

  6. Clinical value of routine serum squamous cell carcinoma antigen in follow-up of patients with locally advanced cervical cancer treated with radiation or chemoradiation

    PubMed Central

    Oh, Jinju; Lee, Hyun Joo; Lee, Tae Sung; Kim, Ju Hyun; Koh, Suk Bong

    2016-01-01

    Objective The objective of this study was to evaluate the clinical benefits of routine squamous cell carcinoma antigen (SCC-Ag) monitoring of patients with locally advanced cervical squamous cell carcinoma treated with radiation or chemoradiation. Methods A total of 53 patients with recurrent cervical squamous cell carcinoma treated with radiotherapy or chemoradiation were enrolled in this study. A retrospective review of medical records was conducted. The role of routine monitoring of serum SCC-Ag was evaluated in terms of cost effectiveness and effect on survival after diagnosis of recurrence. Results Serum SCC-Ag abnormality (≥2.5 ng/mL) was observed in 62.3% of patients when recurrent disease was diagnosed. The first indicator of relapse was abnormal serum SCC-Ag level in 21 patients (39.6%), 10 of whom had asymptomatic recurrent disease amenable to salvage therapy. Adding SCC-Ag measurement to the basic follow up protocol improved the sensitivity for detecting recurrence (The sensitivity of the basic protocol vs. addition of SCC-Ag: 49.1% vs. 88.7%, P<0.001). Twenty-three patients who were candidates for salvage therapy with curative intent showed better survival compared with those who were not candidates for therapy (5-year survival: 36.6% vs. 0%, P=0.012). Conclusion Surveillance with routine serum SCC-Ag monitoring can better detect asymptomatic recurrent disease that is potentially amenable to salvage therapy with curative intent. Early diagnosis of recurrent disease that can be treated with salvage therapy may lead to better survival. PMID:27462593

  7. Comparison of Human Papillomavirus Detection in Urine and Cervical Samples Using High-Risk HPV DNA Testing in Northern Thailand

    PubMed Central

    Settakorn, Jongkolnee; Sukpan, Kornkanok; Lekawanvijit, Suree; Katruang, Narisara; Siriaunkgul, Sumalee

    2016-01-01

    Objective. To evaluate the performance of high-risk human papillomavirus (HPV) DNA testing in urine samples compared to that of cervical sample testing in Northern Thailand. Methods. Paired urine and cervical samples were collected during the follow-up of women with a previous positive HPV test. HPV testing was performed using the Cobas 4800 HPV Test. Linear Array assay was used for genotyping in selected cases. Results. Paired urine and cervical samples were obtained from 168 women. Of 123 paired samples with valid results, agreement in the detection of high-risk HPV DNA was present in 106 cases (86.2%), with a kappa statistic of 0.65 (substantial agreement). Using the cervical HPV results as a reference, the sensitivity of urine HPV testing was 68.6% (24/35) and the specificity 93.2% (82/88). For the detection of histologic high-grade squamous intraepithelial lesion or worse (HSIL+), the sensitivity of urine HPV testing was 80.0% (4/5) and the specificity 78.0% (92/118). Conclusion. Although urine HPV testing had a rather low sensitivity for HPV detection, its sensitivity for histologic HSIL+ detection was high. For clinical use of urine HPV testing, standardization of specimen collection and processing techniques or application of a more sensitive test, especially in the detection of HPV52 and HPV58, is necessary. PMID:28101107

  8. Phototoxicity of Liposomal Zn- and Al-phthalocyanine Against Cervical and Oral Squamous Cell Carcinoma Cells In Vitro

    PubMed Central

    Young, Jason; Yee, Michael; Kim, Hayoung; Cheung, Jennifer; Chino, Takahiro; Düzgüneş, Nejat; Konopka, Krystyna

    2016-01-01

    Background Photodynamic therapy (PDT) utilizes light to activate a photosensitizer in the presence of oxygen, and leads to local photodamage by the generation of highly reactive oxygen species (ROS). Liposomal delivery of photosensitizers is adaptable to the treatment of cancers. We examined the phototoxicity of free or liposome-embedded phthalocyanine photosensitizers using HeLa cervical carcinoma and HSC-3 oral squamous cell carcinoma cells. Material/Methods Liposomes were composed of palmitoyloleoyphosphatidylcholine (POPC): phosphatidylglycerol (PG), and contained either zinc phthalocyanine (ZnPc) or aluminum phthalocyanine chloride (AlPc). Free or liposomal ZnPc and AlPc were incubated with cells for 24 h at 37°C. Cells incubated with ZnPc were exposed to broadband visible light (350–800 nm; light dose 43.2 J/cm2), whereas cells treated with AlPc were exposed to light at 690 nm (light dose 3.6 J/cm2). The effect of folate receptor-targeted liposomal ZnPc was evaluated with HeLa cells. Cytotoxicity was analyzed by the Alamar Blue assay. Results Cell viability, expressed as a percentage of control cells, was calculated according to the formula [(A570–A600) of test cells]×100/[(A570–A600) of control cells]. The relative percentage changes then defined the phototoxic efficacy of the experimental conditions. In HeLa cells, 1 μM free ZnPc and AlPc, reduced cell viability to 52.7±2.1 and 15.4±8.0%, respectively. Liposomal phthalocyanines, at 0.1, 0.5, and 1.0 μM, reduced the viability to 68.0±8.6, 15.1±9.9 and 0% (ZnPc), and to 25.8±8.2, 0 and 0% (AlPc), respectively. In HSC-3 cells, 1 μM free ZnPc and AlPc, reduced cell viability to 22.1±2.8 and 56.6±8.6%, respectively. With 1 μM liposomal ZnPc and AlPc, the viability was reduced to 0 and 21.3±0.3%, respectively. Conclusions The embedding of phthalocyanines in liposomes enhanced their phototoxicity and this effect was dependent on cell type. PMID:27932777

  9. Squamous cell carcinoma of cervical lymph nodes from an unknown primary site: The impact of neck dissection.

    PubMed

    Lou, Jianlin; Wang, Shengye; Wang, Kejing; Chen, Chao; Zhao, Jianqiang; Guo, Liang

    2015-10-01

    To investigate the treatment strategies of squamous cell carcinoma of cervical lymph nodes from an unknown primary site (SCCUP) and the value of neck dissection (ND). The study included 133 patients referred to the Zhejiang Cancer Hospital from 2001 to 2012, with 109 males and 24 females. Distribution of patients by N status was as follows: N1 - 14 cases; N2a - 21 cases; N2b - 78 cases; N2c - 7 cases; and N3 - 13 cases. 104 patients underwent surgeries of ND while 29 patients underwent nonsurgical treatment. Among 104 patients, 24 underwent classic radical ND, 16 modified ND, 53 selective ND, and 11 extended ND. The selection of surgical strategy was determined by the extent and location of disease. According to the range of ND, 50 patients underwent ND for Levels I-V, 46 for Levels II-V, 4 for Levels I-III, 3 for Levels II-VI, and 1 for Levels I-VI. The data were analyzed with SPSS version 16.0. The differences between groups were calculated by χ2 tests. The actual overall survival (OS) rates were calculated by the Kaplan-Meier method. Different factors affecting the OS were determined by the log-rank test on univariate analysis. Cox regression was used to evaluate the multivariate analysis. The 5-year OS rate of the whole cohort was 67.1%; and the median survival time was 70.0 months. The 5-year OS of ND group and of the non-ND group were 71.3% and 53.2%, respectively (P = 0.061). Cox analysis indicated that N stage (P = 0.000), bilateral neck metastasis (P = 0.001), extracapsular spread (ES) (P = 0.016), and ND (P = 0.028) were independent prognostic factors for the OS of SCCUP. 25 patients (18.8%) had neck recurrence or residue. The locoregional failure rate of ND group and of the non-ND group were 13.5% and 37.9%, respectively (P = 0.003). Logistic regression analysis indicated that higher N stage was the main risk factor for locoregional failure (P = 0.015). N stage, bilateral neck metastasis, ES, and ND were the main factors for the survival rate of SCCUP

  10. The interrelation of HIV, cervical human papillomavirus, and neoplasia among antenatal clinic attenders in Tanzania

    PubMed Central

    Mayaud, P.; Gill, D.; Weiss, H.; Uledi, E.; Kopwe, L.; Todd, J.; ka-Gina, G.; Grosskurth, H.; Hayes, R.; Mabey, D. C.; Lacey, C.

    2001-01-01

    * Died April 2000 Objectives: To determine the prevalence and interrelation of cervical human papillomavirus (HPV) genotypes, squamous intraepithelial lesions (SIL), HIV, and other reproductive tract infections (RTIs) among urban antenatal clinic attenders in Mwanza, Tanzania. Methods: Genital swabs were collected from 660 pregnant women and tested for a range of RTIs and for cervical cytology. Cervical HPV-DNA was detected by PCR and genotyped. HIV and syphilis serologies were performed. Results: HPV prevalence was 34% (209/612 women). Of the 144 typeable samples, 83% were high risk (HR-HPV) oncogenic strains (56% HPV 16 related types). SIL was detected in 43 women (7%), with high grade SIL in 3%. There was a high prevalence of HIV (15%), and of any RTI (83%). Genital warts were detected in 20 women (3%). HPV infection was associated with some behavioural factors (short duration of relationship, single status, not using condoms) and gonorrhoea. There was no overall association between HPV and HIV (OR=1.02, 95% CI 0.6–1.6), but a non-significant trend towards a stronger association with HR-HPV in women aged 15–19 (OR=2.79, 95% CI 0.8–9.5) and women aged ≥30 (OR=3.20, 95% CI 0.7–15). SIL was associated with HPV (OR=3.66, 95% CI 1.9–7.0), but not significantly with HIV (OR=1.54, 95% CI 0.7–3.4). Prevalence of SIL was higher among women dually positive for HPV/HIV compared to HPV infection only (21% v 12%), although this difference was not statistically significant (p=0.17). Conclusions: HPV infection was highly prevalent in this young antenatal population. The association of HIV with HR-HPV types in older women may suggest that the principal HIV/HPV interaction in this population is for HIV to upregulate HPV persistence, leading to subsequent development of SIL. Key Words: human papillomavirus; squamous intraepithelial lesion; HIV/AIDS; Africa PMID:11463923

  11. Human papillomavirus hpv-16 DNA as an epitheliotropic virus that induces hyperproliferation in squamous penile tissue.

    PubMed

    Salazar, Edith L; Mercado, E; Calzada, L

    2005-01-01

    The prevalence of human papillomavirus HPV-16DNA sequences in 57 penile carcinoma biopsies was examined using the polymerase chain reaction (PCR) with type specific internal probes, employing HPV consensus primers from the L1 region. The cases comprised 39 typical squamous cell carcinoma and 18 specimens with different subtype. PCR products were analyzed and HPV-16DNA was detected in a high percentage of specimens. Thirty-eight biopsies were HPV-16DNA positive. This determination was correlated with cellular differentiation and growth pattern. Our data corroborates that squamous cell carcinoma was invariably associated with HPV-16DNA.

  12. Human papillomavirus and invasive cervical cancer in Brazil.

    PubMed Central

    Eluf-Neto, J.; Booth, M.; Muñoz, N.; Bosch, F. X.; Meijer, C. J.; Walboomers, J. M.

    1994-01-01

    A hospital-based case-control study was undertaken to examine the role of human papillomavirus (HPV) in the development of invasive cervical cancer in Brazil. The study included 199 histologically confirmed incident cases and 225 age-frequency-matched controls selected from a wide range of diagnostic categories. A polymerase chain reaction technique was used to detect HPV DNA in cervical specimens collected with spatula and brush. HPV DNA was detected in 84% of the cases compared with 17% of controls. Grouping HPV types 16, 18, 31 and 33, 66% of the cases were positive compared with only 6% of the controls. In addition to HPV, number of sexual partners, early age at first intercourse, parity and duration of oral contraceptive use were significantly associated with an increased risk of cervical cancer. A history of previous Papanicolaou smears was significantly associated with a decreased risk. After adjustment, only presence of HPV DNA, parity and history of previous smears remained as independent risk factors. The adjusted odds ratios of cervical cancer associated with HPV 16, 18, 31, and 33 was 69.7 (95% confidence interval 28.7-169.6) and with unidentified types was 12.0 (5.1-28.5). The very high risks found in this study further implicate this virus in the aetiology of cervical cancer. PMID:8286192

  13. The Characteristic of S100A7 Induction by the Hippo-YAP Pathway in Cervical and Glossopharyngeal Squamous Cell Carcinoma

    PubMed Central

    Hu, Enze; Wang, Rui; Wang, Junhao; Liu, Jin; Zhang, Jinsan; He, Dacheng; Xiao, Xueyuan

    2016-01-01

    S100A7 is expressed in many squamous cell carcinomas (SCCs). Our previous study revealed that S100A7 was dramatically induced in several SCC cells and activation of the Hippo pathway significantly promoted S100A7 in epidermoid carcinoma cells. However, whether the Hippo pathway regulates S100A7 expression in SCCs remains largely unknown. Here, we uncover that S100A7 induction by the Hippo-YAP pathway displays different characteristic in cervical and glossopharyngeal SCC. In well differentiated HCC94 cervical cells and FaDu pharyngeal cells, S100A7 is easily induced by both suspension and dense culture, which is accompanied by an increase in YAP phosphorylation and a decrease in nuclear YAP. Strikingly, these correlations of S100A7 and YAP reverse after recovery of cell attachment or relief from dense culture. Further examination finds that S100A7 induction is significantly repressed by nuclear YAP, which is validated by activation or inhibition of the Hippo pathway via loss- and/or gain-of- LATS1 and MST1 function. Subsequently, we prove that TEAD1 is required for YAP transcriptional repression of S100A7. However, S100A7 is hardly induced in poorly differentiated SiHa cervical cells and NCI-H226 pulmonary cells even in suspension or activation of the Hippo pathway. More importantly, cervical and lingual SCC tissues array analyses show that S100A7 expression displays the positive correlation with pYAP-S127 and the negative correlation with nuclear YAP in the majority of well differentiated but not in poorly differentiated tissues. Collectively, our findings demonstrate that the different induction of S100A7 toward activation of the Hippo pathway mainly depends on the degree of cell differentiation in cervical and glossopharyngeal SCC. PMID:27907036

  14. Associations between sexually transmitted infections, high-risk human papillomavirus infection, and abnormal cervical Pap smear results in OB/GYN outpatients.

    PubMed

    Kim, Hye Sun; Kim, Tae Jin; Lee, In Ho; Hong, Sung Ran

    2016-09-01

    This study aimed to examine the meaning and usefulness of sexually transmitted infection (STI) test when caring for patients who have abnormal cervical cytology and/or positive high-risk human papillomavirus (HPV) DNA test results. Among patients who underwent liquid-based cervical cytology and HPV DNA tests at the Obstetrics and Gynecology outpatient clinic, 800 patients who showed abnormal cervical cytology were compared with 200 patients in the control group. Both groups were simultaneously tested via multiplex real-time polymerase chain reaction for seven types of STI-causative microorganisms. The positive rate of high-risk HPV infection in total STIs positive group was 1.47 times higher than that of total STIs negative group. The probability of a cytological diagnosis of a grade equal to or higher than atypical squamous cells-cannot exclude high grade squamous intraepithelial lesion (ASC-H) was significantly higher in patients testing positive for total STIs (1.46 times), Chlamydia trachomatis (3.21 times), or Mycoplasma genitalicum (3.58 times) than in those testing negative. The total STIs positive rate was significantly higher for those having a cytological diagnosis of a grade equal to or higher than atypical squamous cells of undetermined significance (ASC-US) when high-risk HPV test result was negative. Correlations were present not only between STIs and high-risk HPV infection but also between abnormal cervical cytology and STIs. Therefore, additional evaluation of STIs will be helpful to appropriately diagnose and treat patients with abnormal cervical cytology, positive results on high-risk HPV DNA test, or a cytological diagnosis of ASC-US despite negative high-risk HPV DNA test result.

  15. Human papillomavirus types distribution in eastern Sicilian females with cervical lesions. A correlation with colposcopic and histological findings.

    PubMed

    Le Donne, Maria; Giuffrè, Giuseppe; Caruso, Carmela; Nicotina, Piero Antonio; Alibrandi, Angela; Scalisi, Rosalba; Simone, Angela; Chiofalo, Benito; Triolo, Onofrio

    2013-07-01

    To determine human papillomavirus (HPV) types distribution in cervical lesions in a Southern Italian female population in Messina and their relationship between HPV type and grade of colposcopic and histopathological abnormality, a total of 253 women aged 17-68 years, with previous cytological abnormalities, were included in this study. HPV-DNA testing, colposcopy and biopsy were performed. For each sample, cervical cells were collected by centrifugation and DNA was extracted, followed by a PCR-based HPV-DNA assay and reverse dot blot genotyping. HPV-16 was found the most common type (46.6 %) followed by HPV-31 (26.9 %), -6 (18.6 %), -58 (8.8 %), -18 (6.7 %), -66 (5.7 %), -52 and -53 (4.7 %). Out of 62 women with abnormal transformation zone (ATZ) area compatible with squamous intraepithelial lesion (SIL) or cervical cancer (CC), 64.5 % was found high risk (HR) HPV-positive. Moreover the severity of the colposcopic diagnosis was positively correlated with the higher HPV oncogenicity risk (HPV-16 P = 0.023; and HPV-53 P = 0.047). The HPV-16 was found the most prevalent type within each histological category: 66.7 %, 31.2 %, 44 % and 37.2 % of CC, high grade (H)SIL, low grade (L)SIL and chronic cervicitis respectively; followed by HPV-31 present in 25 %, 8 %, and 13.3 % of HSIL, LSIL and chronic cervicitis respectively. A higher HPV incidence than the rest of Italy was found, in agreement with that detected by other authors for the South of the country. These data provide further information about the types prevalence in women with cervical lesions living in Eastern Sicily, suggesting the introduction of new targeted vaccines against a wider spectrum of HPV.

  16. S100A8/A9 induces apoptosis and inhibits metastasis of CasKi human cervical cancer cells.

    PubMed

    Qin, Fengjin; Song, Yao; Li, Zijian; Zhao, Ling; Zhang, Youyi; Geng, Li

    2010-09-01

    S100 proteins, a family of Ca(2+)-binding proteins, have been linked to several human diseases in recent years. Deregulated expression of S100 proteins, including S100A9 and its partner S100A8, was reported to be associated with neoplastic disorders. In our previous study using serial analysis of gene expression, we identified decreased expressions of S100A9 and S100A8 in human cervical squamous cell carcinoma. To investigate the functions of S100A8 and S100A9 in cervical cancer, we purified recombinant S100A8 and S100A9 proteins and treated CaSki human cervical cancer cells with these proteins. We found that S100A8/A9 induced apoptosis and inhibited migration of CaSki cells; S100A8/A9 also reduced the expression of matrix metalloproteinase (MMP)-2 in CaSki cells. In summary, this study suggests that S100A8 and S100A9 have inhibitory effects on the proliferation of CaSki carcinoma cells by inducing cell apoptosis and on the invasiveness of CaSki cells.

  17. Rapid induction of senescence in human cervical carcinoma cells

    NASA Astrophysics Data System (ADS)

    Goodwin, Edward C.; Yang, Eva; Lee, Chan-Jae; Lee, Han-Woong; Dimaio, Daniel; Hwang, Eun-Seong

    2000-09-01

    Expression of the bovine papillomavirus E2 regulatory protein in human cervical carcinoma cell lines repressed expression of the resident human papillomavirus E6 and E7 oncogenes and within a few days caused essentially all of the cells to synchronously display numerous phenotypic markers characteristic of cells undergoing replicative senescence. This process was accompanied by marked but in some cases transient alterations in the expression of cell cycle regulatory proteins and by decreased telomerase activity. We propose that the human papillomavirus E6 and E7 proteins actively prevent senescence from occurring in cervical carcinoma cells, and that once viral oncogene expression is extinguished, the senescence program is rapidly executed. Activation of endogenous senescence pathways in cancer cells may represent an alternative approach to treat human cancers.

  18. Human papillomavirus genotype-specific prevalence across the continuum of cervical neoplasia and cancer.

    PubMed

    Joste, Nancy E; Ronnett, Brigitte M; Hunt, William C; Pearse, Amanda; Langsfeld, Erika; Leete, Thomas; Jaramillo, MaryAnn; Stoler, Mark H; Castle, Philip E; Wheeler, Cosette M

    2015-01-01

    The New Mexico HPV Pap Registry was established to measure the impact of cervical cancer prevention strategies in the United States. Before widespread human papillomavirus (HPV) vaccine implementation, we established the baseline prevalence for a broad spectrum of HPV genotypes across the continuum of cervical intraepithelial neoplasia (CIN) and cancer. A population-based sample of 6,272 tissue specimens was tested for 37 HPV genotypes. The number of specimens tested within each diagnostic category was: 541 negative, 1,411 CIN grade 1 (CIN1), 2,226 CIN grade 2 (CIN2), and 2,094 CIN grade 3 (CIN3) or greater. Age-specific HPV prevalence was estimated within categories for HPV genotypes targeted by HPV vaccines. The combined prevalence of HPV genotypes included in the quadrivalent and nonavalent vaccines increased from 15.3% and 29.3% in CIN1 to 58.4% and 83.7% in CIN3, respectively. Prevalence of HPV types included in both vaccines tended to decrease with increasing age for CIN1, CIN2, CIN3, and squamous cell carcinoma (SCC), most notably for CIN3 and SCC. The six most common HPV types in descending order of prevalence were HPV-16, -31, -52, -58, -33, and -39 for CIN3 and HPV-16, -18, -31, -45, -52, and -33 for invasive cancers. Health economic modeling of HPV vaccine impact should consider age-specific differences in HPV prevalence. Population-based HPV prevalence in CIN is not well described, but is requisite for longitudinal assessment of vaccine impact and to understand the effectiveness and performance of various cervical screening strategies in vaccinated and unvaccinated women. ©2014 American Association for Cancer Research.

  19. Detection of rare and possibly carcinogenic human papillomavirus genotypes as single infections in invasive cervical cancer.

    PubMed

    Geraets, Daan; Alemany, Laia; Guimera, Nuria; de Sanjose, Silvia; de Koning, Maurits; Molijn, Anco; Jenkins, David; Bosch, Xavier; Quint, Wim

    2012-12-01

    The contribution of carcinogenic human papillomavirus (HPV) types to the burden of cervical cancer has been well established. However, the role and contribution of phylogenetically related HPV genotypes and rare variants remains uncertain. In a recent global study of 8977 HPV-positive invasive cervical carcinomas (ICCs), the genotype remained unidentified in 3.7% by the HPV SPF10 PCR-DEIA-LiPA25 (version 1) algorithm. The 331 ICC specimens with unknown genotype were analysed by a novel sequence methodology, using multiple selected short regions in L1. This demonstrated HPV genotypes that have infrequently or never been detected in ICC, ie HPV26, 30, 61, 67, 68, 69, 73 and 82, and rare variants of HPV16, 18, 26, 30, 34, 39, 56, 67, 68, 69, 82 and 91. These are not identified individually by LiPA25 and only to some extent by other HPV genotyping assays. Most identified genotypes have a close phylogenetic relationship with established carcinogenic HPVs and have been classified as possibly carcinogenic by IARC. Except for HPV85, all genotypes in α-species 5, 6, 7, 9 and 11 were encountered as single infections in ICCs. These species of established and possibly carcinogenic HPV types form an evolutionary clade. We have shown that the possibly carcinogenic types were detected only in squamous cell carcinomas, which were often keratinizing and diagnosed at a relatively higher mean age (55.3 years) than those associated with established carcinogenic types (50.9 years). The individual frequency of the possibly carcinogenic types in ICCs is low, but together they are associated with 2.25% of the 8338 included ICCs with a single HPV type. This fraction is greater than seven of the established carcinogenic types individually. This study provides evidence that possibly carcinogenic HPV types occur as single infections in invasive cervical cancer, strengthening the circumstantial evidence of a carcinogenic role.

  20. Clinical Effect of Human Papillomavirus Genotypes in Patients With Cervical Cancer Undergoing Primary Radiotherapy

    SciTech Connect

    Wang, Chun-Chieh; Lai, Chyong-Huey; Huang, Huei-Jean; Chao, Angel; Chang, Chee-Jen; Chang, Ting-Chang; Chou, Hung-Hsueh; Hong, Ji-Hong

    2010-11-15

    Purpose: To study the prognostic value of the human papillomavirus (HPV) genotypes in cervical cancer patients undergoing radiotherapy. Patients and Methods: A total of 1,010 patients with cervical cancer after radiotherapy between 1993 and 2000 were eligible for this study. The HPV genotypes were determined by a genechip, which detects 38 types of HPV. The patient characteristics and treatment outcomes were analyzed using the Cox regression hazard model and classification and regression tree decision tree method. Results: A total of 25 genotypes of HPV were detected in 992 specimens (98.2%). The leading 8 types were HPV16, 58, 18, 33, 52, 39, 31, and 45. These types belong to two high-risk HPV species: alpha-7 (HPV18, 39, 45) and alpha-9 (HPV16, 31, 33, 52, 58). Three HPV-based risk groups, which were independent of established prognostic factors, such as International Federation of Gynecology and Obstetrics stage, age, pathologic features, squamous cell carcinoma antigen, and lymph node metastasis, were associated with the survival outcomes. The high-risk group consisted of the patients without HPV infection or the ones infected with the alpha-7 species only. Patients co-infected with the alpha-7 and alpha-9 species belonged to the medium-risk group, and the others were included in the low-risk group. Conclusion: The results of the present study have confirmed the prognostic value of HPV genotypes in cervical cancer treated with radiotherapy. The different effect of the alpha-7 and alpha-9 species on the radiation response deserves additional exploration.

  1. Prevalence of human papillomavirus types in high-grade cervical intraepithelial neoplasia and cancer in Italy.

    PubMed

    Carozzi, Francesca M; Tornesello, Maria L; Burroni, Elena; Loquercio, Giovanna; Carillo, Giuseppe; Angeloni, Claudio; Scalisi, Aurora; Macis, Rosalba; Chini, Francesco; Buonaguro, Franco M; Giorgi Rossi, Paolo

    2010-09-01

    The aim of this multicentric study was to identify human papillomavirus (HPV) type distribution in invasive cervical cancer and high-grade cervical intraepithelial neoplasia 2/3 (CIN2/3) in Italy. Cases were sampled through the electronic databases at the pathology units of eight centers in six regions from central and southern Italy. HPV types were detected from paraffin-embedded tissue samples and cervical specimens through amplification of HPV DNA with GP5+/GP6+ primers, followed by genotyping with reverse line blot (RLB). Untyped HPV-positive samples were sequenced. HPV-negative samples underwent nested PCR, followed by either RLB or sequencing. Finally, the remaining HPV-negative samples were amplified with primers targeting the virus E6 to E7 regions. From 1,162 cases initially selected, 722 samples were further analyzed: 144 CIN2, 385 CIN3, 157 invasive squamous carcinomas, and 36 adenocarcinomas. Samples (6.9%) were HPV negative. The proportion of HPV16/18 was 60.8%, 76.6%, and 78.8% in CIN2, CIN3, and invasive cancers, respectively (P trend = 0.004). There was a significant decreasing trend of HPV16/18 with age in invasive cancers, going from 92% in women <35 years to 73% in women >55 years (P = 0.036). The proportion of coinfections was 16.8%, 15.5%, and 10.0% in CIN2, CIN3, and invasive cancers, respectively (P trend = 0.07). The proportion of invasive cancers caused by HPV16/18 decreases with age at diagnosis. The absolute risk of an invasive cancer due to non-HPV16/18 in women under 35 is extremely low. This finding might prompt us to rise the age at which public HPV screening for vaccinated women should start. (c)2010 AACR.

  2. Analysis of cervical ribs in a series of human fetuses

    PubMed Central

    Bots, Jessica; Wijnaendts, Liliane C D; Delen, Sofie; Van Dongen, Stefan; Heikinheimo, Kristiina; Galis, Frietson

    2011-01-01

    In humans, an increasing body of evidence has linked the frequency of cervical ribs to stillbirths, other malformations and early childhood cancers. However, the frequency of cervical ribs in a putatively healthy fetal population is not sufficiently known to assess the actual medical risks of these prenatal findings. We therefore analyzed the presence of skeletal anomalies in a series of 199 electively aborted fetuses, which were whole-mount stained with alizarin red specific for skeletal tissues. Results show that approximately 40% of the fetuses had cervical ribs, even though external congenital abnormalities such as craniofacial and limb defects were absent. A literature overview indicates that the observed frequency of cervical ribs is comparable to results previously obtained for deceased fetuses with no or minor congenital anomalies, and higher than expected for healthy fetuses. This unexpected result can probably in part be explained by a higher detection rate of small cervical ribs when using alizarin red staining instead of radiographs. Additionally, studies in the literature suggest that the size of a cervical rib may indicate the severity of abnormalities, but this possibility requires further research. Anomalies of the axial skeleton are known to be caused by a disturbance of early development, which alters Hox gene expression, but in this study the origin of the stress could not be verified as maternal medical data were not available. The co-occurrence of rudimentary or absent 12th ribs in 23.6% of the cases with cervical ribs indicates that in approximately 8% of the fetuses a homeotic shift occurred over a larger part of the vertebral column. This suggests that the expression of multiple Hox genes may have been affected in these fetuses. Together, the high incidence of cervical ribs and also their co-occurrence with rudimentary or absent 12th ribs suggests that there may have been a disturbance of early development such that the studied fetuses are

  3. Analysis of cervical ribs in a series of human fetuses.

    PubMed

    Bots, Jessica; Wijnaendts, Liliane C D; Delen, Sofie; Van Dongen, Stefan; Heikinheimo, Kristiina; Galis, Frietson

    2011-09-01

    In humans, an increasing body of evidence has linked the frequency of cervical ribs to stillbirths, other malformations and early childhood cancers. However, the frequency of cervical ribs in a putatively healthy fetal population is not sufficiently known to assess the actual medical risks of these prenatal findings. We therefore analyzed the presence of skeletal anomalies in a series of 199 electively aborted fetuses, which were whole-mount stained with alizarin red specific for skeletal tissues. Results show that approximately 40% of the fetuses had cervical ribs, even though external congenital abnormalities such as craniofacial and limb defects were absent. A literature overview indicates that the observed frequency of cervical ribs is comparable to results previously obtained for deceased fetuses with no or minor congenital anomalies, and higher than expected for healthy fetuses. This unexpected result can probably in part be explained by a higher detection rate of small cervical ribs when using alizarin red staining instead of radiographs. Additionally, studies in the literature suggest that the size of a cervical rib may indicate the severity of abnormalities, but this possibility requires further research. Anomalies of the axial skeleton are known to be caused by a disturbance of early development, which alters Hox gene expression, but in this study the origin of the stress could not be verified as maternal medical data were not available. The co-occurrence of rudimentary or absent 12th ribs in 23.6% of the cases with cervical ribs indicates that in approximately 8% of the fetuses a homeotic shift occurred over a larger part of the vertebral column. This suggests that the expression of multiple Hox genes may have been affected in these fetuses. Together, the high incidence of cervical ribs and also their co-occurrence with rudimentary or absent 12th ribs suggests that there may have been a disturbance of early development such that the studied fetuses are

  4. Transcriptome Sequencing Demonstrates that Human Papillomavirus is not Active in Cutaneous Squamous Cell Carcinoma

    PubMed Central

    Arron, Sarah Tuttleton; Ruby, J. Graham; Dybbro, Eric; Ganem, Don; DeRisi, Joseph L.

    2011-01-01

    Beta-papillomavirus (β-HPV) DNA is present in some cutaneous squamous cell carcinomas (cuSCC), but no mechanism of carcinogenesis has been determined. We used ultra-high throughput sequencing of the cancer transcriptome to assess whether papillomavirus transcripts are present in these cancers. Sixty-seven cuSCC samples were assayed for β-HPV DNA by PCR, and viral loads were measured with type-specific qPCR. Thirty-one SCCs were selected for whole transcriptome sequencing. Transcriptome libraries were prepared in parallel from the HPV18 positive HeLa cervical cancer cell line and HPV16 positive primary cervical and periungual SCC. Thirty percent (20/67) of the tumors were positive for β-HPV DNA, but there was no difference in β-HPV viral load between tumor and normal tissue (p=0.310). Immunosuppression and age were significantly associated with higher viral load (p=0.016 for immunosuppression; p=0.0004 for age). Transcriptome sequencing failed to identify papillomavirus expression in any of the skin tumors. In contrast, HPV 16 and 18 mRNA transcripts were readily identified in primary cervical and periungual cancers and HeLa cells. These data demonstrate that papillomavirus mRNA expression is not a factor in the maintenance of cuSCC. PMID:21490616

  5. Determination of radiotherapeutic target zones for thoracic esophageal squamous cell cancer with lower cervical lymph node metastasis according to CT-images

    PubMed Central

    Li, Xingde; Zhao, Jin; Liu, Ming; Zhai, Fushan; Zhu, Zhengfei; Yu, Feng; Zhang, Mingyun; Han, Lijie; Zhao, Yue; Wang, Haiyan

    2016-01-01

    Esophageal squamous cell carcinoma (ESCC) is a leading cause of cancer-related deaths worldwide. And radical synchronized chemoradiotherapy has become an important treatment measures for this disease. It is necessary to define the therapeutic target zone based on computer tomography(CT)-images for precise radiotherapy. Therefore, we retrospectively analyzed the regularity of lymph node metastasis in lower cervical section of thoracic esophageal cancer based on CT-images and discussed the range of radiotherapy in supraclavicular zone. The lower cervical lymphatic drainage area was divided into cervical tracheoesophageal groove (CTG), medial supraclavicular zone (MSC zone) and lateral supraclavicular zone (LSC zone) based on CT-images. We found that the rate of lymph node metastasis to medial CTG and MSC zone was relatively high. And rate of lymph node metastasis to the above two zones from middle thoracic section was on an increasing trend with the progress of T stage. Patients at stage T3 and T4 with lymph node metastasis in tracheoesophageal groove in middle thoracic section showed a higher rate of lymph node metastasis in MSC zone. These results demonstrated that the CTG and MSC zone should be clinically included in the supraclavicular target zone for radical radiotherapy, and the T-stage and tumor location should be considered simultaneously. PMID:27147581

  6. Human papillomavirus testing for primary cervical cancer screening.

    PubMed

    Grce, Magdalena; Davies, Philip

    2008-09-01

    Cervical cancer is the second most common cancer in women worldwide and the seventh most common cause of cancer deaths in women in Europe. Today, we know how to prevent almost every case of this disease; organized cervical cancer screening based on the Papanicolaou or Pap smear has been proven to prevent 80% of cervical cancer deaths, while new technologies for the detection of the human papillomavirus (HPV) or the prevention of HPV infection offer the potential to make even more progress in the battle against this disease. Testing for carcinogenic or high-risk HPV types is gaining acceptance for the triage of women with borderline cytology and for follow-up after treatment of high-grade cervical lesions. Now, a number of large-scale randomized controlled trials have shown that HPV testing as a primary screening test can detect approximately 50% more high-grade lesions than the Pap test, albeit with a lower specificity if all HPV-positive women are followed up. However, alternative screening algorithms in which HPV-positive women are triaged with cytology have been shown to have equivalent specificity to the Pap test without compromising the increased sensitivity. Further advantages of HPV testing come from the fact that it is an objective and automatable test with a dichotomous result. These attributes can yield cost savings through reductions in staff numbers and simplification of quality control procedures while reducing turnaround times. In countries seeking to improve cervical cancer prevention, the implementation of HPV testing as the primary screening test with cytology for the triage of HPV-positive women is an option that should be fully evaluated. This review summarizes the recent advances in HPV testing in cervical cancer prevention.

  7. The cortical shell architecture of human cervical vertebral bodies.

    PubMed

    Panjabi, M M; Chen, N C; Shin, E K; Wang, J L

    2001-11-15

    An anatomic study of cervical vertebral bodies. To provide quantitative information on the cortical shell architecture of the middle and lower cervical vertebral bodies. Some external dimensions have been measured, but little quantitative data exists for the cortical shell architecture of the vertebral bodies of the cervical spine. Twenty-one human cervical vertebral bodies (C3-C7) were sectioned along parasagittal planes into five 1.7-mm thin slices for each vertebra. Radiographs of each slice were digitized, and external and internal dimensions were measured. Averages and standard deviations were computed. Single factor analysis of variance was used to determine significant (P < 0.05) differences between the vertebral levels. The superior endplate was thickest in the posterior region (range 0.74-0.89 mm) and thinnest in the anterior region (range 0.44-0.56 mm). The inferior endplate was thickest in the anterior region (range 0.61-0.81 mm) and thinnest in the posterior region (range 0.49-0.62 mm). In the central region, the superior endplate (range 0.42-0.58 mm) was thinner than the inferior endplate (range 0.53-0.64 mm). Variation with vertebral level was dependent on the dimension studied. Comprehensive quantitative anatomic data of the middle and lower cervical vertebral bodies have been obtained. This may be useful in improving the understanding of the three-column and other vertebral-fracture theories, the fidelity of the finite element models of cervical spine, and the designs of surgical instrumentation.

  8. Effects of cyclooxygenase-2 on human esophageal squamous cell carcinoma

    PubMed Central

    Zhang, Li; Wu, Yong-Dong; Li, Peng; Tu, Jun; Niu, Ying-Lin; Xu, Cai-Min; Zhang, Shu-Tian

    2011-01-01

    AIM: To study the relationship between the cyclooxygenase (COX)-2 gene and the proliferation and apoptosis of esophageal squamous carcinoma EC109 cells. METHODS: The techniques of RNA interference (RNAi) and cell transfection, as well as the levels of oncogenicity in nude mice, were used to study the role of COX-2 in the esophageal squamous carcinoma cell (ESCC) line EC109. Following RNAi and transfection, Western blotting analysis was used to determine the expression of the COX-2 protein. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) reduction assay was used to evaluate cell growth, and flow cytometry was used to detect cell apoptosis. RESULTS: Western blotting analysis demonstrated that COX-2 expression was significantly reduced in EC109 cells treated with COX-2-specific short interfering RNA (siRNA) but was increased in EC109 cells transfected with COX-2. Furthermore, COX-2 siRNA treatment inhibited cell proliferation (P < 0.01) and induced apoptosis in EC109 cells, as determined by an MTT assay and by flow cytometry, respectively. In contrast, transfected COX-2 led to increased cell proliferation (P < 0.05) and decreased apoptosis in EC109 cells. In addition, combination treatment of cells with COX-2 siRNA and aspirin had a synergistic effect (P < 0.01). For experiments measuring tumorigenicity, xenograft tumors of a greater volume and weight were found in the COX-2 group compared with other groups (P < 0.05). A large dose of aspirin inhibited tumor growth in nude mice effectively (P < 0.05), and the rate of tumor suppression was 51.8% in the high-dose aspirin group. CONCLUSION: COX-2 plays a very critical role in ESCC carcinogenesis, and COX-2 siRNA combined with aspirin has the potential to be an anticancer therapy for the treatment of ESCC. PMID:22147962

  9. Effect of different segmentation algorithms on metabolic tumor volume measured on 18F-FDG PET/CT of cervical primary squamous cell carcinoma

    PubMed Central

    Xu, Weina; Yu, Shupeng; Ma, Ying; Liu, Changping

    2017-01-01

    Background and purpose It is known that fluorine-18 fluorodeoxyglucose PET/computed tomography (CT) segmentation algorithms have an impact on the metabolic tumor volume (MTV). This leads to some uncertainties in PET/CT guidance of tumor radiotherapy. The aim of this study was to investigate the effect of segmentation algorithms on the PET/CT-based MTV and their correlations with the gross tumor volumes (GTVs) of cervical primary squamous cell carcinoma. Materials and methods Fifty-five patients with International Federation of Gynecology and Obstetrics stage Ia∼IIb and histologically proven cervical squamous cell carcinoma were enrolled. A fluorine-18 fluorodeoxyglucose PET/CT scan was performed before definitive surgery. GTV was measured on surgical specimens. MTVs were estimated on PET/CT scans using different segmentation algorithms, including a fixed percentage of the maximum standardized uptake value (20∼60% SUVmax) threshold and iterative adaptive algorithm. We divided all patients into four different groups according to the SUVmax within target volume. The comparisons of absolute values and percentage differences between MTVs by segmentation and GTV were performed in different SUVmax subgroups. The optimal threshold percentage was determined from MTV20%∼MTV60%, and was correlated with SUVmax. The correlation of MTViterative adaptive with GTV was also investigated. Results MTV50% and MTV60% were similar to GTV in the SUVmax up to 5 (P>0.05). MTV30%∼MTV60% were similar to GTV (P>0.05) in the 50.05) in the 100.05) in the SUVmax of at least 15 group. MTViterative adaptive was similar to GTV in both total and different SUVmax groups (P>0.05). Significant differences were observed among the fixed percentage method and the optimal threshold percentage was inversely correlated with SUVmax. The iterative adaptive segmentation algorithm led

  10. Studying the Physical Function and Quality of Life Before and After Surgery in Patients With Stage I Cervical Cancer

    ClinicalTrials.gov

    2017-08-22

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Lymphedema; Sexual Dysfunction and Infertility; Stage IA1 Cervical Cancer; Stage IA2 Cervical Cancer; Stage IB1 Cervical Cancer

  11. Asian-American variants of human papillomavirus 16 and risk for cervical cancer: a case-control study.

    PubMed

    Berumen, J; Ordoñez, R M; Lazcano, E; Salmeron, J; Galvan, S C; Estrada, R A; Yunes, E; Garcia-Carranca, A; Gonzalez-Lira, G; Madrigal-de la Campa, A

    2001-09-05

    Human papillomavirus 16 (HPV16) has a number of variants, each with a different geographic distribution and some that are associated more often with invasive neoplasias. We investigated whether the high incidence of cervical cancer in Mexico (50 cases per 100 000 women) may be associated with a high prevalence of oncogenic HPV16 variants. Cervical samples were collected from 181 case patients with cervical cancer and from 181 age-matched control subjects, all from Mexico City. HPV16 was detected with an E6/E7 gene-specific polymerase chain reaction, and variant HPV classes and subclasses were identified by sequencing regions of the E6 and L1/MY genes. Clinical data and data on tumor characteristics were also collected. All statistical tests were two-sided. HPV16 was detected in cervical scrapes from 50.8% (92 of 181) of case patients and from 11% (20 of 181) of control subjects. All HPV16-positive samples, except one, contained European (E) or Asian-American (AA) variants. AA and E variants were found statistically significantly more often in case patients (AA = 23.2% [42 of 181]; E = 27.1% [49 of 181]) than in control subjects (AA = 1.1% [two of 181]; E = 10% [18 of 181]) (P<.001 for case versus control subjects for either E or AA variants, chi2 test). However, the frequency of AA variants was 21 times higher in cancer patients than in control subjects, whereas that ratio for E variants was only 2.7 (P =.006, chi2 test). The odds ratio (OR) for cervical cancer associated with AA variants (OR = 27.0; 95% confidence interval [CI] = 6.4 to 113.7) was higher than that associated with E variants (OR = 3.4; 95% CI = 1.9 to 6.0). AA-positive case patients (46.2 +/- 12.5 years [mean +/- standard deviation]) were 7.7 years younger than E-positive case patients (53.9 +/- 12.2 years) (P =.004, Student's t test). AA variants were associated with squamous cell carcinomas and adenocarcinomas, but E variants were associated with only squamous cell carcinomas (P =.014, Fisher

  12. Fatigue responses of the human cervical spine intervertebral discs.

    PubMed

    Yoganandan, Narayan; Umale, Sagar; Stemper, Brain; Snyder, Bryan

    2017-05-01

    Numerous studies have been conducted since more than fifty years to understand the behavior of the human lumbar spine under fatigue loading. Applications have been largely driven by low back pain and human body vibration problems. The human neck also sustains fatigue loading in certain type of civilian occupational and military operational activities, and research is very limited in this area. Being a visco-elastic structure, it is important to determine the stress-relaxation properties of the human cervical spine intervertebral discs to enable accurate simulations of these structures in stress-analysis models. While finite element models have the ability to incorporate viscoelastic material definitions, data specific to the cervical spine are limited. The present study was conducted to determine these properties and understand the responses of the human lower cervical spine discs under large number of cyclic loads in the axial compression mode. Eight disc segments consisting of the adjacent vertebral bodies along with the longitudinal ligaments were subjected to compression, followed by 10,000 cycles of loading at 2 or 4Hz frequency by limiting the axial load to approximately 150 N, and subsequent to resting period, subjected to compression to extract the stress-relaxation properties using the quasi-linear viscoelastic (QLV) material model. The coefficients of the model and disc displacements as a function of cycles and loading frequency are presented. The disc responses demonstrated a plateauing effect after the first 2000 to 4000 cycles, which were highly nonlinear. The paper compares these responses with the "work hardening" phenomenon proposed in clinical literature for the lumbar spine to explain the fatigue behavior of the discs. The quantitative results in terms of QLV coefficients can serve as inputs to complex finite element models of the cervical spine to delineate the local and internal load-sharing responses of the disc segment. Published by Elsevier

  13. Thrombospondin-induced attachment and spreading of human squamous carcinoma cells

    SciTech Connect

    Varani, J.; Dixit, V.M.; Fligiel, S.E.G.; McKeever, P.E.; Carey, T.E.

    1986-12-01

    Thrombospondin (TSP) induced the attachment and spreading of human squamous carcinoma cells on plastic culture dishes and dishes coated with type I or type IV collagen. Increased adhesion was detected as early as 15 min after treatment. Dose-response studies indicated that 1-5 ..mu..g of TSP per 35 mm (diameter) culture dish was sufficient to induce a response and that a half-maximal response occurred at 10 ..mu..g of TSP/dish. The squamous carcinoma cells synthesized TSP as indicated by biosynthetic labeling experiments. TSP was secreted (or shed) into the culture medium by these cells and also became bound to the cell surface. TSP also promoted adhesion of human keratinocytes, fibroblasts and fibrosarcoma cells but did not induce attachment or spreading of human melanoma or glioma cells, although these cells did respond to laminin.

  14. Nonlinear optical microscopy and ultrasound imaging of human cervical structure

    NASA Astrophysics Data System (ADS)

    Reusch, Lisa M.; Feltovich, Helen; Carlson, Lindsey C.; Hall, Gunnsteinn; Campagnola, Paul J.; Eliceiri, Kevin W.; Hall, Timothy J.

    2013-03-01

    The cervix softens and shortens as its collagen microstructure rearranges in preparation for birth, but premature change may lead to premature birth. The global preterm birth rate has not decreased despite decades of research, likely because cervical microstructure is poorly understood. Our group has developed a multilevel approach to evaluating the human cervix. We are developing quantitative ultrasound (QUS) techniques for noninvasive interrogation of cervical microstructure and corroborating those results with high-resolution images of microstructure from second harmonic generation imaging (SHG) microscopy. We obtain ultrasound measurements from hysterectomy specimens, prepare the tissue for SHG, and stitch together several hundred images to create a comprehensive view of large areas of cervix. The images are analyzed for collagen orientation and alignment with curvelet transform, and registered with QUS data, facilitating multiscale analysis in which the micron-scale SHG images and millimeter-scale ultrasound data interpretation inform each other. This novel combination of modalities allows comprehensive characterization of cervical microstructure in high resolution. Through a detailed comparative study, we demonstrate that SHG imaging both corroborates the quantitative ultrasound measurements and provides further insight. Ultimately, a comprehensive understanding of specific microstructural cervical change in pregnancy should lead to novel approaches to the prevention of preterm birth.

  15. Nonlinear optical microscopy and ultrasound imaging of human cervical structure

    PubMed Central

    Reusch, Lisa M.; Feltovich, Helen; Carlson, Lindsey C.; Hall, Gunnsteinn; Campagnola, Paul J.; Eliceiri, Kevin W.

    2013-01-01

    Abstract. The cervix softens and shortens as its collagen microstructure rearranges in preparation for birth, but premature change may lead to premature birth. The global preterm birth rate has not decreased despite decades of research, likely because cervical microstructure is poorly understood. Our group has developed a multilevel approach to evaluating the human cervix. We are developing quantitative ultrasound (QUS) techniques for noninvasive interrogation of cervical microstructure and corroborating those results with high-resolution images of microstructure from second harmonic generation imaging (SHG) microscopy. We obtain ultrasound measurements from hysterectomy specimens, prepare the tissue for SHG, and stitch together several hundred images to create a comprehensive view of large areas of cervix. The images are analyzed for collagen orientation and alignment with curvelet transform, and registered with QUS data, facilitating multiscale analysis in which the micron-scale SHG images and millimeter-scale ultrasound data interpretation inform each other. This novel combination of modalities allows comprehensive characterization of cervical microstructure in high resolution. Through a detailed comparative study, we demonstrate that SHG imaging both corroborates the quantitative ultrasound measurements and provides further insight. Ultimately, a comprehensive understanding of specific microstructural cervical change in pregnancy should lead to novel approaches to the prevention of preterm birth. PMID:23412434

  16. Cervical cancer in the human papillomavirus vaccination era.

    PubMed

    Tay, Sun-Kuie

    2012-02-01

    To evaluate the potential changes in the epidemiology of cervical cancer based on recently emerged information from mass vaccination programs beyond clinical trials. Limited sensitivity and unequal access to screening have resulted in an imbalance in distribution of the burden of cervical cancer between developed and developing countries, between metropolitan and rural areas in developed countries, and among women from different ethnic groups. In screened populations, there is a relative increase in incidence of cervical cancer in young and elderly women, and an increased proportion of adenocarcinoma. A high coverage of the target population has been achieved in human papillomavirus (HPV) vaccination programs in many countries. After 3 years of mass vaccination of adolescent girls, surveillance data in Australia confirmed a significant reduction in high-grade abnormalities for girls aged 18 years and below. HPV vaccination is more feasible than cytology screening for universal implementation across geographic sectors and demographic groups within individual countries and over the world. The high vaccine efficacy should significantly reduce the total burden and unequal distribution of invasive cervical cancer, including adenocarcinoma hitherto observed. These epidemiological changes provoke consideration for appropriate modifications of the current screening program.

  17. Monitoring and ordering practices for human papillomavirus in cervical cytology: findings from the College of American Pathologists Gynecologic Cytopathology Quality Consensus Conference working group 5.

    PubMed

    Booth, Christine N; Bashleben, Christine; Filomena, Carol A; Means, Marilee M; Wasserman, Patricia G; Souers, Rhona J; Henry, Michael R

    2013-02-01

    The association of certain types of human papillomavirus with cervical carcinoma is well established. Human papillomavirus testing is now routinely used to screen for cervical carcinoma and precursor lesions of the cervix (cotesting and reflex testing) and these results are considered in patient triage and management. To provide information about current laboratory practices in human papillomavirus testing and consensus best practice statements based on results from the College of American Pathologists' laboratory-based survey funded by the Centers for Disease Control and Prevention. The College of American Pathologists submitted a paper-based survey to 1245 laboratories in the United States. After review of the initial results, follow-up Web-based survey results, and a literature review by an expert working group, consensus best practice statements were constructed by working group members for presentation at a national consensus conference. These best practice statements were discussed and then voted upon by conference participants. A total of 525 laboratories responded to survey questions about human papillomavirus ordering and monitoring practices, whereas 546 responded to the overall survey. In most laboratories (87.6%), the high-risk human papillomavirus test is ordered as a reflex test by providers. A minority of laboratories (11.9%) routinely bundle low- and high-risk human papillomavirus tests. Most laboratories (84.4%) do not limit testing in patients with atypical squamous cells to women older than 20 years. More than half of laboratories (53.3%) monitor human papillomavirus positive rates in Papanicolaou tests with atypical squamous cells of undetermined significance. It is not appropriate for laboratories to offer low-risk human papillomavirus testing for any clinical circumstance in gynecologic cytology. Laboratories should not order human papillomavirus testing to resolve diagnostic discrepancies. It is a valuable broad measure of laboratory quality

  18. Cervicitis

    MedlinePlus

    ... growth of normal bacteria in the vagina (bacterial vaginosis) can also cause cervicitis. ... a microscope (may show candidiasis , trichomoniasis , or bacterial vaginosis) Pap test Tests for gonorrhea or chlamydia Rarely, ...

  19. Apollon modulates chemosensitivity in human esophageal squamous cell carcinoma

    PubMed Central

    Weng, Shuqiang; Liu, Xijun; Rao, Benqiang; Gu, Jianxin; Chen, She; Wang, Qun; Shen, Xizhong; Xue, Ruyi; Dong, Ling

    2014-01-01

    Patients with esophageal squamous cell carcinoma (ESCC) are often diagnosed with advanced diseases that respond poorly to chemotherapy. Here we reported that Apollon, a membrane-associated inhibitor of apoptosis protein, was overexpressed in ESCC cell lines and clinical ESCC tissues, and Apollon overexpression clinically correlated with poor response to chemotherapy (P = 0.001), and short overall survival (P = 0.021). Apollon knockdown increased cisplatin/docetaxel-induced apoptosis, mitochondrial dysfunction and cytochrome c release in two ESCC cell lines. Apollon knockdown potentiated cisplatin/docetaxel-induced long-term cell growth inhibition, and enhanced chemosensitivity of ESCC cells to cisplatin/docetaxel in xenograft tumor models. Apollon knockdown also enhanced cisplatin/docetaxel-induced activation of caspase-8 (extrinsic pathway) and caspase-9 (intrinsic pathway) in ESCC cells and xenograft tumor models. Mechanism studies revealed that the effect of Apollon on chemosensitivity is mainly mediated by Smac. Apollon expression strongly and negatively correlated with Smac expression in clinical ESCC tissues (P = 0.001). Apollon targeted Smac for degradation in ESCC cells. The effect of Apollon on chemosensitivity was reversed by Smac knockdown in ESCC cells. Taken together, our data show association of Apollon expression with chemotherapeutic response in ESCC, and provide a strong rationale for combining Apollon antagonism with chemotherapy to treat ESCC. PMID:25216531

  20. The clinical performance of APTIMA human papillomavirus and Hybrid Capture 2 assays in the triage of lesser abnormal cervical cytologies.

    PubMed

    Guo, Yanli; You, Ke; Geng, Li; Qiao, Jie

    2014-10-01

    This study was performed to evaluate the clinical performance of APTIMA human papillomavirus (AHPV) assay and Hybrid Capture 2 (HC2) assay in screening for cervical disease, especially in women with atypical squamous cell of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL). A total of 411 women diagnosed with ASC-US or LSIL were referred and further triaged by HC2 test. Prior to colposcopy, liquid-based cytology specimens were collected for the AHPV assay. Sensitivity and specificity were established based on the histological findings of cervical intraepithelial neoplasia (CIN). In all 411 subjects, the positive detection rate of AHPV assay was 70.8% (95% confidence interval [CI], 66.4 to 75.2), which was significantly lower than the positive detection rate of 94.9% obtained using HC2 test (95% CI, 92.3 to 96.8). Only one CIN 3-positive case was detected among the 120 AHPV-negative women, which was then confirmed by Pap smear test to be LSIL. The sensitivities of AHPV and HC2 for CIN 3 were similar (94.1% and 100%, respectively). However, AHPV showed a significantly higher specificity than HC2 test (30.2% and 5.3%, respectively; p<0.001). AHPV assay is effective in identifying CIN 3-positive cases because of its high specificity and lower false-negative rate. The use of AHPV for the triage of ASC-US and LSIL might help to reduce the referral rate of colposcopy during cervical cancer screening.

  1. Bee venom inhibits growth of human cervical tumors in mice

    PubMed Central

    Kim, Tae Myoung; Jung, Yu Yeon; Park, Mi Hee; Oh, Sang Hyun; Yun, Hye Seok; Jun, Hyung Ok; Yoo, Hwan Soo; Han, Sang-Bae; Lee, Ung Soo; Yoon, Joo Hee; Song, Min Jong; Hong, Jin Tae

    2015-01-01

    We studied whether bee venom (BV) inhibits cervical tumor growth through enhancement of death receptor (DR) expressions and inactivation of nuclear factor kappa B (NF-κB) in mice. In vivo study showed that BV (1 mg/kg) inhibited tumor growth. Similar inhibitory effects of BV on cancer growth in primary human cervical cancer cells were also found. BV (1–5 μg/ml) also inhibited the growth of cancer cells, Ca Ski and C33Aby the induction of apoptotic cell death in a dose dependent manner. Agreed with cancer cell growth inhibition, expression of death receptors; FAS, DR3 and DR6, and DR downstream pro-apoptotic proteins including caspase-3 and Bax was concomitantly increased, but the NF-κB activity and the expression of Bcl-2 were inhibited by treatment with BV in tumor mice, human cancer cell and human tumor samples as well as cultured cancer cells. In addition, deletion of FAS, DR3 and DR6 by small interfering RNA significantly reversed BV-induced cell growth inhibitory effects as well as NF-κB inactivation. These results suggest that BV inhibits cervical tumor growth through enhancement of FAS, DR3 and DR6 expression via inhibition of NF-κB pathway. PMID:25730901

  2. Limiting factors for cytopathological diagnosis of high-grade squamous intraepithelial lesions: a cytohistological correlation between findings in cervical smears and loop electrical excision procedure.

    PubMed

    Pinto AP, Alvaro P; Tuon, Felipe F B; Torres, Luiz Fernando Bleggi; Collaço, Luiz Martins

    2002-01-01

    The present study sought possible factors leading to the cytological diagnosis of atypical squamous cells of uncertain significance (ASCUS) in cases of high-grade squamous intraepithelial lesions (HSIL). Based on retrospective histopathological analysis of loop electrical excision procedure (LEEP) products that diagnosed HSIL, two study groups were randomly selected. The first was consisted of cases with two consecutive Papanicolaou (Pap) smears with the diagnosis of ASCUS. The second (control) group was represented by cases diagnosed as HSIL by cytology. From the Pap smears diagnosed as ASCUS, the sampling limitations was different from control group (P < 0.05). The median size of the largest lesion in each case with ASCUS was 2.66 mm (+/- 1.71 mm). In the control group, the median size of the largest lesion was 5.15 mm (+/-2.58 mm) (P < 0.05). The size of the lesion and sample limitations led patients with cervical intraepithelial neoplasms to be diagnosed as ASCUS for two consecutive times, after a 6-mo period. Copyright 2002 Wiley-Liss, Inc.

  3. Human papillomavirus prevalence and type-distribution in women with cervical lesions: a cross-sectional study in Sri Lanka.

    PubMed

    Karunaratne, Kanishka; Ihalagama, Himali; Rohitha, Saman; Molijn, Anco; Gopala, Kusuma; Schmidt, Johannes E; Chen, Jing; Datta, Sanjoy; Mehta, Shailesh

    2014-02-21

    Cervical cancer ranks second among all cancers reported in Sri Lankan women. This study assessed the prevalence and type-distribution of human papillomavirus (HPV) among Sri Lankan women with invasive cervical cancer (ICC) and pre-cancerous lesions. 114 women aged 21 years and above, hospitalized in the National Cancer Institute, Sri Lanka with a diagnosis of ICC or cervical intraepithelial neoplasia (CIN) 2/3 were prospectively enrolled between October 2009 and September 2010 (110430/NCT01221987). The cervical biopsy or excision specimens collected during routine clinical procedures were subjected to histopathological review. DNA was extracted from samples with a confirmed histological diagnosis and was amplified using polymerase chain reaction and HPV DNA was detected using Enzyme Immuno Assay. HPV positive samples were typed using reverse hybridization Line Probe Assay. Of the cervical samples collected, 93.0% (106/114) had a histologically confirmed diagnosis of either ICC (98/106) or CIN 2/3 (8/106). Among all ICC cases, squamous cell carcinoma was diagnosed in the majority of women (81.6% [80/98]). HPV prevalence among ICC cases was 84.7% (83/98). The HPV types most commonly detected in ICC cases with single HPV infection (98.8% [82/83]) were HPV-16 (67.3%) and HPV-18 (9.2%). Infection with multiple HPV types was recorded in a single case (co-infection of HPV-16 and HPV-59). HPV was prevalent in most women with ICC in Sri Lanka; HPV-16 and HPV-18 were the predominantly detected HPV types. An effective prophylactic vaccine against the most prevalent HPV types may help to reduce the burden of ICC disease.

  4. Coexistent squamous cell carcinoma and adenoid basal carcinoma in the uterine cervix and infection with human papillomavirus (HPV 31).

    PubMed

    Lin, Yu-Chieh; Perng, Cherng-Lih; Chang, Yi-Ming; Li, Yao-Feng; Tsai, Yuan-Ming; Wu, Gwo-Jang; Lin, Chih-Kung

    2013-09-01

    Adenoid basal carcinoma (ABC) is an uncommon neoplasm of the uterine cervix. ABC can be accompanied by carcinoma in situ or invasive carcinoma. Most cases are discovered accidentally during radical hysterectomy. ABC is associated with a high risk of human papillomavirus infection (HPV), most often HPV 16 infection. We present a rare case of an 86-year-old Taiwanese married woman who suffered from bloody vaginal discharge and occasional lower abdominal pain and received cervical biopsy. The pathological report revealed squamous cell carcinoma (SCC) of the uterine cervix. After radical hysterectomy, bilateral salpingo-oophorectomy, and bilateral pelvic and para-aortic lymph node dissection, the final pathological report revealed SCC coexisting with ABC, and both of the components were infected by HPV 31. After receiving radiotherapy, she maintained outpatient department follow-up. A literature review revealed that this was a rare case of combined ABC-SCC associated with HPV 31 infection. In this case, the ABC component did not affect the tumor stage because it was confined to the cervix. However, we must avoid overestimating the clinical stage because the ABC component is thought to be a benign lesion. Copyright © 2013. Published by Elsevier B.V.

  5. Circulation of human papillomavirus (HPV) genotypes in women from Córdoba, Argentina, with squamous intraepithelial lesions.

    PubMed

    Venezuela, Raul Fernando; Kiguen, Ana Ximena; Frutos, Maria Celia; Cuffini, Cecilia Gabriela

    2012-01-01

    Human papillomavirus (HPV) can induce a wide spectrum of squamous intraepithelial lesions (SIL) of varying severity. The aim of the present study was to establish the frequency of HPV infection and identify the genotypes circulating in women from Córdoba, Argentina, in relation to age and cytology. A total of 186 women, between 18 and 65 years old, with antecedents of SIL, underwent a pelvic examination and had cervical cells collected for cytology and HPV DNA detection. Ninety-six samples (51.6%) were positive for HPV detection, and sixty-three (65.6%) of them showed the presence of at least one HR-HPV. Low- and high-grade SIL showed significant association in patients younger than 35 years of age. We found 18 different genotypes, with a greater presence of HR-HPV. Genotypes 16 and 6 were the most frequent. Seven (7.3%) multiple infections, 85.7% of which had at least one HR-HPV, were detected. The detection of a large number of different HPV genotypes is a warning sign. It is thus necessary to strengthen the monitoring of the circulation of high-risk genotypes, currently less prevalent in intraepithelial lesions, as a control measure for the possible impact of the implementation of vaccines against genotypes 16 and 18.

  6. Human papilloma virus (HPV) E7-mediated attenuation of retinoblastoma (Rb) induces hPygopus2 expression via Elf-1 in cervical cancer.

    PubMed

    Tzenov, Youlian R; Andrews, Phillip G; Voisey, Kim; Popadiuk, Paul; Xiong, Jieying; Popadiuk, Catherine; Kao, Kenneth R

    2013-01-01

    The human papillomavirus (HPV) is the etiologic agent of cervical cancer. In this study, we provide evidence for the human Pygopus (hPygo)2 gene as a cellular biomarker for HPV-related disease. In a tumor microarray of cervical cancer progression, hPygo2 levels were greater in high-grade lesions and squamous cell carcinomas than in normal epithelia. Similarly, hPygo2 mRNA and protein levels were greater in HPV-positive cervical cancer cells relative to uninfected primary cells. RNA interference (RNAi)-mediated depletion of HPV-E7 increased whereas E74-like factor (Elf)-1 RNAi decreased association of Retinoblastoma (Rb) tumor suppressor with the hPygo2 promoter in cervical cancer cell lines. Transfection of dominant-active Rb inhibited Elf-1-dependent activation of hPygo2, whereas Elf-1 itself increased hPygo2 expression. Chromatin immunoprecipitation assays showed that Rb repressed hPygo2 by inhibiting Elf-1 at the Ets-binding site in the hPygo2 promoter. These results suggested that abrogation of Rb by E7 resulted in derepression of Elf-1, which in turn stimulated expression of hPygo2. Thus, initiation of hPygo2 expression by Elf-1 was required for proliferation of cervical cancer cells and its expression therefore may act as a surrogate marker for dysplasia.

  7. Resistance of human squamous carcinoma cells to transforming growth factor beta 1 is a recessive trait.

    PubMed Central

    Reiss, M; Muñoz-Antonia, T; Cowan, J M; Wilkins, P C; Zhou, Z L; Vellucci, V F

    1993-01-01

    Because most human squamous carcinoma cell lines of the aerodigestive and genital tracts are refractory to the antiproliferative action of transforming growth factor beta 1 (TGF beta 1) in vitro, we have begun to identify the causes for resistance of squamous carcinoma cell lines to TGF beta 1 by using somatic cell genetics. Two stable hybrid cell lines (FaDu-HKc.1 and FaDu-HKc.2) were obtained by fusing a TGF beta 1-resistant human squamous carcinoma cell line, FaDu-HygR, with a human papilloma virus 16-immortalized, TGF beta 1-sensitive, human foreskin keratinocyte cell line, HKc-neoR. Whereas TGF beta 1 did not inhibit DNA synthesis in parental FaDu-HygR cells, it reduced DNA synthetic activity of HKc-neoR, FaDu-HKc.1, and FaDu-HKc.2 cells by 75-85% (IC50, 2-5 pM). Although squamous carcinoma cells express lower than normal levels of TGF beta 1 type II receptors on their cell surface, TGF beta 1 type II receptor mRNA was detected in all four cell lines. Recessive genes involved in TGF beta 1 signaling may be localized to the distal portion of chromosome 18q, as this was the sole chromosomal region of homozygous deletion in parental FaDu-HygR cells. Furthermore, our previous observation that mutant p53 decreases sensitivity of keratinocytes to TGF beta 1 was supported by the finding that the level of the mutant p53 protein expressed by the hybrid cell lines was greatly reduced. In summary, TGF beta 1 resistance of FaDu cells appears to be recessive and is presumably due to the loss of one or more post-receptor elements of the signaling pathway. Images Fig. 1 Fig. 2 Fig. 4 Fig. 5 Fig. 6 PMID:8327510

  8. Squamous cell carcinoma antigen in human liver carcinogenesis.

    PubMed

    Guido, M; Roskams, T; Pontisso, P; Fassan, M; Thung, S N; Giacomelli, L; Sergio, A; Farinati, F; Cillo, U; Rugge, M

    2008-04-01

    Squamous cell carcinoma antigen (SCCA) is a serine protease inhibitor that can be overexpressed in hepatocellular carcinoma (HCC) at both molecular and protein level, but no data are available on its expression in pre-malignant stages. To assess SCCA expression by immunohistochemistry in HCC and its nodular precursors in cirrhotic livers. 55 nodules from 42 explanted livers were evaluated: 7 large regenerative nodules (LRNs), 7 low-grade dysplastic nodules (LG-DNs), 10 high-grade DNs (HG-DNs), and 31 HCC. SCCA expression was semiquantitatively scored on a four-tiered scale. SCCA hepatocyte immunostaining was always restricted to the cytoplasm, mainly exhibiting a granular pattern. Stain intensity varied, ranging from weak to very strong. Within the nodules, positive cells were unevenly distributed, either scattered or in irregular clusters. The prevalence of SCCA expression was 29% in LRNs, 100% in DNs and 93% in HCC. A significant difference emerged in both prevalence and score for LRNs versus LG-DNs (p<0.039), HG-DNs (p = 0.001), and HCC (p = 0.000). A barely significant difference (p = 0.49) was observed between LG-DNs and HG-DNs, while no difference in SCCA expression was detected between HG-DNs and HCC. Cirrhotic tissue adjacent to the nodules was positive in 96% of cases, with a significant difference in the score (p = 0.000) between hepatocytes adjacent to HCC and those surrounding LRNs. This study provides the first evidence that aberrant SCCA expression is an early event in liver cell carcinomatous transformation.

  9. Potential impact of a nine-valent vaccine in human papillomavirus related cervical disease

    PubMed Central

    2012-01-01

    Background Information on human papillomavirus (HPV) type distribution is necessary to evaluate the potential impact of current and future HPV vaccines. We estimated the relative contribution (RC) to invasive cervical cancer (ICC) and precancerous cervical lesions of the nine HPV types (HPV 6/11/16/18/31/33/45/52/58) included in an HPV vaccine currently under development. Methods Estimations on ICC were based on an international study of 8,977 HPV positive cases and estimations on precancerous cervical lesions were extracted from a published meta-analysis including 115,789 HPV positive women. Globocan 2008 and 2010 World Population Prospects were used to estimate current and future projections of new ICC cases. Results RC of the 9 HPV types in ICC was 89.4%, with 18.5% of cases positive for HPV 31/33/45/52/58. Regional variations were observed. RCs varied by histology, ranging between 89.1% in squamous cell carcinomas (SCC) and 95.5% in adenocarcinomas (ADC). HPV 16/18/45 were detected in 94.2% of ADC. RC of the 9 types altogether decreased with age (trend test p < 0.0001), driven by the decrease in older ages of HPV 16/18/45. In contrast, the RC of HPV 31/33/52/58 increased with age. Due to population growth alone, projected estimates of ICC cases attributable to the 9 types are expected to rise from 493,770 new cases in 2012 to 560,887 new cases in 2025. The RCs of individual high risk HPV types varied by cytological and histological grades of HPV-positive precancerous cervical lesions, and there was an under representation of HPV 18 and 45 compared to ICC. Conclusions The addition of HPV 31/33/45/52/58 to HPV types included in current vaccines could prevent almost 90% of ICC cases worldwide. If the nine-valent vaccine achieves the same degree of efficacy than previous vaccines, world incidence rates could be substantially reduced. PMID:23273245

  10. Transient increase in squamous cell carcinoma antigen expression in cultured cervical carcinoma CaSki cells in response to exposure to cis-diamminedichloroplatinum.

    PubMed

    Tateiwa, Y; Yoshida, S; Miyahara, Y; Hamana, S; Motoyama, S; Maruo, T

    2003-01-01

    The present study was conducted to elucidate the molecular mechanism underlying the transient increase in circulating squamous cell carcinoma antigen (SCC Ag) levels in response to CIS-diamminedichloroplatinum (CDDP) infusion using an in vitro model. The uterine cervical squamous carcinoma CaSki cells were cultured for 72 h after 3 h exposure to 5.0 microg/ml CDDP. The effects of CDDP exposure on the proliferative activity and apoptosis in cultured CaSki cells were determined by bromodeoxyuridine (BrdU) uptake and cell counting and by the TUNEL assay, respectively. SCC Ag levels in cultured CaSki cells and culture media were determined with the use of SCC-RIA kit. The expression of SCC Ag-1 mRNA and SCC Ag-2 mRNA in cultured CaSki cells was assessed using semiquantitative RT-PCR with Southern blot analysis. The number of BrdU-positive CaSki cells significantly decreased 6 h after exposure to CDDP, whereas the apoptosis-positive rate of cultured CaSki cells significantly increased 12 h after the CDDP exposure. The number of cultured CaSki cells significantly decreased 72 h after the CDDP exposure. The total SCC Ag protein levels in both cultured CaSki cells and the culture media after the 3-hour CDDP exposure increased in a time-dependent manner during the subsequent incubation for 48 h. Semiquantitative RT-PCR revealed that the expression levels of both SCC Ag-1 and SCC Ag-2 mRNA increased (1.7- and 2.7-fold, respectively) 12 h after the exposure to CDDP relative to those before the subsequent cultures. Exposure of uterine cervical squamous carcinoma CaSki cells to CDDP resulted in a transient increase in SCC Ag protein and mRNA expression in those cells during the initial 12 h after the exposure, being associated with decreased proliferative activity and increased apoptosis of those cells.

  11. Human rights in health equity: cervical cancer and HPV vaccines.

    PubMed

    Erdman, Joanna N

    2009-01-01

    This article seeks to demonstrate that health equity, as an empirical and normative concept, is reflected in the human rights to health and equality under international law. The obligations on government that flow from health equity as a human right are then examined. These include the obligation to act in pursuit of health equity as a policy objective, and the obligation to enact measures to ensure health equity as a policy outcome. These obligations are considered in relation to a promising remedial measure for social disparities in cervical cancer: HPV vaccines.

  12. Prevalence of human papillomavirus genotypes among African women with normal cervical cytology and neoplasia: a systematic review and meta-analysis.

    PubMed

    Ogembo, Rebecca Kemunto; Gona, Philimon Nyakauru; Seymour, Alaina J; Park, Henry Soo-Min; Bain, Paul A; Maranda, Louise; Ogembo, Javier Gordon

    2015-01-01

    Several meta-analyses confirmed the five most prevalent human papillomavirus (HPV) strains in women with and without cervical neoplastic diseases are HPV16, 18, 31, 52, and 58. HPV16/18 are the predominant oncogenic genotypes, causing approximately 70% of global cervical cancer cases. The vast majority of the women studied in previous analyses were from Europe, North America, Asia, and most recently Latin America and the Caribbean. Despite the high burden of cervical cancer morbidity and mortality in Africa, a robust meta-analysis of HPV genotype prevalence and distribution in African women is lacking. We systematically searched 14 major databases from inception to August 2013 without language restriction, following the Meta-Analysis of Observational Studies in Epidemiology and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Seventy-one studies from 23 African countries were identified after screening 1162 citations and data abstracted and study quality appraised from 195 articles. HPV type-specific prevalence and distribution was estimated from 17,273 cases of women with normal cervical cytology; 1019 women with atypical squamous cells of undetermined significance (ASCUS); 1444 women with low-grade squamous intraepithelial lesion (LSIL); 1571 women with high-grade squamous intraepithelial lesion (HSIL); and 4,067 cases of invasive cervical carcinoma (ICC). Overall prevalence of HPV16/18 were 4.4% and 2.8% of women with normal cytology, 12.0% and 4.4% with ASCUS, 14.5% and 10.0% with LSIL, 31.2% and 13.9% with HSIL, and 49.7% and 18.0% with ICC, respectively. Study limitations include the lack of adequate data from Middle and Northern African regions, and variations in the HPV type-specific sensitivity of different genotyping protocols. To our knowledge, this study is the most comprehensive assessment of the overall prevalence and distribution of HPV genotypes in African women with and without different cervical neoplasias. We

  13. Prevalence of Human Papillomavirus Genotypes among African Women with Normal Cervical Cytology and Neoplasia: A Systematic Review and Meta-Analysis

    PubMed Central

    Ogembo, Rebecca Kemunto; Gona, Philimon Nyakauru; Seymour, Alaina J.; Park, Henry Soo-Min; Bain, Paul A.; Maranda, Louise; Ogembo, Javier Gordon

    2015-01-01

    Background Several meta-analyses confirmed the five most prevalent human papillomavirus (HPV) strains in women with and without cervical neoplastic diseases are HPV16, 18, 31, 52, and 58. HPV16/18 are the predominant oncogenic genotypes, causing approximately 70% of global cervical cancer cases. The vast majority of the women studied in previous analyses were from Europe, North America, Asia, and most recently Latin America and the Caribbean. Despite the high burden of cervical cancer morbidity and mortality in Africa, a robust meta-analysis of HPV genotype prevalence and distribution in African women is lacking. Methods and Findings We systematically searched 14 major databases from inception to August 2013 without language restriction, following the Meta-Analysis of Observational Studies in Epidemiology and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Seventy-one studies from 23 African countries were identified after screening 1162 citations and data abstracted and study quality appraised from 195 articles. HPV type-specific prevalence and distribution was estimated from 17,273 cases of women with normal cervical cytology; 1019 women with atypical squamous cells of undetermined significance (ASCUS); 1444 women with low-grade squamous intraepithelial lesion (LSIL); 1571 women with high-grade squamous intraepithelial lesion (HSIL); and 4,067 cases of invasive cervical carcinoma (ICC). Overall prevalence of HPV16/18 were 4.4% and 2.8% of women with normal cytology, 12.0% and 4.4% with ASCUS, 14.5% and 10.0% with LSIL, 31.2% and 13.9% with HSIL, and 49.7% and 18.0% with ICC, respectively. Study limitations include the lack of adequate data from Middle and Northern African regions, and variations in the HPV type-specific sensitivity of different genotyping protocols. Conclusions To our knowledge, this study is the most comprehensive assessment of the overall prevalence and distribution of HPV genotypes in African women with and

  14. Clinical response to glycyrrhizinic acid in genital infection due to human papillomavirus and low-grade squamous intraepithelial lesion

    PubMed Central

    Valencia, Marcelino Hernández; Pacheco, Adia Carrillo; Quijano, Tomás Hernández; Girón, Antonio Vargas; López, Carlos Vargas

    2011-01-01

    Human papilloma virus (HPV) can infect any of the mucosal areas of the body and cause cervical cancer. Until recently, no specific treatments were available for this condition; therefore, any damaged tissue had to be removed or destroyed, which may have presented obstetrical repercussions for some women. Recently, new drugs have been developed that have shown to be effective for the cure of HPV infection. Glycyrrhizinic acid (GA) has shown fewer side effects and its systemic use makes it possible to reach difficult-to-treat lesions. The purpose of this study was to evaluate the clinical outcome of GA to eliminate the epithelial lesion and HPV. We carried out a longitudinal, descriptive study that included women of reproductive age who were diagnosed with HPV associated with low-grade squamous intraepithelial lesion (LSIL). Subjects began treatment based on GA using two routes of administration - systemic (oral) and topical (spray) - with assessments every month to determine the clinical changes of the lesions through colposcopy and Papanicolaou (Pap) smear. Simple statistics were used along with two-tailed Student's t-test; P<0.05 was considered statistically significant before and after treatment. There were 70 eligible patients, of whom 62 fulfilled the inclusion criteria. Age of subjects was 27.8±9.5 years. At the time of the study, 100% of the patients had HPV infection, 40% were associated with LSIL, and only 16% used a barrier contraceptive (condom) method. Resolution was achieved in all patients from 4 weeks of treatment initiation and improvement was achieved in the majority of patients at 12 weeks (74%) (P<0.001). However, there was persistence of LSIL in 27.7% of patients and only one patient progressed to cervical intraepithelial neoplasia (CIN) II. The use of GA proved to be effective in resolving clinical HPV lesions. For cervical lesions with epithelial changes (LSIL), treatment may be required for a longer period as with other drugs used for this

  15. Clinical response to glycyrrhizinic acid in genital infection due to human papillomavirus and low-grade squamous intraepithelial lesion.

    PubMed

    Valencia, Marcelino Hernández; Pacheco, Adia Carrillo; Quijano, Tomás Hernández; Girón, Antonio Vargas; López, Carlos Vargas

    2011-09-28

    Human papilloma virus (HPV) can infect any of the mucosal areas of the body and cause cervical cancer. Until recently, no specific treatments were available for this condition; therefore, any damaged tissue had to be removed or destroyed, which may have presented obstetrical repercussions for some women. Recently, new drugs have been developed that have shown to be effective for the cure of HPV infection. Glycyrrhizinic acid (GA) has shown fewer side effects and its systemic use makes it possible to reach difficult-to-treat lesions. The purpose of this study was to evaluate the clinical outcome of GA to eliminate the epithelial lesion and HPV. We carried out a longitudinal, descriptive study that included women of reproductive age who were diagnosed with HPV associated with low-grade squamous intraepithelial lesion (LSIL). Subjects began treatment based on GA using two routes of administration - systemic (oral) and topical (spray) - with assessments every month to determine the clinical changes of the lesions through colposcopy and Papanicolaou (Pap) smear. Simple statistics were used along with two-tailed Student's t-test; P<0.05 was considered statistically significant before and after treatment. There were 70 eligible patients, of whom 62 fulfilled the inclusion criteria. Age of subjects was 27.8±9.5 years. At the time of the study, 100% of the patients had HPV infection, 40% were associated with LSIL, and only 16% used a barrier contraceptive (condom) method. Resolution was achieved in all patients from 4 weeks of treatment initiation and improvement was achieved in the majority of patients at 12 weeks (74%) (P<0.001). However, there was persistence of LSIL in 27.7% of patients and only one patient progressed to cervical intraepithelial neoplasia (CIN) II. The use of GA proved to be effective in resolving clinical HPV lesions. For cervical lesions with epithelial changes (LSIL), treatment may be required for a longer period as with other drugs used for this

  16. Comparative effectiveness study on human papillomavirus detection methods used in the cervical cancer screening programme

    PubMed Central

    Nygård, Mari; Røysland, Kjetil; Campbell, Suzanne; Dillner, Joakim

    2014-01-01

    Objectives To compare the short-term and long-term effectiveness of human papillomavirus (HPV) tests in Norwegian Cervical Cancer Screening Programme (NCCSP). Design Nationwide register-based prospective follow-up study. Setting In 2005, the NCCSP implemented HPV testing in follow-up of unsatisfactory, atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL) cytology. Participants 19 065 women with repeat cytology and HPV test after unsatisfactory ASC-US or LSIL screening result in 2005–2009. Interventions Through individual registry linkages we observed how women were treated in the regular medical care. Main outcome measures We estimated cumulative incidence of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in 6 months and 3 years after repeat cytology and HPV test. Patients diagnosed with CIN2+ in 6 months and 3 years were assessed for initial HPV positivity. Results 5392 had ASC-US/LSIL and 13 673 had normal/unsatisfactory repeat cytology; for HPV detection 4715 used AMPLICOR HPV Test (Roche Diagnostics, Basel, Switzerland), 9162 Hybrid Capture 2 (HC2) High-Risk HPV DNA Test (QIAGEN, Gaithersburg, Maryland, USA) and 5188 PreTect HPV-Proofer (NorChip, Klokkarstua, Norway). Among those with ASC-US/LSIL repeat cytology, 3-year risk of CIN2+ was 15-fold in Amplicor/HC2-positives compared with Amplicor/HC2-negatives and sevenfold in Proofer-positives compared with Proofer-negatives; a 3-year risk of CIN2+ was 2.1% (95% CI 0.7% to 3.4%) in Amplicor-negatives and 7.2% (95% CI 5.4% to 8.9%) in Proofer-negatives. Close to 100% of patients with CIN2+ diagnosed within 6 months tested positive to HPV (all methods). Considering all patients diagnosed with CIN2+ in 3-year follow-up, 97% were initially positive in the Amplicor group and more than 94% in the HC2 group, compared with less than 80% in the Proofer group. Conclusions While the long-term evaluation of new screening routines

  17. Overexpression of the oncostatin M receptor in cervical squamous cell carcinoma cells is associated with a pro-angiogenic phenotype and increased cell motility and invasiveness.

    PubMed

    Winder, David M; Chattopadhyay, Anasuya; Muralidhar, Balaji; Bauer, Julien; English, William R; Zhang, Xiao; Karagavriilidou, Konstantina; Roberts, Ian; Pett, Mark R; Murphy, Gillian; Coleman, Nicholas

    2011-11-01

    Oncostatin M receptor (OSMR) shows frequent copy number gain and overexpression in advanced cervical squamous cell carcinoma (SCC). We used cell-based in vitro assays, RNA interference, and integrative gene expression profiling to investigate the functional significance of this observation. CaSki and SW756 were selected as representative cervical SCC cells that overexpressed OSMR, and ME180 and MS751 as cells that did not. The STAT-dependent pro-angiogenic factors VEGF-A and ID1 were rapidly induced by OSM in CaSki/SW756 but not in ME180/MS751. However, rapid induction did occur in MS751 following forced OSMR overexpression, while depleting OSMR in CaSki abrogated VEGF-A expression. Conditioned medium from both CaSki and SW756 stimulated endothelial tube formation in vitro, effects that were inhibited by depleting OSMR in the SCC cells. For both CaSki and SW756, migration in a wound healing assay and invasion through Matrigel were stimulated by OSM and consistently inhibited by OSMR depletion. The phenotype was rescued by transfection with OSMR containing a silent mutation that provided specific siRNA resistance. Overall, there was a positive correlation between OSMR levels and invasiveness. We used gene expression profiling to identify genes induced by OSM in CaSki/SW756 but not in ME180/MS751. The most prominent gene ontology category groups for the differentially expressed genes were cell motility/invasion, angiogenesis, signal transduction, and apoptosis. We also profiled 23 cervical SCC samples, identifying genes that were differentially expressed in cases with OSMR overexpression versus those without. Integration of the datasets identified 15 genes that showed consistent differential expression in association with OSMR levels in vitro and in vivo. We conclude that OSMR overexpression in cervical SCC cells provides increased sensitivity to OSM, which induces pro-malignant changes. OSMR is a potential prognostic and therapeutic target in cervical SCC. The genes

  18. Histological assessment of cervical lymph node identifies patients with head and neck squamous cell carcinoma (HNSCC): who would benefit from chemoradiation after surgery?

    PubMed

    Wan, Xiao Chloe; Egloff, Ann Marie; Johnson, Jonas

    2012-12-01

    Postoperative chemoradiation (CRT) has been shown to be more effective than postoperative radiotherapy (RT) alone in high risk head and neck squamous cell carcinoma (HNSCC) patients. Multimodality therapy is associated with more treatment related-toxicity. In this study, we assessed cervical lymph node histological characteristics to detect prognostic and predictive value differences to help guide therapeutic decision making. Retrospective analysis of Cancer Registry data. HNSCC surgical patients who had tumor resection and neck dissection at our institution from 1980 to 2008 were identified (n=1510). Multivariable Cox proportional hazards regression models were developed to identify significant predictors of three outcomes: overall survival (OS), disease-specific survival (DSS), and neck disease recurrence (NDR). Hazard ratios were estimated for the number of cervical nodal metastases and presence of extracapsular spread (ECS) by adjuvant treatment after controlling for significant covariates. Increasing number of positive nodes was significantly associated with poorer outcomes in OS, DSS, and NDR models (p<0.0001, p<0.0001, p=0.0002, respectively). OS and DSS associated with adjuvant treatment (none, RT, or CRT) were modified by number of positive nodes, ECS status, and cancer site. The presence of ECS was associated with reduced OS and DSS (p=0.077, p=0.001 respectively), but not significantly associated with NDR (p=0.179). Nodal positive patients benefited from adjuvant therapy regardless of ECS status. CRT consistently conferred a survival advantage over RT across all nodal categories, although the difference was not statistically significant. We observed a consistent survival advantage with CRT over RT for patients with positive cervical nodal metastasis, although the difference was not statistically significant. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

  19. Low frequency of human papillomavirus infection in conjunctival squamous cell carcinoma of Mexican patients

    PubMed Central

    2011-01-01

    Background The relationship between Human Papillomavirus (HPV) infection and conjunctiva cancer is controversial. HPV detection will provide more information about the role of this infectious agent in the biology of conjunctiva cancer. In the present study, DNA extracted and purified from 36 Conjunctival Squamous Cell Carcinomas (CSCC) was evaluated by PCR for HPV DNA sequences. The results were correlated with the clinical and histopathological variables. Results The results showed that HPV DNA was present in 8 CSCC samples (22%); HPV16 was the sole type detected. Significant association was found between HPV detection and the limbus tumor subtype (p = 0.03). All the samples were non-metastatic squamous cell carcinoma. Conclusions The HPV presence in CSCC from Mexican patients is not a common event. PMID:22099431

  20. Cytotoxicity of Thymus vulgaris essential oil towards human oral cavity squamous cell carcinoma.

    PubMed

    Sertel, Serkan; Eichhorn, Tolga; Plinkert, Peter K; Efferth, Thomas

    2011-01-01

    Oral cavity squamous cell carcinoma (OCSCC) accounts for 2% to 3% of all malignancies and has a high mortality rate. The majority of anticancer drugs are of natural origin. However, it is unknown whether the medicinal plant Thymus vulgaris L. (thyme) is cytotoxic towards head and neck squamous cell carcinoma (HNSCC). Cytotoxicity of thyme essential oil was investigated on the HNSCC cell line, UMSCC1. The IC₅₀ of thyme essential oil extract was 369 μg/ml. Moreover, we performed pharmacogenomics analyses. Genes involved in the cell cycle, cell death and cancer were involved in the cytotoxic activity of thyme essential oil at the transcriptional level. The three most significantly regulated pathways by thyme essential oil were interferon signaling, N-glycan biosynthesis and extracellular signal-regulated kinase 5 (ERK5) signaling. Thyme essential oil inhibits human HNSCC cell growth. Based on pharmacogenomic approaches, novel insights into the molecular mode of anticancer activity of thyme are presented.

  1. Imaging and tracking HIV viruses in human cervical mucus

    NASA Astrophysics Data System (ADS)

    Boukari, Fatima; Makrogiannis, Sokratis; Nossal, Ralph; Boukari, Hacène

    2016-09-01

    We describe a systematic approach to image, track, and quantify the movements of HIV viruses embedded in human cervical mucus. The underlying motivation for this study is that, in HIV-infected adults, women account for more than half of all new cases and most of these women acquire the infection through heterosexual contact. The endocervix is believed to be a susceptible site for HIV entry. Cervical mucus, which coats the endocervix, should play a protective role against the viruses. Thus, we developed a methodology to apply time-resolved confocal microscopy to examine the motion of HIV viruses that were added to samples of untreated cervical mucus. From the images, we identified the viruses, tracked them over time, and calculated changes of the statistical mean-squared displacement (MSD) of each virus. Approximately half of tracked viruses appear constrained while the others show mobility with MSDs that are proportional to τα+ν2τ2, over time range τ, depicting a combination of anomalous diffusion (0<α<0.4) and flow-like behavior. The MSD data also reveal plateaus attributable to possible stalling of the viruses. Although a more extensive study is warranted, these results support the assumption of mucus being a barrier against the motion of these viruses.

  2. Human Papillomavirus in Brazilian women with and without cervical lesions

    PubMed Central

    2011-01-01

    Background Human Papillomavirus (HPV) high-risk (HR) types are the causal factor for cervical cancer and premalignant dysplasia. Data on frequency of HPV types provide a basis to design and evaluate HPV prevention programs. Taking into account the heterogeneity of HPV types across and within populations this study aims to access the HPV frequency in Brazilian women. Results We identified 24 different types of HPV, including a Betapapillomavirus and a likely new type, previously reported, from 132 women positive for the virus analysed by Hybrid Capture II assay. These women were infected by a single or multiple HPV types and 142 HPV strains were identified. HR types were found in 75% of women and HPV types 16, 18, 45, 58, and 66 had the highest frequency. Significant differences in frequency of HR HPV types were found for presence of cervical lesions, and for different HPV species and women age. Conclusions Compared with previous studies in Brazil, our data indicated differences in frequency and HPV type diversity, a significant association of other HR-types but HPV16 and 18 and cervical lesions, and a trend for distinct distribution of HPV types by age. PMID:21208414

  3. APOPTOSIS INDUCTION OF EPIFRIEDELINOL ON HUMAN CERVICAL CANCER CELL LINE.

    PubMed

    Yang, Jie; Fa, Jing; Li, Bingxing

    2017-01-01

    Present investigation evaluates the antitumor activity of epifriedelinol for the management of cervical cancer by inducing process of apoptosis. Human Cervical Cancer Cell Line, C33A and HeLa were selected for study and treated with epifriedelinol at a concentration of (50-1000 µg/ml). Cytotoxicity of epifriedelinol was estimated by MTT assay and induction of apoptosis was assessed by estimating the activity of caspase 3, 8 and 9 enzyme, apoptosis assay and translocation of cytochrome c. Moreover an expression of several proteins that plays role in the apoptosis process was estimated by western blot method. Result of the study suggested that treatment with epifriedelinol significantly decrease the viability count of cancerous cell in a dose perndent manner and also enhances the formation of oligonucleosome in both the cell lines. However activity of caspase enzymes and translocation of cytochrome c were enhanced after treatment with epifriedelinol. It was also observed that epifriedelinol treatment alters the ratio of pro-apoptotic to anti-apoptotic proteins and enhances the expressions of inhibitor of apoptosis proteins (IAP). Result of our study proves the anticancer activity of epifriedelinol in cervical cancer by inducing apoptosis as treatment with it enhances the production of oligonucleosomes, translocation of cytochrome c and activity caspase enzymes.

  4. Human papillomavirus genotypes and cervical cancer in northeast Thailand.

    PubMed

    Natphopsuk, Sitakan; Settheetham-Ishida, Wannapa; Pientong, Chamsai; Sinawat, Supat; Yuenyao, Pissamai; Ishida, Takafumi; Settheetham, Dariwan

    2013-01-01

    Human papillomavirus (HPV) is a major cause of cervical cancer. More than 100 HPV genotypes have been identified; however the distribution varies geographically and according to ethnicity. The purpose of this study was to investigate the prevalence and distribution of HPV subtypes among Northeast Thai women. Subjects included 198 cases of SCCA and 198 age-matched, healthy controls. HPV-DNA was amplified by PCR using the consensus primers GP5+/6+ system followed by reverse line blot hybridization genotyping. The prevalence of high-risk HPV infection was 21 (10.1%) and 152 (76.8%) in the controls and in the cases, respectively. High-risk HPV significantly increased the risk for cervical cancer with an OR of 42.4 (95%CI: 22.4-81.4, p<0.001) and an adjusted OR of 40.7-fold (95%CI: 21.5-76.8, p <0.001). HPV-16 was the most prevalent HPV type in the SCCA (56.2%) followed by HPV-58 (17.8%) and HPV-18 (13.6%); whereas HPV-58 (46.4%) was a prominent genotype in the controls followed by HPV-16 (39.3%) and unidentified HPV types (25.0%). These findings indicate that HPV infection remains a critical risk factor for SCCA; particularly, HPV-16, HPV-58 and HPV-18. In order to eradicate cervical cancer, sustained health education, promoted use of prophylactics and a HPV-58 vaccine should be introduced in this region.

  5. Introduction of liquid-based cytology and human papillomavirus testing in cervical cancer screening in Luxembourg.

    PubMed

    Latsuzbaia, Ardashel; Hebette, Gaëtan; Fischer, Marc; Arbyn, Marc; Weyers, Steven; Vielh, Philippe; Schmitt, Fernando; Mossong, Joël

    2017-05-01

    In 2014, liquid-based cytology with HPV triage replaced conventional cytology. The aim of our study was to compare conventional and liquid-based cytology (LBC), estimate the prevalence of abnormal cervical cytology and high risk HPV (hrHPV) infection and their correlation, among screened women in Luxembourg. Between the first January 2013 and 31st December 2015, 315,868 cervical samples from 150,815 women (mean age 42.2 years) were investigated by the national cytology laboratory. Slides were prepared and screened according to European Guidelines. All cytological results were classified according to the Bethesda 2001 system terminology. The prevalence of abnormal cervical lesions was as follows: atypical squamous cells of undetermined significance (ASC-US), 1.3%; low-grade squamous intraepithelial lesion (LSIL), 1.9%; high-grade squamous intraepithelial lesion (HSIL), 0.4%. The detection rate of cytological lesions was significantly higher with LBC than with conventional cytology. Based on 11,838 samples with concomitant cytology and HPV testing, hrHPV was detected in 9.5, 45.3, 70.0, and 92.6% of women with negative cytology, ASC-US, LSIL, and HSIL, respectively. More cervical lesions were identified using LBC compared to conventional cytology. HrHPV infection was correlated with the severity of intraepithelial lesions. The current findings provide important information to evaluate the prevention of cervical cancer in Luxembourg and for monitoring the future impact of HPV vaccination. Diagn. Cytopathol. 2017;45:384-390. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  6. Cervicitis

    MedlinePlus

    ... uterine lining and the fallopian tubes, resulting in pelvic inflammatory disease (PID), an infection of the female reproductive organs that can cause fertility problems if left untreated. Cervicitis can also ... incidentally during a routine pelvic exam and Pap test and may not require ...

  7. Characterization and functional analysis of the expression of intercellular adhesion molecule-1 in human papillomavirus-related disease of cervical keratinocytes.

    PubMed Central

    Coleman, N.; Greenfield, I. M.; Hare, J.; Kruger-Gray, H.; Chain, B. M.; Stanley, M. A.

    1993-01-01

    We have investigated the expression of intercellular adhesion molecule-1 (ICAM-1) in squamous neoplasia of the cervix and have noted a significant induction of the molecule in high-grade intra-epithelial lesions. Using monolayer and organotypic in vitro tissue culture systems, we have shown that there is no constitutive ICAM-1 expression on cervical keratinocytes immortalized but not transformed by human papillomavirus type 16, whereas two human papillomaviruses type 16 containing and fully transformed cervical keratinocyte lines do constitutively express the molecule. All cell types, including human papillomavirus-negative normal cervical keratinocytes, can be induced to up-regulate their expression of ICAM-1 by pro-inflammatory cytokines such as interferon-gamma. In addition, we have used an in vitro adhesion assay to show that ICAM-1:lymphocyte function antigen-1 interaction is functionally important in lymphocyte binding to cervical keratinocytes, suggesting a role for ICAM-1 in retaining and enabling functional activity of lymphocytes in the cervix in intraepithelial neoplasia. Images Figure 1 Figure 2 Figure 5 Figure 9 PMID:8102029

  8. Expression of chemokine receptor CCR7 is associated with cervical lymph node metastasis of oral squamous cell carcinoma.

    PubMed

    Shang, Zheng Jun; Liu, Ke; Shao, Zhe

    2009-06-01

    Tumor cell migration and metastasis share many similarities with leukocyte trafficking, which is critically regulated by chemokines and their receptors. The present study was designed to examine the expression of chemokine receptor CCR7 in oral squamous cell carcinoma (OSCC), and to investigate the possible role of CCR7/CCL21 interaction in neck lymph node metastasis of OSCC. By using immunohistochemistry, RT-PCR and Western Blot, expression of CCR7 was examined in 85 cases of oral squamous cell carcinoma, and Tca8113 and ACC cell lines. CCL21-mediated cell migration was assayed in Matrigel-coated chemotaxis chamber. In vitro adhesion assay was shown for banding of tumor cell lines to submandibular lymph nodes with or without anti-CCR7 antibody treatment. Immunohistochemical staining showed 65.9% (56/85) of positive CCR7 expression in OSCC tissues. CCR7 expression was significantly higher in patients with lymph node metastasis compared with those without lymph node metastasis (P=0.015) and was also associated with tumor size (P=0.014), and clinical stage (P=0.009). RT-PCR and Western Blot also confirmed positive CCR7 expression in oral squamous cell carcinoma and Tca8113 cell line, and negative CCR7 expression in normal oral mucosa and ACC cell line. CCL21 stimulation increased the ability of CCR7-positive Tca8113 cells passing through the Matrigel membrane. CCR7-positive Tca8113 cells also showed stronger adhesion to lymph nodes, which could be partly blocked by anti-CCR7 antibody incubation. These results indicated that the chemotactic CCR7/CCL21 interaction may be a possible mechanism for induction of directional lymph node metastasis by oral squamous cell carcinoma.

  9. Evidence regarding human papillomavirus testing in secondary prevention of cervical cancer.

    PubMed

    Arbyn, Marc; Ronco, Guglielmo; Anttila, Ahti; Meijer, Chris J L M; Poljak, Mario; Ogilvie, Gina; Koliopoulos, George; Naucler, Pontus; Sankaranarayanan, Rengaswamy; Peto, Julian

    2012-11-20

    More than ever, clinicians need regularly updated reviews given the continuously increasing amount of new information regarding innovative cervical cancer prevention methods. A summary is given from recent meta-analyses and systematic reviews on 3 possible clinical applications of human papillomavirus (HPV) testing: triage of women with equivocal or low-grade cytologic abnormalities; prediction of the therapeutic outcome after treatment of cervical intraepithelial neoplasia (CIN) lesions, and last not but not least, primary screening for cervical cancer and pre-cancer. Consistent evidence is available indicating that HPV-triage with the Hybrid Capture(®) 2 assay (Qiagen Gaithersburg, Inc., MD, USA [previously Digene Corp.] (HC2) is more accurate (higher sensitivity, similar specificity) than repeat cytology to triage women with equivocal Pap smear results. Several other tests show at least similar accuracy but mRNA testing with the APTIMA(®) (Gen-Probe Inc., San Diego, CA, USA) test is similarly sensitive but more specific compared to HC2. In triage of low-grade squamous intraepithelial lesions (LSIL), HC2 is more sensitive but its specificity is substantially lower compared to repeat cytology. The APTIMA(®) test is more specific than HC2 without showing a loss in sensitivity. Identification of DNA of HPV types 16 and/or 18, or RNA from the five most carcinogenic HPV types allow selecting women at highest risk for CIN3+ but the sensitivity and negative predictive value of these markers are lower than full-range high-risk HPV (hrHPV) testing. After conservative treatment of cervical pre-cancer, HPV testing picks up more quickly, with higher sensitivity and not lower specificity, residual or recurrent high-grade CIN than follow-up cytology. Primary screening for hrHPV generally detects more CIN2, CIN3 or cancer compared to cytology at cut-off atypical squamous cells of undetermined significance (ASC-US) or LSIL, but is less specific. Combined HPV and cytology

  10. Targeting the eIF4E/β-catenin axis sensitizes cervical carcinoma squamous cells to chemotherapy

    PubMed Central

    Xu, Hai; Wang, Zhiyin; Xu, Lang; Mo, Guoyan; Duan, Gangfeng; Wang, Yali; Sun, Zhengang; Chen, Hao

    2017-01-01

    Chemotherapy has improved the clinical outcomes of cervical cancer patients. However, patients develop chemoresistance, whose underlying mechanisms are not well understood. In this study, we investigated the phosphorylation levels of eukaryotic translation initiation factor 4E (eIF4E) in cervical cancer cells subjected to chemotherapy. Results showed that chemotherapeutic drugs significantly increased eIF4E phosphorylation at S209 in HeLa and SiHa cells. Upregulation of phosphorylated eIF4E (p-eIF4E) levels has also been shown in cisplatin-resistant HeLa cells and has been observed to be a common response of cervical cancer patients undergoing chemotherapy. We further showed that chemotherapeutic drugs increase β-catenin activity and mRNA levels of Wnt/β-catenin target genes in cervical cancer cells but not in eIF4E-depleted cells, suggesting that chemotherapeutic drugs activate Wnt/β-catenin signaling in an eIF4E-dependent manner. Inhibiting eIF4E via siRNA knockdown or Wnt/β-catenin using the Wnt inhibitor pyrvinium effectively enhanced the anti-proliferative and pro-apoptotic effects of cisplatin in cervical cancer cells both in vitro and in vivo. Our findings demonstrate that eIF4E/β-catenin signaling plays a positive regulatory role in the resistance of cervical cancer cell to chemotherapy and thus highlight the therapeutic value of eIF4E or β-catenin inhibition in overcoming chemoresistance. PMID:28386346

  11. Control of growth and squamous differentiation in normal human bronchial epithelial cells by chemical and biological modifiers and transferred genes.

    PubMed Central

    Pfeifer, A M; Lechner, J F; Masui, T; Reddel, R R; Mark, G E; Harris, C C

    1989-01-01

    The majority of human lung cancers arise from bronchial epithelial cells. The normal pseudostratified bronchial epithelium is composed of basal, mucous, and ciliated cells. This multi-differentiated epithelium usually responds to xenobiotics and physical injury by undergoing basal cell hyperplasia, mucous cell hyperplasia, and squamous metaplasia. One step of the multistage process of carcinogenesis is thought to involve aberrations in control of the squamous metaplastic processes. Decreased responsiveness to regulators of terminal squamous differentiation may confer a selective clonal expansion advantage to an initiated cell. We studied the effects of endogenous [e.g., transforming growth factor beta 1 (TGF-beta 1) and serum] and exogenous [e.g., 12-O-tetradecanoyl-13-phorbol-acetate (TPA), tobacco smoke condensate, and aldehydes] modifiers of normal human bronchial epithelial (NHBE) cell in a serum-free culture system. NHBE cells are growth inhibited by all of these compounds and induced to undergo squamous differentiation by TGF-beta 1 or TPA. In contrast, lung carcinoma cell lines are relatively resistant to inducers of terminal squamous differentiation which may provide them with a selective growth advantage. Chemical agents and activated protooncogenes (ras,raf,myc) altered the response to endogenous and exogenous inducers of squamous differentiation and caused extended cellular lifespan, aneuploidy, and/or tumorigenicity. The data suggest a close relationship between dysregulation of terminal differentiation pathways and neoplastic transformation of human bronchial epithelial cells. PMID:2538323

  12. Immunologic consequences of signal transducers and activators of transcription 3 activation in human squamous cell carcinoma.

    PubMed

    Albesiano, Emilia; Davis, Meghan; See, Alfred P; Han, James E; Lim, Michael; Pardoll, Drew M; Kim, Young

    2010-08-15

    Paracrine cross-talk between tumor cells and immune cells within the tumor microenvironment underlies local mechanisms of immune evasion. Signal transducer and activator of transcription 3 (STAT3), which is constitutively activated in diverse cancer types, is a key regulator of cytokine and chemokine expression in murine tumors, resulting in suppression of both innate and adaptive antitumor immunity. However, the immunologic effects of STAT3 activation in human cancers have not been studied in detail. To investigate how STAT3 activity in human head and neck squamous cell carcinoma (HNSCC) might alter the tumor microenvironment to enable immune escape, we used small interfering RNA and small-molecule inhibitors to suppress STAT3 activity. STAT3 inhibition in multiple primary and established human squamous carcinoma lines resulted in enhanced expression and secretion of both proinflammatory cytokines and chemokines. Although conditioned medium containing supernatants from human HNSCC inhibited lipopolysaccharide-induced dendritic cell activation in vitro, supernatants from STAT3-silenced tumor cells reversed this immune evasion mechanism. Moreover, supernatants from STAT3-silenced tumor cells were able to stimulate the migratory behavior of lymphocytes from human peripheral blood in vitro. These results show the importance of STAT3 activation in regulating the immunomodulatory mediators by human tumors and further validate STAT3 as a promising target for therapeutic intervention. (c)2010 AACR.

  13. DNA probes for papillomavirus strains readied for cervical cancer screening

    SciTech Connect

    Merz, B.

    1988-11-18

    New Papillomavirus tests are ready to come to the aid of the standard Papanicolauo test in screening for cervical cancer. The new tests, which detect the strains of human papillomavirus (HPV) most commonly associated with human cervical cancer, are designed to be used as an adjunct to rather than as a replacement for the Papanicolaou smears. Their developers say that they can be used to indicated a risk of developing cancer in women whose Papanicolaou smears indicate mild cervical dysplasia, and, eventually, to detect papillomavirus infection in normal Papanicolaou smears. The rationale for HPV testing is derived from a growing body of evidence that HPV is a major factor in the etiology of cervical cancer. Three HPV tests were described recently in Chicago at the Third International Conference on Human Papillomavirus and Squamous Cervical Cancer. Each relies on DNA probes to detect the presence of papillomavirus in cervical cells and/or to distinguish the strain of papillomavirus present.

  14. Interest of human papillomavirus DNA quantification and genotyping in paired cervical and urine samples to detect cervical lesions.

    PubMed

    Ducancelle, A; Legrand, M C; Pivert, A; Veillon, P; Le Guillou-Guillemette, H; De Brux, M A; Beby-Defaux, A; Agius, G; Hantz, S; Alain, S; Catala, L; Descamps, P; Postec, E; Caly, H; Charles-Pétillon, F; Labrousse, F; Lunel, F; Payan, C

    2014-08-01

    Cervical cancer is caused by persistent infection with high-risk human papillomavirus (HR-HPV). Conventional human papillomavirus (HPV) testing requires cervical sampling. However, vaginal and urine self-sampling methods are more acceptable for patients and result in increased participation when they are available in screening programs. In this context, we have developed a non-invasive screening method via the detection of HPV DNA in urine samples. To compare HPV viral loads and genotypes in paired cervical and urine samples, and to assess correlation between virological and cytological results in women seeking gynecological consultation. Paired urine and cervical specimens were collected and analyzed from 230 of 245 women participating in the previously described prospective PapU study. HPV DNA detection and quantification were performed using a real-time PCR method with short fragment PCR primers. Genotyping was carried out using the INNO-LiPA HPV genotyping assay. The prevalence of HPV in the 230 paired urine and cervical smear samples was 42 and 49 %, respectively. Overall agreement for HPV positivity and negativity between the paired samples was 90 % (κ = 0.80). High HPV viral load in both cervical and urine samples was associated with cytological abnormalities. HPV-positive women were mostly infected with HR-HPV types. The agreement between high- and low-risk HPV (LR-HPV) detection in both samples was 97 % (κ = 0.95 for HR-HPV and κ = 0.97 for LR-HPV). High concordance rates for HPV-DNA quantification and high/low-risk HPV genotyping in paired urine/cervical samples suggest that urinary HPV DNA testing could be useful for cervical lesion screening.

  15. Human Papillomavirus Detection from Human Immunodeficiency Virus-Infected Colombian Women's Paired Urine and Cervical Samples

    PubMed Central

    Munoz, Marina; Camargo, Milena; Soto-De Leon, Sara C.; Sanchez, Ricardo; Parra, Diana; Pineda, Andrea C.; Sussmann, Otto; Perez-Prados, Antonio; Patarroyo, Manuel E.; Patarroyo, Manuel A.

    2013-01-01

    Infection, coinfection and type-specific human papillomavirus (HPV) distribution was evaluated in human immunodeficiency virus (HIV)-positive women from paired cervical and urine samples. Paired cervical and urine samples (n = 204) were taken from HIV-positive women for identifying HPV-DNA presence by using polymerase chain reaction (PCR) with three generic primer sets (GP5+/6+, MY09/11 and pU1M/2R). HPV-positive samples were typed for six high-risk HPV (HR-HPV) (HPV-16, -18, -31, -33, -45 and -58) and two low-risk (LR-HPV) (HPV-6/11) types. Agreement between paired sample results and diagnostic performance was evaluated. HPV infection prevalence was 70.6% in cervical and 63.2% in urine samples. HPV-16 was the most prevalent HPV type in both types of sample (66.7% in cervical samples and 62.0% in urine) followed by HPV-31(47.2%) in cervical samples and HPV-58 (35.7%) in urine samples. There was 55.4% coinfection (infection by more than one type of HPV) in cervical samples and 40.2% in urine samples. Abnormal Papanicolau smears were observed in 25.3% of the women, presenting significant association with HPV-DNA being identified in urine samples. There was poor agreement of cervical and urine sample results in generic and type-specific detection of HPV. Urine samples provided the best diagnosis when taking cytological findings as reference. In conclusion including urine samples could be a good strategy for ensuring adherence to screening programs aimed at reducing the impact of cervical cancer, since this sample is easy to obtain and showed good diagnostic performance. PMID:23418581

  16. Human papillomavirus detection from human immunodeficiency virus-infected Colombian women's paired urine and cervical samples.

    PubMed

    Munoz, Marina; Camargo, Milena; Soto-De Leon, Sara C; Sanchez, Ricardo; Parra, Diana; Pineda, Andrea C; Sussmann, Otto; Perez-Prados, Antonio; Patarroyo, Manuel E; Patarroyo, Manuel A

    2013-01-01

    Infection, coinfection and type-specific human papillomavirus (HPV) distribution was evaluated in human immunodeficiency virus (HIV)-positive women from paired cervical and urine samples. Paired cervical and urine samples (n = 204) were taken from HIV-positive women for identifying HPV-DNA presence by using polymerase chain reaction (PCR) with three generic primer sets (GP5+/6+, MY09/11 and pU1M/2R). HPV-positive samples were typed for six high-risk HPV (HR-HPV) (HPV-16, -18, -31, -33, -45 and -58) and two low-risk (LR-HPV) (HPV-6/11) types. Agreement between paired sample results and diagnostic performance was evaluated. HPV infection prevalence was 70.6% in cervical and 63.2% in urine samples. HPV-16 was the most prevalent HPV type in both types of sample (66.7% in cervical samples and 62.0% in urine) followed by HPV-31(47.2%) in cervical samples and HPV-58 (35.7%) in urine samples. There was 55.4% coinfection (infection by more than one type of HPV) in cervical samples and 40.2% in urine samples. Abnormal Papanicolau smears were observed in 25.3% of the women, presenting significant association with HPV-DNA being identified in urine samples. There was poor agreement of cervical and urine sample results in generic and type-specific detection of HPV. Urine samples provided the best diagnosis when taking cytological findings as reference. In conclusion including urine samples could be a good strategy for ensuring adherence to screening programs aimed at reducing the impact of cervical cancer, since this sample is easy to obtain and showed good diagnostic performance.

  17. The Prevalence of Human Papilloma Virus in Esophageal Squamous Cell Carcinoma

    PubMed Central

    Noori, Sadat; Monabati, Ahmad; Ghaderi, Abbasali

    2012-01-01

    Background: Carcinomas of esophagus, mostly squamous cell carcinomas, occur throughout the world. There are a number of suspected genetic or environmental etiologies. Human papilloma virus (HPV) is said to be a major etiology in areas with high incidence of esophageal carcinoma, while it is hardly detectable in low incidence regions. This study was designed to evaluate the prevalence of HPV in esophageal squamous cell carcinoma (ESCC) cases diagnosed in Pathology Department, Medical School, Shiraz University of Medical Sciences. Methods: DNA material for PCR amplification of HPV genome was extracted from formalin-fixed paraffin-embedded tissue blocks of 92 cases of ESCC, diagnosed during 20 years from 1982 to 2002. Polymerase chain reaction was performed for amplification and detection of common HPV and type specific HPV-16 and HPV-18 genomic sequences in the presence of positive control (HPV-18 and HPV positive biopsies of uterine exocervix) and additional internal controls i.e. beta-globin and cytotoxic T lymphocyte antigen 4 (CTLA4). Result: Good amplification of positive control and internal controls was observed. However, no amplification of HPV genome was observed. Conclusion: There is no association between HPV infection and the development of esophageal squamous cell carcinoma in the cases evaluated. PMID:23115442

  18. Prevalence of human papillomavirus in women without cervical cancer: a population-based study in Eastern India.

    PubMed

    Dutta, Sankhadeep; Begum, Rakiba; Mazumder Indra, Dipanjana; Mandal, Shyam Sundar; Mondal, Ranajit; Biswas, Jaydip; Dey, Bindu; Panda, Chinmay Kumar; Basu, Partha

    2012-03-01

    Despite the high incidence of cervical cancer, population-based data on prevalence of human papillomavirus (HPV) are limited in India. This study aimed to evaluate the prevalence of any HPV type and type-specific prevalence of HPV 16/18 in women without cervical cancer. HPV viral load was measured and correlated with cytologic abnormalities of the cervix. A total of 2501 women between 25 and 65 years of age and without cervical cancer were screened by pap smear cytology. HPV DNA was detected from cervical scrapes by nested polymerase chain reaction. Detection of HPV 16/18 was carried out by polymerase chain reaction using type-specific primers and was confirmed by Southern hybridization. Viral load was determined by absolute real-time polymerase chain reaction. Population prevalence of any HPV was found to be 9.9%. The risk of HPV infection was higher in women aged 25 to 34 years (odds ratio, 1.11), in married women below 20 years of age (odds ratio, 1.80), and in women with parity ≥4 (odds ratio, 1.04). Prevalence of HPV 18 (1.4%) was greater than that of HPV 16 (0.6%) in the overall screened population. High-grade squamous intraepithelial lesion cytology was more frequent in women infected with HPV 16 than in those infected with HPV 18 and other types. A gradual increase in HPV copy numbers was associated with progressive cytologic severity. In this study, HPV prevalence is comparable to HPV prevalence reported by other studies among Indian and Asian women. Although the prevalence of HPV 18 was more than that of HPV 16, type 16 infection was associated with higher oncogenicity.

  19. Impact of Possibly Oncogenic High-Risk Human Papillomavirus (HPV) Types in Triage for ASC-US Cervical Cytology Results.

    PubMed

    Amarosa, Emily J; Winer, Rachel L; Hong, Karen J; Mao, Constance

    2015-10-01

    Current guidelines recommend including 13 or 14 high-risk human papillomavirus (HPV) types for triage of atypical squamous cells of undetermined significance (ASC-US) cervical cytology; however, at least 13 additional types are considered possibly oncogenic. We evaluated the effect of including possibly oncogenic HPV types in the test panel. Outcomes for all women 30 years or older with ASC-US and positive HPV testing who underwent colposcopic biopsy at University of Washington Medical Center-affiliated clinics between 2010 and 2011 were reviewed. We compared biopsy results between cases that were HPV positive for 1 or more of 13 possibly oncogenic types only (26/53/55/62/64/67/69/71/73/82/83/84/IS39) versus 1 or more of the 14 established high-risk types (16/18/31/33/35/39/45/51/52/56/58/59/66/68). We used the Fisher exact test to compare cervical intraepithelial neoplasia grade 2 or higher (CIN2+) diagnoses between HPV risk groups. Three hundred twenty-six ASC-US HPV-positive cervical cytology results were identified, with 170 that were linked to subsequent cervical biopsy results. Among 51 cases positive for possibly oncogenic types only, 31 (61%) had no neoplasia, 20 (39%) had CIN1, and none had CIN2+. Among 119 controls positive for at least one established high-risk type, 64 (53%) had no neoplasia, 42 (35%) had CIN1, and 13 (11%) had CIN2+ (p = .01 for the comparison of CIN2+ diagnoses between groups). The inclusion of possibly oncogenic types in the HPV test panel led to an additional 51 colposcopy biopsies (33% increase), with no additional cases of CIN 2+. Our results suggest that including possibly oncogenic HPV types increases the number of colposcopy biopsies with minimal improvements in detection of CIN2 +.

  20. Genital Tract HIV RNA Levels and Their Associations with Human Papillomavirus Infection and Risk of Cervical Pre-Cancer

    PubMed Central

    GHARTEY, Jeny; KOVACS, Andrea; BURK, Robert D.; MASSAD, L. Stewart; MINKOFF, Howard; XIE, Xianhong; D’SOUZA, Gypsyamber; XUE, Xiaonan; WATTS, D. Heather; LEVINE, Alexandra M.; EINSTEIN, Mark H.; COLIE, Christine; ANASTOS, Kathryn; ELTOUM, Isam-Eldin; HEROLD, Betsy C.; PALEFSKY, Joel M.; STRICKLER, Howard D.

    2014-01-01

    Objective Plasma HIV RNA levels have been associated with risk of human papillomavirus (HPV) and cervical neoplasia in HIV-seropositive women. However, little is known regarding local genital tract HIV RNA levels and their relation with cervical HPV and neoplasia. Design/Methods In an HIV-seropositive women’s cohort with semi-annual follow-up, we conducted a nested case-control study of genital tract HIV RNA levels and their relation with incident high-grade squamous intraepithelial lesions sub-classified as severe (severe HSIL), as provided for under the Bethesda 2001 classification system. Specifically, 66 incident severe HSIL were matched to 130 controls by age, CD4+ count, HAART use, and other factors. We also studied HPV prevalence, incident detection, and persistence in a random sample of 250 subjects. Results Risk of severe HSIL was associated with genital tract HIV RNA levels (odds ratio comparing HIV RNA ≥ the median among women with detectable levels versus undetectable [ORVL] 2.96; 95% CI: 0.99–8.84; Ptrend=0.03). However, this association became non-significant (Ptrend=0.51) following adjustment for plasma HIV RNA levels. There was also no association between genital tract HIV RNA levels and the prevalence of any HPV or oncogenic HPV. However, the incident detection of any HPV (Ptrend=0.02) and persistence of oncogenic HPV (Ptrend=0.04) were associated with genital tract HIV RNA levels, after controlling plasma HIV RNA levels. Conclusion These prospective data suggest that genital tract HIV RNA levels are not a significant independent risk factor for cervical pre-cancer in HIV-seropositive women, but leave open the possibility that they may modestly influence HPV infection, an early stage of cervical tumoriogenesis. PMID:24694931

  1. Characterization of genomic changes in the cervical pre-cancerous lesions and tumors induced by different types of human papillomaviruses.

    PubMed

    Grozdanov, Petar; Hadjidekova, Savina; Dimova, Ivanka; Nikolova, Ivanka; Toncheva, Draga; Ganchev, Gancho; Zlatkov, Victor; Galabov, Angel S

    2016-09-01

    Cervical carcinoma is the second most common malignancy among women in both incidence and mortality. Although much is known about the etiology and treatment of cervical cancer, the role of genetic alterations in the multistep pathway of cervical tumorigenesis is largely unknown. The aim of this study was to characterize the genomic changes in the cervical pre-cancerous lesions and tumors, induced by different types of human papillomaviruses. In this research was used the BlueGnome CytoChip oligo 2 × 105 K microarray for whole-genome oligo-array CGH. Microarray CGH analysis of 40 specimens was carried out-12 specimens from patients with early-stage squamous cell carcinomas; 19 specimens from patients with mild to moderate dysplasia and 9 with severe dysplasia. First we performed microarray CGH analysis of five DNA pools which contained the DNA from homogeneous groups of patients. The results revealed presence of micro chromosomal aberrations in chromosome region 14q11.2. According to the genome database these aberrations represent polymorphisms. Microarray analysis of DNA from 9 separate carcinoma lesions revealed a total of 26 aberrations in 14 chromosomes of nine patients. Our results showed the advantages of high-resolution chips in the clinical diagnosis of patients with cancerous and precancerous lesions caused by viral infection with HPV, but also highlight the need for extensive population studies revealing the molecular nature and clinical significance of different CNVs and the creation of detailed maps of variations in the Bulgarian population. This would facilitate extremely precise interpretation of specific genomic imbalances in the clinical aspect.

  2. A reference map of human nasopharyngeal squamous carcinoma proteome.

    PubMed

    Li, Feng; Xiao, Zhiqiang; Zhang, Pengfei; Li, Jianling; Li, Maoyu; Feng, Xueping; Guan, Yongjun; Chen, Zhuchu

    2007-05-01

    In order to conduct a comparative proteomics study of human nasopharyngeal carcinoma (NPC) to understand the molecular mechanisms that participate in the formation of NPC, the two-dimensional gel electrophoresis (2-DE) reference map of human NPC tissue proteome was described. To provide a high level of reproducibility between gels and accurately array each protein expressed in NPC tissue proteome, the two-dimensional polyacrylamide gel electrophoresis system, modified colloidal Coomassie Brilliant Blue staining method and ImageMaster 2D Platinum image analysis software were used. The NPC 2-DE maps show that high quality and good reproducibility of the 2-DE gel pattern was attained. An average total of 1,100 protein spots were separated by 2-DE, visualized by a modified colloidal Coomassie Brilliant Blue staining method. A synthesized 2-DE reference gel was acquired after detailed analysis of the NPC 2-DE gel maps, and 216 medium to high abundant spots were identified as landmark spots of NPC 2-DE gel, which expressed on >75% of gels. To provide an unambiguous identification of the landmark spots in gels, MALDI-TOF, ESI-Q-TOF mass spectrometry and database search were used to identify the proteins expressed in NPC tissue proteome. Between the 216 landmark spots, all proteins were identified with MALDI-TOF at first, 41 of which were identified with both MALDI-TOF and ESI-Q-TOF. All identified proteins were classified in terms of their subcellular localization and physiological function with information from SWISS-PROT and NCBI websites. According to our knowledge this is the first 2-DE reference map of human NPC. This reference map will serve as a basis for further studies of human NPC and the reference map data will be used to expand the proteome database of human NPC, which can be accessed in our website (http://www.xyproteomics.org/).

  3. Human papilloma virus infection and cervical cytomorphological changing among intrauterine contraception users.

    PubMed

    Frega, A; Manzara, F; Schimberni, M; Guarino, A; Catalano, A; Bianchi, P; Marziani, R; Cozza, G; Milazzo, G N; French, D; Caserta, D

    2016-09-01

    The increased use of the intrauterine contraception (IUC) in female population and its probable relationship with cervical squamous intraepithelial lesions and cervical cancer make necessary clarify the possible interaction between the device and the pre-neoplastic lesions. Seven hundred and eighty-nine patients users of IUC and 1491 patients ever users of IUC were followed every 6 months for 3 years. Each clinical control included Papanicolau test, colposcopy, HPV-DNA test and HPV-mRNA test. Also, in patients IUC users we analyzed the type of device, years of use and average age. Cytological sampling, histological examination, HPV-DNA test and HPV-mRNA test showed that there are not significantly differences between patients with or without IUC. None difference arose regarding persistence and progression between patients IUC users and IUC no users, for this reason, intrauterine contraception does not seem to be a co-causal factor in the possible development of cervical cancer.

  4. Identification of distinct layers within the stratified squamous epithelium of the adult human true vocal fold.

    PubMed

    Dowdall, Jayme R; Sadow, Peter M; Hartnick, Christopher; Vinarsky, Vladimir; Mou, Hongmei; Zhao, Rui; Song, Phillip C; Franco, Ramon A; Rajagopal, Jayaraj

    2015-09-01

    A precise molecular schema for classifying the different cell types of the normal human vocal fold epithelium is lacking. We hypothesize that the true vocal fold epithelium has a cellular architecture and organization similar to that of other stratified squamous epithelia including the skin, cornea, oral mucosa, and esophagus. In analogy to disorders of the skin and gastrointestinal tract, a molecular definition of the normal cell types within the human vocal fold epithelium and a description of their geometric relationships should serve as a foundation for characterizing cellular changes associated with metaplasia, dysplasia, and cancer. Qualitative study with adult human larynges. Histologic sections of normal human laryngeal tissue were analyzed for morphology (hematoxylin and eosin) and immunohistochemical protein expression profile, including cytokeratins (CK13 and CK14), cornified envelope proteins (involucrin), basal cells (NGFR/p75), and proliferation markers (Ki67). We demonstrated that three distinct cell strata with unique marker profiles are present within the stratified squamous epithelium of the true vocal fold. We used these definitions to establish that cell proliferation is restricted to certain cell types and layers within the epithelium. These distinct cell types are reproducible across five normal adult larynges. We have established that three layers of cells are present within the normal adult stratified squamous epithelium of the true vocal fold. Furthermore, replicating cell populations are largely restricted to the parabasal strata within the epithelium. This delineation of distinct cell populations will facilitate future studies of vocal fold regeneration and cancer. N/A. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

  5. Progressive squamous epithelial neoplasia in K14-human papillomavirus type 16 transgenic mice.

    PubMed Central

    Arbeit, J M; Münger, K; Howley, P M; Hanahan, D

    1994-01-01

    To model human papillomavirus-induced neoplastic progression, expression of the early region of human papillomavirus type 16 (HPV16) was targeted to the basal cells of the squamous epithelium in transgenic mice, using a human keratin 14 (K14) enhancer/promoter. Twenty-one transgenic founder mice were produced, and eight lines carrying either wild-type or mutant HPV16 early regions that did not express the E1 or E2 genes were established. As is characteristic of human cancers, the E6 and E7 genes remained intact in these mutants. The absence of E1 or E2 function did not influence the severity of the phenotype that eventually developed in the transgenic mice. Hyperplasia, papillomatosis, and dysplasia appeared at multiple epidermal and squamous mucosal sites, including ear and truncal skin, face, snout and eyelids, and anus. The ears were the most consistently affected site, with pathology being present in all lines with 100% penetrance. This phenotype also progressed through discernible stages. An initial mild hyperplasia was followed by hyperplasia, which further progressed to dysplasia and papillomatosis. During histopathological progression, there was an incremental increase in cellular DNA synthesis, determined by 5-bromo-2'-deoxyuridine incorporation, and a profound perturbation in keratinocyte terminal differentiation, as revealed by immunohistochemistry to K5, K14, and K10 and filaggrin. These K14-HPV16 transgenic mice present an opportunity to study the role of the HPV16 oncogenes in the neoplastic progression of squamous epithelium and provide a model with which to identify genetic and epigenetic factors necessary for carcinogenesis. Images PMID:7515971

  6. Prevalence of human papillomavirus in 5,072 consecutive cervical SurePath samples evaluated with the Roche cobas HPV real-time PCR assay.

    PubMed

    Preisler, Sarah; Rebolj, Matejka; Untermann, Anette; Ejegod, Ditte Møller; Lynge, Elsebeth; Rygaard, Carsten; Bonde, Jesper

    2013-01-01

    New commercially available Human Papillomavirus (HPV) assays need to be evaluated in a variety of cervical screening settings. Cobas HPV Test (cobas) is a real-time PCR-based assay allowing for separate detection of HPV genotypes 16 and 18 and a bulk of 12 other high-risk genotypes. The aim of the present study, Horizon, was to assess the prevalence of high-risk HPV infections in an area with a high background risk of cervical cancer, where women aged 23-65 years are targeted for cervical screening. We collected 6,258 consecutive cervical samples from the largest cervical screening laboratory in Denmark serving the whole of Copenhagen. All samples were stored in SurePath media. In total, 5,072 samples were tested with cobas, Hybrid Capture 2 High Risk HPV DNA test (HC2) and liquid-based cytology. Of these, 27% tested positive on cobas. This proportion decreased by age, being 43% in women aged 23-29 years and 10% in women aged 60-65 years. HC2 assay was positive in 20% of samples, and cytology was abnormal (≥ atypical squamous cells of undetermined significance) for 7% samples. When only samples without recent abnormalities were taken into account, 24% tested positive on cobas, 19% on HC2, and 5% had abnormal cytology. The proportion of positive cobas samples was higher than in the ATHENA trial. The age-standardized cobas positivity vs. cytology abnormality was 3.9 in our study and 1.7 in ATHENA. If in Copenhagen the presently used cytology would be replaced by cobas in women above age 30 years, an extra 11% of women would based on historical data be expected to have a positive cobas test without an underlying cervical intraepithelial lesion grade 3 or worse. Countries with a high prevalence of HPV infections should therefore proceed to primary HPV-based cervical screening with caution.

  7. In vitro demineralisation of the cervical region of human teeth.

    PubMed

    He, Li-Hong; Xu, Yingzhi; Purton, David G

    2011-05-01

    The aim of this study was to investigate a possible role for demineralisation of the cervical region of human teeth in the development of non-carious cervical lesions (NCCLs). Freshly extracted human premolars were demineralised and prepared for nanoindentation and scanning electron microscope (SEM) observation. After 1 day or 2 days demineralisation in a solution of pH 4.5, specimens were embedded, cut and polished to 1 μm diamond paste. Nanoindentation was done at the cementum-enamel junction (CEJ) region with an interval of 30 μm, to develop mechanical properties maps. After the indentation, SEM with back-scatter detector was employed to observe the degree of demineralisation at the CEJ. After 1 day and 2 days demineralisation, the mechanical properties of enamel and dentine at the CEJ decreased by ∼50% and ∼90%, respectively. SEM images illustrate that artificial demineralisation generated typical demineralised zones in enamel near the CEJ. Moreover, 2 days demineralisation penetrated the sound enamel at the CEJ, and the dentine beneath was undermined. One day and 2 days demineralisation reduced the mechanical properties of teeth at the CEJ significantly. Demineralised enamel and dentine with low mechanical properties are prone to wear and abrasion. The findings of the investigation indicate that acid typical of that produced by dental plaque may compromise the mechanical properties of enamel and dentine at the CEJ to the extent that they would be susceptible to tooth brush abrasion, producing NCCLs. Copyright © 2010 Elsevier Ltd. All rights reserved.

  8. Innovations in understanding the biology of cervical cancer.

    PubMed

    Wolf, Judith K; Franco, Eduardo L; Arbeit, Jeffery M; Shroyer, Kenneth R; Wu, Tzyy-Choou; Runowicz, Carolyn D; Tortolero-Luna, Guillermo; Herrero, Rolando; Crum, Christopher P

    2003-11-01

    Revelation of the connection between the human papillomavirus (HPV) and cervical neoplasia and invasive cervical cancer is prompting new investigations to expand that understanding and promote vaccines, gene therapy, and other interventions. At the Second International Conference on Cervical Cancer (Houston, TX, April 11-14, 2002), laboratory and clinical researchers reported advances in new studies meant to increase understanding of the natural history of HPV and cervical intraepithelial neoplasia, to evaluate new cervical cancer screening techniques, and to promote new therapies. Using K14-HPV type 16 transgenic mice, researchers are investigating the effects of estrogen on cervical cancer carcinogenesis, and results are lending support to epidemiological theories showing a difference in HPV infection rates and the development of cervical lesions in women using oral contraceptives. Other work involves investigating genes that are up-regulated by HPV infection and the role of the p53 homologue, p63, in cervical neoplasia evolution. Telomerase also is under investigation as a biomarker in high-risk populations. Gene therapy that replaced p53 in cervical cancer cell lines in vitro and a nude mouse model inhibited cell and tumor growth, confirming previous findings in squamous epithelial carcinomas of the head and neck. Furthermore, research in intracellular targeting of antigens to subcellular locations shows promise for treating cervical cancer preclinically. Identification of molecular changes in cervical cancer and knowledge about the importance of HPV infection in cervical cancer can lead to new therapies to treat existing cervical cancer and, in the long term, prevent the disease.

  9. Ancillary Studies in Determining Human Papillomavirus Status of Squamous Cell Carcinoma of the Oropharynx: A Review

    PubMed Central

    Cantley, Richard L.; Gabrielli, Eleonora; Montebelli, Francesco; Cimbaluk, David; Gattuso, Paolo; Petruzzelli, Guy

    2011-01-01

    Squamous cell carcinoma (SCC) of the oral cavity and pharynx represents the sixth most common form of malignancy worldwide. A significant proportion of these cases are related to human papillomavirus (HPV) infection. In general, HPV-associated SCC is more commonly nonkeratinizing and poorly differentiated, whereas non-HPV-associated SCC is typically keratinizing and moderately differentiated. Nevertheless, significant overlap in morphology is seen between these two forms of SCC. The purpose of this paper is to highlight the utility of ancillary studies in the establishment of HPV status of oropharyngeal SCC, including p16 immunohistochemistry, high-risk HPV in situ hybridization, polymerase chain reaction, and newer HPV detection modalities. PMID:21772959

  10. Cervical Microbiota Associated with Higher Grade Cervical Intraepithelial Neoplasia in Women Infected with High-Risk Human Papillomaviruses.

    PubMed

    Piyathilake, Chandrika J; Ollberding, Nicholas J; Kumar, Ranjit; Macaluso, Maurizio; Alvarez, Ronald D; Morrow, Casey D

    2016-05-01

    It is increasingly recognized that microbes that reside in and on human body sites play major roles in modifying the pathogenesis of several diseases, including cancer. However, specific microbes or microbial communities that can be mechanistically linked to cervical carcinogenesis remain largely unexplored. The purpose of the study was to examine the association between cervical microbiota and high-grade cervical intraepithelial neoplasia (CIN 2+) in women infected with high-risk (HR) human papillomaviruses (HPV) and to assess whether the cervical microbiota are associated with oxidative DNA damage as indicated by the presence of cervical cells positive for 8-hydroxy-2'-deoxyguanosine. The study included 340 women diagnosed with CIN 2+ (cases) and 90 diagnosed with CIN 1 (non-cases). Microbiota composition was determined by Illumina sequencing of the 16S rRNA gene amplified from DNA extracted from cervical mucus samples. Measures of alpha/beta-diversity were not associated with either CIN severity or oxidative DNA damage. However, a cervical mucosal community type (CT) dominated by L. iners and unclassified Lactobacillus spp was associated with CIN 2+ (OR = 3.48; 95% CI, 1.27-9.55). Sequence reads mapping to Lactobacillaceae, Lactobacillus, L. reuteri, and several sub-genus level Lactobacillus operational taxonomic units were also associated with CIN 2+ when examined independently (effect size >2.0; P < 0.05). Our 16S rRNA sequencing results need confirmation in independent studies using whole-genome shotgun sequencing and that would allow sharpening the suggested associations at finer taxonomic levels. Our results provide little evidence that DNA oxidative damage mediates the effect of the microbiome on the natural history of HPV infection and CIN severity. Cancer Prev Res; 9(5); 357-66. ©2016 AACR. ©2016 American Association for Cancer Research.

  11. Piperlongumine Suppresses Proliferation of Human Oral Squamous Cell Carcinoma through Cell Cycle Arrest, Apoptosis and Senescence.

    PubMed

    Chen, San-Yuan; Liu, Geng-Hung; Chao, Wen-Ying; Shi, Chung-Sheng; Lin, Ching-Yen; Lim, Yun-Ping; Lu, Chieh-Hsiang; Lai, Peng-Yeh; Chen, Hau-Ren; Lee, Ying-Ray

    2016-04-23

    Oral squamous cell carcinoma (OSCC), an aggressive cancer originating in the oral cavity, is one of the leading causes of cancer deaths in males worldwide. This study investigated the antitumor activity and mechanisms of piperlongumine (PL), a natural compound isolated from Piper longum L., in human OSCC cells. The effects of PL on cell proliferation, the cell cycle, apoptosis, senescence and reactive oxygen species (ROS) levels in human OSCC cells were investigated. PL effectively inhibited cell growth, caused cell cycle arrest and induced apoptosis and senescence in OSCC cells. Moreover, PL-mediated anti-human OSCC behavior was inhibited by an ROS scavenger N-acetyl-l-cysteine (NAC) treatment, suggesting that regulation of ROS was involved in the mechanism of the anticancer activity of PL. These findings suggest that PL suppresses tumor growth by regulating the cell cycle and inducing apoptosis and senescence and is a potential chemotherapy agent for human OSCC cells.

  12. Human papillomavirus typing of invasive cervical cancers in Italy.

    PubMed

    Del Mistro, Annarosa; Salamanca, Helena Frayle; Trevisan, Rossana; Bertorelle, Roberta; Parenti, Anna; Bonoldi, Emanuela; Zambon, Paola; Minucci, Daria

    2006-12-27

    Human papilloma viruses (HPV) are the necessary cause of invasive cervical cancer (ICC). Of the many different types identified so far, only a few of them account for the great majority of cases worldwide, with geographical differences in their distribution. Data on the local distribution are now of interest in view of the soon-to-come introduction of HPV type-specific prophylactic vaccines. We have investigated HPV type distribution in samples of 48 ICC cases occurred in women living in North-East Italy in the years 1997-1999. Cases were extracted from the Venetian Tumour Registry files, as incident cases whose specimens had been processed in two Pathology Departments. Search and typing were performed by polymerase chain reaction (PCR) using GP5+/GP6+ primers, followed by direct sequencing or reverse dot blot. Three cases were PCR negative using the housekeeping primers and hence excluded. One case was negative by all HPV tests used. HPV 16 was present in 32 (72.7%) cases, as single infection in 28, in mixed infection in 4. Of the 44 positive cases, HPV 16 and HPV 18 accounted for 33 (75%), as single or mixed infections. The other high risk HPV types accounted for 11 (25%) of the remaining infections. Of the 32 HPV 16 positive cases, sequencing of the E6 gene could be performed in 25; the prototype isolate was identified in 7, and the variant T350G in 18; in 4 cases one or more additional mutations were present. Our results suggest that HPV 16 has a very high prevalence among women with invasive cervical cancer in Italy; therefore, the use of a prophylactic vaccine for HPV types 16 and 18 could prevent up to 75% of invasive cervical cancers in Italy.

  13. Zidovudine, abacavir and lamivudine increase the radiosensitivity of human esophageal squamous cancer cell lines.

    PubMed

    Chen, Xuan; Wang, Cong; Guan, Shanghui; Liu, Yuan; Han, Lihui; Cheng, Yufeng

    2016-07-01

    Telomerase is a type of reverse transcriptase that is overexpressed in almost all human tumor cells, but not in normal tissues, which provides an opportunity for radiosensitization targeting telomerase. Zidovudine, abacavir and lamivudine are reverse transcriptase inhibitors that have been applied in clinical practice for several years. We sought to explore the radiosensitization effect of these three drugs on human esophageal cancer cell lines. Eca109 and Eca9706 cells were treated with zidovudine, abacavir and lamivudine for 48 h before irradiation was administered. Samples were collected 1 h after irradiation. Clonal efficiency assay was used to evaluate the effect of the combination of these drugs with radiation doses of 2, 4, 6 and 8 Gy. DNA damage was measured by comet assay. Telomerase activity (TA) and relative telomere length (TL) were detected and evaluated by real-time PCR. Apoptosis rates were assessed by flow cytometric analysis. The results showed that all the drugs tested sensitized the esophageal squamous cell carcinoma (ESCC) cell lines to radiation through an increase in radiation-induced DNA damage and cell apoptosis, deregulation of TA and decreasing the shortened TL caused by radiation. Each of the drugs investigated (zidovudine, abacavir and lamivudine) could be used for sensitizing human esophageal cancer cell lines to radiation. Consequently, the present study supports the potential of these three drugs as therapeutic agents for the radiosensitization of esophageal squamous cell cancer.

  14. Cytotoxicity and radiosensitization effect of TRA-8 on radioresistant human larynx squamous carcinoma cells.

    PubMed

    Wu, F; Hu, Y; Long, J; Zhou, Y J; Zhong, Y H; Liao, Z K; Liu, S Q; Zhou, F X; Zhou, Y F; Xie, C H

    2009-02-01

    TRAIL induces apoptosis in a variety of tumorigenic and transformed cell lines, but not in many normal cells. Recent studies have demonstrated that death receptor 5 (DR5), one of the two death receptors bound by TRAIL, showed expression in most malignantly transformed cells. This study evaluated effects of a monoclonal antibody (TRA-8) to human death receptor 5, combined with ionizing radiation, on radioresistant human larynx squamous carcinoma cell line (Hep-2R). Cells were treated with TRA-8 alone or in combination with radiation, cell viability inhibition was measured by MTT assay, and the induction of apoptosis was determined by Annexin V staining. Radionsensitivity of Hep-2R cells treated with TRA-8 were investigated with long-term clonogenic assays. Regulation of DR5 expression in cells after radiation was analyzed by indirect immunofluorescence using murine TRA-8 in combination with flow cytometry. The results suggested that TRA-8 enhanced radionsensitivity of Hep-2R cells, and that TRA-8 regulated Hep-2R cell cycle arrest at G2/M phase. Irradiation up-regulated the expression of DR5, and when combined with TRA-8 yielded optimal survival benefit. Therefore, TRA-8 can be used in combination with irradiation in radioresistant human larynx squamous carcinoma cells. Monoclonal antibodies such as TRA-8 may play an important role in the development of an effective treatment strategy for patients with radioresistant cancers.

  15. Squamous epitheliotropism of Enterovirus A71 in human epidermis and oral mucosa.

    PubMed

    Phyu, Win Kyaw; Ong, Kien Chai; Kong, Chee Kwan; Alizan, Abdul Khalil; Ramanujam, Tindivanam Muthurangam; Wong, Kum Thong

    2017-03-21

    Hand-foot-and-mouth disease is a self-limiting paediatric infectious disease commonly caused by Enterovirus A71 (Genus: Enterovirus, Family: Picornaviridae). Typical lesions in and around the hands, feet, oral cavity and other places may rarely be complicated by acute flaccid paralysis and acute encephalomyelitis. Although virus is readily cultured from skin vesicles and oral secretions, the cellular target/s of Enterovirus A71 in human skin and oral mucosa are unknown. In Enterovirus A71-infected human skin and oral mucosa organotypic cultures derived from the prepuce and lip biopsies, focal viral antigens and viral RNA were localized to cytoplasm of epidermal and mucosal squamous cells as early as 2 days post-infection. Viral antigens/RNA were associated with cytoplasmic vacuolation and cellular necrosis. Infected primary prepuce epidermal keratinocyte cultures showed cytopathic effects with concomitant detection of viral antigens from 2 days post-infection. Supernatant and/or tissue homogenates from prepuce skin organotypic cultures and primary prepuce keratinocyte cultures showed viral titres consistent with active viral replication. Our data strongly support Enterovirus A71 squamous epitheliotropism in the human epidermis and oral mucosa, and suggest that these organs are important primary and/or secondary viral replication sites that contribute significantly to oral and cutaneous viral shedding resulting in person-to-person transmission, and viraemia, which could lead to neuroinvasion.

  16. Squamous epitheliotropism of Enterovirus A71 in human epidermis and oral mucosa

    PubMed Central

    Phyu, Win Kyaw; Ong, Kien Chai; Kong, Chee Kwan; Alizan, Abdul Khalil; Ramanujam, Tindivanam Muthurangam; Wong, Kum Thong

    2017-01-01

    Hand-foot-and-mouth disease is a self-limiting paediatric infectious disease commonly caused by Enterovirus A71 (Genus: Enterovirus, Family: Picornaviridae). Typical lesions in and around the hands, feet, oral cavity and other places may rarely be complicated by acute flaccid paralysis and acute encephalomyelitis. Although virus is readily cultured from skin vesicles and oral secretions, the cellular target/s of Enterovirus A71 in human skin and oral mucosa are unknown. In Enterovirus A71-infected human skin and oral mucosa organotypic cultures derived from the prepuce and lip biopsies, focal viral antigens and viral RNA were localized to cytoplasm of epidermal and mucosal squamous cells as early as 2 days post-infection. Viral antigens/RNA were associated with cytoplasmic vacuolation and cellular necrosis. Infected primary prepuce epidermal keratinocyte cultures showed cytopathic effects with concomitant detection of viral antigens from 2 days post-infection. Supernatant and/or tissue homogenates from prepuce skin organotypic cultures and primary prepuce keratinocyte cultures showed viral titres consistent with active viral replication. Our data strongly support Enterovirus A71 squamous epitheliotropism in the human epidermis and oral mucosa, and suggest that these organs are important primary and/or secondary viral replication sites that contribute significantly to oral and cutaneous viral shedding resulting in person-to-person transmission, and viraemia, which could lead to neuroinvasion. PMID:28322333

  17. Triapine With Chemotherapy and Radiation Therapy in Treating Patients With IB2-IVA Cervical or Vulvar Cancer

    ClinicalTrials.gov

    2017-09-12

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Stage IB Vulvar Cancer; Stage IB2 Cervical Cancer; Stage II Vulvar Cancer; Stage IIA1 Cervical Cancer; Stage IIA2 Cervical Cancer; Stage IIB Cervical Cancer; Stage IIIA Cervical Cancer; Stage IIIA Vulvar Cancer; Stage IIIB Cervical Cancer; Stage IIIB Vulvar Cancer; Stage IIIC Vulvar Cancer; Stage IVA Cervical Cancer; Stage IVA Vulvar Cancer; Vulvar Adenocarcinoma; Vulvar Squamous Cell Carcinoma

  18. Dynamic Mechanical Properties of Intact Human Cervical Spine Ligaments

    PubMed Central

    Ivancic, Paul C.; Coe, Marcus P.; Ndu, Anthony B.; Tominaga, Yasuhiro; Carlson, Erik J.; Rubin, Wolfgang; (FH), Dipl-Ing; Panjabi, Manohar M.

    2009-01-01

    BACKGROUND CONTEXT Most previous studies have investigated ligaments mechanical properties at slow elongation rates of less than 25 mm/s. PURPOSE To determine the tensile mechanical properties, at a fast elongation rate, of intact human cervical anterior and posterior longitudinal, capsular, and interspinous and supraspinous ligaments, middle-third disc, and ligamentum flavum. STUDY DESIGN/SETTING In vitro biomechanical study. METHODS A total of 97 intact bone-ligament-bone specimens (C2–C3 to C7-T1) were prepared from six cervical spines (average age: 80.6 years, range, 71 to 92 years) and were elongated to complete rupture at an average (SD) peak rate of 723 (106) mm/s using a custom-built apparatus. Non-linear force vs. elongation curves were plotted and peak force, peak elongation, peak energy, and stiffness were statistically compared (P<0.05) among ligament. A mathematical model was developed to determine the quasi-static physiological ligament elongation. RESULTS Highest average peak force, up to 244.4 and 220.0 N in the ligamentum flavum and capsular ligament, respectively, were significantly greater than in the anterior longitudinal ligament and middle-third disc. Highest peak elongation reached 5.9 mm in the intraspinous and supraspinous ligaments, significantly greater than in the middle-third disc. Highest peak energy of 0.57 J was attained in the capsular ligament, significantly greater than in the anterior longitudinal ligament and middle-third disc. Average stiffness was generally greatest in the ligamentum flavum and least in the intraspinous and supraspinous ligaments. For all ligaments, peak elongation was greater than average physiological elongation computed using the mathematical model. CONCLUSIONS Comparison of the present results with previously reported data indicated that high speed elongation may cause cervical ligaments to fail at a higher peak force and smaller peak elongation and may be stiffer and absorb less energy, as compared to a

  19. Prognostic Value of Neutrophil-Related Factors in Locally Advanced Cervical Squamous Cell Carcinoma Patients Treated with Cisplatin-Based Concurrent Chemoradiotherapy.

    PubMed

    Wang, Yan-Yang; Bai, Zhou-Lan; He, Jian-Li; Yang, Yan; Zhao, Ren; Hai, Ping; Zhe, Hong

    2016-01-01

    The aim of this study was to explore the relationship between neutrophil-related factors, including neutrophil-lymphocyte ratio (NLR) and the responses of neutrophil to granulocyte colony-stimulating factors (RNG), and the prognosis of patients with locally advanced cervical squamous cell carcinoma (LACSCC) undergoing cisplatin-based concurrent chemoradiotherapy (CCCRT). A total of sixty LACSCC patients were enrolled in this study. We analyzed the association of NLR or RNG with clinicopathologic characteristics of these patients. The prognostic factors were evaluated by univariate and multivariate survival analysis. The optimal cut-off value of the NLR was determined to be 2.0 for the overall survival (OS). A higher level of the NLR was associated with younger age (P = 0.017) and higher baseline platelet count (P = 0.040). NLR was identified to be the only independent prognostic factor for OS by multivariate analysis (P = 0.037). The median RNG was 3.01, with a range of 1.19-16.84. RNG level was significantly associated with lymph node metastasis of these patients (P = 0.023). And higher RNG was identified as being a closely independent poor prognostic factor for OS (P = 0.055). This study showed that NLR and RNG may be used as potential biomarkers for survival prediction in patients with LACSCC receiving CCCRT.

  20. [Cervical infection epidemiology of human papillomavirus in Ushuaia, Argentina].

    PubMed

    Sijvarger, C C; González, J V; Prieto, A; Messmer, A G; Mallimaci, M C; Alonio, V L; Teyssié, A R; Picconi, M A

    2006-01-01

    Genital infection with human papillomavirus (HPV) is decisive in the causation of cervical cancer. In order to evaluate the epidemiology of HPV infection in Ushuaia, Province of Tierra del Fuego, Argentina, 132 endocervical cytobrushes from preneoplastic and neoplastic cases and controls were studied. Detection and typing of the viral genome was performed by polymerase chain reaction, combined with a restriction fragment length polymorphism assay or hybridization. The overall prevalence of HPV infection was 41% in the population examined, with a frequency of 26% in the controls and 71% in the cases under study. The 14-24 age group showed the highest HPV prevalence. The most common viral types in the infected population were HPV 16 (23%), HPV 18 (11%), HPV 33 (8%) and HPV 35 (8%), while high risk viral types were detected in 30% of the samples, 16% of the controls and 60% of the cases. This study provides the first data on the predominant viral types in Ushuaia. Our results show lower levels of infection than in regions with a high incidence of cervical cancer, HPV 16 being the most prevalent viral type. This research may be useful for selecting a specific vaccine targeting the population examined.

  1. Human cervical spine ligaments exhibit fully nonlinear viscoelastic behavior.

    PubMed

    Troyer, Kevin L; Puttlitz, Christian M

    2011-02-01

    Spinal ligaments provide stability and contribute to spinal motion patterns. These hydrated tissues exhibit time-dependent behavior during both static and dynamic loading regimes. Therefore, accurate viscoelastic characterization of these ligaments is requisite for development of computational analogues that model and predict time-dependent spine behavior. The development of accurate viscoelastic models must be preceded by rigorous, empirical evidence of linear viscoelastic, quasi-linear viscoelastic (QLV) or fully nonlinear viscoelastic behavior. This study utilized multiple physiological loading rates (frequencies) and strain amplitudes via cyclic loading and stress relaxation experiments in order to determine the viscoelastic behavior of the human lower cervical spine anterior longitudinal ligament, the posterior longitudinal ligament and the ligamentum flavum. The results indicated that the cyclic material properties of these ligaments were dependent on both strain amplitude and frequency. This strain amplitude-dependent behavior cannot be described using a linear viscoelastic formulation. Stress relaxation experiments at multiple strain magnitudes indicated that the shape of the relaxation curve was strongly dependent on strain magnitude, suggesting that a QLV formulation cannot adequately describe the comprehensive viscoelastic response of these ligaments. Therefore, a fully nonlinear viscoelastic formulation is requisite to model these lower cervical spine ligaments during activities of daily living. Copyright © 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  2. Evaluation of the association of NKG2C copy number variations with susceptibility to human papillomavirus-induced cervical lesions.

    PubMed

    Vilchez, José R; Torres-Moreno, Daniel; Martínez-Senac, María M; Trujillo-Santos, Javier; Conesa-Zamora, Pablo

    2013-10-01

    Squamous intraepithelial lesions (SIL) and cervical cancer are primary due to suboptimal host-dependent immune response against human papillomavirus (HPV). Natural killer cells (NK) are innate-immune response components against virus and tumors. We studied whether the null allele of NKG2C NK cell receptor could be associated with low-grade (LSIL) to high-grade SIL (HSIL) transition or likelihood of HPV infection. Eight-hundred and sixty-seven subjects (263 LSIL, 309 HSIL and 295 controls) were genotyped for NKG2C using a novel multiplex PCR protocol. HPV genotype information was obtained from the cases. NKG2C genotype distributions in LSIL were WT/WT: 69.2%, WT/null: 26.2% and null/null: 4.6%; whereas in HSIL were WT/WT: 65.4%, WT/null: 28.5% and null/null: 6.1% and no statistical differences were observed (LSIL vs. HSIL p=0.541; LSIL vs. controls p=0.230; HSIL vs. controls p=0.624) nor when restricting to HPV positive, HR-HPV nor co-infection. This study demonstrates that NKG2Cnull does not seem to constitute a risk factor for HPV-induced cervical lesions. Copyright © 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  3. Head and cervical spine posture in behaving rats: implications for modeling human conditions involving the head and cervical spine.

    PubMed

    Griffin, C; Choong, W Y; Teh, W; Buxton, A J; Bolton, P S

    2015-02-01

    The aim of this study was to define the temporal and spatial (postural) characteristics of the head and cervical vertebral column (spine) of behaving rats in order to better understand their suitability as a model to study human conditions involving the head and neck. Time spent in each of four behavioral postures was determined from video tape recordings of rats (n = 10) in the absence and presence of an intruder rat. Plain film radiographic examination of a subset of these rats (n = 5) in each of these postures allowed measurement of head and cervical vertebral column positions adopted by the rats. When single they were quadruped or crouched most (∼80%) of the time and bipedal either supported or free standing for only ∼10% of the time. The introduction of an intruder significantly (P < 0.0001) reduced the proportion of time rats spent quadruped (median, from 71% to 47%) and bipedal free standing (median, from 2.9% to 0.4%). The cervical spine was orientated (median, 25-75 percentile) near vertical (18.8°, 4.2°-30.9°) when quadruped, crouched (15.4°, 7.6°-69.3°) and bipedal supported (10.5°, 4.8°-22.6°) but tended to be less vertical oriented when bipedal free standing (25.9°, 7.7°-39.3°). The range of head positions relative to the cervical spine was largest when crouched (73.4°) and smallest when erect free standing (17.7°). This study indicates that, like humans, rats have near vertical orientated cervical vertebral columns but, in contrast to humans, they displace their head in space by movements at both the cervico-thoracic junction and the cranio-cervical regions.

  4. Finite element analysis of moment-rotation relationships for human cervical spine.

    PubMed

    Zhang, Qing Hang; Teo, Ee Chon; Ng, Hong Wan; Lee, Vee Sin

    2006-01-01

    A comprehensive, geometrically accurate, nonlinear C0-C7 FE model of head and cervical spine based on the actual geometry of a human cadaver specimen was developed. The motions of each cervical vertebral level under pure moment loading of 1.0 Nm applied incrementally on the skull to simulate the movements of the head and cervical spine under flexion, tension, axial rotation and lateral bending with the inferior surface of the C7 vertebral body fully constrained were analysed. The predicted range of motion (ROM) for each motion segment were computed and compared with published experimental data. The model predicted the nonlinear moment-rotation relationship of human cervical spine. Under the same loading magnitude, the model predicted the largest rotation in extension, followed by flexion and axial rotation, and least ROM in lateral bending. The upper cervical spines are more flexible than the lower cervical levels. The motions of the two uppermost motion segments account for half (or even higher) of the whole cervical spine motion under rotational loadings. The differences in the ROMs among the lower cervical spines (C3-C7) were relatively small. The FE predicted segmental motions effectively reflect the behavior of human cervical spine and were in agreement with the experimental data. The C0-C7 FE model offers potentials for biomedical and injury studies.

  5. University Students' Knowledge and Attitudes Regarding Cervical Cancer, Human Papillomavirus, and Human Papillomavirus Vaccines in Turkey

    ERIC Educational Resources Information Center

    Koç, Zeliha

    2015-01-01

    Objectives: The current descriptive study aimed to determine university students' knowledge and attitudes regarding cervical cancer, human papillomavirus (HPV), and HPV vaccines in Turkey. Participants: A total of 800 students participated. Methods: This study was carried out between September 1, 2012, and October 30, 2012, in 8 female…

  6. University Students' Knowledge and Attitudes Regarding Cervical Cancer, Human Papillomavirus, and Human Papillomavirus Vaccines in Turkey

    ERIC Educational Resources Information Center

    Koç, Zeliha

    2015-01-01

    Objectives: The current descriptive study aimed to determine university students' knowledge and attitudes regarding cervical cancer, human papillomavirus (HPV), and HPV vaccines in Turkey. Participants: A total of 800 students participated. Methods: This study was carried out between September 1, 2012, and October 30, 2012, in 8 female…

  7. Frequency of bilateral cervical metastases in hypopharyngeal squamous cell carcinoma: a retrospective analysis of 203 cases after bilateral neck dissection.

    PubMed

    Olzowy, Bernhard; Hillebrand, Matthias; Harréus, Ulrich

    2017-08-24

    The decision whether to perform an elective neck dissection in patients with head and neck squamous cell carcinoma and clinically negative lymph nodes (cN0) is made based on the probability of micrometastases in the neck for the given subsite and size of the primary. A retrospective chart review was performed of 203 patients with hypopharyngeal SCC who received a bilateral neck dissection. The frequency of histologically unveiled bilateral neck metastases was determined. A high frequency of contralateral metastases above 20% was detected for all carcinomas affecting the midline and those involving the medial wall of the pyriform sinus except of T1-stages (13%) and a low frequency for laterally located primaries (3%). Ipsilateral nodal status predicted contralateral neck metastases. Bilateral neck dissection should be recommended for primaries affecting the midline and T2-4 tumors involving the medial wall of the pyriform sinus.

  8. Suicide gene therapy using adenovirus vector for human oral squamous carcinoma cell line in vitro.

    PubMed

    Yamamoto, Noriyuki; Hayashi, Yasushi; Kagami, Hideaki; Fukui, Takafumi; Fukuhara, Hirokazu; Tohnai, Iwai; Ueda, Minoru; Mizuno, Masaaki; Yoshida, Jun

    2005-06-01

    Recently, suicide gene therapy using the herpes simplex virus thymidine kinase (HSVtk) gene followed by ganciclovir (GCV) administration was evaluated for the treatment of cancer. The purpose of this study was to investigate the effectiveness of suicide gene therapy using the replication-deficient recombinant adenovirus vector for human oral squamous carcinoma cell lines. To evaluate transduction efficiency, each cell line was transduced in vitro with an adenovirus vector containing the beta-galactosidase gene. By 24 hours after transduction, nearly 100% of the cells were transduced at a multiplicity of infection (MOI) of 10, and from 30 to 10% at an MOI of 1. Next, each cell line was transduced with an adenovirus vector containing the HSVtk gene, and a subsequent administration of GCV for the assessment of suicide gene therapy. A subsequent administration of GCV resulted in complete tumor cell death. In addition, we conducted a morphological analysis of that cell death using video-enhanced contrast differential interference contrast microscopy, and we observed that it included both apoptosis and necrosis after HSVtk gene and GCV treatment. These results suggest that adenovirus-mediated suicide gene therapy induced remarkable cytotoxicity with a bystander effect in human oral squamous cell carcinoma thus suggesting an effective treatment strategy for that tumor.

  9. The Epidemiological, Morphological, and Clinical Aspects of the Cervical Ribs in Humans

    PubMed Central

    Spadliński, Łukasz; Cecot, Tomasz; Majos, Agata; Stefańczyk, Ludomir; Pietruszewska, Wioletta; Wysiadecki, Grzegorz; Topol, Mirosław

    2016-01-01

    A familiarity with the anatomy of some types of bone anomalies is necessary for clinicians involved in many medical areas. The aim of this paper is to review the newest literature concerning the morphology, embryology, clinical image, and therapeutic methods of the cervical ribs in the humans. The incidence of cervical ribs has been found to vary from 0.58% in Malaysian population to 6.2% in Turkish population. Cervical ribs have clinical implications that are generally divided into neurological or vascular. This study is of particular importance for clinicians, as early identification of cervical ribs may prevent life-threatening complications. PMID:27975060

  10. Chemoradiation Therapy and Ipilimumab in Treating Patients With Stages IB2-IIB or IIIB-IVA Cervical Cancer

    ClinicalTrials.gov

    2017-09-28

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Positive Para-Aortic Lymph Node; Positive Pelvic Lymph Node; Stage IB2 Cervical Cancer; Stage II Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage IIIB Cervical Cancer; Stage IVA Cervical Cancer

  11. Measuring cervical dilatation in human parturition using the Hall effect.

    PubMed

    Kriewall, T J; Work, B A

    1977-01-01

    An instrument was developed to continuously measure cervical dilatation in human labor. The instrument utilizes a small magnetic field source, which is attached to one edge of the cervix while a magnetic field sensor is attached to the diametrically opposite edge of the cervix. The sensor, using two Hall generators, measures orthogonal components of the field to minimize the effects of angular orientation between the source and sensor. The instrument's characteristics indicate that it can measure dilation throughout the range of 1-10 cm, but because its clinical reliability is consistent from only 1-7 cm, the equipment needs to be improved in the ways outlined in the text. This measurement, especially when analyzed with the continous measurement of intrauterine pressure, can provide the obstetrician with new insight into the physiology of labor.

  12. P16 and Ki-67 expression improves the diagnostic accuracy of cervical lesions but not predict persistent high risk human papillomavirus infection with CIN1

    PubMed Central

    Zhong, Pingping; Li, Jifeng; Gu, Yiqun; Liu, Yu; Wang, Aichun; Sun, Yunfei; Lu, Lijuan

    2015-01-01

    Objective: To determine the association between the expression of p16 and Ki-67 and cervical lesions, and to evaluate the role of p16 and Ki-67 as prognostic markers for persistent high risk human papillomavirus (hr-HPV) infection. Methods: Totally 1,154 cases of cervical biopsies were enrolled, 331 cases with negative for dysplasia (NEG), 462 with cervical intraepithelial neoplasia 1 (CIN1), 176 with CIN2, 163 with CIN3 and 22 with cervical squamous cell carcinoma (SCC). Furthermore, 283 women with CIN1 were recruited into 12-month follow-up, and HPV specific gene detection by polymerase chain reaction was used to detect hr-HPV of cervical secretions at 6-month-interval for 12-month follow-up period. 40 women were infected with persistent hr-HPV, 182 with transient infection and 61 unfected with hr-HPV. The expression of p16 and Ki-67 were evaluated by immunohistochemical method. The immunostaining results of p16 and Ki-67 were classified into four categories: negative, 1+, 2+ and 3+. Results: There was significant increase in the expression of p16 (P < 0.001) and Ki-67 (P < 0.001) from NEG to SCC. The expression of Ki-67 (P < 0.001) but not p16 (P = 0.254) significantly increased in CIN2, CIN3. Ratio of p16 (P = 0.215) and Ki-67 (P = 0.495) positivity were not correlated with persistent hr-HPV infection. Conclusion: P16 and Ki-67 can improve the diagnostic accuracy of cervical lesions but can not predict persistent hr-HPV infection with CIN1. PMID:26045807

  13. P16 and Ki-67 expression improves the diagnostic accuracy of cervical lesions but not predict persistent high risk human papillomavirus infection with CIN1.

    PubMed

    Zhong, Pingping; Li, Jifeng; Gu, Yiqun; Liu, Yu; Wang, Aichun; Sun, Yunfei; Lu, Lijuan

    2015-01-01

    To determine the association between the expression of p16 and Ki-67 and cervical lesions, and to evaluate the role of p16 and Ki-67 as prognostic markers for persistent high risk human papillomavirus (hr-HPV) infection. Totally 1,154 cases of cervical biopsies were enrolled, 331 cases with negative for dysplasia (NEG), 462 with cervical intraepithelial neoplasia 1 (CIN1), 176 with CIN2, 163 with CIN3 and 22 with cervical squamous cell carcinoma (SCC). Furthermore, 283 women with CIN1 were recruited into 12-month follow-up, and HPV specific gene detection by polymerase chain reaction was used to detect hr-HPV of cervical secretions at 6-month-interval for 12-month follow-up period. 40 women were infected with persistent hr-HPV, 182 with transient infection and 61 unfected with hr-HPV. The expression of p16 and Ki-67 were evaluated by immunohistochemical method. The immunostaining results of p16 and Ki-67 were classified into four categories: negative, 1+, 2+ and 3+. There was significant increase in the expression of p16 (P<0.001) and Ki-67 (P<0.001) from NEG to SCC. The expression of Ki-67 (P<0.001) but not p16 (P=0.254) significantly increased in CIN2, CIN3. Ratio of p16 (P=0.215) and Ki-67 (P=0.495) positivity were not correlated with persistent hr-HPV infection. P16 and Ki-67 can improve the diagnostic accuracy of cervical lesions but can not predict persistent hr-HPV infection with CIN1.

  14. Structural studies of sialylated oligosaccharides of human midcycle cervical mucin.

    PubMed

    Yurewicz, E C; Matsuura, F; Moghissi, K S

    1987-04-05

    It was previously shown that reductive alkali treatment of purified human cervical mucin releases a heterogeneous population of reduced neutral, sialylated, and sulfated oligosaccharides (Yurewicz, E. C., and Moghissi, K. S. (1981) J. Biol. Chem. 256, 11895-11904). Four major sialylated oligosaccharide fractions were isolated with approximate compositions of Fuc:GlcNac:Gal:NeuAc:N-acetylgalactosaminitol (GalNAcol) = 0:0:0:1:1 (B1a), 0:0:1:1:1 (B2b), 0:1:2:1:1 (B3a), and 1:1:2:1:1 (B4a), where Fuc is fucose. They comprised roughly 3, 11, 7, and 6% of recovered oligosaccharide chains, respectively. On the basis of periodate oxidations, methylation analyses, and sequential degradations with glycosidases, the following structures were determined. (Formula: see text) Oligosaccharides 1 and 2 are characterized by the presence of N-acetylneuraminic acid in alpha 2,6-linkage to N-acetylgalactosaminitol. The remaining oligosaccharides contain N-acetylneuraminic acid in alpha 2,3-linkage to galactose residues. Oligosaccharides 3 and 4 and oligosaccharides 5 and 6 were isolated as unresolved isomeric mixtures in fractions B3a and B4a, respectively. Oligosaccharides 3 and 4 were distinguished on the basis of susceptibility to digestion with Aspergillus niger beta-galactosidase whereas oligosaccharides 5 and 6 were distinguished on the basis of differential rates of digestion with beef kidney alpha-fucosidase. The structural data indicate the presence of at least two sialyltransferases in human cervical epithelium and further suggest a potential physiologically significant competition between sialyltransferase and beta-N-acetylglucosaminyltransferase for C-6 of the N-acetylgalactosamine residue O-glycosidically linked to serine/threonine of the polypeptide core.

  15. Static and dynamic bending responses of the human cervical spine.

    PubMed

    Voo, L M; Pintar, F A; Yoganandan, N; Liu, Y K

    1998-12-01

    The quasi-static and dynamic bending responses of the human mid-lower cervical spine were determined using cadaver intervertebral joints fixed at the base to a six-axis load cell. Flexion bending moment was applied to the superior end of the specimen using an electrohydraulic piston. Each specimen was tested under three cycles of quasi-static load-unload and one high-speed dynamic load. A total of five specimens were included in this study. The maximum intervertebral rotation ranged from 11.0 to 15.4 deg for quasi-static tests and from 22.9 to 34.4 deg for dynamic tests. The resulting peak moments at the center of the intervertebral joint ranged from 3.8 to 6.9 Nm for quasi-static tests and from 14.0 to 31.8 Nm for dynamic tests. The quasi-static stiffness ranged from 0.80 to 1.35 Nm/deg with a mean of 1.03 Nm/deg (+/- 0.11 Nm/deg). The dynamic stiffness ranged from 1.08 to 2.00 Nm/deg with a mean of 1.50 Nm/deg (+/- 0.17 Nm/deg). The differences between the two stiffnesses were statistically significant (p < 0.01). Exponential functions were derived to describe the quasi-static and dynamic moment-rotation responses. These results provide input data for lumped-parameter models and validation data for finite element models to better investigate the biomechanics of the human cervical spine.

  16. Detection Rate of High-Grade Cervical Neoplasia and Cost-Effectiveness of High-Risk Human Papillomavirus Genotyping with Reflex Liquid-based Cytology in Cervical Cancer Screening.

    PubMed

    Tay, Sun Kuie; Lin, Lynette Eo; Goh, Ronald Ch

    2017-07-01

    This study aimed to determine the prevalence of cervical intraepithelial neoplasia grade 3 or worse (≥CIN3) and cost-effectiveness of human papillomavirus (HPV) genotyping with reflex liquid-based cytology (LBC) for cervical cancer screening in Singapore. Women who were ≥25 years old and undertook co-testing with LBC and HPV-genotyping (Cobas-4800, Roche, USA) for HPV-16, HPV-18 and 12 high-risk HPV types in a single institution were studied retrospectively. A single cervical smear in ThinPrep® PreservCyt® solution (Hologic, USA) was separated for tests in independent cytology and molecular pathology laboratories. The results were reviewed by a designated gynaecologist according to institutional clinical management protocols. Those who tested positive for HPV-16 and/or HPV-18 (regardless of cytology results), cytology showing low-grade squamous intraepithelial lesions (LSIL) or high-grade SIL (HSIL), or atypical squamous cells of undetermined significance (ASCUS) with positive 12 high-risk HPV types were referred for colposcopy. Colposcopy was performed by experienced colposcopists. Cervical biopsy, either directed punch biopsies or excisional biopsy, was determined by a colposcopist. The diagnosis of ≥CIN3 was reviewed by a gynaecologic pathologist. Cost-effectiveness of HPV-based screening in terms of disease and financial burden was analysed using epidemiological, clinical and financial input data from Singapore. Of 1866 women studied, 167 (8.9%) had abnormal cytology (≥ASCUS) and 171 (9.2%) tested positive for high-risk HPV. Twenty-three CIN were detected. Three of the 10 ≥CIN3 cases had negative cytology but positive HPV-16. Compared to cytology, HPV genotyping detected more ≥CIN3 (OR: 1.43). HPV+16/18 genotyping with reflex LBC was superior in terms of cost-effectiveness to LBC with reflex HPV, both for disease detection rate and cost per case of ≥CIN2 detected. Compared to cytology, HPV+16/18 genotyping with reflex LBC detected more ≥CIN3

  17. Variation of neck muscle strength along the human cervical spine.

    PubMed

    Oi, Nelson; Pandy, Marcus G; Myers, Barry S; Nightingale, Roger W; Chancey, Valeta Carol

    2004-11-01

    The aim of this study was to describe and explain the variation of neck muscle strength along the cervical spine. A three-dimensional model of the head-neck complex was developed to test the hypothesis that the moment-generating capacity of the neck musculature is lower in the upper cervical spine than in the lower cervical spine. The model calculations suggest that the neck muscles can protect the lower cervical spine from injury during extension and lateral bending. The maximum flexor moment developed in the lower cervical spine was 2 times higher than that developed in the upper spine. The model also predicted that the neck musculature is 30% stronger in the lower cervical spine during lateral bending. Peak compressive forces (up to 3 times body weight) were higher in the lower cervical spine. These results are consistent with the clinical finding that extension loading of the neck often leads to injuries in the upper cervical spine. Analysis of the model results showed that neck flexor strength was greater in the lower cervical spine because of the relatively large size of the sternocleidomastoid muscle. The hyoid muscles developed significant flexor moments about the joints of the upper cervical spine, as these muscles had relatively large flexor moment arms; however, this effect was offset by the action of the sternocleidomastoid, which exerted a large extensor moment in the upper spine. Lateral bending strength of the neck muscles was governed by geometry (i.e., moment arms) rather than by muscle size.

  18. Prevalence of human papillomavirus (HPV) types in cervical cancer 2003-2008 in Stockholm, Sweden, before public HPV vaccination.

    PubMed

    Du, Juan; Näsman, Anders; Carlson, Joseph W; Ramqvist, Torbjörn; Dalianis, Tina

    2011-11-01

    Human papillomavirus (HPV) infection is the major cause of cervical cancer, but the prevalence of different HPV types varies depending on geographical location and may change dramatically after introduction of HPV vaccination. Here, we aimed to gain some information regarding the recent prevalence of different HPV types, in cancer of the uterine cervix in the Stockholm region, before the introduction of public HPV vaccination in Sweden. From 215 diagnosed cervical cancer patients 2003-2008 at the Karolinska University Hospital, 160 pretreatment cervical cancer samples, including both squamous cell carcinomas (SCC) and adenocarcinomas (ADC) could be obtained. DNA was extracted from 154/160 of the SCC and ADC samples and assayed by Luminex Multiplex for 24 different HPV types, including 15 high-risk (HR), three putative HR and six low-risk types (LR). We successfully analysed 154/215 (71.6%) of the locally diagnosed cases and found a high prevalence of HPV with 92.9% in all uterine cervix cancer cases, and 93.3% and 91.4 % in SCC and ADC, respectively. All HPV positive cases harboured HR types, either alone or as multiple infections. In SCC HPV16 dominated and together with HPV18 accounted for 69.7% of the cases, followed in prevalence by HPV33, 31 and 45. In ADC, HPV18 was more common than HPV16, and they were observed in all except one of the HPV positive samples. The prevalence of HPV16 and 18, followed by HPV33, 31 and 45 is high in SCC and ADC in the Stockholm region. Public HPV vaccination could potentially inhibit a large proportion of such tumours underlining the urgency to initiate HPV vaccination.

  19. Type-specific human papillomavirus distribution in invasive cervical carcinomas in Paraguay. A study of 432 cases.

    PubMed

    Kasamatsu, Elena; Cubilla, Antonio L; Alemany, Laia; Chaux, Alcides; Tous, Sara; Mendoza, Laura; Paez, Malvina; Klaustermeier, Jo Ellen; Quint, Wim; Lloveras, Belen; de Sanjose, Silvia; Muñoz, Nubia; Bosch, Francisco Xavier

    2012-10-01

    Cervical carcinoma is the most common malignant tumor among woman in Paraguay. Cytological screening programs have not been successful and a plan for human papillomavirus (HPV) based-screening program and/or vaccination is under evaluation. This study aimed to identify the contribution of HPV genotypes in invasive cervical cancer in Paraguay to provide essential background data to guide and assess the introduction and impact of new preventive strategies based on HPV. Four hundred thirty two histologically confirmed cases (1960-2004) were analyzed. HPV detection in paraffin blocks was performed at the Catalan Institute of Oncology using PCR with SPF-10 broad spectrum primers followed by DNA enzyme immunoassay and genotyping with a reverse hybridization line probe analysis. The majority of cases were squamous cell carcinoma (92.8%). Mean patients age was 48 years old. HPV DNA was detected in 73.1% of the cases and single infections were predominant (97.8%). The most common HPV single types were 16, 18, 45, 33, 31, 52, 35, and 39. 73.1% of HPV positive cases had an HPV 16, 18 as single infection. HPV16 was frequent in SCC whereas HPV 18 and 45 were prevalent in glandular tumors. Significant decrease of HPV 16 with age groups (P-trend = 0.022) and increase in other HPV types (P-trend > 0.001) were observed. The potential impact of HPV 16 and 18 for a vaccination program was 73.1%. The study provide a profile of the HPV situation in the country, with robust clinical, pathological and virological data which would permit a better cervical cancer screening and vaccination programs.

  20. Distribution of human papillomavirus types in cervical cancers in Hong Kong: current situation and changes over the last decades.

    PubMed

    Chan, Paul K S; Ho, Wendy C S; Yu, Mei-Yung; Pong, Wai-Mei; Chan, Alexander C L; Chan, Amanda K C; Cheung, Tak-Hong; Wong, Martin C S; To, Ka-Fai; Ng, Ho-Keung

    2009-10-01

    Human papillomavirus (HPV) type distribution among cervical cancers and its possible changes over time are key issues that determine the cost-effectiveness of HPV vaccines. Cervical cancers diagnosed during 3 periods (1997-2007, N = 280; 1984-1986, N = 74; 1972-1973, N = 81) in Hong Kong were examined for HPV type distribution using sensitive broad-catching methods. The results showed a variation in HPV distribution between histological groups. Among cervical squamous cell carcinoma (SCC) cases diagnosed over the past 10 years, HPV16 was most commonly found (61.2%), followed by HPV18 (17.7%), HPV52 (14.7%) and HPV58 (9.9%), whereas adeno/adenosquamous cell carcinoma was dominated by HPV18 (56.3%) and HPV16 (50.0%). The proportion of HPV16-positive SCC showed a significant linear trend of increase with time (45.2% for 1972-1973, 58.8% for 1984-1986, 61.2% for 1997-2007; p(Trend) = 0.023), whereas HPV52-positive SCC decreased with time (30.1% for 1972-1973; 29.4% for 1984-1986, 14.7% for 1997-2007; p(Trend) = 0.001). Vaccines comprising HPV16/18 cover 62.6% of SCC and 93.8% of adeno/adenosquamous carcinoma in Hong Kong, and inclusion of HPV52 and HPV58 can increase the coverage by 18.4% for SCC and 4.1% for adeno/adenosquamous cell carcinoma. HPV type distribution may change over time. Further investigations to reveal the determinants for such changes and continuous monitoring for possible type replacement as a result of widespread long-term use of HPV vaccines are warranted. Multiple infections are commonly revealed by sensitive broad-catching methods such as those used in this study. However, their implication on vaccine efficacy and cost-effective analyses should be taken cautiously.

  1. Prevalence of human papillomavirus infection, distribution of viral types and risk factors in cervical samples from human immunodeficiency virus-positive women attending three human immunodeficiency virus-acquired immune deficiency syndrome reference centres in northeastern Brazil

    PubMed Central

    Martins, Albert Eduardo Silva; Lucena-Silva, Norma; Garcia, Renan Gomes; Welkovic, Stefan; Barboza, Aureliana; Menezes, Maria Luiza Bezerra; Maruza, Magda; Tenório, Terezinha; Ximenes, Ricardo AA

    2014-01-01

    Human immunodeficiency virus (HIV)-positive patients have a greater prevalence of coinfection with human papillomavirus (HPV) is of high oncogenic risk. Indeed, the presence of the virus favours intraepithelial squamous cell lesion progression and may induce cancer. The aim of this study was to evaluate the prevalence of HPV infection, distribution of HPV types and risk factors among HIV-positive patients. Cervical samples from 450 HIV-positive patients were analysed with regard to oncotic cytology, colposcopy and HPV presence and type by means of polymerase chain reaction and sequencing. The results were analysed by comparing demographic data and data relating to HPV and HIV infection. The prevalence of HPV was 47.5%. Among the HPV-positive samples, 59% included viral types of high oncogenic risk. Multivariate analysis showed an association between HPV infection and the presence of cytological alterations (p = 0.003), age greater than or equal to 35 years (p = 0.002), number of partners greater than three (p = 0.002), CD4+ lymphocyte count < 200/mm3 (p = 0.041) and alcohol abuse (p = 0.004). Although high-risk HPV was present in the majority of the lesions studied, the low frequency of HPV 16 (3.3%), low occurrence of cervical lesions and preserved immunological state in most of the HIV-positive patients were factors that may explain the low occurrence of precancerous cervical lesions in this population. PMID:25317701

  2. [Prevalence of epithelial squamous cell abnormalities and associated factors in women of a rural town of Colombia].

    PubMed

    Grisales, Hugo; Vanegas, Angela Patricia; Gaviria, Angela M; Castaño, Jorge; Mora, Martín Alonso; Borrero, Mauricio; Rojas, Carlos; Arbeláez, María Patricia; Sánchez, Gloria I

    2008-06-01

    In spite of implementation of cytology-based cervical cancer screening in Colombia, mortality rates remain stable. The description of factors associated to cervical pre-neoplasic lesions is needed to establish strategies for mortality prevention. The prevalence of epithelial squamous cell abnormalities was determined to explore the association of cytology abnormalities with described risk factors. This population-based, cross-sectional study included 739 women randomly selected by age. A validated face-to-face questionnaire and conventional cervical cytology were used to collect the information. To establish the association between cervical abnormalities and some qualitative variables, the independent chi squared test was used. We also calculated prevalence ratio with their 95% confidence intervals. A logistic regression model was used to explore variables that potentially explain cytology abnormalities. The prevalence of squamous cell abnormality was 15.8%. Among women with abnormal cytology, 10% presented atypical squamous cells of undetermined significance, 3.9% low grade squamous intra-epithelial lesion and 1.9% high grade squamous intra-epithelial lesion. The adjusted logistical regression analysis showed that history of sexual transmitted disease, two or more sexual partners during entire life and previous abnormal cytology were associated with cytology abnormalities. The relation of epithelial squamous cell abnormalities with sexual behavior history reflexes the link between human papiloma virus infection and cervical cancer pre-neoplasic lesions. The frequency of use and knowledge about the purpose of cytology were factors that suggested other diagnostic limitations such as quality of cervical cytology or barriers to access health care. These latter factors may be the underlying basis for the high cervical cancer mortality rates.

  3. Overexpression of Dishevelled-2 contributes to proliferation and migration of human esophageal squamous cell carcinoma.

    PubMed

    Zhou, Guoren; Ye, Jinjun; Sun, Lei; Zhang, Zhi; Feng, Jifeng

    2016-06-01

    Dishevelled-2 (Dvl2) was associated with tumor cell proliferation and migration. We aimed to examine the mechanism of Dvl2 in esophageal squamous cell carcinoma (ESCC). Dvl2 was overexpressed in human ESCC tissues and cell lines ECA109 and TE1 cells. CCK-8 and colony formation assay was performed to evaluate the proliferation in ECA109 cells transfected with Dvl2-shRNA. Wound-healing assay and transwell assay were used to examine the activities of migration and invasion in Dvl2-silenced ESCC cells. Knockdown of Dvl2 significantly reduced ECA109 cell proliferation and migration. Moreover, we demonstrated that the proliferation and migration ability of Dvl2 might through the activation of Wnt pathway by targeting the Cyclin D1 and MMP-9. We came to the conclusion that the proliferation and migration effects of Dvl2 might contribute to malignant development of human ESCC.

  4. A retrospective study of neoadjuvant chemotherapy plus radical hysterectomy versus radical hysterectomy alone in patients with stage II cervical squamous cell carcinoma presenting as a bulky mass

    PubMed Central

    Takatori, Eriko; Shoji, Tadahiro; Takada, Anna; Nagasawa, Takayuki; Omi, Hideo; Kagabu, Masahiro; Honda, Tatsuya; Miura, Fumiharu; Takeuchi, Satoshi; Sugiyama, Toru

    2016-01-01

    Objective In order to evaluate the usefulness of neoadjuvant chemotherapy (NAC) for stage II cervical squamous cell carcinoma with a bulky mass, we retrospectively compared patients receiving NAC followed by radical hysterectomy (RH; NAC group) with patients who underwent RH without NAC (Ope group). Patients and methods The study period was from June 2002 to March 2014. The subjects were 28 patients with a stage II bulky mass in the NAC group and 17 such patients in the Ope group. The chi-square test was used to compare operative time, volume of intraoperative blood loss, use of blood transfusion, and time from surgery to discharge between the two groups. Moreover, the log-rank test using the Kaplan–Meier method was performed to compare disease-free survival (DFS) and overall survival (OS) between the groups. Results There were no statistically significant differences between the two groups in operative time, volume of intraoperative blood loss, or use of blood transfusion. However, the time from surgery to discharge was 18 days (14–25 days) in the NAC group and 25 days (21–34 days) in the Ope group; the patients in the NAC group were discharged earlier (P=0.032). The hazard ratio for DFS in the NAC group as compared with that in the Ope group was 0.36 (95% CI 0.08–0.91), and the 3-year DFS rates were 81.2% and 41.0%, respectively (P=0.028). Moreover, the hazard ratio for OS was 0.39 (95% CI 0.11–1.24), and the 3-year OS rates were 82.3% and 66.4%, respectively (P=0.101). Conclusion NAC with cisplatin and irinotecan was confirmed to prolong DFS as compared with RH alone. The results of this study suggest that NAC might be a useful adjunct to surgery in the treatment of stage II squamous cell carcinoma presenting as a bulky mass. PMID:27695343

  5. Expression of HIWI in human esophageal squamous cell carcinoma is significantly associated with poorer prognosis

    PubMed Central

    2009-01-01

    Background HIWI, the human homologue of Piwi family, is present in CD34+ hematopoietic stem cells and germ cells, but not in well-differentiated cell populations, indicating that HIWI may play an impotent role in determining or maintaining stemness of these cells. That HIWI expression has been detected in several type tumours may suggest its association with clinical outcome in cancer patients. Methods With the methods of real-time PCR, western blot, immunocytochemistry and immunohistochemistry, the expression of HIWI in three esophageal squamous cancer cell lines KYSE70, KYSE140 and KYSE450 has been characterized. Then, we investigated HIWI expression in a series of 153 esophageal squamous cell carcinomas using immunohistochemistry and explored its association with clinicopathological features. Results The expression of HIWI was observed in tumour cell nuclei or/and cytoplasm in 137 (89.5%) cases, 16 (10.5%) cases were negative in both nuclei and cytoplasm. 86 (56.2%) were strongly positive in cytoplasm, while 49 (32.0%) were strongly positive in nuclei. The expression level of HIWI in cytoplasm of esophageal cancer cells was significantly associated with histological grade (P = 0.011), T stage (P = 0.035), and clinic outcome (P < 0.001), while there was no correlation between the nuclear HIWI expression and clinicopathological features. Conclusion The expression of HIWI in the cytoplasm of esophageal cancer cells is significantly associated with higher histological grade, clinical stage and poorer clinical outcome, indicating its possible involvement in cancer development. PMID:19995427

  6. Diagnosis of squamous cell carcinoma of human skin by Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Pereira, Riziene d. M. F.; Martin, Airton A.; Tierra-Criollo, Carlos J.; Santos, Ivan D.

    2004-07-01

    The development of a technique that gives early diagnosis and is non-invasive is of crucial importance for public health. Raman spectroscopy is a technique that can full fill these requirements. The main goal of this work was to use the FT-Raman spectroscopy to differentiate between normal skin and the squamous cell carcinoma (SCC) tissues in vitro. The samples used in this study were collected by traditional human biopsy of skin tissue. The samples removed from the patients were washed in physiologic serum and frozen in liquid nitrogen. The FT-Raman device used was the RFS 100- Bruker, with a 1064nm from the Nd:YAG as an excitation source. After the Raman measurement the samples were submitted for histopathological study for comparation. The Raman spectra in the normal tissue showed the presence of vibrational bands in 860 cm-1 and 939 cm-1 with higher intensity than in the carcinoma spectra. These modes were assigned to the vibration of proline and hydroxiproline. The shift region of 1555 to 1560 cm-1 showed a difference of intensity to the samples of squamous cell carcinoma, which were attributed to the nucleic acid.

  7. Current and future techniques for human papilloma virus (HPV) testing in oropharyngeal squamous cell carcinoma.

    PubMed

    Qureishi, Ali; Mawby, Thomas; Fraser, Lisa; Shah, Ketan A; Møller, Henrik; Winter, Stuart

    2017-03-11

    Despite a reduction in smoking and alcohol consumption, the incidence of oropharyngeal squamous cell carcinoma (OPSCC) is rising. This is attributed to human papilloma virus (HPV) infection and screening for HPV is now recommended in all cases of OPSCC. Despite a variety of clinically available tests and new non-invasive test strategies there is no consensus on which technique is best. This review reports on current techniques for HPV detection in OPSCC and the clinical applicability of emerging techniques. Literature searches of Medline, Embase and clinicaltrials.gov using the search terms 'head and neck neoplasms', 'squamous cell carcinoma' and 'HPV testing' were performed. 45 studies were identified and included. p16 immunohistochemistry (IHC), HPV DNA in situ hybridization (ISH) and HPV polymerase chain reaction (PCR) are the commonest tests to determine HPV status. p16 IHC and HPV DNA PCR are highly sensitive whilst HPV DNA ISH is more specific, these techniques conventionally utilize surgical biopsies. New tests using PCR to screen fine needle aspirates, saliva, brush cytology and serum for HPV are promising but have variable sensitivity and specificity. These non-invasive samples avoid the morbidity of surgical biopsies and need for tissue blocks; their clinical role in screening and surveillance remains largely untested. Further work is needed to validate these tests and define their role.

  8. DETECTION OF HUMAN PAPILLOMA VIRUS IN HEAD AND NECK SQUAMOUS CELL CARCINOMAS: A LITERATURE REVIEW.

    PubMed

    Jelihovschi, I; Bidescu, Aida Corina; Tucaliuc, Simona Elena; Iancu, Luminiţa Smaranda

    2015-01-01

    Human papilloma viruses (HPV) are the most common sexually transmitted viruses. There is mounting evidence that incriminates HPV as a risk factor for malignant transformation of oropharyngeal epithelium. In 2011 the International Research Agency of Cancer and National Cancer Institute (USA) declared HPV-16 as an independent risk factor for oropharyngeal squamous cell carcinoma (OPSCC). Leaders in the field of HPV research admit that this subtype of head and neck cancer is a sexually transmitted entity and its global incidence is on the rise. In the 1980s, clinicians observed a new group of patients with head and neck squamous cell carcinoma (HNSCC) independent of tobacco smoking or alcohol use. The new HNSCC patient is a middle-aged man, non-smoker, non-drinker with higher social status and the suspected risk factors for HNSCC being related to sexual practices (oral sex, multiple sexual partners, unprotected sex and drug use). Routine HPV testing of HNSCC patients is seriously considered as HPV-positive oropharyngeal cancers comprise a distinct molecular, clinical and pathologic entity that has a markedly better prognosis than HPV-negative oropharyngeal cancers. The current treatment protocols for OPSCC include radiation, chemotherapy and surgery alone or in combination, involving high toxicity levels. Future therapeutic concepts for OPSCC may be personalized in relation to HPV-status to avoid unnecessary toxicity. The current review summarizes the contemporary trends in the diagnosis of HPV-related head and neck cancers, presenting the advantages and disadvantages of the main methods.

  9. ANTI-CANCER ACTIVITY OF ASTER TATARICUS ON SCC-9 HUMAN ORAL SQUAMOUS CARCINOMA.

    PubMed

    Wang, Rui; Xiao, Sha; Niu, Zhongying

    2017-01-01

    Oral squamous carcinoma is a head and neck cancer, which is one of the types of malignant cancers. Present study evaluates the anticancer activity of Aster tataricus (AT) on SCC-9 human oral squamous carcinoma. Ethanol extract of AT was prepared by a standard procedure of maceration. AT extract was used in different concentrations like 10, 20, 40, 80, 160, 320 and 640 μg/ml for the evaluation of its anticancer activity. Effect of AT extract on SCC9 cells were observed by microscope and cytotoxicity by 3-(4, 5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay. Moreover, clonogenic assay was used for the estimation of effect of AT extract on colony forming ability of SCC9 cells. Result of the study suggested that treatment with AT extract causes cytotoxicity to SCC9 cancerous cells. In addition, AT extract treatment reduces clonogenic potential of SCC9 cell and it also inhibits the proliferation of cell significantly (p<0.001) in G2/M phase. Thus, given study concludes that AT extract effectively attenuates the growth of SCC-9 cancerous cells by the virtue of its cytotoxic and anti clonogenic activity.

  10. In situ hybridization analysis of human papillomavirus in anal squamous cell carcinoma.

    PubMed

    Gal, A A; Saul, S H; Stoler, M H

    1989-09-01

    To investigate the association between human papillomavirus (HPV) infection and anal carcinoma, we applied a sensitive in situ hybridization technique to detect HPV messenger RNA (HPV m-RNA) in formalin-fixed, paraffin-embedded sections from 18 patients. Using tritium-labeled probes, HPV m-RNA was detected in 12/18 (67%) patients. HPV 6 was detected in four patients, coexisting with HPV 18 in two cases, and HPV 16 was found in eight patients. In six patients, hybridization failed to demonstrate the presence of HPV. With respect to histology, HPV 6 was detected in 1/4 cases of well differentiated invasive squamous cell carcinoma. Ten of thirteen moderately or poorly differentiated invasive squamous cell carcinomas demonstrated HPV m-RNA (HPV 16, eight cases; HPV 6, one case; HPV 6 and 18, one case). HPV 31 was not detected in any specimens. These results suggest that HPV infection may play an important role in the pathogenesis of anal carcinoma.

  11. DEC2 expression antagonizes cisplatin‑induced apoptosis in human esophageal squamous cell carcinoma.

    PubMed

    Sato, Hidenobu; Wu, Yunyan; Kato, Yukio; Liu, Qiang; Hirai, Hideaki; Yoshizawa, Tadashi; Morohashi, Satoko; Watanabe, Jun; Kijima, Hiroshi

    2017-07-01

    Differentiated embryonic chondrocyte expressed gene 1 (DEC1) and differentiated embryonic chondrocyte expressed gene 2 (DEC2) belong to the Hairy/Enhancer of Split subfamily of basic helix‑loop‑helix factors. Previous studies have demonstrated that DEC proteins are involved in the regulation of circadian rhythms, response to hypoxia, and tumorigenesis. However, the roles of DEC1 and DEC2 in apoptosis of esophageal carcinoma remain unclear. In the present study, alterations in expression of apoptosis‑related markers in human esophageal squamous cell carcinoma TE‑11 cells treated with cisplatin were examined by western blot, while overall cell viability and apoptosis were analyzed by MTS assay and hematoxylin and eosin staining, respectively. Following cisplatin treatment, expression of DEC2 was downregulated, whereas expression of DEC1 was upregulated. DEC2 overexpression during cisplatin treatment markedly inhibited expression of the pro‑apoptotic factor Bim and slightly increased the anti‑apoptotic factor Bcl‑xL. However, overexpression of DEC1 during cisplatin treatment failed to affect expression of these markers. Additionally, overexpression of DEC2 improved cell viability and decreased cell apoptosis induced by cisplatin. These results suggested that DEC2 exhibits anti‑apoptotic effects in TE‑11 esophageal squamous cell carcinoma cells. Inhibiting DEC2 may therefore have therapeutic potential for the treatment of esophageal cancer, in combination with cisplatin.

  12. The detective, prognostic, and predictive value of DNA methylation in human esophageal squamous cell carcinoma.

    PubMed

    Ma, Kai; Cao, Baoping; Guo, Mingzhou

    2016-01-01

    Esophageal cancer is one of the most common malignancies in the world. Squamous cell carcinoma accounts for approximately 90 % of esophageal cancer cases. Genetic and epigenetic changes have been found to accumulate during the development of various cancers, including esophageal squamous carcinoma (ESCC). Tobacco smoking and alcohol consumption are two major risk factors for ESCC, and both tobacco and alcohol were found to induce methylation changes in ESCC. Growing evidence demonstrates that aberrant epigenetic changes play important roles in the multiple-step processes of carcinogenesis and tumor progression. DNA methylation may occur in the key components of cancer-related signaling pathways. Aberrant DNA methylation affects genes involved in cell cycle, DNA damage repair, Wnt, TGF-β, and NF-κB signaling pathways, including P16, MGMT, SFRP2, DACH1, and ZNF382. Certain genes methylated in precursor lesions of the esophagus demonstrate that DNA methylation may serve as esophageal cancer early detection marker, such as methylation of HIN1, TFPI-2, DACH1, and SOX17. CHFR methylation is a late stage event in ESCC and is a sensitive marker for taxanes in human ESCC. FHIT methylation is associated with poor prognosis in ESCC. Aberrant DNA methylation changes may serve as diagnostic, prognostic, and chemo-sensitive markers. Characterization of the DNA methylome in ESCC will help to better understand its mechanisms and develop improved therapies.

  13. Optimal Cervical Cancer Screening in Women Vaccinated Against Human Papillomavirus.

    PubMed

    Kim, Jane J; Burger, Emily A; Sy, Stephen; Campos, Nicole G

    2017-02-01

    Current US cervical cancer screening guidelines do not differentiate recommendations based on a woman's human papillomavirus (HPV) vaccination status. Changes to cervical cancer screening policies in HPV-vaccinated women should be evaluated. We utilized an individual-based mathematical model of HPV and cervical cancer in US women to project the health benefits, costs, and harms associated with screening strategies in women vaccinated with the bivalent, quadrivalent, or nonavalent vaccine. Strategies varied by the primary screening test, including cytology, HPV, and combined cytology and HPV "cotesting"; age of screening initiation and/or switching to a new test; and interval between routine screens. Cost-effectiveness analysis was conducted from the societal perspective to identify screening strategies that would be considered good value for money according to thresholds of $50 000 to $200 000 per quality-adjusted life-year (QALY) gained. Among women fully vaccinated with the bivalent or quadrivalent vaccine, optimal screening strategies involved either cytology or HPV testing alone every five years starting at age 25 or 30 years, with cost-effectiveness ratios ranging from $34 680 to $138 560 per QALY gained. Screening earlier or more frequently was either not cost-effective or associated with exceedingly high cost-effectiveness ratios. In women vaccinated with the nonavalent vaccine, only primary HPV testing was efficient, involving decreased frequency (ie, every 10 years) starting at either age 35 years ($40 210 per QALY) or age 30 years ($127 010 per QALY); with lower nonavalent vaccine efficacy, 10-year HPV testing starting at earlier ages of 25 or 30 years was optimal. Importantly, current US guidelines for screening were inefficient in HPV-vaccinated women. This model-based analysis suggests screening can be modified to start at later ages, occur at decreased frequency, and involve primary HPV testing in HPV-vaccinated women, providing more health benefit at

  14. Sun exposure, sexual behavior and uterine cervical human papilloma virus.

    PubMed

    Hrushesky, William J M; Sothern, Robert B; Rietveld, Wop J; Du-Quiton, Jovelyn; Boon, Mathilde E

    2006-01-01

    We have previously observed marked seasonal fluctuations in the frequency of cervical smears positive for human papilloma virus (HPV) in a series of smears obtained in Holland, with a peak in the summer months, especially August. Here, we tested two possible mechanisms that might underlie this summer peak: (1) enhanced transmission of HPV due to increased seasonal sexual activity, or (2) suppression of immunity due to summertime population exposure to solar ultraviolet (UV) radiation. Data derived from a continuous series of >900,000 independent cervical smears obtained from 1983 to 1998 were assessed for histopathologic epithelial changes pathognomonic of HPV. The rate of HPV positivity was then compared to both the rate of sexual activity (using conception frequency as a readily available surrogate) as well as yearly and monthly fluctuations in solar-UV fluency. The rate of HPV positivity was found to be twice as high during the summer months, with a peak in August corresponding with maximal UV fluency. Furthermore, over these 16 consecutive years of continuous observation, maximum HPV detection rate and maximum UV fluency are positively correlated (r=0.59, P<0.01); the sunnier the year, the greater the rate of HPV. Likewise, there is a positive correlation of the monthly UV fluency, and monthly HPV discovery rate (r=0.16, P<0.03). In contrast, conception frequency (and, presumably, population sexual HPV transmission) was maximal near the vernal equinox, with relatively modest (<10%) seasonal fluctuation, i.e., not fully explaining this prominent August peak in HPV discovery. There is a clear relationship between the detection of HPV-positive cervical smears and sunlight exposure. We speculate that the well-known phenomenon of UV-mediated suppression of immune surveillance may be causally related to this unusual increase in cytologically defined active HPV infections during the summer months in northern countries such as Holland. Confirming this relationship

  15. Human papilloma virus infection and cervical intraepithelial neoplasia in transplanted patients.

    PubMed

    Paternoster, D M; Cester, M; Resente, C; Pascoli, I; Nanhorngue, K; Marchini, F; Boccagni, P; Cillo, U; Ribaldone, R; Amoruso, E; Cocca, N; Cuccolo, V; Bertolino, M; Surico, N; Stratta, P

    2008-01-01

    Progress in diagnosis and treatment has led to an increased number of transplantation patients who consequently have immunological depression and emergence of tumors. The incidence of cervical neoplasia, according to previous studies, is 11%; this tumor is the only one that can be investigated by screening before and after a graft. Our purpose was to evaluate whether transplanted patients showed an increased incidence of genital human papilloma virus (HPV) infection and whether this infection produced greater progression of disease in cases of low-risk HPV infections. Our study involved 151 transplant patients who underwent Papanicolaou (Pap) and HPV tests. Patients listed for grafts underwent Pap and HPV tests 6 months before and 6 months after transplantation. All patients had negative Pap tests before their grafts. After their grafts 16 patients (10.59%) had negative Pap tests, but positive viral typing. Eleven patients (7.28%) showed positive Pap tests, 6 of whom had low-grade squamous intraepithelial lesion (SIL) and 5 patients high-grade SIL. The final HPV infection incidence (15.23%) was consistent with the literature. The incidence of lower female genital tract intraepithelial lesions (7.28%) was higher than the healthy population or analogous studies (4.5%-8.5%). We showed a constant association between high-risk HPV infection and gynecologic intraepithelial neoplasia, whereas there was no association between low-risk broods HPV infection and neoplasia. In conclusion, screening should start at almost 6 months before grafting to avoid an irreversible situation that is difficult to treat.

  16. Prevalence of human papillomavirus genotypes associated with cervical and breast cancers in iran.

    PubMed

    Hossein, Rassi; Behzad, Salehi; Tahar, Mohammadian; Azadeh, Nahavandi Araghi

    2013-12-01

    Cancer is a multi-step disease, and infection with a DNA virus could play a role in one or more of the steps in this pathogenic process. High-risk human papillomaviruses (HPV) are the causative agent of several cancers. In this study, we determined the prevalence and genotype distribution of HPV infection among Iranian patients with cervix lesions (CL) and breast cancer (BC). The study group consisted of postoperative tissues from patients diagnosed with cervix lesions and breast cancer. We analyzed 250 formalin-fixed, paraffin-embedded tissue blocks from 100 cervix lesions and 150 breast cancer samples. Verification of each cancer reported in a relative was sought through the pathology reports of the hospital records. Cervix lesions were collected from 100 patients with squamous metaplasia (SM, n=50), cervical intraepithelial neoplasia (CINI, n=18, CINII or III, n=8), and cervical carcinoma (CC, n=24). In this study we evaluated the prevalence of HPV by multiplex PCR in cervix lesions and breast cancer. For paraffin-embedded tissues, DNA extracted by the simple boiling method yielded higher proportions of successful gene amplification (99%) for b-actin gene. Overall prevalence of HPV infection was 6% in the SM group, 34.61% in the CIN group, 75% in the CC group, and 34.66% in the BC group. Furthermore, MY09/11 consensus PCR failed to detect 44 (55.69%) of all HPV infections and interestingly, the predominant genotype detected in all cancers was the oncogenic variant HPV16/18; about 34% of women aged 24 to 54 were infected with at least one type of HPV. Our results demonstrate that DNA derived from archival tissues that archived for less than 8 years could be used successfully for HPV genotyping by multiplex PCR. Infection with HPV was prevalent among Iranian women with CC and BC. The results indicate a likely causal role for high-risk HPV in CC and BC, and also offer the possibility of primary prevention of these cancers by vaccination against HPV in Iran.

  17. Development of a finite element model of the human cervical spine.

    PubMed

    Zafarparandeh, Iman; Erbulut, Deniz U; Lazoglu, Ismail; Ozer, Ali Fahir

    2014-01-01

    The finite element model has been used as an effective tool in human spine biomechanics. Biomechanical finite element models have provided basic insights into the workings of the cervical spine system. Advancements in numerical methods during the last decade have enabled researchers to propose more accurate models of the cervical spine. The new finite element model of the cervical spine considers the accurate representation of each tissue regarding the geometry and material. The aim of this paper is to address the new advancements in the finite element model of the human cervical spine. The procedures for creating a finite element model are introduced, including geometric construction, material-property assignment, boundary conditions and validation. The most recent and published finite element models of the cervical spine are reviewed.

  18. Human Papillomavirus at Multiple Sites Associated with Anal Squamous Intraepithelial Lesions in HIV-Seropositive Individuals

    PubMed Central

    Chuang, Eleanore; Lim, Eunjung; Milne, Cris; Zhu, Xuemei; Agsalda, Melissa; Killeen, Jeffrey; Miller, F DeWolfe; Hernandez, Brenda Y.; Shiramizu, Bruce

    2016-01-01

    Objective HIV-Seropositive patients have higher risk of HPV infection even on anti-retroviral therapy. Infection with high-risk HPV genotypes can cause dysplasia leading to cancer. This study assessed HPV at different anatomical sites in HIV-seropositive individuals and factors associated with anal squamous intraepithelial lesions (ASIL). Methods Specimens were obtained from multiple anatomical sites for each participant in conjunction with routine screening for anal dysplasia. Female specimens included cervical and anal cytologies and oral wash. Male specimens included anal cytologies, oral wash, and exfoliated cells from penile head, penile shaft, scrotum, and from uncircumcised subjects, inner foreskin. Demographic and clinical characteristics were recorded. Following DNA extraction, HIV DNA copy was assessed by qPCR; HPV was genotyped. Statistical analyses included calculation of odds ratios (OR) and 95% confidence intervals (CI), t-tests or Mann-Whitney tests. Results Males were more likely to have ASIL: 29/50 (58%) compared to 1/11 females (9%) (OR=13.81, 95% CI: 1.64–116.32). HPV 6 or 11 in anal specimens was significantly associated with ASIL (OR= 6.29, 95% CI: 1.49–26.44). Number of HPV genotypes in anal specimens was also significant: ASIL+ (3.4 ± 3.1) versus ASIL− (1.6 ± 3.1) (p=0.009). Among 44 males, HPV was detected from at least one anatomical site for 33 participants (75%): 27 anus (61%), 19 oral wash (44%), 17 penile shaft (39%), 11 scrotum (26%), 10 penile head (23%), 0 foreskin. Detection of HPV in penile shaft specimens was significantly associated with ASIL (OR=6.79, 95% CI: 1.57–29.36) as was number of HPV genotypes in penile shaft specimens: ASIL+ (2.4 ± 4.0) versus ASIL− (0.6 ± 1.7) (p=0.025). Only 1/11 females had ASIL; only 1/11 females had cervical dysplasia: OR was not estimable due to small numbers. Conclusions Males were more prone to ASIL than females. HPV at anal as well as non-anal sites may be indicative of ASIL. PMID

  19. Correlation between koilocytes and human papillomavirus detection by PCR in oral and oropharynx squamous cell carcinoma biopsies.

    PubMed

    Miyahara, Glauco Issamu; Simonato, Luciana Estevam; Mattar, Neivio José; Camilo Jr, Deolino João; Biasoli, Eder Ricardo

    2011-03-01

    The purpose of this study was to compare the histopathological analysis with polymerase chain reaction (PCR) methods to predict the presence of human papillomavirus (HPV) infection in oral squamous cell carcinoma biopsies. Eighty-three paraffin-embedded tissue specimens from patients with oropharynx and mouth floor squamous cell carcinoma were submitted to histopathological analysis under light microscopy, specifically for the determination of the presence of koilocytes. Subsequently, DNA wa