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Sample records for human cervical squamous

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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.

  7. 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

  8. 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.

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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. .

  16. 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

  17. 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

  18. 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.

  19. 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

  20. 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.

  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. [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.

  3. 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

  4. 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.

  5. 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.

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

    PubMed Central

    LU, XIAOQIN; CUI, JINQUAN; FU, MEIZHOU; WANG, WULIANG

    2016-01-01

    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. PMID:27347120

  7. 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.

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. 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

  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. [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.

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. 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

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

    ClinicalTrials.gov

    2017-03-08

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

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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.

  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. 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.

  18. 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

  19. 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.

  20. 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

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

    ClinicalTrials.gov

    2016-03-16

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

  2. 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

  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. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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

  9. [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.

  10. 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

  11. 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

  12. 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.

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. Sex-determining region Y-related high mobility group box (SOX)-2 is overexpressed in cervical squamous cell carcinoma and contributes cervical cancer cell migration and invasion in vitro.

    PubMed

    Chang, Xiaohan; Zhang, Jing; Huang, Chenglin; Pang, Xiaoao; Luo, Qingshuang; Zhang, Huijie; Zhang, Shulan

    2015-09-01

    Sex-determining region Y-related high mobility group box 2 (SOX-2) is a key pluripotency-associated transcription factor and may be implicated in the pathogenesis of cervical squamous cell carcinoma (SCC). The aim of this study was to explore SOX-2 expression in cervical SCC tissues and to examine whether and how SOX-2 regulates the malignant behaviors of cervical SCC cells in vitro. We here found that SOX-2 expression in the examined cervical SCC tissues was higher than that in the normal cervical and cervical intraepithelial neoplasia (CIN) tissues. Higher protein level of SOX-2 (nuclear positive staining cells ≥50 %) was detected in 34.9 % (29 out of 83 cases) of cervical SCC patients. We also noted that 100 % of well-differentiated and 66.7 % of moderately differentiated cervical SCCs showed lower SOX-2 expression (nuclear positive staining cells <50 %), while 58.8 % of poorly differentiated tumors had higher SOX-2 expression (P < 0.05). Furthermore, the migratory and invasive capabilities of SiHa cervical cancer cells were enhanced when SOX-2 was upregulated whereas suppressed when SOX-2 was downregulated. Also, the phosphorylation levels of protein kinase B (Akt) and extracellular regulated protein kinases (ERK) 1/2 were increased in SOX-2-overexpressed cancer cells but decreased in SOX-2-depleted cells. Additionally, LY294002 (Akt pathway inhibitor) or U0126 (ERK pathway inhibitor) significantly suppressed SOX-2-overexpression-induced migration and invasion in SiHa cells. Our results indicate that differentially expressed SOX-2 is associated with tumor differentiation (P < 0.05) and that SOX-2 contributes to the migratory and invasive behaviors of cervical SCC in vitro.

  3. 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.

  4. 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

  5. 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

  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. 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

  8. 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

  9. [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.

  10. 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

  11. 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.

  12. [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.

  13. 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.

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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.

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

    ClinicalTrials.gov

    2017-02-08

    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

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. 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

  16. [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).

  17. 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

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. 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

  3. 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

  4. Associations between sexually transmitted infections, high-risk human papillomavirus infection, and abnormal cervical Pap smear results in OB/GYN outpatients

    PubMed Central

    Kim, Tae Jin

    2016-01-01

    Objective 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. Methods 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. Results 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. Conclusion 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. PMID:27329197

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. Studying the Physical Function and Quality of Life Before and After Surgery in Patients With Stage I Cervical Cancer

    ClinicalTrials.gov

    2016-10-26

    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

  13. 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

  14. 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

  15. Cervicitis

    MedlinePlus

    ... results from a sexually transmitted infection, such as chlamydia or gonorrhea. Cervicitis can develop from noninfectious causes, ... from common sexually transmitted infections (STIs), including gonorrhea, chlamydia, trichomoniasis and genital herpes. Allergic reactions. An allergy, ...

  16. Cervicitis

    MedlinePlus

    ... much growth of normal bacteria in the vagina (bacterial vaginosis) can also cause cervicitis. ... under a microscope (may show candidiasis , trichomoniasis , or bacterial vaginosis) Pap test Tests for gonorrhea or chlamydia Rarely, ...

  17. 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.

  18. 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

  19. 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

  20. 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

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. 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

  18. Triapine With Chemotherapy and Radiation Therapy in Treating Patients With IB2-IVA Cervical or Vulvar Cancer

    ClinicalTrials.gov

    2017-01-31

    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

  19. 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.

  20. 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

  1. Chemoradiation Therapy and Ipilimumab in Treating Patients With Stages IB2-IIB or IIIB-IVA Cervical Cancer

    ClinicalTrials.gov

    2017-03-08

    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

  2. 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.

  3. [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.

  4. 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.

  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. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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

  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. 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.

  13. 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.

  14. 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

  15. Automated image analysis of uterine cervical images

    NASA Astrophysics Data System (ADS)

    Li, Wenjing; Gu, Jia; Ferris, Daron; Poirson, Allen

    2007-03-01

    Cervical Cancer is the second most common cancer among women worldwide and the leading cause of cancer mortality of women in developing countries. If detected early and treated adequately, cervical cancer can be virtually prevented. Cervical precursor lesions and invasive cancer exhibit certain morphologic features that can be identified during a visual inspection exam. Digital imaging technologies allow us to assist the physician with a Computer-Aided Diagnosis (CAD) system. In colposcopy, epithelium that turns white after application of acetic acid is called acetowhite epithelium. Acetowhite epithelium is one of the major diagnostic features observed in detecting cancer and pre-cancerous regions. Automatic extraction of acetowhite regions from cervical images has been a challenging task due to specular reflection, various illumination conditions, and most importantly, large intra-patient variation. This paper presents a multi-step acetowhite region detection system to analyze the acetowhite lesions in cervical images automatically. First, the system calibrates the color of the cervical images to be independent of screening devices. Second, the anatomy of the uterine cervix is analyzed in terms of cervix region, external os region, columnar region, and squamous region. Third, the squamous region is further analyzed and subregions based on three levels of acetowhite are identified. The extracted acetowhite regions are accompanied by color scores to indicate the different levels of acetowhite. The system has been evaluated by 40 human subjects' data and demonstrates high correlation with experts' annotations.

  16. 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

  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. 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

  19. Infection and Cervical Neoplasia: Facts and Fiction

    PubMed Central

    Al-Daraji, Wael I; Smith, John HF

    2009-01-01

    Whilst there is strong evidence that human papillomavirus (HPV) is the principal aetiological agent in cervical neoplasia, some other sexually transmitted agents may either contribute or protect against cervical carcinogenesis, such as the herpes virus family (HSV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), human immunodeficiency virus (HIV) or Chlamydia trachomatis (CT). Epidemiological studies suggest that HSV may have a role in cervical neoplasia, but there is no clear supportive experimental evidence. Serological studies have also failed to reveal a difference in the prevalence of antibodies to CMV and EBV between patients with cervical cancer and controls. However, longitudinal seroepidemiological studies have provided evidence that CT is an independent risk factor for the development of cervical squamous carcinoma and this association is serotype specific. The increased risk of cervical neoplasia in patients infected with HIV has been recognised for over a decade and HIV may interact with HPV either by alternating HPV gene transcription or by immunosuppression. Finally extensive experimental and limited epidemiological evidence suggests that adeno-associated viruses (AAV) may have antioncogenic activity in man and may protect against the development of cervical cancer. At present the mechanism of this action is unclear but may relate to AAV-induced regulation of HPV gene expression and the HPV life cycle. In this review we summarize the current literature relating to the associations and mechanisms of cervical carcinogenesis by each of these infectious microorganisms. PMID:18830380

  20. 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.

  1. Genotype distribution of human papillomavirus (HPV) in histological sections of cervical intraepithelial neoplasia and invasive cervical carcinoma in Madrid, Spain

    PubMed Central

    2012-01-01

    Background Human Papillomavirus (HPV) genotype distribution and co-infection occurrence was studied in cervical specimens from the city of Madrid (Spain), as a contribution to the knowledge of Human Papillomavirus genotype distribution and prevalence of carcinogenic HPV types in cervical lesions in Spain. Methods A total of 533 abnormal specimens, from the Hospital General Universitario “Gregorio Marañón” of Madrid, were studied. These included 19 benign lesions, 349 cervical intraepithelial neoplasias 1 (CIN1), 158 CIN2-3 and 7 invasive cervical carcinomas (ICC). HPV genotyping was performed using PCR and tube array hybridization. Results We detected 20 different HPV types: 13 carcinogenic high-risk HPV types (HR-HPVs), 2 probably carcinogenic high-risk HPV types (PHR-HPVs) and 5 carcinogenic low-risk HPV types (LR-HPVs). The most frequent HPV genotypes found in all specimens were HPV16 (26.0%), 31 (10.7%) and 58 (8.0%). HPV 18 was only detected in 5.0%. Co-infections were found in 30.7% of CIN 1 and 18.4% cases of CIN2-3. The highest percentage of HR HPVs was found in those specimens with a CIN2-3 lesion (93.7%). Conclusion As our study shows the current tetravalent vaccine could be effective in our geographical area for preventing all the invasive cervical carcinomas. In addition, upon the estimates of the important presence of other HR-HPV types – such as 31, 58, 33 and 52 – in different preneoplasic lesions the effectiveness of HPV vaccination in our geographical area, and others with similar genotype distribution, should be limited. PMID:23167826

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. Integration of human papillomavirus type 16 in cervical cancer cells

    PubMed Central

    Kanopiene, Daiva; Stumbryte, Ausra; Bausyte, Raminta; Kirvelaitis, Edgaras; Simanaviciene, Vaida; Zvirbliene, Aurelija

    2015-01-01

    Cervical cancer remains an important cause of women morbidity and mortality. The progression of cervical pathology correlates with the HPV integration into the host genome. However, the data on the viral integration status in cervical dysplasias are controversial. The aim of the current study was to evaluate the status of HPV integration in two types of cervical pathology – invasive and non invasive cervical cancer (e.g. carcinoma in situ). 156 women were included in the study: 66 women were diagnosed with invasive cervical cancer (CC) and 90 with non invasive cervical cancer (carcinoma in situ, CIS). 74.2% [95% PI: 63.64÷84.76] of specimens collected from women with diagnosed CC and 85.6% [95% PI: 85.53÷92.85] of CIS specimens were positive for HPV. The most prevalent HPV genotype in both groups was HPV16. To evaluate HPV integration, three selected HPV16 E2 gene fragments were analyzed by PCR. In the majority of CC and CIS specimens the amplification of all three HPV16 E2 gene fragments was observed. The episomal HPV16 form was detected in the majority of CC and CIS specimens. The deletion of all three HPV16 E2 gene fragments was detected in 9.4% of CC specimens and 2.2% of CIS specimens. Finally, integration status could not be used as diagnostical additional test to distinguish between invasive and non invasive cervical cancer. PMID:28352670

  9. The clinical impact of p16 status in fine-needle aspirates of cervical lymph node metastasis of head and neck squamous cell carcinomas.

    PubMed

    Jakscha, Jens; Zlobec, Inti; Storck, Claudio; Obermann, Ellen C; Tornillo, Luigi; Terracciano, Luigi M; Fischer, Claude A

    2013-02-01

    Lymph node involvement is prognostically the most determinant clinical factor for patients with head and neck squamous cell carcinomas (HNSCCs). Ultrasound of the neck and fine-needle aspiration (FNA) cytology is one of the first diagnostic procedures and the most accurate diagnostic staging tool for the neck. Patients with HPV-positive oropharyngeal carcinomas (OPSCC) show a significantly better prognosis when compared with HPV-negative OPSCC. P16 overexpression is accepted as surrogate marker for HPV-positive in OPSCC. These HPV/p16-positive OPSCC are localized either in the palatal tonsils or the base of tongue and frequently present with lymph node metastases. We analyzed the correlation and reliability of p16 expression of the FNA of the lymph node metastasis with the immunohistochemical expression of p16 of the same lymph node metastasis and its corresponding primary tumor, as it could be of importance for determining the localization and different prognosis of the primary tumor. 54 HNSCC patients were evaluated, p16 expression of the primary tumors and their lymph node metastases correlated precisely. In 25 of the 54 HNSCC patients, a FNA of the lymph node metastases was taken before the treatment. The positive cytological and immunohistochemical p16 staining correlated exactly. Of the 17 histologically p16-negative lymph node metastases 15 FNA were p16-negative, whereas two samples were p16-positive. In our view, a cytological p16 analysis of cervical lymph node metastasis can facilitate the correct localization of the primary tumor and discriminate reliably HPV-positive OPSCC from HPV-negative HNSCC with their significantly diverse prognosis.

  10. 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

  11. 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 was purified from the same paraffin-embedded specimens and submitted to PCR. Fisher's exact test showed no statistically significant correlation between the two methods. The results suggest that the presence of koilocytes is unreliable for the detection of HPV presence in oral and oropharynx squamous cell carcinoma.

  12. Association of Genital Infections Other Than Human Papillomavirus with Pre-Invasive and Invasive Cervical Neoplasia

    PubMed Central

    Mandal, Ranajit; Kundu, Pratip; Biswas, Jaydip

    2016-01-01

    Human papillomavirus (HPV) is a well-established causative agent of malignancy of the female genital tract and a common Sexually Transmitted Infection. The probable co-factors that prevent spontaneous clearance of HPV and progression to neoplasia are genital tract infections from organisms like Chlamydia, Trichomonas vaginalis etc, smoking, nutritional deficiencies and multiparity. Inflammatory conditions can lead to pre-neoplastic manifestations in the cervical epithelium; however their specific role in cervical carcinogenesis is not yet established. Therefore it is imperative to study the likely association between HPV and co-infection with various common pathogens in the genital tract of women having cervical precancer or cancer. A “Pubmed” search was made for articles in Literature on this topic using the words: Cervical neoplasia, HPV, co-infections, Cervical Intraepithelial Neoplasia (CIN), Trichomonas vaginalis, Candida, Chlamydia and the relevant information obtained was used to draft the review. PMID:27042571

  13. Analysis of human papillomavirus E7 protein status in C-33A cervical cancer cells.

    PubMed

    Kaiser, Andreas; Jenewein, Brigitte; Pircher, Haymo; Rostek, Ursula; Jansen-Dürr, Pidder; Zwerschke, Werner

    2015-02-01

    High-risk human papillomaviruses (HPV) are the main etiologic factor for the development of cervical cancer. Infections by these viruses have been detected in virtually all cervical cancers. C-33A is one of the rare cervical cancer derived cell lines considered as HPV-negative. Employing monoclonal antibodies raised against a conformational epitope of the HPV-16 E7 oncoprotein, we present evidence suggesting that E7-positive cells can be sporadically and transiently detected in C-33A cell cultures. Immunoblotting with affinity-purified rabbit polyclonal anti-HPV 16 E7 antisera and q-RT-PCR analysis suggest that these cells do probably not express HPV-16 E7. Moreover, we show that the HPV E7 protein level differs considerably between individual cells in cultures of several established cervical cancer cell lines. Our data suggest that expression of the E7 protein is variable in established cervical cancer cell lines including C-33A cells.

  14. Cisplatin and Radiation Therapy With or Without Carboplatin and Paclitaxel in Patients With Locally Advanced Cervical Cancer

    ClinicalTrials.gov

    2016-10-26

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma; Chemotherapeutic Agent Toxicity; Cognitive Side Effects of Cancer Therapy; Psychological Impact of Cancer; Radiation Toxicity; Sexual Dysfunction and Infertility; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer

  15. Cervical Cancer

    MedlinePlus

    ... cervical cancers are caused by the human papillomavirus (HPV). Cervical cancer is the easiest gynecological cancer to prevent with ... HPV on a woman's cervix. Certain types of HPV can lead to cervical cancer. Your doctor will swab the cervix for cells. ...

  16. Human papillomavirus (HPV) E6/E7 mRNA detection in cervical exfoliated cells: a potential triage for HPV-positive women*

    PubMed Central

    Yao, Ye-li; Tian, Qi-fang; Cheng, Bei; Cheng, Yi-fan; Ye, Jing; Lu, Wei-guo

    2017-01-01

    Cytology triage has been generally recommended for human papillomavirus (HPV)-positive women, but is highly dependent on well-trained cytologists. The present study was designed to explore whether HPV E6/E7 mRNA detection in cervical exfoliated cells can be a potential triage for HPV-positive women from a clinic-based population. Both the primary HPV testing and Papanicolaou (Pap) test were performed on all eligible HPV-positive women. HPV E6/E7 mRNA was detected by QuantiVirus® HPV E6/E7 mRNA assay in cervical exfoliated cells. All HPV-positive women underwent colposcopy and further biopsy if indicated. The data were assessed by Pearson’s Chi-squared test and the receiver operating characteristic curve. A total of 404 eligible HPV-positive women were enrolled. Positive rate of E6/E7 mRNA in high-grade squamous intraepithelial lesion (HSIL) cases was higher than that in low-grade squamous intraepithelial lesion (LSIL) or normal cases. There was no statistical difference found between mRNA and cytological testing with sensitivity (89.52% vs. 86.67%, P=0.671), specificity (48.96% vs. 48.96%, P=1.000), positive predictive value (39.00% vs. 38.24%, P=1.000), and negative predictive value (92.76% vs. 90.97%, P=0.678) for detecting ≥HSIL. HPV E6/E7 mRNA detection in cervical exfoliated cells shows the same performance as Pap triage for HSIL identification for HPV-positive women. Detection of HPV E6/E7 mRNA may be used as a new triage option for HPV-positive women. PMID:28271661

  17. Human papillomavirus (HPV) E6/E7 mRNA detection in cervical exfoliated cells: a potential triage for HPV-positive women.

    PubMed

    Yao, Ye-Li; Tian, Qi-Fang; Cheng, Bei; Cheng, Yi-Fan; Ye, Jing; Lu, Wei-Guo

    Cytology triage has been generally recommended for human papillomavirus (HPV)-positive women, but is highly dependent on well-trained cytologists. The present study was designed to explore whether HPV E6/E7 mRNA detection in cervical exfoliated cells can be a potential triage for HPV-positive women from a clinic-based population. Both the primary HPV testing and Papanicolaou (Pap) test were performed on all eligible HPV-positive women. HPV E6/E7 mRNA was detected by QuantiVirus(®) HPV E6/E7 mRNA assay in cervical exfoliated cells. All HPV-positive women underwent colposcopy and further biopsy if indicated. The data were assessed by Pearson's Chi-squared test and the receiver operating characteristic curve. A total of 404 eligible HPV-positive women were enrolled. Positive rate of E6/E7 mRNA in high-grade squamous intraepithelial lesion (HSIL) cases was higher than that in low-grade squamous intraepithelial lesion (LSIL) or normal cases. There was no statistical difference found between mRNA and cytological testing with sensitivity (89.52% vs. 86.67%, P=0.671), specificity (48.96% vs. 48.96%, P=1.000), positive predictive value (39.00% vs. 38.24%, P=1.000), and negative predictive value (92.76% vs. 90.97%, P=0.678) for detecting ≥HSIL. HPV E6/E7 mRNA detection in cervical exfoliated cells shows the same performance as Pap triage for HSIL identification for HPV-positive women. Detection of HPV E6/E7 mRNA may be used as a new triage option for HPV-positive women.

  18. Cervical Cancer Screening after Perimenopause: How Is Human Papillomavirus Test Performed?

    PubMed

    Chung, Soo-Ho

    2016-08-01

    Cervical cancer is the third most prevalent cancer in women around the world. Recently in Korea, the incidence of cervical cancer has decreased, but in all stages of cervical intraepithelial neoplasia (CIN), CIN has shown a 91% increase from 1999 to 2008. Persistent human papillomavirus (HPV) infection has been found to be the main cause of cervical cancer. HPV types 16 and 18 have been found in 70% of cervical cancer patients around the world. Cervical cancer screening such as cytology has limitations in terms of sensitivity and specificity. A discussion about the need for the HPV test is becoming active in order to compensate for the limitation of cytology. After the role of HPV in cervical cancer was identified, the importance of HPV detection test as a screening was emphasized. Several tests have been developed and each test has its own advantages and disadvantages, and new test method to overcome the disadvantages is still being developed. Today's guidelines and tests are those you would choose from among the large number of cervical cancer screening guidelines and tests, based on the consideration that the selected guidelines and the test are effective.

  19. Cervical and Anal Human Papillomavirus Infection in Adult Women in American Samoa

    PubMed Central

    Hernandez, Brenda Y.; Ka’opua, Lana S.; Scanlan, Luana; Ah Ching, John; Kamemoto, Lori E.; Thompson, Pamela J.; Zhu, Xuemei; Shvetsov, Yurii B.; Tofaeono, Jennifer; Williams, Victor Tofaeono

    2015-01-01

    The prevalence of cervical and anal human papillomavirus (HPV) and risk factors associated with infections were evaluated in a cross-sectional study of 211 adult women in American Samoa. Overall, 53% of women reported ever having a Pap smear. Cervical and anal HPV was detected in 10% and 16% of women, respectively; 4% of women had concurrent cervical and anal HPV. The most common cervical genotypes were HPV 6, HPV 16, and HPV 53. Cutaneous HPV types were detected in 40% of anal infections. Cervical HPV infection was associated with anal HPV (age-adjusted odds ratio = 3.32, 1.10–10.00). After age adjustment, cervical HPV was associated with being unmarried, postsecondary education, hot running water at home, multiple sexual partners, nulliparity, condom use, and other contraceptive methods. In multivariate analyses, only age remained associated with cervical HPV and anal HPV. Cervical and anal HPV was more prevalent among younger women; only anal HPV was detected in older women. PMID:22652246

  20. Detection of cervical lymph node micrometastasis and isolated tumor cells in oral squamous cell carcinoma using immunohistochemistry and serial sectioning

    PubMed Central

    Dhawan, Isha; Sandhu, Simarpreet V; Bhandari, Rajat; Sood, Neena; Bhullar, Ramanpreet Kaur; Sethi, Neerja

    2016-01-01

    Introduction: Oral squamous cell carcinoma (OSCC) comprises one of the largest subsets of cancers with a tendency for regional metastasis. Nodal status is a key prognostic indicator in patients with OSCC, particularly with N0 neck. Occult metastasis in the form of micrometastasis (MM) and isolated tumor cells (ITCs), often goes undetected by routine hematoxylin and eosin (H&E) examination using 1–2 sections for analysis. This limitation could be overcome by combining serial sectioning (SS) with immunohistochemistry (IHC) for the detection of MM and ITC. Pan-cytokeratin (pan-CK) (AE1/AE3) is particularly a useful marker to detect these deposits as their presence has resulted in varied interpretations and different applications of the tumor-node-metastasis system. Objectives: The objective of the study was to identify a suitable method for detecting MM and ITC in lymph nodes (LNs) of OSCC by combining SS and IHC and to compare it with conventional H&E staining. Materials and Methods: This laboratory-based, prospective study was conducted on 133 LNs harnessed from ten patients treated with radical neck dissection for primary OSCC. The LNs were subjected to SS at 100 μm intervals. The sections were stained with routine H&E staining, pan-CK and analyzed for MM and ITC according to criteria laid by Hermanek et al. Statistical Analysis: The obtained data were subjected to statistical analysis using Chi-square test. Results: The application of combination of SS and IHC using pan-CK (AE1/AE3) in our study revealed the presence of MM and ITC in 2.25% of the LNs diagnosed as negative on routine H&E examination. The detection of these occult metastatic deposits resulted in upstaging of 33.33% of the patients. Conclusion: In the view of crucial role of occult LN metastasis in prognosis and survival of OSCC patients with N0 neck, diagnostic tools such as IHC staining, particularly with pan-CK (AE1/AE3), combined with SS should be preferred over conventional methods as they

  1. Primary Screening for Cervical Cancer Based on High-Risk Human Papillomavirus (HPV) Detection and HPV 16 and HPV 18 Genotyping, in Comparison to Cytology

    PubMed Central

    Constantinidis, Theocharis; Constantinidis, Theodoros C.

    2015-01-01

    Objectives The objective of the present study is to assess the performance of a high-risk human papillomavirus (HR-HPV) DNA test with individual HPV-16/HPV-18 genotyping as a method for primary cervical cancer screening compared with liquid-based cytology (LBC) in a population of Greek women taking part in routine cervical cancer screening. Methods The study, conducted by the “HEllenic Real life Multicentric cErvical Screening” (HERMES) study group, involved the recruitment of 4,009 women, aged 25–55, who took part in routine cervical screening at nine Gynecology Departments in Greece. At first visit cervical specimens were collected for LBC and HPV testing using the Roche Cobas 4800 system. Women found positive for either cytology or HPV were referred for colposcopy, whereas women negative for both tests will be retested after three years. The study is ongoing and the results of the first screening round are reported herein. Results Valid results for cytology and HPV testing were obtained for 3,993 women. The overall prevalence of HR-HPV was 12.7%, of HPV-16 2.7% and of HPV-18 1.4%. Of those referred for colposcopy, cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was detected in 41 women (1.07%). At the threshold of CIN2+, cytology [atypical squamous cells of undetermined significance (ASC-US) or worse] and HPV testing showed a sensitivity of 53.7% and 100% respectively, without change between age groups. Cytology and HPV testing showed specificity of 96.8% and 90.3% respectively, which was increased in older women (≥30) in comparison to younger ones (25–29). Genotyping for HPV16/18 had similar accuracy to cytology for the detection of CIN2+ (sensitivity: 58.5%; specificity 97.5%) as well as for triage to colposcopy (sensitivity: 58.5% vs 53.7% for cytology). Conclusion HPV testing has much better sensitivity than cytology to identify high-grade cervical lesions with slightly lower specificity. HPV testing with individual HPV-16/HPV-18

  2. Hsp90 Inhibitor AT13387 in Treating Patients With Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck Receiving Radiation Therapy and Cisplatin

    ClinicalTrials.gov

    2017-01-31

    Human Papillomavirus Infection; Stage III Hypopharyngeal Squamous Cell Carcinoma; Stage III Laryngeal Squamous Cell Carcinoma; Stage III Oral Cavity Squamous Cell Carcinoma; Stage III Oropharyngeal Squamous Cell Carcinoma; Stage IVA Hypopharyngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Squamous Cell Carcinoma; Stage IVA Oral Cavity Squamous Cell Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma; Stage IVB Hypopharyngeal Squamous Cell Carcinoma; Stage IVB Laryngeal Squamous Cell Carcinoma; Stage IVB Oral Cavity Squamous Cell Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma

  3. Fracture and Viscoelastic Characteristics of the Human Cervical Spine,

    DTIC Science & Technology

    1986-01-01

    were taken from the upper cervical region, one from the central (C3- C5 ) region, and three from the lower cervical spine . b . .- -9- A noninvasive...the seven vertebrae are designated C1 through C7 . The cervical spine consists of 7 FSU’s beginning with articulation between the head (occiput) and C1...then separated by dissection at the discs into three functional vertebral segments (FVS’s), either C2-C3-C4 and C5 - VON" C6- C7 segments or C3-C4- C5

  4. Eosinophils in human oral squamous carcinoma; role of prostaglandin D2.

    PubMed

    Davoine, Francis; Sim, Adrian; Tang, Charlie; Fisher, Sibina; Ethier, Caroline; Puttagunta, Lakshmi; Wu, Yingqi; McGaw, W Tim; Yu, Donald; Cameron, Lisa; Adamko, Darryl J; Moqbel, Redwan

    2013-01-31

    Eosinophils are often predominant inflammatory leukocytes infiltrating oral squamous carcinoma (OSC) sites. Prostaglandins are secreted by oral carcinomas and may be involved in eosinophil infiltration. The objective of this study was to determine the factors contributing to eosinophil migration and potential anti-neoplastic effects on OSC. Eosinophil degranulation was evaluated by measuring release of eosinophil peroxidase (EPO). Eosinophil chemotaxis towards OSC cells was assessed using artificial basement membrane. Eosinophil infiltration was prominent within the tissue surrounding the OSC tumor mass. We observed growth inhibition of the OSC cell line, SCC-9, during co-culture with human eosinophils, in vitro, which correlated with EPO activity that possesses growth inhibitory activity. The PGD2 synthase inhibitor, HQL-79, abrogated migration towards SCC-9. Our data suggest that OSC-derived PGD2 may play an important role via CRTH2 (the PGD2 receptor on eosinophils) in eosinophil recruitment and subsequent anti-tumor activity through the action of eosinophil cationic proteins.

  5. Oral squamous papilloma and condyloma acuminatum as manifestations of buccal-genital infection by human papillomavirus

    PubMed Central

    dos Reis, Helena Lucia B.; Rabelo, Priscila C.; de Santana, Maria Rúbia F.; Ferreira, Dennis Carvalho; Filho, Antônio C.

    2009-01-01

    Genital infection by human papillomavirus (HPV), a sexually transmitted disease (STD), has increased considerably due to the changes in sexual behaviour and an increase in the practice of oral sex. HPV, in a parallel manner, has been closely studied due to its oncogenic potential. We present the case of a 27-year-old patient, with a multi-partner sexual history and frequent practice of oral sex, who suffered from warts lesions on the genitalia and tongue. Squamous papilloma was diagnosed from a tongue biopsy. The treatment of the oral lesion was by way of surgery, without relapse in the first two years. Our discussion in this report is regarding the HPV infection in the oral cavity. PMID:21938114

  6. Development of aggressive squamous cell carcinoma in epidermodysplasia verruciformis associated with human papillomavirus type 22b.

    PubMed

    Kim, Taegyun; Park, Jae Chan; Roh, Mi Ryung; Park, Jin Mo; Kim, Se Heon; Cho, Nam Hoon; Lee, Min-Geol

    2010-01-01

    Epidermodysplasia verruciformis (EV) is a rare genetic disease characterized by abnormal susceptibility to infection with EV-related human papillomavirus (HPV), now known as the beta-papillomavirus (beta-PV). Clinically specific beta-PV-type-associated EV, especially HPV-5 and -8, shows a high rate of progression to squamous cell carcinoma (SCC). In this report, we describe a 39-year-old Korean man with HPV-22b-associated EV who developed a rapidly progressing SCC. The patient presented with a huge destructive mass on the nose. Histopathological evaluation of the mass was compatible with well-differentiated SCC. HPV typing results from both EV and SCC specimens demonstrated HPV-22b which has not been considered to be associated with SCC in EV patients so far. The patient underwent surgical excision and postoperative radiotherapy for locoregional control. This is the first report presenting the association of an SCC arising from previous EV with HPV-22b infection only.

  7. Do high-risk human papillomaviruses cause oral cavity squamous cell carcinoma?

    PubMed

    Mirghani, H; Amen, F; Moreau, F; Lacau St Guily, J

    2015-03-01

    High-risk human papillomaviruses (HR-HPV) are an established etiologic factor for a growing number of oropharyngeal cancers. However, their potential role in other upper aerodigestive tract locations is still a matter of debate, particularly in the oral cavity. This is of paramount importance as in the future diagnosis, treatment and follow up in head and neck squamous cell carcinoma may vary according to HPV status. This article reviews the recent published data and highlights some of the pitfalls that have hampered the accurate assessment of HR-HPV oncological role outside the oropharynx. We demonstrate that, in contrast to the oropharynx, only a small fraction of cancers located in the oral cavity seem to be HPV-related even in young non-smoking non-drinking patients. We emphasize several relevant factors to consider in assumed HPV-induced oral cavity cancers and discuss the current theories that explain why HPV-induced cancers arise preferentially in the oropharynx.

  8. KTP laser and neutral red phototherapy of human squamous cell carcinoma.

    PubMed

    VanderWerf, Q M; Castro, D J; Nguyen, R D; Paiva, M B; Chao, K H; Santillanes, M E; Saxton, R E

    1997-03-01

    Neutral red (NR) is a cationic, nontoxic vital dye employed as a histologic stain for proliferating cells; it has been used clinically for photodynamic treatment of herpes simplex virus lesions. NR is selectively taken up and concentrated by mitotic cells, an important characteristic for more effective antineoplastic agents. In the present study, UCLA-SO-P3 human squamous carcinoma cells displayed minimal toxicity when incubated with up to 50 microg/ml NR in the absence of light. However, cells incubated with greater than 0.5 microg/ml NR followed by exposure to KTP laser light at 532 nm exhibited nearly 100% tumor cell death. The degree of cell toxicity was proportional to NR dose and laser light fluence. This study demonstrates that NR is an excellent cancer cell photosensitizer in vitro, and, after adding additional in vivo preclinical testing, may prove to be a useful agent in photodynamic destruction of head and neck tumors.

  9. Metastasis occurring eleven years after diagnosis of human papilloma virus-related oropharyngeal squamous cell carcinoma

    PubMed Central

    Ley, Jessica; Wildes, Tanya; El-Mofty, Samir; Adkins, Douglas

    2014-01-01

    Human papilloma virus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) is associated with a favourable prognosis, although approximately 20–25% of patients ultimately develop recurrent cancer. Most disease recurrence events appear within 3 years; however, long-term follow-up of reported studies are limited, and the risk of late recurrence is unknown. We present a case report of a patient who developed distant metastases of HPV-related SCC 11 years after initial diagnosis and treatment of HPV-related OPSCC. Late disease recurrence may occur after initial diagnosis of HPV-related OPSCC. This observation has implications on the appropriate duration of follow-up and surveillance of these patients. PMID:25435908

  10. Human papillomavirus DNA in plasma of patients with cervical cancer

    PubMed Central

    Pornthanakasem, Wichai; Shotelersuk, Kanjana; Termrungruanglert, Wichai; Voravud, Narin; Niruthisard, Somchai; Mutirangura, Apiwat

    2001-01-01

    Background Human papillomavirus (HPV) is a crucial etiological factor for cervical cancer (CC) development. From a diagnostic view-point, the consistent presence of HPV in CC allows the viral DNA to be used as a genetic marker. The aims of this study were to evaluate the presence, physical status and clinical significant of HPV DNA in circulation of CC patients. Results Whereas 6 out of 50 (12%) HPV positive CC patients revealed plasma HPV DNA, it was detected in none of 20 normal controls or 13 HPV negative CC cases. The plasma DNA exhibited an HPV type identical to the HPV in the primary tumors and the DNA from both sources was integrated into host genome. Interestingly, several findings suggested an association between plasma HPV DNA and metastasis. First, three of the HPV DNA positive cases were CC patients with clinical stage IVB or recurrence with distance metastases (P = 0.001, RR = 15.67). Second, the amount of plasma HPV DNA from metastatic patients to be three times more than three other patients without metastases. Finally, the later cases had tendency to develop recurrence distant metastases within one year after complete treatment when compared with other HPV associated CC patients with the same stage but without the present of plasma HPV DNA. Conclusions The plasma HPV DNA originated from the CC, was associated with metastasis and could be used as a marker representing the circulating free CC DNA. PMID:11244579

  11. Role of the human papilloma virus in the development of cervical intraepithelial neoplasia and malignancy

    PubMed Central

    Jastreboff, A; Cymet, T

    2002-01-01

    Human papilloma virus (HPV) is a public health problem as a sexually transmitted disease and as a critical factor in the pathogenesis of various cancers. The clinical manifestations, epidemiology, and virology that are critical to understanding the process of cervical dysplasia and neoplasia are reviewed. A discussion of the cervical transformation zone and the classification of cervical dysplasia and neoplasia leads into the importance of the Papanicolaou smear in prevention of potentially devastating sequelae of this virus. The role of the immune system in the progression of the disease and how it relates to vaccines, as well as treatment and prevention of HPV, are reviewed. PMID:11930025

  12. Synchronous high-grade squamous intraepithelial lesion and adenocarcinoma in situ of cervix in a young woman presenting with hyperchromatic crowded groups in the cervical cytology specimen: report of a case.

    PubMed

    Zafar, Nadeem; Balazs, Louisa; Benstein, Barbara D

    2008-11-01

    We report a 29-year-old woman who underwent routine gynecologic evaluation at a community clinic and had a cervical sample drawn for liquid-based cytologic evaluation. At cytology, many hyperchromatic crowded groups (HCG) were present, but a consensus could not be established whether the abnormal cells were primarily glandular or squamous with secondary endocervical glandular involvement. An interpretation of atypical endocervical cells, favor neoplastic, was rendered and biopsy advised if clinically appropriate. At biopsy, the cervix contained synchronous squamous cell carcinoma in situ, secondarily involving endocervical glands, and neighboring adenocarcinoma in situ. Immunohistochemistry for Ki-67 and p16(INK4A) crisply and precisely stained both the lesions, clearly separating them from the adjacent uninvolved mucosa. This case re-emphasizes the challenge associated with accurate evaluation of HCG at cytology, the significance of ancillary testing for surrogate markers of high-risk HPV (HR-HPV) infection, the need for adjunct testing for HPV-DNA in the setting of HCG at cervical cytology, and a recommendation to set up studies to evaluate the role of surrogate markers of HR-HPV infection in cytologic samples with HCG.

  13. Morphology of the cervical vertebrae in the fetal-neonatal human skeleton

    PubMed Central

    CASTELLANA, C.; KÓSA, F.

    1999-01-01

    The gross anatomical features of human cervical vertebrae during the fetal-neonatal period were investigated in order to develop morphological standards for the individual ossification centres for use in forensic and anthropological osteology. It was found that the morphology of the cervical vertebral arches and the centra cannot be used for the determination of fetal age although the dens of the axis displays some developmental differences which may be useful for the determination of fetal maturity. PMID:10227677

  14. Inhibition of autophagy augments apoptosis in human oral squamous cell carcinoma under nutrient depletion.

    PubMed

    Jiang, Li-Cheng; Xin, Zhi-Yuan; Deborah, Baremberg; Zhang, Jun-Sheng; Yuan, Dao-Ying; Xu, Kai; Liu, Xian-Bin; Jiang, Hu-Quan; Fan, Qing-Chun; Zhang, Bin; Li, Ke-Yi

    2015-05-01

    There has been little research conducted regarding autophagy in oral squamous cell carcinoma (OSCC). Given the prevalence of oral cancers which are OSCC and the severe side effects of current treatments, there is a pressing need to develop effective alternative therapies. In this study, we have endeavored to explore the biological characteristics of oral squamous cell carcinoma cell line KB cells, in particular with regard to the role played by autophagy in their survival. Autophagy was activated by nutrient depletion via culturing cells in Earle's balanced salts (EBSS) and was measured via indices relating to Beclin 1, microtubule-associated protein light chain 3 (MAPLC3, LC3), p62, and Green fluorescent protein-light chain 3 plasmid transfection (GFP-LC3). Cell death and apoptosis induced by nutrient depletion was measured using both MTT assay and flow cytometry (FCM). Compared to initial levels at 0 h, Beclin 1 density in EBSS-treated cells was found to have increased at 6, 12, and 18 h in a time-dependent manner and was found to have subsequently declined at 24 and 48 h. p62 levels, LC3-II/LC3-I ratio, and GFP-LC3 levels increased at 6, 12, 18, 24, and 48 h in a time-dependent manner. 3-methyladenine (3-MA) was found to inhibit autophagy and the expression of Beclin 1 and significantly enhanced nutrient depletion-induced apoptosis and death. We concluded that nutrient depletion enhances OSCC cell autophagy in time-course patterns and that the inhibition of autophagy augments apoptosis in OSCC cells. We also deduced that Beclin 1 takes part in the development and progression of autophagy, potentially playing an important role in the crosstalk between apoptosis and autophagy in OSCC cells. These findings suggest that nutrient depletion may be an effective way to explore autophagy and that autophagy inhibitors should be investigated as a potential novel agent for the adjuvant treatment of human OSCC.

  15. Human Papilloma Virus prevalence and type-specific relative contribution in invasive cervical cancer specimens from Italy

    PubMed Central

    2010-01-01

    Background Cervical cancer represents an important global public health problem. It is the 2nd most common cancer among women worldwide. Human Papillomavirus (HPV) infection is now well-established as a necessary cause of invasive cervical cancer (ICC) development. Only a few studies on HPV prevalence and type-specific distribution in ICC have been conducted in Italy. Aim To describe the prevalence of HPV and the HPV type-specific distribution in ICC cases identified in Rome, Italy. Methods 140 paraffin embedded tissue blocks of primary ICC diagnosed between 2001 and 2006 were identified at the Regina Elena Cancer Institute in Rome (Italy). HPV was detected through amplification of HPV DNA using SPF-10 HPV broad-spectrum primers followed by DEIA and then genotyping by LiPA25 (version 1). Results 134 cases were considered suitable for HPV DNA detection after histological evaluation; and overall, 90.3% (121/134) HPV prevalence was detected. 111 cases had a single HPV type, 4 cases had an uncharacterized type (HPVX) and 6 cases had multiple HPV infections. The five most common single HPV types among positive cases were: HPV16 (71/121; 58.7%), HPV18 (12/121; 9.9%), HPV31, HPV45 and HPV58 (5/121; 4.1% each). 2 (1.5%) of the single infections and 2 (1.5%) of the multiple infections contained low risk types. Statistically significant differences in the relative contribution of HPV18 were found when comparing squamous cell carcinomas with adenocarcinomas. Conclusions HPV16 and HPV18 accounted for almost 70% of all the HPV positive ICC cases. The study provides baseline information for further evaluation on the impact of recently introduced HPV vaccines in Italy. PMID:20525370

  16. Human papillomavirus genotypes in women with cervical cytological abnormalities from an area with high incidence of cervical cancer.

    PubMed

    Deluca, Gerardo Daniel; Lucero, Raúl Horacio; Martin de Civetta, María T; Vicente, Lilian; de Gorodner, Ofelia L Z; Schelover, Eduardo; Alonso, José Mario

    2004-01-01

    It has been well demonstrated the relationship between the infection with high-risk human papillomavirus (HPVs) genotypes and cervical cancer. In Northeastern Argentina a high incidence of this pathology has been described and therefore a high prevalence of HPV infection is expected. In order to identify HPV genotypes associated with malignant and pre-malignant cervical lesions present in the area, 53 ecto-endo cervical cell specimens obtained from women with cytohistological alterations were studied by a PCR-RFLP technique. Out of 53 patients, 34 (64.2%) were positive for HPV infection, being HPV-16 (32.3%) the most frequently found genotype, followed by HPV-58 (14.7%), -6, -18 and -45 (5.9%), -33, -52, -53, -54, -56, -66, -MM4 and -LVX100 (2.9%). Also 5 cases of infection caused by multiple genotypes were found, which corresponded to 14.7% of the positive cases. Results indicate that besides HPV-16 and -18, the most prevalent high-risk HPV genotypes worldwide, others like -45 and -58 as well as co-infection cases are frequent between women of Northeastern Argentina, and a particular attention should be paid to this circumstance because it could be an epidemiological feature of regional importance and a useful information for a future vaccination program.

  17. The role of MALAT1 correlates with HPV in cervical cancer

    PubMed Central

    JIANG, YAN; LI, YUEHUI; FANG, SHUJUAN; JIANG, BINYUAN; QIN, CHANGFEI; XIE, PINGLI; ZHOU, GUOHUA; LI, GUANCHENG

    2014-01-01

    Cervical cancer, the second most common type of cancer in women worldwide, is responsible for >275,100 mortalities each year and is associated with high-risk human papilloma virus (HR-HPV). HPVs have two important oncogenes, E6 and E7, which have crucial roles in malignant transformation in cervical cancer. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA originally identified in non-small cell lung cancer. Previous studies have revealed that MALAT1 is expressed in numerous tissue types, and is significant in maintaining the normal function of the body. However, it also appeared to be notably upregulated in numerous carcinoma types compared with adjacent non-cancerous tissues. In the present study, it was identified that MALAT1 expression was upregulated in cervical cancer cell lines compared with normal cervical squamous cell samples. Further study into the effect of MALAT1 on cellular phenotype revealed that MALAT1 was able to promote cell migration and proliferation. Of note, it was revealed that the expression of MALAT1 was decreased with the knockdown of HPV16 E6/E7 in CaSki cells. Furthermore, the investigations in clinical samples also revealed that MALAT1 was expressed in HPV-positive cervical squamous cells, but not in HPV-negative normal cervical squamous cells. These results indicate that HPV correlates with MALAT1 deregulation in cervical cancer. PMID:24932303

  18. Chromosomal radiosensitivity of human immunodeficiency virus positive/negative cervical cancer patients in South Africa

    PubMed Central

    HERD, OLIVIA; FRANCIES, FLAVIA; KOTZEN, JEFFREY; SMITH, TRUDY; NXUMALO, ZWIDE; MULLER, XANTHENE; SLABBERT, JACOBUS; VRAL, ANNE; BAEYENS, ANS

    2016-01-01

    Cervical cancer is the second most common cancer amongst South African women and is the leading cause of cancer-associated mortality in this region. Several international studies on radiation-induced DNA damage in lymphocytes of cervical cancer patients have remained inconclusive. Despite the high incidence of cervical cancer in South Africa, and the extensive use of radiotherapy to treat it, the chromosomal radiosensitivity of South African cervical cancer patients has not been studied to date. Since a high number of these patients are human immunodeficiency virus (HIV)-positive, the effect of HIV infection on chromosomal radiosensitivity was also investigated. Blood samples from 35 cervical cancer patients (20 HIV-negative and 15 HIV-positive) and 20 healthy controls were exposed to X-rays at doses of 6 MV of 2 and 4 Gy in vitro. Chromosomal radiosensitivity was assessed using the micronucleus (MN) assay. MN scores were obtained using the Metafer 4 platform, an automated microscopic system. Three scoring methods of the MNScore module of Metafer were applied and compared. Cervical cancer patients had higher MN values than healthy controls, with HIV-positive patients having the highest MN values. Differences between groups were significant when using a scoring method that corrects for false positive and false negative MN. The present study suggested increased chromosomal radiosensitivity in HIV-positive South African cervical cancer patients. PMID:26549042

  19. Survivin expression in canine epidermis and in canine and human cutaneous squamous cell carcinomas.

    PubMed

    Bongiovanni, Laura; Colombi, Isabella; Fortunato, Carmine; Della Salda, Leonardo

    2009-10-01

    Survivin, a member of the inhibitor of apoptosis protein (IAP) family, is ubiquitously expressed during tissue development, undetectable in most normal tissues, but re-expressed in most cancers, including skin malignancies. Expression of survivin was evaluated retrospectively in 19 canine cutaneous squamous cell carcinomas (SCCs; one in situ; 16 well differentiated; one invasive, one lymph node metastasis) and 19 well differentiated SCCs from human beings. Seven specimens of normal canine skin were included. Immunohistochemical expression of full-length survivin was determined using a commercially available antibody. In addition, apoptotic rate [Terminal deoxynucleotidyl Transferase Biotin-dUTP Nick End Labelling index (TUNEL) index] and mitotic index (MI), counting mitoses in 10 high power fields (HPF), were determined. Scattered survivin positive nuclei were identified in the epidermal basal cell layer of normal canine skin. Nuclear survivin expression was identified in 18 of 19 human and in all canine SCCs, mainly along the base of the tumour cell population. Cytoplasmic survivin expression was rarely observed in human SCCs and in 84.2% of canine SCCs. The TUNEL index ranged from 0.1 to 2.6 in human beings and from 7.5 to 69.4 in dogs, while MIs ranged from 0 to 4 in human beings and dogs. No correlation was found between survivin expression and apoptotic or mitotic rates. Canine and human tumours showed similar nuclear survivin expression, indicating similar functions of the molecule. We demonstrated survivin expression in normal adult canine epidermis. Increased nuclear survivin expression in pre-neoplastic and neoplastic lesions demonstrates a possible association of survivin with development of SCCs in human beings and dogs.

  20. Inhibitory Effect of Progesterone on Cervical Tissue Formation in a Three-Dimensional Culture System with Human Cervical Fibroblasts1

    PubMed Central

    House, Michael; Tadesse-Telila, Serkalem; Norwitz, Errol R.; Socrate, Simona; Kaplan, David L.

    2013-01-01

    ABSTRACT Progesterone supplementation is recommended to prevent preterm birth in women with a short cervix, but the mechanism is unclear. We hypothesize that progesterone acts by altering the composition of the cervical extracellular matrix (ECM). We tested this hypothesis using human cervical fibroblasts in both two-dimensional (2D) and three-dimensional (3D) cultures. For 2D culture, cells were seeded in 6-well plates and cultured with media supplemented with estradiol (10−8 M), progesterone (10−7 or 10−6 M), and vehicle. For 3D culture, the cells were cultured on a porous silk protein scaffold system. Progesterone and estrogen receptors were documented by immunohistochemistry and Western blot analysis. In both 2D and 3D cultures, decreased collagen synthesis was seen with increased progesterone concentration. Three-dimensional cultures could be maintained significantly longer than 2D cultures, and the morphology of 3D cultures appeared similar to native cervical tissue. Thus, further studies were performed in 3D culture. To determine the effect of progesterone concentration, the 3D scaffolds were cultured with estradiol (10−8 M) and five conditions: vehicle; 10−9, 10−8, or 10−7 M progesterone; or 10−7 M progesterone plus 10−6 M mifepristone. The highest progesterone concentration correlated with the least amount of collagen synthesis. Collagen synthesis progressively increased as progesterone concentration decreased. This effect was partially antagonized by mifepristone, suggesting the mechanism is mediated by the progesterone receptor. This hormonally responsive 3D culture system supports the hypothesis that progesterone has a direct effect on remodeling cervical ECM during pregnancy. The 3D culture system could be useful for studying the mechanism of progesterone effects on the cervix. PMID:24285720

  1. History of the use of HPV testing in cervical screening and in the management of abnormal cervical screening results.

    PubMed

    Cox, J Thomas

    2009-07-01

    Twenty years have passed since the first studies using human papillomavirus (HPV) testing began in clinical settings. At that time controversy regarding the role of HPV in cervical carcinogenesis still divided the scientific world. Epidemiological and natural history studies on HPV and cervical cancer in the ensuing two decades secured the necessary role of high-risk (carcinogenic) HPV in the genesis of cervical cancer, providing the rationale for testing for its cause. Subsequently, cross sectional studies and large randomized trials have provided clinical validation for high-risk HPV testing in triage of atypical squamous cells of undetermined significance (ASC-US), in postcolposcopy management of women referred for ASC-US, atypical squamous cells "cannot rule out high grade" (ASC-H), atypical glandular cells "not otherwise specified" (AGC NOS) and low grade squamous intraepithelial lesion (LSIL) and not found to have cervical intraepithelial neoplasia (CIN) 2+ or adenocarcinoma in situ (AIS) at initial colposcopy, in post-treatment of CIN 2+ surveillance, and in cotesting with the Papanicolaou (Pap) test of women age 30 and over. This is the story of the road traveled that brought the clinical use of HPV testing from its genesis only a few years after Dr. zur Hausen's discovery to its present eminent role in both primary cervical cancer screening and abnormal Pap management.

  2. Carvacrol suppresses proliferation and invasion in human oral squamous cell carcinoma

    PubMed Central

    Dai, Wei; Sun, Changfu; Huang, Shaohui; Zhou, Qing

    2016-01-01

    Carvacrol, a component of thyme oil, as a novel antitumor agent, has been implicated in several types of cancer cells. However, the mechanisms underlying the effect of carvacrol in human oral squamous cell carcinoma (OSCC) remain unclear. Here, we report that carvacrol significantly inhibits tumor cell proliferation, metastasis and invasion, and induces apoptosis in OSCC. Our results demonstrated that the molecular mechanisms of the effect of carvacrol in Tca-8113 induces G1/S cell cycle arrest through downregulation of CDK regulator CCND1 and CDK4, and upregulation of CDK inhibitor P21. Further analysis demonstrated that carvacrol also inhibited Tca-8113 cells’ clone formation in clonogenic cell survival assay. Student’s t-test (two-tailed) was used to compare differences between groups, and the significance level was P<0.01. Then, treatment of Tca-8113 cells with carvacrol resulted in downregulation of Bcl-2, Cox2, and upregulation of Bax. Carvacrol significantly inhibited the migration and invasion of human OSCC cells by blocking the phosphorylation of FAK and MMP-9 and MMP-2, transcription factor ZEB1, and β-catenin proteins’ expression. Taken together, these results provide novel insights into the mechanism of carvacrol and suggest potential therapeutic strategies for human OSCC. PMID:27143925

  3. Carvacrol suppresses proliferation and invasion in human oral squamous cell carcinoma.

    PubMed

    Dai, Wei; Sun, Changfu; Huang, Shaohui; Zhou, Qing

    2016-01-01

    Carvacrol, a component of thyme oil, as a novel antitumor agent, has been implicated in several types of cancer cells. However, the mechanisms underlying the effect of carvacrol in human oral squamous cell carcinoma (OSCC) remain unclear. Here, we report that carvacrol significantly inhibits tumor cell proliferation, metastasis and invasion, and induces apoptosis in OSCC. Our results demonstrated that the molecular mechanisms of the effect of carvacrol in Tca-8113 induces G1/S cell cycle arrest through downregulation of CDK regulator CCND1 and CDK4, and upregulation of CDK inhibitor P21. Further analysis demonstrated that carvacrol also inhibited Tca-8113 cells' clone formation in clonogenic cell survival assay. Student's t-test (two-tailed) was used to compare differences between groups, and the significance level was P<0.01. Then, treatment of Tca-8113 cells with carvacrol resulted in downregulation of Bcl-2, Cox2, and upregulation of Bax. Carvacrol significantly inhibited the migration and invasion of human OSCC cells by blocking the phosphorylation of FAK and MMP-9 and MMP-2, transcription factor ZEB1, and β-catenin proteins' expression. Taken together, these results provide novel insights into the mechanism of carvacrol and suggest potential therapeutic strategies for human OSCC.

  4. Development and evaluation of topotecan loaded solid lipid nanoparticles: A study in cervical cancer cell lines.

    PubMed

    Chen, Zhao-Jie; Zhang, Zhen; Xie, Bei-Bei; Zhang, Hai-Yan

    2016-12-01

    The study aims at statistical development of solid lipid nanoparticles (SLNs) loaded with topotecan hydrochloride for avoiding the drawbacks of conventional drug therapies used in cervical cancer. Twenty SLN batches were prepared using organic solvent evaporation method to provide response surface curves. Thereafter, optimized SLNs were obtained using numeric method based on desirability functions providing maximum drug loading and appropriate particle size. Physical characterization of optimized TPH loaded SLNs was performed in terms of particle size, zeta potential, transmission and scanning electron microscopic evaluation. Cytotoxicity studies were performed against cervical cancer cell lines, including cervical squamous cell carcinoma cell line (HeLa) and human squamous cell carcinoma cell line (SiHa). Also, Swiss mouse embryo fibroblast cells (3T3-L1) and African green monkey kidney epithelial (Vero) cells were used to evaluate biocompatibility in normal cells. As pronounced from the results, optimized SLNs may provide an attractive alternative to conventional cervical cancer drug products.

  5. Fludeoxyglucose F 18 PET Scan, CT Scan, and Ferumoxtran-10 MRI Scan Before Chemotherapy and Radiation Therapy in Finding Lymph Node Metastasis in Patients With Locally Advanced Cervical Cancer or High-Risk Endometrial Cancer

    ClinicalTrials.gov

    2016-11-14

    Cervical Adenocarcinoma; Cervical Adenosquamous Cell Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma; Endometrial Clear Cell Carcinoma; Endometrial Papillary Serous Carcinoma; Stage I Endometrial Carcinoma; Stage IB Cervical Cancer; Stage II Endometrial Carcinoma; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage III Endometrial Carcinoma; Stage IVA Cervical Cancer

  6. Prognostic value of human papillomavirus 16/18 genotyping in low-grade cervical lesions preceded by mildly abnormal cytology*

    PubMed Central

    Ye, Jing; Cheng, Bei; Cheng, Yi-fan; Yao, Ye-li; Xie, Xing; Lu, Wei-guo; Cheng, Xiao-dong

    2017-01-01

    Histological low-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 1 (LSIL/CIN1) preceded by normal or mildly abnormal cytology is recommended for conservative follow-up, with no separated management. In this study, we assessed the triage value of human papillomavirus (HPV) 16/18 genotyping in 273 patients with LSIL/CIN1. HPV16/18 genotyping was performed at baseline and follow-up was at 6-monthly intervals for up to 2 years. At each follow-up, women positive for cytology or high-risk HPV (hrHPV) were referred for colposcopy. Enrollment cytology, HPV16/18 genotyping, and questionnaire-obtained factors were linked to the 2-year cumulative progression rate. Univariate and multivariate analyses were performed taking into account time-to-event with Cox proportional hazard regression. The results showed that 190 cases (69.6%) regressed, 37 (13.6%) persisted, and 46 (16.8%) progressed. HPV16/18 positivity (hazard ratio (HR), 2.708; 95% confidence interval (CI), 1.432–5.121; P=0.002) is significantly associated with higher 2-year cumulative progression rate. Sub-analysis by enrollment cytology and age restricted the positive association among patients preceded by mildly abnormal cytology and aged 30 years or older. Immediate treatment is a rational recommendation for the high-risk subgroup, when good compliance is not assured. PMID:28271660

  7. The impact of glucocorticoids and anti-cd20 therapy on cervical human papillomavirus infection risk in women with systemic lupus erythematosus

    PubMed Central

    Mendoza-Pinto, Claudia; Garcia-Carrasco, Mario; Vallejo-Ruiz, Veronica; Taboada-Cole, Alejandro; Muñoz-Guarneros, Margarita; Solis-Poblano, Juan Carlos; Pezzat-Said, Elias; Aguilar-Lemarroy, Adriana; Jave-Suarez, Luis Felipe; de Lara, Luis Vazquez; Ramos-Alvarez, Gloria; Reyes-Leyva, Julio; Lopez-Colombo, Aurelio

    2013-01-01

    OBJECTIVE: To identify the prevalence and factors associated with cervical human papillomavirus infection in women with systemic lupus erythematosus METHODS: This cross-sectional study collected traditional and systemic lupus erythematosus-related disease risk factors, including conventional and biologic therapies. A gynecological evaluation and cervical cytology screen were performed. Human papillomavirus detection and genotyping were undertaken by PCR and linear array assay. RESULTS: A total of 148 patients were included, with a mean age and disease duration of 42.5±11.8 years and 9.7±5.3 years, respectively. The prevalence of squamous intraepithelial lesions was 6.8%. The prevalence of human papillomavirus infection was 29%, with human papillomavirus subtype 59 being the most frequent. Patients with human papillomavirus were younger than those without the infection (38.2±11.2 vs. 44.2±11.5 years, respectively; p = 0.05), and patients with the virus had higher daily prednisone doses (12.8±6.8 vs. 9.7±6.7 mg, respectively; p = 0.01) and cumulative glucocorticoid doses (14.2±9.8 vs. 9.7±7.3 g, respectively; p = 0.005) compared with patients without. Patients with human papillomavirus infection more frequently received rituximab than those without (20.9% vs. 8.5%, respectively; p = 0.03). In the multivariate analysis, only the cumulative glucocorticoid dose was associated with human papillomavirus infection. CONCLUSIONS: The cumulative glucocorticoid dose may increase the risk of human papillomavirus infection. Although rituximab administration was more frequent in patients with human papillomavirus infection, no association was found. Screening for human papillomavirus infection is recommended in women with systemic lupus erythematosus. PMID:24473503

  8. The natural history of cervical human papillomavirus infections and cervical cancer: gaps in knowledge and future horizons.

    PubMed

    Wheeler, Cosette Marie

    2013-06-01

    Genital human papillomavirus (HPV) infection is the most common sexually transmitted infection. Most HPV infections are benign and resolve on their own, but some women develop persistent HPV infections. Persistent HPV infection with certain high-risk HPV genotypes is the necessary cause of most epithelial lesions of the uterine cervix. The importance of latent or quiescent HPV, waning immunity, hormonal milieu, microbiota, and other factors modifying the natural history of HPV infections across a woman's lifetime deserves further study. Promising biomarkers are emerging that may aid in defining which HPV-infected women are at risk of developing invasive cervical cancer.

  9. A Gene Encoding Antigenic Peptides of Human Squamous Cell Carcinoma Recognized by Cytotoxic T Lymphocytes

    PubMed Central

    Shichijo, Shigeki; Nakao, Masanobu; Imai, Yasuhisa; Takasu, Hideo; Kawamoto, Mayumi; Niiya, Fumihiko; Yang, Damu; Toh, Yuji; Yamana, Hideaki; Itoh, Kyogo

    1998-01-01

    Except for melanomas, tumor antigens recognized by cytotoxic T lymphocytes (CTLs) are yet unidentified. We have identified a gene encoding antigenic peptides of human squamous cell carcinomas (SCCs) recognized by human histocompatibility leukocyte antigens (HLA)- A2601–restricted CTLs. This gene showed no similarity to known sequences, and encoded two (125- and 43-kilodalton [kD]) proteins. The 125-kD protein with the leucine zipper motif was expressed in the nucleus of the majority of proliferating cells tested, including normal and malignant cells. The 43-kD protein was expressed in the cytosol of most SCCs from various organs and half of lung adenocarcinomas, but was not expressed in other cancers nor in a panel of normal tissues. The three nonapeptides shared by the two proteins were recognized by the KE4 CTLs, and one of the peptides induced in vitro from peripheral blood mononuclear cells (PBMCs) the CTLs restricted to the autologous tumor cells. The 43-kD protein and this nonapeptide (KGSGKMKTE) may be useful for the specific immunotherapy of HLA-A2601+ epithelial cancer patients. PMID:9449708

  10. Overexpression of leucine aminopeptidase 3 contributes to malignant development of human esophageal squamous cell carcinoma.

    PubMed

    Zhang, Shu; Yang, Xiaojing; Shi, Hui; Li, Mei; Xue, Qun; Ren, Hanru; Yao, Li; Chen, Xueyu; Zhang, Jianguo; Wang, Huijie

    2014-06-01

    Leucine aminopeptidases (LAPs) were associated with tumor cell proliferation, invasion and/or angiogenesis. We aimed to examine the biological function of LAP3 in esophageal squamous cell carcinoma (ESCC). LAP3 expressions were examined in human ESCC tissue and cell lines ECA109 and TE1 cells. Recombinant pSilencer4.1-LAP3-shRNA was transfected into ECA109 cells to silence LAP3 expression. The effects of LAP3 silencing on ECA109 cell proliferation in vitro were evaluated. Flow cytometry profiling was used to detect the differentiate cell cycle distribution in LAP3-silenced ECA109 cells. Wound-healing assay and transwell assay were used to examine the activities of migration and invasion in LAP3-silenced ECA109 cells. We overexpressed LAP3 in TE1 cells to find out the corresponding results. LAP3 expression level was abundance in ESCC tissue. LAP3 silencing significantly reduced ECA109 cell proliferation and colony formation. The knockdown of LAP3 resulted in cell cycle arrest at G1-phase. Moreover, over expression of LAP3 favors TE1 cell proliferation and invasiveness which also confirms its contribution in malignant development. We came to the conclusion that LAP3 contributed to ESCC progression by overcoming cell cycle arrest. The proliferative and migration effects of LAP3 might contribute to malignant development of human ESCC.

  11. Galangin inhibits growth of human head and neck squamous carcinoma cells in vitro and in vivo.

    PubMed

    Zhu, Liping; Luo, Qingqiong; Bi, Jianjun; Ding, Jieying; Ge, Shengfang; Chen, Fuxiang

    2014-12-05

    Galangin, an active flavonoid component extracted from the propolis and root of Alpinia officinarum Hance, has anti-tumor activity, but the mechanisms by which galangin affects various cancers, including human head and neck squamous cell carcinoma (HNSCC) remain unclear. In this study, we demonstrated for the first time that galangin suppressed the growth of HNSCC in vivo. With the cell culture system, galangin inhibited the proliferation and colony formation of HNSCC cells in a dose-dependent manner. Galangin induced significant cell cycle arrest of the tumor cells at the G0/G1 phase, which was accompanied by reduced AKT phosphorylation and mammalian target of rapamycin and S6 kinase activation. Decreased expression of cyclin D1, cyclin-dependent kinase (CDK)4, CDK6 and phosphorylation of retinoblastoma protein was observed in galangin-treated HNSCC cells. In addition, galangin induced apoptosis of HNSCC cells, downregulating antiapoptotic protein Bcl-2 and Bcl-xL and upregulating proapoptotic protein Bax and cleaved caspase 3. Immunohistochemical analysis showed a dose-dependent reduction in cyclin-D1-positive cancer cells and an increase in TUNEL-positive cancer cells in galangin-administrated mouse tumor sections. Therefore, galangin may be a novel therapeutic option in human HNSCC treatment.

  12. Evaluation of an Array-Based Method for Human Papillomavirus Detection and Genotyping in Comparison with Conventional Methods Used in Cervical Cancer Screening▿

    PubMed Central

    García-Sierra, Nerea; Martró, Elisa; Castellà, Eva; Llatjós, Mariona; Tarrats, Antoni; Bascuñana, Elisabet; Díaz, Rosana; Carrasco, María; Sirera, Guillem; Matas, Lurdes; Ausina, Vicente

    2009-01-01

    Cervical cancer is the second-most prevalent cancer in young women around the world. Infection with human papillomavirus (HPV), especially high-risk HPV types (HR-HPV), is necessary for the development of this cancer. HPV-DNA detection is increasingly being used in cervical cancer screening programs, together with the Papanicolau smear test. We evaluated the usefulness of introducing this new array-based HPV genotyping method (i.e., Clinical Arrays Papillomavirus Humano) in the cervical cancer screening algorithm in our center. The results obtained using this method were compared to those obtained by the hybrid capture II high-risk HPV DNA test (HC-II) and Papanicolau in a selected group of 408 women. The array-based assay was performed in women that were HC-II positive or presented cytological alterations. Among 246 array-positive patients, 123 (50%) presented infection with ≥2 types, and HR-HPV types were detected in 206 (83.7%), mainly HPV-16 (24.0%). Up to 132 (33.2%) specimens were classified as ASCUS (for atypical squamous cells of undetermined significance), and only 48 (36.4%) of them were HPV-DNA positive by either assay; however, 78.7% of these cases were caused by HR-HPV types. The agreement between both HPV-DNA detection techniques was fairly good (n = 367). Screening with Papanicolau smear and HC-II tests, followed by HPV detection and genotyping, provided an optimal identification of women at risk for the development of cervical cancer. Furthermore, with the identification of specific genotypes, either in single or multiple infections, a better prediction of disease progression was achieved. The array method also made allowed us to determine the possible contribution of the available vaccines in our setting. PMID:19439534

  13. Antiapoptotic effects of estrogen in normal and cancer human cervical epithelial cells.

    PubMed

    Wang, Qifang; Li, Xin; Wang, Liqin; Feng, Ying-Hong; Zeng, Robin; Gorodeski, George

    2004-12-01

    The present study investigated the antiapoptotic effects of estrogen in normal and cancer human cervical cells and the mechanisms involved. Baseline apoptosis in human cervical epithelial cells is mediated predominantly by P2X7-receptor-induced, Ca(2+)-dependent activation of the mitochondrial (caspase-9) pathway. Treatment with 10 nM 17beta-estradiol blocked apoptosis induced by the P2X7-receptor ligands ATP and 2',3'-0-(4-benzoylbenzoyl)-ATP in normal human cervical epithelial cells (hECEs) and attenuated the effect in hECEs immortalized with human papillomavirus-16 (ECE16-1) and the cancer cervical cells HT3 and CaSki. Diethylstilbestrol and to a lesser degree estrone could mimic the effects of 17beta-estradiol, whereas actinomycin-D and cycloheximide attenuated the response. The antiapoptotic effect of estrogen did not depend on cell cycle phase, and in both normal and cancer cervical cells, it involved attenuation of activation of caspase-9 and the terminal caspase-3. However, involvement of cascades upstream to the caspase-9 differed in normal vs. cancer cervical cells. In the normal hECEs estrogen blocked P2X7-receptor-induced calcium influx. In contrast, in the cancer CaSki cells, estrogen up-regulated expression of Bcl-2 and attenuated Ca(2+)-induced mitochondrial swelling (i.e. formation of mitochondrial permeability transition pores). Estrogen had no effect on P2X7-receptor-induced apoptosis in the anaplastic SiHa and Hela cells. These results point to a novel antiapoptotic effect of estrogen in the cervix that is independent of its mitogenic function. The results also suggest that cancer cervical cells evolved antiapoptotic mechanisms that enable the cells to evade apoptosis and could therefore promote tumor progression.

  14. Near-Infrared Micro-Raman Spectroscopy for in Vitro Detection of Cervical Cancer

    PubMed Central

    KAMEMOTO, LORI E.; MISRA, ANUPAM K.; SHARMA, SHIV K.; GOODMAN, MARC T.; LUK, HUGH; DYKES, AVA C.; ACOSTA, TAYRO

    2010-01-01

    Near-infrared Raman spectroscopy is a powerful analytical tool for detecting critical differences in biological samples with minimum interference in the Raman spectra from the native fluorescence of the samples. The technique is often suggested as a potential screening tool for cancer. In this article we report in vitro Raman spectra of squamous cells in normal and cancerous cervical human tissue from seven patients, which have good signal-to-noise ratio and which were found to be reproducible. These preliminary results show that several Raman features in these spectra could be used to distinguish cancerous cervical squamous cells from normal cervical squamous cells. In general, the Raman spectra of cervical cancer cells show intensity differences compared to those of normal squamous cell spectra. For example, several well-defined Raman peaks of collagen in the 775 to 975 cm −1 region are observed in the case of normal squamous cells, but these are below the detection limit of normal Raman spectroscopy in the spectra of invasive cervical cancer cells. In the high frequency 2800 to 3100 cm −1 region, it is found that the peak area under the CH stretching band is lower by a factor of approximately six in the spectra of cervical cancer cells as compared with that of the normal cells. The Raman chemical maps of regions of cancer and normal cells in the cervical epithelium made from the spectral features in the 775 to 975 cm −1 and 2800 to 3100 cm −1 regions are also found to show good correlation with each other. PMID:20223058

  15. Human papillomavirus type 16 DNA detected in pulmonary metastases from a penile squamous cell carcinoma: a case study.

    PubMed

    Lorenzon, Laura; Benevolo, Maria; Visca, Paolo; Venturo, Irene; Filippetti, Massimo; Piro, Francesca Romana; Rollo, Francesca; Vocaturo, Amina

    2013-02-01

    This report describe the case of a patient presenting with pulmonary metastases from a penile cancer, where the presence of the human papillomavirus (HPV) type 16 DNA both in the primary tumor and in the distant metastases confirmed the spreading of the disease, ruling out a possible primary lung squamous cell carcinoma. Indeed, according to the findings, the HPV genotyping test might help in the identification of metastatic disease from anogenital malignancies or other HPV-related cancers.

  16. Knowledge of Human Papillomavirus Infection, Cervical Cancer and Willingness to pay for Cervical Cancer Vaccination among Ethnically Diverse Medical Students in Malaysia.

    PubMed

    Maharajan, Mari Kannan; Rajiah, Kingston; Num, Kelly Sze Fang; Yong, Ng Jin

    2015-01-01

    The primary objective of this study was to assess the knowledge of medical students and determine variation between different cultural groups. A secondary aim was to find out the willingness to pay for cervical cancer vaccination and the relationships between knowledge and attitudes towards Human Papillomavirus vaccination. A cross-sectional survey was conducted in a private medical university between June 2014 and November 2014 using a convenient sampling method. A total of 305 respondents were recruited and interviewed with standard questionnaires for assessment of knowledge, attitudes and practice towards human papilloma virus and their willingness to pay for HPV vaccination. Knowledge regarding human papilloma virus, human papilloma virus vaccination, cervical cancer screening and cervical cancer risk factors was good. Across the sample, a majority (90%) of the pupils demonstrated a high degree of knowledge about cervical cancer and its vaccination. There were no significant differences between ethnicity and the participants' overall knowledge of HPV infection, Pap smear and cervical cancer vaccination. Some 88% of participants answered that HPV vaccine can prevent cervical cancer, while 81.5% of medical students said they would recommend HPV vaccination to the public although fewer expressed an intention to receive vaccination for themselves.

  17. NHERF1 Enhances Cisplatin Sensitivity in Human Cervical Cancer Cells

    PubMed Central

    Tao, Tao; Yang, Xiaomei; Qin, Qiong; Shi, Wen; Wang, Qiqi; Yang, Ying; He, Junqi

    2017-01-01

    Cervical cancer is one of the most common female malignancies, and cisplatin-based chemotherapy is routinely utilized in locally advanced cervical cancer patients. However, resistance has been the major limitation. In this study, we found that Na+/H+ Exchanger Regulatory Factor 1 (NHERF1) was downregulated in cisplatin-resistant cells. Analysis based on a cervical cancer dataset from The Cancer Genome Atlas (TCGA) showed association of NHERF1 expression with disease-free survival of patients received cisplatin treatment. NHERF1 overexpression inhibited proliferation and enhanced apoptosis in cisplatin-resistant HeLa cells, whereas NHERF1 knockdown had inverse effects. While parental HeLa cells were more resistant to cisplatin after NHERF1 knockdown, NHERF1 overexpression in CaSki cells promoted cisplatin sensitivity. Overexpression and knockdown studies also showed that NHERF1 significantly inhibited AKT and extracellular signal–regulated kinase (ERK) signaling pathways in cisplatin-resistant cells. Taken together, our results provide the first evidence that NHERF1 can sensitize cisplatin-refractory cervical cancer cells. This study may help to increase understanding of the molecular mechanisms underlying cisplatin resistance in tumors. PMID:28085111

  18. Role of papillomavirus oncogenes in human cervical cancer: Transgenic animal studies

    SciTech Connect

    Griep, A.E.; Lambert, P.F.

    1994-05-01

    Human papillomaviruses are believed to be etiologic agents for the majority of human cervical carcinoma, a common cancer that is a leading cause of death by cancer among women worldwide. In cervical carcinoma, a subset of papillomaviral genes, namely E6 and E7, are expressed. In vitro tissue culture studies indicate that HPV E6 and E7 are oncogenes, and that their oncogenicity is due in part to their capacity to inactivate cellular tumor suppressor genes. The behavior of E6 and E7 in vitro and the genetic evidence from analysis of human cancers suggest that the E6 and E7 genes play a significant role in the development of cervical cancer. This hypothesis is now being tested using animal models. In this review, we summarize our current knowledge of the oncogenicity of papillomavirus genes that has been generated through their study in transgenic mice. 82 refs., 4 figs., 1 tab.

  19. Association of human papillomavirus type 16 and its genetic variants with cervical lesion in Korea.

    PubMed

    Park, Jeong Su; Shin, Sue; Kim, Eui-Chong; Kim, Ji Eun; Kim, Yong Beom; Oh, Sohee; Roh, Eun Youn; Yoon, Jong Hyun

    2016-11-01

    Persistent human papillomavirus type 16 (HPV16) is the major risk factor for cervical cancer. HPV16 intratypic variants differ in their geographical distribution and oncogenic potential. This study aimed to analyze the distribution of HPV16 variants and their association with cervical lesion histopathology in Korean women. In total, 133 HPV16-positive cervical samples from women admitted to Seoul National University Boramae Hospital were analyzed by sequencing E6, E7, and L1 genes and the long control region (LCR), and the variant distribution according to cervical lesion grade was determined. Isolates were grouped into a phylogenetic lineage, and A1-3, A4, C, and D sublineages were detected in 54.1, 37.8, 0.7, and 7.4% of samples, respectively. The most commonly observed LCR variations were 7521G>A (91.5%), 7730A>C (59.6%), and 7842G>A (59.6%). Furthermore, A4 or D sublineage-positive women had a higher risk for cervical cancer than women who were positive for A1-3. Among HPV phylogenetic clusters, A1-3 was the predominant sublineage, and within A1-3, the 350G polymorphism was highly frequent. These results differed from those of previous studies in Korea and other Asian countries. The findings suggest that cervical neoplasia incidence in HPV16-infected patients could be affected by the distribution of HPV16 variants in the population.

  20. Knowledge and acceptability of human papillomavirus vaccination and cervical cancer screening among women in Karnataka, India.

    PubMed

    Montgomery, Martha P; Dune, Tanaka; Shetty, Prasanna K; Shetty, Avinash K

    2015-03-01

    Cervical cancer is the leading cause of cancer-related mortality among women in India; however, participation in prevention and screening is low and the reasons for this are not well understood. In a cross-sectional survey in August 2008, 202 healthy women in Karnataka, India completed a questionnaire regarding knowledge, attitudes, and practices related to human papillomavirus (HPV) and cervical cancer. Factors associated with vaccination and Papanicolau (Pap) smear screening acceptance were explored. Thirty-six percent of women had heard of HPV while 15% had heard of cervical cancer. Five percent of women reported ever having a Pap smear, and 4% of women felt at risk of HPV infection. Forty-six percent of women were accepting of vaccination, but fewer (21%) were willing to have a Pap smear. Overall, knowledge related to HPV and cervical cancer topics was low. Women with negative attitudes toward HPV infection were 5.3 (95% confidence interval (CI) 2.8-10) times more likely to accept vaccination but were not significantly more likely to accept Pap smear (odds ratio 1.5, 95% CI 0.7-3.0). Cost and a low level of perceived risk were the most frequent factors cited as potential barriers. Improving awareness of HPV and cervical cancer through health care providers in addition to increasing access to vaccination and screening through government-sponsored programs may be feasible and effective methods to reduce cervical cancer burden in India.

  1. Activation of miR-9 by human papillomavirus in cervical cancer.

    PubMed

    Liu, Weijun; Gao, Ge; Hu, Xiaoxia; Wang, Yuhui; Schwarz, Julie K; Chen, Jason J; Grigsby, Perry W; Wang, Xiaowei

    2014-11-30

    Cervical cancer is the third most common cancer in women worldwide, leading to about 300,000 deaths each year. Most cervical cancers are caused by human papillomavirus (HPV) infection. However, persistent transcriptional activity of HPV oncogenes, which indicates active roles of HPV in cervical cancer maintenance and progression, has not been well characterized. Using our recently developed assays for comprehensive profiling of HPV E6/E7 transcripts, we have detected transcriptional activities of 10 high-risk HPV strains from 87 of the 101 cervical tumors included in the analysis. These HPV-positive patients had significantly better survival outcome compared with HPV-negative patients, indicating HPV transcriptional activity as a favorable prognostic marker for cervical cancer. Furthermore, we have determined microRNA (miRNA) expression changes that were correlated with tumor HPV status. Our profiling and functional analyses identified miR-9 as the most activated miRNA by HPV E6 in a p53-independent manner. Further target validation and functional studies showed that HPV-induced miR-9 activation led to significantly increased cell motility by downregulating multiple gene targets involved in cell migration. Thus, our work helps to understand the molecular mechanisms as well as identify potential therapeutic targets for cervical cancer and other HPV-induced cancers.

  2. Arsenic trioxide inhibits cell proliferation and human papillomavirus oncogene expression in cervical cancer cells.

    PubMed

    Wang, Hongtao; Gao, Peng; Zheng, Jie

    2014-09-05

    Arsenic trioxide (As2O3) has shown therapeutic effects in some leukemias and solid cancers. However, the molecular mechanisms of its anticancer efficacy have not been clearly elucidated, particularly in solid cancers. Our previous data showed that As2O3 induced apoptosis of human papillomavirus (HPV) 16 DNA-immortalized human cervical epithelial cells and cervical cancer cells and inhibited the expression of HPV oncogenes in these cells. In the present study, we systemically examined the effects of As2O3 on five human cervical cancer cell lines and explored the possible molecular mechanisms. MTT assay showed that HPV-negative C33A cells were more sensitive to growth inhibition induced by As2O3 than HPV-positive cervical cancer cells, and HPV 18-positive HeLa and C4-I cells were more sensitive to As2O3 than HPV 16-positive CaSki and SiHa cells. After As2O3 treatment, both mRNA and protein levels of HPV E6 and E7 obviously decreased in all HPV positive cell lines. In contrast, p53 and Rb protein levels increased in all tested cell lines. Transcription factor AP-1 protein expression decreased significantly in HeLa, CaSki and C33A cells with ELISA method. These results suggest that As2O3 is a potential anticancer drug for cervical cancer.

  3. The effect of methylenetetrahydrofolate reductase polymorphisms on susceptibility to human papilloma virus infection and cervical cancer.

    PubMed

    Hajiesmaeil, Mogge; Tafvizi, Farzaneh; Sarmadi, Soheila

    2016-12-01

    Cervical cancer is the third most common cancer among women worldwide. Several factors lead to cervical cancer, among which human papilloma virus (HPV) infection has a prominent role. Methylenetetrahydrofolate reductase (MTHFR) is crucial in folate metabolic pathway and plays an important role in DNA synthesis and DNA methylation. MTHFR gene polymorphisms, including C677T and A1298C, lead to reduced enzyme activity. This case-control study aims to illustrate the association between MTHFR gene polymorphisms and the risk of cervical cancer. This study was conducted on 196 samples, which included 96 cervical biopsy samples compared to 100 Pap smear samples of normal healthy women without HPV infection. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used for the MTHFR polymorphism detection, followed by fluorescent amplification-based specific hybridization PCR method to detect HPV16 and HPV18. The results show that the MTHFR 677TT genotype plays a protective role in cervical cancer (P=0.0030) (OR=0.21, 95% confidence interval [CI]: 0.07-0.59). Furthermore, there was a strong significant association between MTHFR 1298CC genotype and the risk of cervical cancer (OR=10.69; 95% CI: 4.28-26.71, P=0.0001). It can be concluded that A1298C polymorphism is a genetic risk factor for cervical cancer in the assessed Iranian population group. It seems that MTHFR 1298CC genotype is more susceptible to HPV 16 infection. Combination analysis of MTHFR C677T and A1298C polymorphisms revealed that combined MTHFR 677CC and 1298CC are strongly associated with a risk of cervical cancer.

  4. Type-specific prevalence of human papillomavirus by cervical cytology among women in Brasov, Romania.

    PubMed

    Moga, Marius Alexandru; Irimie, Marius; Oanta, Alexandru; Pascu, Alina; Burtea, Victoria

    2014-01-01

    The oncogenic role of human papillomavirus (HPV) in triggering cervical cancer, the second most common cancer in women worldwide, is well established. Romania ranks in first place in Europe in terms of the incidence of cervical cancer. Geographical widespread data on HPV type-distribution are essential for estimating the impact of HPV vaccines and cervical cancer screening programmes. In this study we aimed to identify the prevalence of HPV genotypes and to establish correlations with abnormal cervical cytology among the female population of Brasov County, Romania. A total of 1,000 women aged 17.3-57 years, attending routine cervical examination in the Obstetrics and Gynecology Hospital of Brasov, Romania, and undergoing both cytological examination and HPV genotyping were screened. Infection with 35 different HPV genotypes was detected in 39.6% of cytological specimens. Overall HPV infections were highest in young women under 25 years (p<0.0001), in which cervical cytological abnormalities also reached the highest prevalence. Patients infected by HPV-16 or HPV-18 showed the highest prevalence of cervical cytological abnormalities. Some 48.2% of women with abnormal cytology were infected with high-risk HPV types whereas less than 3% of them were infected only with low-risk HPV types. Our study showed that the prevalence of high-risk HPV infection among Romanian women is higher compared to other studies in other geographic areas. Thus, we consider that in areas where there is an increased prevalence of high-risk HPV infections, HPV genotyping should be performed in all women aged between 18 and 45 years, and Pap test should be performed every 6 months in women with high-risk HPV infection, even those with previous normal cervical cytology.

  5. Association between FOXM1 and hedgehog signaling pathway in human cervical carcinoma by tissue microarray analysis

    PubMed Central

    Chen, Hong; Wang, Jingjing; Yang, Hong; Chen, Dan; Li, Panpan

    2016-01-01

    Forkhead box M1 (FOXM1) and hedgehog (Hh) signaling pathway are implicated in the formation and development of human tumors, including cervical cancer. Previous studies have indicated that FOXM1 may be a downstream target gene of the Hh signaling pathway, but their association in cervical cancer is largely unknown. In the present study, the expression of FOXM1 and Hh signaling molecules was evaluated by immunohistochemical analysis in a tissue microarray that contained 70 cervical cancer tissues and 10 normal cervical tissues. In addition, the association of these molecules with clinicopathological parameters, and the association between FOXM1 and various molecules involved in the Hh signaling pathway was investigated. The results indicated that FOXM1 and Hh signaling molecules were overexpressed in cervical cancer tissues. The protein expression levels of FOXM1, glioma-associated oncogene 1 (GLI1) and smoothened (SMO) correlated with the clinical stage of the tumors, while the protein expression levels of Sonic Hh (SHh), patched 1 (PTCH1) and GLI1 correlated with the pathological grade of the tumors. The expression levels of GLI1 were lower in tissues without lymph node metastasis than in tissues with lymph node metastasis. In addition, FOXM1 expression correlated with GLI1, SHh and PTCH1 expression in cancer tissues. These findings confirmed the participation of FOXM1 and the Hh signaling pathway in cervical cancer. Furthermore, the finding that FOXM1 may be a downstream target gene of the Hh signaling pathway in cervical cancer provides a potential novel diagnostic and therapeutic target for cervical cancer. PMID:27698840

  6. Long non-coding RNA HOTAIR is associated with human cervical cancer progression.

    PubMed

    Kim, Hee Jung; Lee, Dae Woo; Yim, Ga Won; Nam, Eun Ji; Kim, Sunghoon; Kim, Sang Wun; Kim, Young Tae

    2015-02-01

    The functions of many long non-coding RNAs (lncRNAs) in human cancers remain to be clarified. The lncRNA Hox transcript antisense intergenic RNA (HOTAIR) has been reported to reprogram chromatin organization and promote breast and colorectal cancer metastasis, the involvement of lncRNAs in cervical cancer is just beginning to be studied. In the present study, we examined the expression and the functional role of HOTAIR in cervical cancer. HOTAIR expression was determined in cervical cancer tissues (n=111) and corresponding normal tissues (n=40) by using real-time polymerase chain reaction, and its correlation with clinical parameters and prognosis were analyzed. To determine the effect of HOTAIR knockdown and overexpression in cervical cancer cell lines, we used the CCK-8 assay, wound healing migration and matrigel invasion assay. The expression level of HOTAIR in cervical cancer tissues was higher than that in corresponding non-cancerous tissues. High HOTAIR expression correlated with lymph node metastasis, and reduced overall survival. A multivariate analysis showed that HOTAIR was a prognostic factor for predicting cervical cancer recurrence. Knockdown of HOTAIR reduced cell proliferation, migration, and invasion in cervical cancer cell lines. Moreover, HOTAIR regulated the expression of vascular endothelial growth factor, matrix metalloproteinase-9 and epithelial-to-mesenchymal transition (EMT)-related genes, which are important for cell motility and metastasis. Therefore, HOTAIR may promote tumor aggressiveness through the upregulation of VEGF and MMP-9 and EMT-related genes. These findings indicate that HOTAIR may represent a novel biomarker for predicting recurrence and prognosis and serve as a promising therapeutic target in cervical cancer.

  7. Six-month natural history of oral versus cervical human papillomavirus infection.

    PubMed

    D'Souza, Gypsyamber; Fakhry, Carole; Sugar, Elizabeth A; Seaberg, Eric C; Weber, Kathleen; Minkoff, Howard L; Anastos, Kathryn; Palefsky, Joel M; Gillison, Maura L

    2007-07-01

    Human papillomavirus (HPV) infection is etiologically associated with a subset of oral cancers, and yet, the natural history of oral HPV infection remains unexplored. The feasibility of studying oral HPV natural history was evaluated by collecting oral rinse samples on 2 occasions at a 6-month interval from 136 HIV-positive and 63 HIV-negative participants. Cervical vaginal lavage samples were concurrently collected for comparison. HPV genomic DNA was detected in oral and cervical samples by consensus primer PCR and type-specified for 37 HPV types. The six-month cumulative prevalence of oral HPV infection was significantly less than for cervical infection (p < 0.0001). HIV-positive women were more likely than HIV-negative women to have an oral (33 vs. 15%, p = 0.016) or cervical (78 vs. 51%, p < 0.001) infection detected. Oral HPV infections detected at baseline were as likely as cervical infections to persist to 6 months among HIV-negative (60% vs. 51%, p = 0.70) and HIV-positive (55% vs. 63%, p = 0.27) women. Factors that independently elevated odds for oral HPV persistence differed from cervical infection and included current smoking (OR = 8, 95% CI = 1.3-53), age above 44 years (OR = 20, 95% CI = 4.1-83), CD4 < 500 (OR = 6, 95% CI = 1.1-26), use of HAART therapy (OR = 12, 95% CI = 1.0-156), and time on HAART therapy (trend p = 0.04). The rate of oral HPV infections newly detected at follow-up was significantly lower than cervical infection among HIV-positive (p < 0.001) and HIV-negative women (p < 0.001). Our study not only demonstrates that it is feasible to study the natural history of oral HPV infection with oral rinse sampling, but also indicates that oral and cervical HPV natural history may differ.

  8. Differentiation patterns in two- and three-dimensional culture systems of human squamous carcinoma cell lines.

    PubMed Central

    Knuechel, R.; Keng, P.; Hofstaedter, F.; Langmuir, V.; Sutherland, R. M.; Penney, D. P.

    1990-01-01

    Relative quantification of the pattern of differentiation of two squamous carcinoma cell lines of the female genital tract, A431 and CaSki, was studied in various experimental tissue culture states that are frequently used to evaluate drug and radiation effects on human tumors. Two- and three-dimensional in vitro cultures, ie, monolayers and multicellular tumor spheroids (MCTS), and nude mice-xenograft tumors as in vivo tumor models were compared. In addition, epidermal growth factor (EGF) was used comparatively in the in vitro studies. Morphologic signs of epithelial differentiation could be recognized in both cell lines gradually increasing from monolayers to MCTS to xenograft tumors. Cytokeratin (CK) expression is described as stable in A431 cells. Using immunohistochemistry, however, partial masking of CK antigens was found when applying the antibody 8.12 on monolayer cells and could be quantified by flow cytometric measurements. Fundamental cellular changes were found in a CaSki xenograft tumor, which showed newly established features of a keratinizing carcinoma after late onset of tumor growth. Epidermal growth factor caused reduction of both intercellular contacts and later onset of necrosis in MCTS, leading to an increased viability of the spheroids. Significant differences in differentiation of the tumor model systems indicates that the characterization of differentiation with immunohistochemistry and flow cytometry is necessary to assist interpretation of data obtained with these different tumor models. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:1698031

  9. Two Cases of Cutaneous Squamous Cell Carcinoma Arising in Immunosuppressed Patients with Chronic Human Papillomavirus Infection

    PubMed Central

    Kuma, Yuki; Ito, Takamichi; Nagae, Konosuke; Mizote, Yukihiro; Nakahara, Takeshi; Uchi, Hiroshi; Yamada, Yuichi; Okura, Masae; Oda, Yoshinao; Yamashita, Toshiharu; Furue, Masutaka

    2015-01-01

    Increasing evidence has suggested that human papillomaviruses (HPVs) are linked to a large subset of numerous malignant tumors, including mucosal squamous cell carcinoma (SCC); however, its involvement in cutaneous SCC has not fully been elucidated. Cutaneous SCC is the second most common type of skin cancer and is increasing in frequency every year. Since we have no satisfactory treatment for advanced SCC, it is important to provide a definitive diagnosis and appropriate therapeutic intervention at an early stage. Here, we present two cases of SCC arising in immunosuppressed patients. In these cases, we suspected the association between SCC and HPV infection histopathologically and succeeded in proving the presence of high-risk type HPV by PCR analysis (HPV 14 in case 1 and HPV 23 and 38 in case 2). Although it is unclear whether HPV actually induced SCC in our cases, our cases showed rapid progression comparing to typical courses of actinic keratosis (AK)/SCC. SCC and AK are common diseases; in daily practice, dermatologists examine many patients with immunosuppression of various causes. We should apply increased oncological vigilance to these patients to prevent an aggressive course of SCC/AK. PMID:26351427

  10. Cutaneous Human Papillomavirus Infection and Development of Subsequent Squamous Cell Carcinoma of the Skin

    PubMed Central

    Reed, Rhianna A.; Bezalel, Spencer; Cameron, Michael; Cherpelis, Basil; Fenske, Neil; Sondak, Vernon K.; Messina, Jane; Tommasino, Massimo; Gheit, Tarik; Rollison, Dana E.

    2016-01-01

    The role of cutaneous human papillomavirus (HPV) infection in the development of subsequent cutaneous squamous cell carcinoma (SCC) is unknown. Pathologically confirmed cases of SCC (n = 150) enrolled in a previously conducted case-control study were included in a retrospective cohort study to examine the association of cutaneous HPV at the time of SCC diagnosis with the risk of subsequent SCC development. Data on HPV seropositivity, HPV DNA in eyebrow hairs (EB) and SCC tumors were available from the parent study. Incidence of subsequent SCC was estimated using person-years of follow up. Cox Proportional Hazards ratios were estimated to evaluate the associations of both, HPV seropositivity and HPV DNA positivity with subsequent SCC. The five year cumulative incidence of subsequent SCC was 72%. Seropositivity to cutaneous HPV was not associated with the risk of subsequent SCC (HR = 0.83, 95% CI = 0.41–1.67). Any beta HPV infection in EB was associated with reduced risk (HR = 0.30, 95% CI = 0.11–0.78) of subsequent SCC among cases who were positive for beta HPV DNA in tumor tissue. Infection with beta HPV type 2 (HR = 0.32, 95% CI = 0.12–0.86) in EB was associated with reduced risk of subsequent SCC among HPV DNA positive SCCs. In conclusion, beta HPV infection was inversely associated with the risk of subsequent SCC. PMID:27891253

  11. The role of human papillomavirus infection in the pathogenesis of penile squamous cell carcinomas.

    PubMed

    Chaux, Alcides; Cubilla, Antonio L

    2012-05-01

    Emerging evidence suggests that penile cancer follows 2 etiologic pathways, 1 related to human papillomavirus (HPV) infection and the other related to other factors including phimosis, chronic inflammation, and lichen sclerosus. HPV DNA is found in 47% to 48% of all penile tumors, and most of these cases correspond to high-risk genotypes, preferentially HPV-16. HPV status is associated with histologic subtype, with higher detection ratios in warty-basaloid carcinomas and lower detection ratios in keratinizing variants (ie, verrucous, papillary, and usual squamous cell carcinomas). It is the cell type, rather than a distinctive architecture, that is more strongly associated with HPV presence. The detection ratio is higher in tumors composed entirely or partially of cells with basaloid features. In addition, a few studies have evaluated the impact of HPV infection on the prognosis of patients with penile cancer. However, results are controversial, and more data are needed to clarify this matter. A proper understanding of the role of HPV in penile carcinogenesis might help in planning intervention strategies such as vaccination against HPV infection.

  12. Effects and mechanisms of aloe-emodin on cell death in human lung squamous cell carcinoma.

    PubMed

    Lee, H Z; Hsu, S L; Liu, M C; Wu, C H

    2001-11-23

    Aloe-emodin (1,8-dihydroxy-3-(hydroxymethyl)-anthraquinone) is an active component from the root and rhizome of Rheum palmatum. The study investigated the effects and mechanisms of aloe-emodin-induced cell death in human lung squamous cell carcinoma cell line CH27. Aloe-emodin (40 microM)-induced CH27 cell apoptosis was confirmed by DNA fragmentation (DNA ladders and sub-G(1) formation). Aloe-emodin-induced apoptosis of CH27 cells involved modulation of the expression of Bcl-2 family proteins, such as BclX(L), Bag-1, and Bak, and was associated with the translocation of Bak and Bax from cytosolic to particulate fractions. Aloe-emodin-treated CH27 cells had an increased relative abundance of cytochrome c in the cytosolic fraction. Results demonstrated that the activation of caspase-3, caspase-8, and caspase-9 is an important determinant of apoptotic death induced by aloe-emodin. These results suggest that aloe-emodin induces CH27 cell death by the Bax and Fas death pathway.

  13. Lycopene inhibits the cell proliferation and invasion of human head and neck squamous cell carcinoma.

    PubMed

    Ye, Min; Wu, Qundan; Zhang, Min; Huang, Jinbei

    2016-10-01

    Lycopene has been shown to be associated with anticancer effects in numerous tumor types. However, the underlying mechanisms of lycopene in human head and neck squamous cell carcinoma (HNSCC) remain to be determined. The present study aimed to investigate the involvement of lycopene overload and the cytotoxic effects of lycopene on HNSCC cells, and to determine the possible mechanisms involved. Treatment with lycopene at a dose of >10 µM for >24 h inhibited the growth of FaDu and Cal27 cells in a time‑ and dose‑dependent manner. The clearest increase in growth inhibition was due to the apoptotic population being significantly increased. The invasion abilities decreased with 25 µM lycopene exerting significant inhibitory effects (P<0.01). Mechanistic studies revealed that lycopene induced the upregulation of the pro‑apoptotic protein, B‑cell lymphoma‑associated X protein, and therefore, resulted in the inhibition of the protein kinase B and mitogen‑activated protein kinase signaling pathway. These data provided insights into the antitumor activity of lycopene in HNSCC cells.

  14. Lycopene inhibits the cell proliferation and invasion of human head and neck squamous cell carcinoma

    PubMed Central

    Ye, Min; Wu, Qundan; Zhang, Min; Huang, Jinbei

    2016-01-01

    Lycopene has been shown to be associated with anticancer effects in numerous tumor types. However, the underlying mechanisms of lycopene in human head and neck squamous cell carcinoma (HNSCC) remain to be determined. The present study aimed to investigate the involvement of lycopene overload and the cytotoxic effects of lycopene on HNSCC cells, and to determine the possible mechanisms involved. Treatment with lycopene at a dose of >10 µM for >24 h inhibited the growth of FaDu and Cal27 cells in a time- and dose-dependent manner. The clearest increase in growth inhibition was due to the apoptotic population being significantly increased. The invasion abilities decreased with 25 µM lycopene exerting significant inhibitory effects (P<0.01). Mechanistic studies revealed that lycopene induced the upregulation of the pro-apoptotic protein, B-cell lymphoma-associated X protein, and therefore, resulted in the inhibition of the protein kinase B and mitogen-activated protein kinase signaling pathway. These data provided insights into the antitumor activity of lycopene in HNSCC cells. PMID:27510325

  15. Increased expression of the PRL-3 gene in human oral squamous cell carcinoma and dysplasia tissues.

    PubMed

    Hassan, Nur Mohammad Monsur; Hamada, Jun-ichi; Kameyama, Takeshi; Tada, Mitsuhiro; Nakagawa, Koji; Yoshida, Shoko; Kashiwazaki, Haruhiko; Yamazaki, Yutaka; Suzuki, Yukiko; Sasaki, Akira; Nagatsuka, Hitoshi; Inoue, Nobuo; Moriuchi, Tetsuya

    2011-01-01

    Phosphatase of regenerating liver (PRL) belongs to a class of the protein tyrosine phosphatase family, which is known so far to consist of 3 members, PRL-1, PRL-2, and PRL-3. The aim of this study was to uncover the role of PRL genes in development of oral malignancy. We analyzed expression levels of the 3 PRL genes in 50 human oral squamous cell carcinomas (OSCCs), 11 dysplasia and 12 normal mucosa tissues by a real-time RT-PCR method. PRL-3 but not PRL-1 or PRL-2 expressions were significantly higher in OSCC and dysplasia than in normal mucosa tissues. Additionally, PRL-3 expressions were significantly higher in OSCC tissues harboring dominant-negative p53 or recessive p53 mutation than in those harboring wild-type p53. These results suggest that PRL-3 plays a role in oral cancer development and can be useful as a marker of pre-malignant and malignant lesion of oral mucosa.

  16. Synthetic Isoliquiritigenin Inhibits Human Tongue Squamous Carcinoma Cells through Its Antioxidant Mechanism

    PubMed Central

    Hou, Cuilan; Li, Wenguang; Li, Zengyou; Gao, Jing; Chen, Zhenjie; Zhao, Xiqiong; Yang, Yaya

    2017-01-01

    Isoliquiritigenin (ISL), a natural antioxidant, has antitumor activity in different types of cancer cells. However the antitumor effect of ISL on human tongue squamous carcinoma cells (TSCC) is not clear. Here we aimed to investigate the effects of synthetic isoliquiritigenin (S-ISL) on TSCC and elucidate the underlying mechanisms. S-ISL was synthesized and elucidated from its nuclear magnetic resonance spectrum and examined using high performance liquid chromatography. The effects of S-ISL on TSCC cells (Tca8113) were evaluated in relation to cell proliferation, apoptosis and adhesion, migration, and invasion using sulforhodamine B assay, fluorescence microscopy technique, flow cytometry (FCM) analysis, and Boyden chamber assay. The associated regulatory mechanisms were examined using FCM and fluorescence microscopy for intracellular reactive oxygen species (ROS) generation, Gelatin zymography assay for matrix metalloproteinase (MMP) activities, and Western blot for apoptosis regulatory proteins (Bcl-2 and Bax). Our data indicated that S-ISL inhibited Tca8113 cell proliferation, adhesion, migration, and invasion while promoting the cell apoptosis. Such effects were accompanied by downregulation of Bcl-2 and upregulation of Bax, reduction of MMP-2 and MMP-9 activities, and decreased ROS production. We conclude that S-ISL is a promising agent targeting TSCC through multiple anticancer effects, regulated by its antioxidant mechanism. PMID:28203317

  17. Antitumoral Effect of Hibiscus sabdariffa on Human Squamous Cell Carcinoma and Multiple Myeloma Cells.

    PubMed

    Malacrida, Alessio; Maggioni, Daniele; Cassetti, Arianna; Nicolini, Gabriella; Cavaletti, Guido; Miloso, Mariarosaria

    2016-10-01

    Cancer is a leading cause of death worldwide. Despite therapeutic improvements, some cancers are still untreatable. Recently there has been an increasing interest in the use of natural substances for cancer prevention and treatment. Hibiscus sabdariffa (HS) is a plant, belonging to Malvaceae family, widespread in South Asia and Central Africa. HS extract (HSE) used in folk medicine, gained researchers' interest thanks to its antioxidant, anti-inflammatory, and chemopreventive properties. In the present study, we initially assessed HSE effect on a panel of human tumor cell lines. Then we focused our study on the following that are most sensitive to HSE action cell lines: Multiple Myeloma (MM) cells (RPMI 8226) and Oral Squamous Cell Carcinoma (OSCC) cells (SCC-25). In both RPMI 8226 and SCC-25 cells, HSE impaired cell growth, exerted a reversible cytostatic effect, and reduced cell motility and invasiveness. We evaluated the involvement of MAPKs ERK1/2 and p38 in HSE effects by using specific inhibitors, U0126 and SB203580, respectively. For both SCC-25 and RPMI 8226, HSE cytostatic effect depends on p38 activation, whereas ERK1/2 modulation is crucial for cell motility and invasiveness. Our results suggest that HSE may be a potential therapeutic agent against MM and OSCC.

  18. Tissue spray ionization mass spectrometry for rapid recognition of human lung squamous cell carcinoma

    NASA Astrophysics Data System (ADS)

    Wei, Yiping; Chen, Liru; Zhou, Wei; Chingin, Konstantin; Ouyang, Yongzhong; Zhu, Tenggao; Wen, Hua; Ding, Jianhua; Xu, Jianjun; Chen, Huanwen

    2015-05-01

    Tissue spray ionization mass spectrometry (TSI-MS) directly on small tissue samples has been shown to provide highly specific molecular information. In this study, we apply this method to the analysis of 38 pairs of human lung squamous cell carcinoma tissue (cancer) and adjacent normal lung tissue (normal). The main components of pulmonary surfactants, dipalmitoyl phosphatidylcholine (DPPC, m/z 757.47), phosphatidylcholine (POPC, m/z 782.52), oleoyl phosphatidylcholine (DOPC, m/z 808.49), and arachidonic acid stearoyl phosphatidylcholine (SAPC, m/z 832.43), were identified using high-resolution tandem mass spectrometry. Monte Carlo sampling partial least squares linear discriminant analysis (PLS-LDA) was used to distinguish full-mass-range mass spectra of cancer samples from the mass spectra of normal tissues. With 5 principal components and 30 - 40 Monte Carlo samplings, the accuracy of cancer identification in matched tissue samples reached 94.42%. Classification of a tissue sample required less than 1 min, which is much faster than the analysis of frozen sections. The rapid, in situ diagnosis with minimal sample consumption provided by TSI-MS is advantageous for surgeons. TSI-MS allows them to make more informed decisions during surgery.

  19. Stromal interaction molecule 1 regulates growth, cell cycle, and apoptosis of human tongue squamous carcinoma cells.

    PubMed

    Cui, Xiaobo; Song, Laixiao; Bai, Yunfei; Wang, Yaping; Wang, Boqian; Wang, Wei

    2017-04-30

    Oral tongue squamous cell carcinoma (OTSCC) is the most common type of oral carcinomas. However, the molecular mechanism by which OTSCC developed is not fully identified. Stromal interaction molecule 1 (STIM1) is a transmembrane protein, mainly located in the endoplasmic reticulum (ER). STIM1 is involved in several types of cancers. Here, we report that STIM1 contributes to the development of human OTSCC. We knocked down STIM1 in OTSCC cell line Tca-8113 with lentivirus-mediated shRNA and found that STIM1 knockdown repressed the proliferation of Tca-8113 cells. In addition, we also showed that STIM1 deficiency reduced colony number of Tca-8113 cells. Knockdown of STIM1 repressed cells to enter M phase of cell cycle and induced cellular apoptosis. Furthermore, we performed microarray and bioinformatics analysis and found that STIM1 was associated with p53 and MAPK pathways, which may contribute to the effects of STIM1 on cell growth, cell cycle, and apoptosis. Finally, we confirmed that STIM1 controlled the expression of MDM2, cyclin-dependent kinase 4 (CDK4), and growth arrest and DNA damage inducible α (GADD45A) in OTSCC cells. In conclusion, we provide evidence that STIM1 contributes to the development of OTSCC partially through regulating p53 and MAPK pathways to promote cell cycle and survival.

  20. Expression levels of B7-H3 and TLT-2 in human oral squamous cell carcinoma

    PubMed Central

    ZHANG, SHAN-SHAN; TANG, JING; YU, SHU-YI; MA, LI; WANG, FENG; XIE, SHU-LE; JIN, LONG; YANG, HONG-YU

    2015-01-01

    The aim of the present study was to investigate the role of immune regulatory molecules B7-H3 [also known as cluster of differentiation 276] and triggering receptor expressed on myeloid cell-like transcript-2 (TLT-2) in patients with oral squamous cell carcinoma (OSCC). Human OSCC samples were obtained from 76 patients (female, 32; male, 44; age range, 23–81 years; median age, 50.9 years) that underwent resection for OSCC at Peking University Shenzhen Hospital (Shenzhen, China) between 2007 and 2010. In addition, control oral mucosal samples were obtained from 76 healthy individuals (female, 36; male, 40; age range, 21–62 years; median age, 45.3 years) during wisdom tooth extraction. Protein and gene expression levels of B7-H3 and TLT-2 were determined by immunohistochemical analysis and reverse transcription-polymerase chain reaction (RT-PCR). In the healthy oral mucosa samples, B7-H3 expression was identified to be weak, while the expression of TLT-2 was only detected sporadically in the cell membrane and cytoplasm. By contrast, the two regulatory molecules were widely expressed in the aforementioned localizations in human OSCC specimens upon immunohistochemical examination. Furthermore, quantitative RT-PCR confirmed the presence of significantly higher B7-H3 and TLT-2 expression levels in OSCC specimens compared with the oral mucosa of healthy individuals. The significantly higher expression levels of B7-H3 and TLT-2 in human OSCC specimens may indicate an inhibitory role of these molecules in the antitumoral immune response. To investigate interactions between these two molecules and individual antitumoral immune response in OSCC patients, prospective clinical studies with an adequate sample size are required. PMID:26622626

  1. Isolation of a hemidesmosome-rich fraction from a human squamous cell carcinoma cell line

    SciTech Connect

    Hirako, Yoshiaki; Yonemoto, Yuki; Yamauchi, Tomoe; Nishizawa, Yuji; Kawamoto, Yoshiyuki; Owaribe, Katsushi

    2014-06-10

    Hemidesmosomes are cell-to-matrix adhesion complexes anchoring keratinocytes to basement membranes. For the first time, we present a method to prepare a fraction from human cultured cells that are highly enriched in hemidesmosomal proteins. Using DJM-1 cells derived from human squamous cell carcinoma, accumulation of hemidesmosomes was observed when these cells were cultured for more than 10 days in a commercial serum-free medium without supplemental calcium. Electron microscopy demonstrated that numerous electron-dense adhesion structures were present along the basal cell membranes of DJM-1 cells cultured under the aforementioned conditions. After removing cellular materials using an ammonia solution, hemidesmosomal proteins and deposited extracellular matrix were collected and separated by electrophoresis. There were eight major polypeptides, which were determined to be plectin, BP230, BP180, integrin α6 and β4 subunits, and laminin-332 by immunoblotting and mass spectrometry. Therefore, we designated this preparation as a hemidesmosome-rich fraction. This fraction contained laminin-332 exclusively in its unprocessed form, which may account for the promotion of laminin deposition, and minimal amounts of Lutheran blood group protein, a nonhemidesmosomal transmembrane protein. This hemidesmosome-rich fraction would be useful not only for biological research on hemidesmosomes but also for developing a serum test for patients with blistering skin diseases. - Highlights: • A defined condition promoted accumulation of hemidesmosomes in human cultured cells. • A fraction isolated from the cells contained eight major polypeptides. • The polypeptides were the five major hemidesmosome proteins and laminin-332. • The cultured cells deposited laminin-332 in its unprocessed form under the condition. • We report a method to prepare a fraction highly enriched in hemidesmosome proteins.

  2. Integrated genomic and molecular characterization of cervical cancer.

    PubMed

    2017-03-16

    Cervical cancer remains one of the leading causes of cancer-related deaths worldwide. Here we report the extensive molecular characterization of 228 primary cervical cancers, one of the largest comprehensive genomic studies of cervical cancer to date. We observed notable APOBEC mutagenesis patterns and identified SHKBP1, ERBB3, CASP8, HLA-A and TGFBR2 as novel significantly mutated genes in cervical cancer. We also discovered amplifications in immune targets CD274 (also known as PD-L1) and PDCD1LG2 (also known as PD-L2), and the BCAR4 long non-coding RNA, which has been associated with response to lapatinib. Integration of human papilloma virus (HPV) was observed in all HPV18-related samples and 76% of HPV16-related samples, and was associated with structural aberrations and increased target-gene expression. We identified a unique set of endometrial-like cervical cancers, comprised predominantly of HPV-negative tumours with relatively high frequencies of KRAS, ARID1A and PTEN mutations. Integrative clustering of 178 samples identified keratin-low squamous, keratin-high squamous and adenocarcinoma-rich subgroups. These molecular analyses reveal new potential therapeutic targets for cervical cancers.

  3. Bidirectional functions of arsenic as a carcinogen and an anti-cancer agent in human squamous cell carcinoma.

    PubMed

    Thang, Nguyen Dinh; Yajima, Ichiro; Kumasaka, Mayuko Y; Kato, Masashi

    2014-01-01

    Bidirectional cancer-promoting and anti-cancer effects of arsenic for cancer cells have been revealed in previous studies. However, each of these effects (cancer-promoting or anti-cancer) was found in different cells at different treated-concentration of arsenic. In this study, we for the first time indicated that arsenic at concentration of 3 µM, equal to average concentration in drinking water in cancer-prone areas in Bangladesh, simultaneously expressed its bidirectional effects on human squamous cell carcinoma HSC5 cells with distinct pathways. Treatment with 3 µM of arsenic promoted cell invasion via upregulation of expression of MT1-MMP and downregulation of expression of p14ARF and simultaneously induced cell apoptosis through inhibition of expression of N-cadherin and increase of expression of p21(WAF1/CIP1) at both transcript and protein levels in HSC5 cells. We also showed that inhibition of MT1-MMP expression by NSC405020 resulted in decrease of arsenic-mediated invasion of HSC5 cells involving decrease in phosphorylated extracellular signal-regulated kinases (pERK). Taken together, our biological and biochemical findings suggested that arsenic expressed bidirectional effects as a carcinogen and an anti-cancer agent in human squamous cell carcinoma HSC5 cells with distinct pathways. Our results might play an important scientific evident for further studies to find out a better way in treatment of arsenic-induced cancers, especially in squamous cell carcinoma.

  4. Loss of Dependence on Continued Expression of the Human Papillomavirus 16 E7 Oncogene in Cervical Cancers and Precancerous Lesions Arising in Fanconi Anemia Pathway-Deficient Mice

    PubMed Central

    Park, Soyeong; Park, Jung Wook; Pitot, Henry C.

    2016-01-01

    ABSTRACT   Fanconi anemia (FA) is a rare genetic disorder caused by defects in DNA damage repair. FA patients often develop squamous cell carcinoma (SCC) at sites where high-risk human papillomaviruses (HPVs) are known to cause cancer, including the cervix. However, SCCs found in human FA patients are often HPV negative, even though the majority of female FA patients with anogenital cancers had preexisting HPV-positive dysplasia. We hypothesize that HPVs contribute to the development of SCCs in FA patients but that the continued expression of HPV oncogenes is not required for the maintenance of the cancer state because FA deficiency leads to an accumulation of mutations in cellular genes that render the cancer no longer dependent upon viral oncogenes. We tested this hypothesis, making use of Bi-L E7 transgenic mice in which we temporally controlled expression of HPV16 E7, the dominant viral oncogene in HPV-associated cancers. As seen before, the persistence of cervical neoplastic disease was highly dependent upon the continued expression of HPV16 E7 in FA-sufficient mice. However, in mice with FA deficiency, cervical cancers persisted in a large fraction of the mice after HPV16 E7 expression was turned off, indicating that these cancers had escaped from their dependency on E7. Furthermore, the severity of precancerous lesions also failed to be reduced significantly in the mice with FA deficiency upon turning off expression of E7. These findings confirm our hypothesis and may explain the fact that, while FA patients have a high frequency of infections by HPVs and HPV-induced precancerous lesions, the cancers are frequently HPV negative. Importance   Fanconi anemia (FA) patients are at high risk for developing squamous cell carcinoma (SCC) at sites where high-risk human papillomaviruses (HPVs) frequently cause cancer. Yet these SCCs are often HPV negative. FA patients have a genetic defect in their capacity to repair damaged DNA. HPV oncogenes cause an

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

    DTIC Science & Technology

    1982-11-01

    25 Faililre Tests ............................................ 27 CERVICAL SPINE GEOMETRY ......................... 27 MEASURFMENT TECHNIQUE...Ci - TI for Specimens EJ 4!, GS 28, Hf 23, PW 35, SWE 23, SWE 25 . . . . . . . Cl-C38 C39-C44 Projected Vertehrpe Areas (MM2 ) for Specimens EJ 41, GS...28, HI 23, PW 35, SWE 23, S U: 25 ........ C39-C44 C45-C50 Normal Unit Vector to Centrun. for Snecimens EJ 41, GS 28, HI 23, PW 35, SWE 23, SWE 25

  6. Antitumor effects of recombinant human adenovirus-p53 against human cutaneous squamous cell carcinoma in mice

    PubMed Central

    Li, Yuanchao; He, Wei; Wang, Rupeng; Yang, Libin; Zhou, Chunli; Zhang, Bin

    2016-01-01

    The present study was conducted to identify the anti-tumor effects of rAd/p53, which is a recombinant human serotype 5 adenovirus, in cutaneous squamous cell carcinoma (cSCC). Mouse models of human cSCC were constructed by injecting human cutaneous squamous cell carcinoma cells into both flanks of nude mice. Subsequently, the 75 nude mice with cSCC xenograft tumors were randomly divided into recombinant human serotype 5 adenovirus (rAd)/p53, rAd/p53 + 5-fluorouracil (5-Fu) and 5-Fu groups. One side of the tumors was administered the therapeutic agents as the therapeutic group, whereas the remaining side was treated with medical saline as the control. At 24, 48, 72, 120 and 168 h post-intratumoral injection, alterations in tumor volume, tumor necrosis and the expression of several tumor-associated genes, including Smad4, Brca1 and matrix metalloproteinase (MMP-2), were analyzed. Compared with its control group, the rAd/P53 group exhibited a significantly increased tumor necrosis ratio. In addition, Smad4 and Brca1 expression levels increased significantly at various time points (P<0.05), and MMP-2 expression decreased significantly (P<0.05). In the rAd/p53 + 5-Fu group, the tumor necrosis ratio, and Smad4 and Brca1 expression levels also significantly increased at various time points (P<0.05). MMP-2 gene transcription gradually decreased, high expression of Smad4 was prolonged, and high expression of Brca1 was observed in the early period following treatment compared with the rAd/P53 group. In addition, p53 expression exhibited a positive correlation with the tumor necrosis ratio and Smad4 expression, and showed a negative correlation with MMP-2 gene transcription (P<0.05). These findings indicate that rAd/p53 has a potent anti-tumor effect in cSCC via the promotion of tumor necrosis and regulating the expression of various tumor-associated genes. PMID:28105142

  7. Acquired immune response to oncogenic human papillomavirus associated with prophylactic cervical cancer vaccines.

    PubMed

    Einstein, Mark H

    2008-04-01

    Human papillomavirus (HPV) is a common infection among women and a necessary cause of cervical cancer. Oncogenic HPV types infecting the anogenital tract have the potential to induce natural immunity, but at present we do not clearly understand the natural history of infection in humans and the mechanisms by which the virus can evade the host immune response. Natural acquired immune responses against HPV may be involved in the clearance of infection, but persistent infection with oncogenic virus types leads to the development of precancerous lesions and cancer. B cell responses are important for viral neutralization, but antibody responses in patients with cervical cancer are poor. Prophylactic vaccines targeting oncogenic virus types associated with cervical cancer have the potential to prevent up to 80% of cervical cancers by targeting HPV types 16 and 18. Clinical data show that prophylactic vaccines are effective in inducing antibody responses and in preventing persistent infection with HPV, as well as the subsequent development of high-grade cervical intraepithelial neoplasia. This article reviews the known data regarding natural immune responses to HPV and those developed by prophylactic vaccination.

  8. Arsenic trioxide inhibits cell proliferation and human papillomavirus oncogene expression in cervical cancer cells

    SciTech Connect

    Wang, Hongtao; Gao, Peng; Zheng, Jie

    2014-09-05

    Highlights: • As{sub 2}O{sub 3} inhibits growth of cervical cancer cells and expression of HPV oncogenes in these cells. • HPV-negative cervical cancer cells are more sensitive to As{sub 2}O{sub 3} than HPV-positive cervical cancer cells. • HPV-18 positive cervical cancer cells are more sensitive to As{sub 2}O{sub 3} than HPV-16 positive cancer cells. • Down-regulation of HPV oncogenes by As{sub 2}O{sub 3} is partially due to the diminished AP-1 binding. - Abstract: Arsenic trioxide (As{sub 2}O{sub 3}) has shown therapeutic effects in some leukemias and solid cancers. However, the molecular mechanisms of its anticancer efficacy have not been clearly elucidated, particularly in solid cancers. Our previous data showed that As{sub 2}O{sub 3} induced apoptosis of human papillomavirus (HPV) 16 DNA-immortalized human cervical epithelial cells and cervical cancer cells and inhibited the expression of HPV oncogenes in these cells. In the present study, we systemically examined the effects of As{sub 2}O{sub 3} on five human cervical cancer cell lines and explored the possible molecular mechanisms. MTT assay showed that HPV-negative C33A cells were more sensitive to growth inhibition induced by As{sub 2}O{sub 3} than HPV-positive cervical cancer cells, and HPV 18-positive HeLa and C4-I cells were more sensitive to As{sub 2}O{sub 3} than HPV 16-positive CaSki and SiHa cells. After As{sub 2}O{sub 3} treatment, both mRNA and protein levels of HPV E6 and E7 obviously decreased in all HPV positive cell lines. In contrast, p53 and Rb protein levels increased in all tested cell lines. Transcription factor AP-1 protein expression decreased significantly in HeLa, CaSki and C33A cells with ELISA method. These results suggest that As{sub 2}O{sub 3} is a potential anticancer drug for cervical cancer.

  9. Monitoring PAI-1 and VEGF Levels in 6 Human Squamous Cell Carcinoma Xenografts During Fractionated Irradiation

    SciTech Connect

    Bayer, Christine; Kielow, Achim; Schilling, Daniela; Maftei, Constantin-Alin; Zips, Daniel; Yaromina, Ala; Baumann, Michael; Molls, Michael; Multhoff, Gabriele

    2012-11-01

    Purpose: Previous studies have shown that the plasminogen activator inhibitor type-1 (PAI-1) and vascular endothelial growth factor (VEGF) are regulated by hypoxia and irradiation and are involved in neoangiogenesis. The aim of this study was to determine in vivo whether changes in PAI-1 and VEGF during fractionated irradiation could predict for radiation resistance. Methods and Materials: Six xenografted tumor lines from human squamous cell carcinomas (HSCC) of the head and neck were irradiated with 0, 3, 5, 10, and 15 daily fractions of 2 Gy. The PAI-1 and VEGF antigen levels in tumor lysates were determined by enzyme-linked immunosorbent assay kits. The amounts of PAI-1 and VEGF were compared with the dose to cure 50% of tumors (TCD{sub 50}). Colocalization of PAI-1, pimonidazole (hypoxia), CD31 (endothelium), and Hoechst 33342 (perfusion) was examined by immunofluorescence. Results: Human PAI-1 and VEGF (hVEGF) expression levels were induced by fractionated irradiation in UT-SCC-15, UT-SCC-14, and UT-SCC-5 tumors, and mouse VEGF (msVEGF) was induced only in UT-SCC-5 tumors. High hVEGF levels were significantly associated with radiation sensitivity after 5 fractions (P=.021), and high msVEGF levels were significantly associated with radiation resistance after 10 fractions (P=.007). PAI-1 staining was observed in the extracellular matrix, the cytoplasm of fibroblast-like stroma cells, and individual tumor cells at all doses of irradiation. Colocalization studies showed PAI-1 staining close to microvessels. Conclusions: These results indicate that the concentration of tumor-specific and host-specific VEGF during fractionated irradiation could provide considerably divergent information for the outcome of radiation therapy.

  10. Altered epigenetic regulation of homeobox genes in human oral squamous cell carcinoma cells

    PubMed Central

    Marcinkiewicz, Katarzyna M.; Gudas, Lorraine J.

    2013-01-01

    To gain insight into oral squamous cell carcinogenesis, we performed deep sequencing (RNAseq) of non-tumorigenic human OKF6-TERT1R and tumorigenic SCC-9 cells. Numerous homeobox genes are differentially expressed between OKF6-TERT1R and SCC-9 cells. Data from Oncomine, a cancer microarray database, also show that homeobox (HOX) genes are dysregulated in oral SCC patients. The activity of Polycomb repressive complexes (PRC), which causes epigenetic modifications, and retinoic acid (RA) signaling can control HOX gene transcription. HOXB7, HOXC10, HOXC13, and HOXD8 transcripts are higher in SCC-9 than in OKF6-TERT1R cells; using ChIP (chromatin immunoprecipitation) we detected PRC2 protein SUZ12 and the epigenetic H3K27me3 mark on histone H3 at these genes in OKF6-TERT1R, but not in SCC-9 cells. In contrast, IRX1, IRX4, SIX2 and TSHZ3 transcripts are lower in SCC-9 than in OKF6-TERT1R cells. We detected SUZ12 and the H3K27me3 mark at these genes in SCC-9, but not in OKF6-TERT1R cells. SUZ12 depletion increased HOXB7, HOXC10, HOXC13, and HOXD8 transcript levels and decreased the proliferation of OKF6-TERT1R cells. Transcriptional responses to RA are attenuated in SCC-9 versus OKF6-TERT1R cells. SUZ12 and H3K27me3 levels were not altered by RA at these HOX genes in SCC-9 and OKF6-TERT1R cells. We conclude that altered activity of PRC2 is associated with dysregulation of homeobox gene expression in human SCC cells, and that this dysregulation potentially plays a role in the neoplastic transformation of oral keratinocytes. PMID:24076275

  11. Altered epigenetic regulation of homeobox genes in human oral squamous cell carcinoma cells.

    PubMed

    Marcinkiewicz, Katarzyna M; Gudas, Lorraine J

    2014-01-01

    To gain insight into oral squamous cell carcinogenesis, we performed deep sequencing (RNAseq) of non-tumorigenic human OKF6-TERT1R and tumorigenic SCC-9 cells. Numerous homeobox genes are differentially expressed between OKF6-TERT1R and SCC-9 cells. Data from Oncomine, a cancer microarray database, also show that homeobox (HOX) genes are dysregulated in oral SCC patients. The activity of Polycomb repressive complexes (PRC), which causes epigenetic modifications, and retinoic acid (RA) signaling can control HOX gene transcription. HOXB7, HOXC10, HOXC13, and HOXD8 transcripts are higher in SCC-9 than in OKF6-TERT1R cells; using ChIP (chromatin immunoprecipitation) we detected PRC2 protein SUZ12 and the epigenetic H3K27me3 mark on histone H3 at these genes in OKF6-TERT1R, but not in SCC-9 cells. In contrast, IRX1, IRX4, SIX2 and TSHZ3 transcripts are lower in SCC-9 than in OKF6-TERT1R cells. We detected SUZ12 and the H3K27me3 mark at these genes in SCC-9, but not in OKF6-TERT1R cells. SUZ12 depletion increased HOXB7, HOXC10, HOXC13, and HOXD8 transcript levels and decreased the proliferation of OKF6-TERT1R cells. Transcriptional responses to RA are attenuated in SCC-9 versus OKF6-TERT1R cells. SUZ12 and H3K27me3 levels were not altered by RA at these HOX genes in SCC-9 and OKF6-TERT1R cells. We conclude that altered activity of PRC2 is associated with dysregulation of homeobox gene expression in human SCC cells, and that this dysregulation potentially plays a role in the neoplastic transformation of oral keratinocytes.

  12. Photodynamic therapy of human squamous cell carcinoma in vitro and in xenografts in nude mice.

    PubMed

    Megerian, C A; Zaidi, S I; Sprecher, R C; Setrakian, S; Stepnick, D W; Oleinick, N L; Mukhtar, H

    1993-09-01

    Photodynamic therapy (PDT) of cancer is an experimental tumor therapy which is based on the combined use of a systematically administered photosensitizer to a tumor-bearing host and local illumination of the lesion by a high-intensity visible light source, typically a tunable argon dye laser. Human squamous cell carcinoma (HSCC) is the most frequently encountered malignancy of the head and neck. In this study, responses of HSCC cells to PDT were examined in in vitro and in vivo systems. In in vitro studies, the HSCC cells showed a positive photodynamic response with Photofrin-II (Pf-II), chloroaluminum phthalocyanine tetrasulfonate (AlPcTS), and a newly synthesized silicon phthalocyanine (SiPc IV). Single cell suspension of HSCC injected subcutaneously on the back of athymic nude mice resulted in a well-circumscribed tumor mass. The animals required a low tumor dose for the successful establishment of a tumor. The tumor was minimally immunogenic and showed neither macroscopic signs of early metastasis to lung, kidney, liver, or spleen nor evidence of surrounding erythema, fluctuation, or tenderness until the late stages of necrosis. Intraperitoneal administration of AlPcTS or SiPc IV to tumor-bearing mice resulted in rapid uptake of the photosensitizers in liver, skin, and tumor tissue. Twenty-four hours following the intraperitoneal administration of AlPcTS or SiPc IV to tumor-bearing animals, the tumor to normal skin ratio of the photosensitizer was 1.6 or 1.5, respectively. Administration of Pf-II (5 mg/kg) to tumor-bearing animals followed 24 hours later by irradiation of the tumor (135 J/cm2, 630 nm light from an argon pumped-dye laser) resulted in greater than 80% ablation in tumor volume 24 hours post-PDT. These characteristics make this tumor model system suitable for PDT studies of human tumor cells in vitro as well as in vivo.

  13. Primary human cervical carcinoma cells require human papillomavirus E6 and E7 expression for ongoing proliferation

    SciTech Connect

    Magaldi, Thomas G.; Almstead, Laura L.; Bellone, Stefania; Prevatt, Edward G.; Santin, Alessandro D.; DiMaio, Daniel

    2012-01-05

    Repression of human papillomavirus (HPV) E6 and E7 oncogenes in established cervical carcinoma cell lines causes senescence due to reactivation of cellular tumor suppressor pathways. Here, we determined whether ongoing expression of HPV16 or HPV18 oncogenes is required for the proliferation of primary human cervical carcinoma cells in serum-free conditions at low passage number after isolation from patients. We used an SV40 viral vector expressing the bovine papillomavirus E2 protein to repress E6 and E7 in these cells. To enable efficient SV40 infection and E2 gene delivery, we first incubated the primary cervical cancer cells with the ganglioside GM1, a cell-surface receptor for SV40 that is limiting in these cells. Repression of HPV in primary cervical carcinoma cells caused them to undergo senescence, but the E2 protein had little effect on HPV-negative primary cells. These data suggest that E6 and E7 dependence is an inherent property of human cervical cancer cells.

  14. Differential effects of human papillomavirus type 6, 16, and 18 DNAs on immortalization and transformation of human cervical epithelial cells

    SciTech Connect

    Pecoraro, G.; Morgan, D.; Defendi, V. )

    1989-01-01

    The human papillomaviruses (HPVs) are associated with specific benign and malignant lesions of the skin and mucosal epithelia. Cloned viral DNAs from HPV types 6b, 16, and 18 associated with different pathological manifestations of genital neoplasia in vivo were introduced into primary human cervical epithelial cells by electroporation. Cells transfected with HPV16 or HPV18 DNA acquired indefinite lifespans, distinct morphological alterations, and anchorage-independent growth (HPV18), and contain integrated transcriptionally active viral genomes. HPV6b or plasmid electroporated cells senesced at low passage. The alterations in growth and differentiation of the cells appear to reflect the progressive oncogenic processes that result in cervical carcinoma in vivo.

  15. The significance of marked nuclear atypia in grade 1 cervical intraepithelial neoplasia.

    PubMed

    Fadare, Oluwole; Rodriguez, Rosemarie

    2009-10-01

    Approximately 10% to 15% of cases of grade 1 cervical intraepithelial neoplasia are found to have progressed to a high-grade squamous intraepithelial lesion or higher at follow-up, and there are presently no reliable morphological predictors of this subset. It has recently been reported that cases of grade 1 cervical intraepithelial neoplasia that display marked nuclear atypia (defined as cases with at least 5 epithelial cells with nuclear enlargement of at least 5 times the size of an intermediate cell, and/or multinucleation of at least 5 nuclei.) have a substantially higher rate of high-grade squamous intraepithelial lesion on short-term follow-up and may, therefore, require more aggressive initial management. We report herein our experience with a cohort of such cases. After a review of consecutive cervical biopsies, 352 cases with grade 1 cervical intraepithelial neoplasia were classified into group 1 (grade 1 cervical intraepithelial neoplasia with marked atypia, n = 31) and group 2 (grade 1 cervical intraepithelial neoplasia without marked atypia, n = 321). The average follow-up rates for groups 1 and 2 were 93.55% (29/31) and 90.65% (291/321), respectively. Average follow-up durations were 14.3 and 17.9 months, respectively. The follow-up high-grade squamous intraepithelial lesion rate of the cases with marked atypia was 10.34%, as compared with 11.68% for cases without marked atypia. The follow-up interpretive frequency (in cytologic samples) of "low-grade squamous intraepithelial lesion" was significantly higher in group 1(19/29 versus 114/291, P = .009). However, no significant differences were identified between groups 1 and 2 regarding the interpretive frequencies of either high-grade squamous intraepithelial lesion (3/29 versus 34/291, P = 1) or "negative for intraepithelial lesion or malignancy" (6/29 versus 56/291, P = .8) in follow-up cytologic samples. In subsets of both groups in which high-risk human papillomavirus testing was performed in the

  16. Intensity-Modulated Radiotherapy for Cervical Node Squamous Cell Carcinoma Metastases From Unknown Head-and-Neck Primary Site: M. D. Anderson Cancer Center Outcomes and Patterns of Failure

    SciTech Connect

    Frank, Steven J.; Rosenthal, David I.; Petsuksiri, Janjira; Ang, K. Kian; Morrison, William H.; Weber, Randal S.; Glisson, Bonnie S.; El-Naggar, Adel K.; Garden, Adam S.

    2010-11-15

    Purpose: Conventional therapy for cervical node squamous cell carcinoma metastases from an unknown primary can cause considerable toxicity owing to the volume of tissues to be irradiated. In the present study, hypothesizing that using intensity-modulated radiotherapy (IMRT) would provide effective treatment with minimal toxicity, we reviewed the outcomes and patterns of failure for head-and-neck unknown primary cancer at a single tertiary cancer center. Methods and Materials: We retrospectively reviewed the records of 52 patients who had undergone IMRT for an unknown primary at M.D. Anderson Cancer Center between 1998 and 2005. The patient and treatment characteristics were extracted and the survival rates calculated using the Kaplan-Meier method. Results: Of the 52 patients, 5 presented with Stage N1, 11 with Stage N2a, 23 with Stage N2b, 6 with Stage N2c, 4 with Stage N3, and 3 with Stage Nx disease. A total of 26 patients had undergone neck dissection, 13 before and 13 after IMRT; 14 patients had undergone excisional biopsy and presented for IMRT without evidence of disease. Finally, 14 patients had received systemic chemotherapy. All patients underwent IMRT to targets on both sides of the neck and pharyngeal axis. The median follow-up time for the surviving patients was 3.7 years. The 5-year actuarial rate of primary mucosal tumor control and regional control was 98% and 94%, respectively. Only 3 patients developed distant metastasis with locoregional control. The 5-year actuarial disease-free and overall survival rate was 88% and 89%, respectively. The most severe toxicity was Grade 3 dysphagia/esophageal stricture, experienced by 2 patients. Conclusion: The results of our study have shown that IMRT can produce excellent outcomes for patients who present with cervical node squamous cell carcinoma metastases from an unknown head-and-neck primary tumor. Severe late complications were uncommon.

  17. Cidofovir is active against human papillomavirus positive and negative head and neck and cervical tumor cells by causing DNA damage as one of its working mechanisms

    PubMed Central

    Mertens, Barbara; Nogueira, Tatiane; Stranska, Ruzena; Naesens, Lieve; Andrei, Graciela; Snoeck, Robert

    2016-01-01

    Human papillomavirus (HPV) causes cervical cancer and a large fraction of head and neck squamous cell carcinomas (HNSCC). Cidofovir (CDV) proved efficacious in the treatment of several HPV-induced benign and malignant hyper proliferations. To provide a better insight into how CDV selectively eradicates transformed cells, HPV+ and HPV− cervical carcinoma and HNSCC cell lines were compared to normal cells for antiproliferative effects, CDV metabolism, drug incorporation into cellular DNA, and DNA damage. Incorporation of CDV into cellular DNA was higher in tumor cells than in normal cells and correlated with CDV antiproliferative effects, which were independent of HPV status. Increase in phospho-ATM levels was detected following CDV exposure and higher levels of γ-H2AX (a quantitative marker of double-strand breaks) were measured in tumor cells compared to normal cells. A correlation between DNA damage and CDV incorporation into DNA was found but not between DNA damage and CDV antiproliferative effects. These data indicate that CDV antiproliferative effects result from incorporation of the drug into DNA causing DNA damage. However, the anti-tumor effects of CDV cannot be exclusively ascribed to DNA damage. Furthermore, CDV can be considered a promising broad spectrum anti-cancer agent, not restricted to HPV+ lesions. PMID:27331622

  18. Rapid, sensitive, type specific PCR detection of the E7 region of human papillomavirus type 16 and 18 from paraffin embedded sections of cervical carcinoma.

    PubMed

    Lesnikova, Iana; Lidang, Marianne; Hamilton-Dutoit, Steven; Koch, Jørn

    2010-01-22

    Human papillomavirus (HPV) infection, and in particularly infection with HPVs 16 and 18, is a central carcinogenic factor in the uterine cervix. We established and optimized a PCR assay for the detection and discrimination of HPV types 16 and 18 in archival formaldehyde fixed and paraffin embedded (FFPE) sections of cervical cancer.Tissue blocks from 35 cases of in situ or invasive cervical squamous cell carcinoma and surrogate FFPE sections containing the cell lines HeLa and SiHa were tested for HPV 16 and HPV18 by conventional PCR using type specific primers, and for the housekeeping gene beta-actin. Using HPV 16 E7 primers, PCR products with the expected length were detected in 18 of 35 of FFPE sections (51%). HPV 18 E7 specific sequences were detected in 3 of 35 FFPE sections (9%).In our experience, the PCR technique is a robust, simple and sensitive way of type specific detection of HPV16 and HPV18 genes in FFPE tissue. That makes this technique applicable to routine practices of HPV detection.

  19. The terminology of pre-invasive cervical lesions in the UK cervical screening programme.

    PubMed

    Herrington, C S

    2015-12-01

    The terminology of non-invasive epithelial abnormalities associated with an elevated risk of having or developing invasive cervical carcinoma (pre-invasive lesions) has been modified frequently over time as understanding of the underlying biology, and approaches to disease management, have changed. The arguments are now converging on the conclusion that the most appropriate terminology for cervical squamous intraepithelial abnormalities should be two-tier rather than three-tier. Given the findings of the Lower Anogenital Squamous Terminology (LAST) project in the USA, which have recently been endorsed by the World Health Organisation classification of tumours of female reproductive organs, the recommended terms are low-grade and high-grade squamous intraepithelial lesion (SIL), with the option of including the relevant cervical intraepithelial neoplasia (CIN) grade in parentheses. Although, at first sight, this appears to represent only a small change, there is a fundamental conceptual difference between the systems. The CIN system requires, first, the identification of a CIN lesion and, second, the determination of its grade on a continuum, with subsequent division into three grades. The SIL system is based on the existence of two different forms of human papillomavirus (HPV) infection, with productive infection leading to low-grade SIL and transforming infection leading to high-grade SIL.

  20. NR2F6 Expression Correlates with Pelvic Lymph Node Metastasis and Poor Prognosis in Early-Stage Cervical Cancer

    PubMed Central

    Niu, Chunhao; Sun, Xiaoying; Zhang, Weijing; Li, Han; Xu, Liqun; Li, Jun; Xu, Benke; Zhang, Yanna

    2016-01-01

    Background: There is an abnormal expression of nuclear receptor subfamily 2 group F member 6 (NR2F6) in human cancers such as breast cancer, colon cancer, and acute myelogenous leukemia. However, its clinical significance in cervical cancer has not been established. We explored NR2F6 expression and its clinicopathological significance in early-stage cervical cancer. Methods: NR2F6 expression in cervical cancer cell lines and cervical cancer tissues was determined by Western blotting, real-time PCR, and immunochemistry (IHC). NR2F6 expression in 189 human early-stage cervical cancer tissue samples was evaluated using IHC. The relevance between NR2F6 expression and early-stage cervical cancer prognosis and clinicopathological features was determined. Results: There was marked NR2F6 mRNA and protein overexpression in the cervical cancer cells and clinical tissues compared with an immortalized squamous cell line and adjacent noncancerous cervical tissues, respectively. In the 189 cervical cancer samples, NR2F6 expression was positively related to International Federation of Gynecology and Obstetrics (FIGO) stage (p = 0.006), squamous cell carcinoma antigen (p = 0.006), vital status (p < 0.001), tumor recurrence (p = 0.001), chemotherapy (p = 0.039), and lymph node metastasis (p < 0.001). Overall and disease-free survival was shorter in patients with early-stage cervical cancer and higher NR2F6 levels than in patients with lower levels of NR2F6. Univariate and multivariate analysis determined that NR2F6 was an independent prognostic factor of survival in early-stage cervical cancer. Conclusions: Taken together, our findings suggest that high NR2F6 expression predicts pelvic lymph node metastasis, tumor recurrence and poor prognosis in early-stage cervical cancer. NR2F6 might be a novel prognostic biomarker and potential therapeutic target of cervical cancer. PMID:27775588

  1. KLF4 is downregulated but not mutated during human esophageal squamous cell carcinogenesis and has tumor stage-specific functions

    PubMed Central

    Yang, Yizeng; Katz, Jonathan P.

    2016-01-01

    ABSTRACT The transcriptional regulator Krüppel-like factor 4 (KLF4) is decreased in human esophageal squamous cell cancer (ESCC), and Klf4 deletion in mice produces squamous cell dysplasia. Nonetheless the mechanisms of KLF4 downregulation in ESCC and the functions of KLF4 during ESCC development and progression are not well understood. Here, we sought to define the regulation of KLF4 and delineate the stage-specific effects of KLF4 in ESCC. We found that KLF4 expression was decreased in human ESCC and in 8 of 9 human ESCC cell lines. However, by genomic sequencing, we observed no KLF4 mutations or copy number changes in any of 52 human ESCC, suggesting other mechanisms for KLF4 silencing. In fact, KLF4 expression in human ESCC cell lines was increased by the DNA methylation inhibitor 5-azacytidine, suggesting an epigenetic mechanism for KLF4 silencing. Surprisingly, while KLF4 decreased in high-grade dysplasia and early stage tumors, KLF4 increased with advanced cancer stage, and KLF4 expression in ESCC was inversely correlated with survival. Interestingly, KLF4 promoted invasion of human ESCC cells, providing a functional link to the stage-specific expression of KLF4. Taken together, these findings suggest that KLF4 loss is necessary for esophageal tumorigenesis but that restored KLF4 expression in ESCC promotes tumor spread. Thus, the use of KLF4 as a diagnostic and therapeutic target in cancer requires careful consideration of context. PMID:26934576

  2. KLF4 is downregulated but not mutated during human esophageal squamous cell carcinogenesis and has tumor stage-specific functions.

    PubMed

    Yang, Yizeng; Katz, Jonathan P

    2016-04-02

    The transcriptional regulator Krüppel-like factor 4 (KLF4) is decreased in human esophageal squamous cell cancer (ESCC), and Klf4 deletion in mice produces squamous cell dysplasia. Nonetheless the mechanisms of KLF4 downregulation in ESCC and the functions of KLF4 during ESCC development and progression are not well understood. Here, we sought to define the regulation of KLF4 and delineate the stage-specific effects of KLF4 in ESCC. We found that KLF4 expression was decreased in human ESCC and in 8 of 9 human ESCC cell lines. However, by genomic sequencing, we observed no KLF4 mutations or copy number changes in any of 52 human ESCC, suggesting other mechanisms for KLF4 silencing. In fact, KLF4 expression in human ESCC cell lines was increased by the DNA methylation inhibitor 5-azacytidine, suggesting an epigenetic mechanism for KLF4 silencing. Surprisingly, while KLF4 decreased in high-grade dysplasia and early stage tumors, KLF4 increased with advanced cancer stage, and KLF4 expression in ESCC was inversely correlated with survival. Interestingly, KLF4 promoted invasion of human ESCC cells, providing a functional link to the stage-specific expression of KLF4. Taken together, these findings suggest that KLF4 loss is necessary for esophageal tumorigenesis but that restored KLF4 expression in ESCC promotes tumor spread. Thus, the use of KLF4 as a diagnostic and therapeutic target in cancer requires careful consideration of context.

  3. Evaluation of Human Papilloma Virus Communicative Education Strategies: A Pilot Screening Study for Cervical Cancer

    ERIC Educational Resources Information Center

    Barrera-Clavijo, Lizeth K.; Wiesner-Ceballos, Carolina; Rincón-Martínez, Lina M.

    2016-01-01

    Background: High-risk human papilloma virus (HR-HPV) is highly prevalent in sexually active men and women; HR-HPV has been classified as a sexually transmitted infection (STI) and as a necessary, but not sufficient, causal agent for cervical cancer. Women who test positive for HPV often experience serious psychosocial consequences such as fear,…

  4. The state of the p53 and retinoblastoma genes in human cervical carcinoma cell lines

    SciTech Connect

    Scheffner, M.; Muenger, K.; Byrne, J.C.; Howley, P.M. )

    1991-07-01

    Human cervical carcinoma cell lines that were either positive or negative for human papillomavirus (HPV) DNA sequences were analyzed for evidence of mutation of the p53 and retinoblastoma genes. Each of five HPV-positive cervical cancer cell lines expressed normal pRB and low levels of wild-type p53 proteins, which are presumed to be altered in function as a consequence of association with HPV E7 and E6 oncoproteins, respectively. In contrast, mutations were identified in the p53 and RB genes expressed in the C-33A and HT-3 cervical cancer cell lines, which lack HPV DNA sequences. Mutations in the p53 genes mapped to codon 273 and codon 245 in the C33-A and HT-3 cell lines, respectively, located in the highly conserved regions of p53, where mutations appear in a variety of human cancers. Mutations in RB occurred at splice junctions, resulting in in-frame deletions, affecting exons 13 and 20 in the HT-3 and C-33A cell lines, respectively. These mutations resulted in aberrant proteins that were not phosphorylated and were unable to complex with the adenovirus E1A oncoprotein. These results support the hypothesis that the inactivation of the normal functions of the tumor-suppressor proteins pRB and p53 are important steps in human cervical carcinogenesis, either by mutation or from complex formation with the HPV E6 and E7 oncoproteins.

  5. Perception of Human Papillomavirus Infection, Cervical Cancer and HPV Vaccination in North Indian Population

    PubMed Central

    Hussain, Showket; Nasare, Vilas; Kumari, Malasha; Sharma, Shashi; Khan, Mohammad Aijaz; Das, Bhudev C.; Bharadwaj, Mausumi

    2014-01-01

    Background Human Papillomavirus (HPV) -associated cervical cancer is the second-most common cancer in women worldwide but it is the most frequent gynaecological cancer and cancer associated death in India women. The objective of this study was to assess knowledge about cervical cancer, HPV, HPV vaccine, HPV vaccine acceptance among school and undergraduates students and their parent’s perception about acceptance of HPV vaccine in Northern part of India (Delhi and NCR regions). Materials and Methods A qualitative questionnaire based survey among 2500 urban/rural students aged 12–22 years was conducted. Results Overall, a low frequency (15%) of HPV and cervical cancer awareness was observed in students and their parents. However, the awareness was much higher in females belonging to urban setup compared to boys with a perception that HPV causes cervical cancer in women only. Additionally, only (13%) participants who were aware of cervical cancer and HPV) were willing to accept HPV vaccination. Apparently, parents of female students were two times more willing to accept HPV vaccination for their ward than male students (p<0.001; OR 95%CI = 2.09 (1.58–2.76). Conclusion Cervical cancer and HPV awareness among school, undergraduate students and also to their parents was found to be very low in this part of India. The level of awareness and education appears to be insignificant determinants in rural compared to urban setup. Better health education will be needed to maximize public awareness for cervical cancer prevention. PMID:25386964

  6. Immortalization of human foreskin keratinocytes by various human papillomavirus DNAs corresponds to their association with cervical carcinoma

    SciTech Connect

    Woodworth, C.D.; Doniger, J.; DiPaolo, J.A.

    1989-01-01

    Normal human foreskin keratinocytes cotransfected with the neomycin resistance gene and recombinant human papillomavirus (HPV) DNAs (types 16, 18, 31, and 33) that have a high or moderate association with cervical malignancy acquired immortality and contained integrated and transcriptionally active viral genomes. Only transcripts from the intact E6 and E7 genes were detected in at least one cell line, suggesting that one or both of these genes are responsible for immortalization. Recombinant HPV DNAs with low or no oncogenic potential for cervical cancer (HPV1a, -5, -6b, and -11) induced small G418-resistant colonies that senesced as did the nontransfected cells. These colonies contained only episomal virus DNA; therefore, integration of HPV sequences is important for immortalization of keratinocytes. This study suggests that the virus-encoded immortalization function contributes to the pathogenesis of cervical carcinoma.

  7. Characterization of human cervical remodeling throughout pregnancy using in vivo Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    O'Brien, Christine M.; Vargis, Elizabeth; Slaughter, Chris; Rudin, Amy P.; Herington, Jennifer L.; Bennett, Kelly A.; Reese, Jeff; Mahadevan-Jansen, Anita

    2015-02-01

    Globally, fifteen million babies are born preterm each year, affecting 1 in 8 pregnancies in the US alone. Cervical remodeling includes a biochemical cascade of changes that ultimately result in the thinning and dilation of the cervix for passage of a fetus. This process is poorly understood and is the focus of this study. Our group is utilizing Raman spectroscopy to evaluate biochemical changes occurring in the human cervix throughout pregnancy. This technique has high molecular specificity and can be performed in vivo, with the potential to unveil new molecular dynamics essential for cervical remodeling.

  8. Radiation Therapy and Cisplatin With or Without Triapine in Treating Patients With Newly Diagnosed Stage IB2, II, or IIIB-IVA Cervical Cancer or Stage II-IVA Vaginal Cancer

    ClinicalTrials.gov

    2017-03-23

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

  9. The SNP at −592 of human IL-10 gene is associated with serum IL-10 levels and increased risk for human papillomavirus cervical lesion development

    PubMed Central

    2012-01-01

    Background Women with Human Papilloma Virus (HPV) persistence are characterized by high levels of IL-10 at cervix. We have determined whether polymorphisms of IL-10 gene promoter might be associated with increased risk of squamous intraepithelial cervical lesions (SICL) and whether exist significative differences of IL-10 mRNA expression at cervix and systemic and serum IL-10 protein between SICL cases and non-Cervical Lesions (NCL). Methods Peripheral blood samples from SICL (n = 204) and NCL (n = 166) were used to detect IL-10 promoter polymorphisms at loci -592A/C (rs1800872), -819C/T (rs1800871), -1082A/G (rs1800896), -1352A/G (rs1800893), by allelic discrimination and to evaluate serum IL-10 protein. Cervical epithelial scrapings from NCL and biopsies from SICLs were used for HPV-typing and to evaluate IL-10 mRNA expression level. The systemic and local IL-10 mRNA expression levels were measured by real time-PCR. Genotypic and allelic frequencies of the selected polymorphisms were analyzed by logistic regression, adjusting by age and HPV-genotype, to determine the association with SICL. Results No significant differences were found between genotype frequencies at loci −819, -1082, and −1352. Individuals carrying at least one copy of risk allele A of polymorphism −592 had a two-fold increased risk of developing SICL [adjusted odds ratio (OR), 2.02 (95% CI, 1.26-3.25), p = 0.003], compared to NCL. The IL-10 mRNA expression and serum IL-10 protein, were significantly higher in SICL cases (p < 0.01), being higher in patients carrying the risk allele A. Conclusions The −592 polymorphism is associated with increased risk of SICL and can serve as a marker of genetic susceptibility to SICL among Mexican women. According to IL-10 levels found in SICL, IL-10 can be relevant factor for viral persistence and progression disease. PMID:23148667

  10. Evidence of disrupted high-risk human papillomavirus DNA in morphologically normal cervices of older women.

    PubMed

    Leonard, Sarah M; Pereira, Merlin; Roberts, Sally; Cuschieri, Kate; Nuovo, Gerard; Athavale, Ramanand; Young, Lawrence; Ganesan, Raji; Woodman, Ciarán B

    2016-02-15

    High-risk human papillomavirus (HR-HPV) causes nearly 100% of cervical carcinoma. However, it remains unclear whether HPV can establish a latent infection, one which may be responsible for the second peak in incidence of cervical carcinoma seen in older women. Therefore, using Ventana in situ hybridisation (ISH), quantitative PCR assays and biomarkers of productive and transforming viral infection, we set out to provide the first robust estimate of the prevalence and characteristics of HPV genomes in FFPE tissue from the cervices of 99 women undergoing hysterectomy for reasons unrelated to epithelial abnormality. Our ISH assay detected HR-HPV in 42% of our study population. The majority of ISH positive samples also tested HPV16 positive using sensitive PCR based assays and were more likely to have a history of preceding cytological abnormality. Analysis of subsets of this population revealed HR-HPV to be transcriptionally inactive as there was no evidence of a productive or transforming infection. Critically, the E2 gene was always disrupted in those HPV16 positive cases which were assessed. These findings point to a reservoir of transcriptionally silent, disrupted HPV16 DNA in morphologically normal cervices, re-expression of which could explain the increase in incidence of cervical cancer observed in later life.

  11. Immunotherapy for human papillomavirus-associated disease and cervical cancer: review of clinical and translational research

    PubMed Central

    2016-01-01

    Cervical cancer is the fourth most lethal women's cancer worldwide. Current treatments against cervical cancer include surgery, radiotherapy, chemotherapy, and anti-angiogenic agents. However, despite the various treatments utilized for the treatment of cervical cancer, its disease burden remains a global issue. Persistent infection of human papillomavirus (HPV) has been identified as an essential step of pathogenesis of cervical cancer and many other cancers, and nation-wide HPV screening as well as preventative HPV vaccination program have been introduced globally. However, even though the commercially available prophylactic HPV vaccines, Gardasil (Merck) and Cervarix (GlaxoSmithKline), are effective in blocking the entry of HPV into the epithelium of cervix through generation of HPV-specific neutralizing antibodies, they cannot eliminate the pre-existing HPV infection. For these reason, other immunotherapeutic options against HPV-associated diseases, including therapeutic vaccines, have been continuously explored. Therapeutic HPV vaccines enhance cell-mediated immunity targeting HPV E6 and E7 antigens by modulating primarily dendritic cells and cytotoxic T lymphocyte. Our review will cover various therapeutic vaccines in development for the treatment of HPV-associated lesions and cancers. Furthermore, we will discuss the potential of immune checkpoint inhibitors that have recently been adopted and tested for their treatment efficacy against HPV-induced cervical cancer. PMID:27329199

  12. Immunotherapy for human papillomavirus-associated disease and cervical cancer: review of clinical and translational research.

    PubMed

    Lee, Sung Jong; Yang, Andrew; Wu, T C; Hung, Chien Fu

    2016-09-01

    Cervical cancer is the fourth most lethal women's cancer worldwide. Current treatments against cervical cancer include surgery, radiotherapy, chemotherapy, and anti-angiogenic agents. However, despite the various treatments utilized for the treatment of cervical cancer, its disease burden remains a global issue. Persistent infection of human papillomavirus (HPV) has been identified as an essential step of pathogenesis of cervical cancer and many other cancers, and nation-wide HPV screening as well as preventative HPV vaccination program have been introduced globally. However, even though the commercially available prophylactic HPV vaccines, Gardasil (Merck) and Cervarix (GlaxoSmithKline), are effective in blocking the entry of HPV into the epithelium of cervix through generation of HPV-specific neutralizing antibodies, they cannot eliminate the pre-existing HPV infection. For these reason, other immunotherapeutic options against HPV-associated diseases, including therapeutic vaccines, have been continuously explored. Therapeutic HPV vaccines enhance cell-mediated immunity targeting HPV E6 and E7 antigens by modulating primarily dendritic cells and cytotoxic T lymphocyte. Our review will cover various therapeutic vaccines in development for the treatment of HPV-associated lesions and cancers. Furthermore, we will discuss the potential of immune checkpoint inhibitors that have recently been adopted and tested for their treatment efficacy against HPV-induced cervical cancer.

  13. Comparative evaluation of three commercial systems for detection of high-risk human papillomavirus in cervical and vaginal ThinPrep PreservCyt samples and correlation with biopsy results.

    PubMed

    Binnicker, M J; Pritt, B S; Duresko, B J; Espy, M J; Grys, T E; Zarka, M A; Kerr, S E; Henry, M R

    2014-10-01

    Genital human papillomavirus (HPV) is the etiologic agent of more than 99% of all cervical cancers worldwide, with 14 genotypes being considered oncogenic or "high risk" because of their association with severe dysplasia and cervical carcinoma. Among these 14 high-risk types, HPV-16 and -18 account for approximately 70% of cervical cancers. The aim of this study was to evaluate three FDA-approved HPV nucleic acid-based tests for the ability to predict high-grade cervical intraepithelial neoplasias (CIN2 or worse) in corresponding tissue biopsy specimens. Residual specimens (total n = 793, cervical n = 743, vaginal n = 50) collected in ThinPrep PreservCyt medium with a cytologic result of ≥ atypical squamous cells of undetermined significance were tested by the Hybrid Capture 2 (HC2) assay (Qiagen, Gaithersburg, MD), the cobas HPV test (Roche Diagnostics, Indianapolis, IN), and the APTIMA HPV assay (Hologic, San Diego, CA). Genotyping for HPV-16 and HPV-18 was simultaneously performed by the cobas HPV test. Results were compared to cervical or vaginal biopsy findings, when they were available (n = 350). Among the 350 patients with corresponding biopsy results, 81 (23.1%) showed ≥ CIN2 by histopathology. The ≥ CIN2 detection sensitivity was 91.4% by the cobas and APTIMA assays and 97.5% by HC2 assay. The specificities of the cobas, APTIMA, and HC2 assays were 31.2, 42.0, and 27.1%, respectively. When considering only positive HPV-16 and/or HPV-18 genotype results, the cobas test showed a sensitivity and a specificity of 51.9 and 86.6%, respectively. While the HC2, cobas, and APTIMA assays showed similar sensitivities for the detection of ≥ CIN2 lesions, the specificities of the three tests varied, with the greatest specificity (86.6%) observed when the HPV-16 and/or HPV-18 genotypes were detected.

  14. Potential anti-cancer effect of curcumin in human lung squamous cell carcinoma

    PubMed Central

    Zhao, Wei; Wang, Yan; Wang, Ying; Gao, Nan; Han, Zhifeng; Yu, Haixiang

    2015-01-01

    Background To explore the molecular mechanisms of the anti-cancer effect of curcumin in human lung squamous cell carcinoma (LSQCC) SK-MES-1 cells. Methods Cell viability was determined using MTT assay. Ribonucleic acid sequencing was performed to measure expression levels of transcripts in LSQCC cells treated with 15 μmol/L curcumin (treatment groups) or an equal amount of dimethylsulfoxide (control). Cuffdiff software was used to identify differentially expressed genes (DEGs) in treatment groups, followed by enrichment analysis of DEGs using the Database for Annotation, Visualization and Integration Discovery. The protein-protein interaction (PPI) networks for up and downregulated DEGs were constructed by Cytoscape software using Search Tool for the Retrieval of Interacting Genes data to identify hub nodes. Results Curcumin significantly reduced cell viability in LSQCC cells. In total, 380 DEGs including 154 upregulated and 126 downregulated genes were found in the treatment groups. The upregulated genes were enriched in base excision repair (BER, such as PCNA, POLL, and MUTYH) and Janus kinase-signal transducer and activator of transcription (JAT-STAT) signaling pathways (such as AKT1 and STAT5A), while the downregulated genes were enriched in nine pathways, including the vascular endothelial growth factor (VEGF) signaling pathway (such as PTK2, VEGFA, MAPK1, and MAPK14) and mitogen-activated protein kinase (MAPK) signaling pathway (ARRB2, MAPK1, MAPK14, and NFKB1). PCNA and AKT1 were the hub nodes in the PPI network of upregulated genes while MAPK1, MAPK14, VEGFA, and NFKB1 were the hub nodes in the PPI network of downregulated genes. Conclusions Curcumin might exert anti-cancer effects on LSQCC via regulating BER, JAT-STAT, VEGF, and MAPK signaling pathways. PMID:26273408

  15. Distribution of Human Papillomavirus Genotypes in Sardinian Patients with Oral Squamous Cell Carcinoma

    PubMed Central

    Montaldo, Caterina; Mastinu, Andrea; Zorco, Stefania; Santini, Noemi; Pisano, Elisabetta; Piras, Vincenzo; Denotti, Gloria; Peluffo, Carla; Erriu, Matteo; Garau, Valentino; Orrù, Germano

    2010-01-01

    Human papillomaviruses (HPVs) seem to play an important role in the pathogenesis of gynecological carcinomas and in head and neck carcinomas. The aim of this study was to detect and genotype HPVs in fresh oral squamous cell carcinoma (OSCC) from a Sardinian population, and to determine whether HPV presence was significantly associated with the development of OSCC. The oral mucosa tissues were obtained from 120 samples (68 OSCC and 52 control samples) taken from a Sardinian population seen at the Dental Clinic of the Department of Surgery and Odontostomatological Sciences, University of Cagliari (Italy) and the “ Ospedale SS Trinità”, Cagliari (A.S.L. 8) between 2007 and 2008. PCR was used for the detection of HPV DNA and the genotype was determined by DNA sequencing. The frequency of HPV infection was evaluated in relation to age, sex, smoking and alcohol use. Statistical analysis was performed using the SPSS 11.5 software. The results showed the presence of HPV-DNA in 60.3% of OSCC with HPV-16 (51.2%) being the most frequent genotype. In these Sardinian OSCC patients, HPV-DNA was detected more in males (65.8%) than in females (34.1%) while controls show a 0% of HPV presence. HPV positive was highly associated with OSCC among subjects with a history of heavy tobacco and alcohol use and among those with no such history. A greater frequency of high risk HPV presence was observed in patients with OSCC compared to health control patients. In addition these results suggested that oral HPV presence could be associated in OSCC subjects. Our results need more analyses to detect the HPV-DNA integration into tumoral cells. PMID:21249161

  16. Human papillomavirus 16 infection predicts poor outcome in patients with esophageal squamous cell carcinoma

    PubMed Central

    Xi, Ruxing; Zhang, Xiaozhi; Chen, Xin; Pan, Shupei; Hui, Beina; Zhang, Li; Fu, Shenbo; Li, Xiaolong; Zhang, Xuanwei; Gong, Tuotuo; Guo, Jia; Che, Shaomin

    2015-01-01

    Background Previous studies indicate that human papillomavirus 16 (HPV16) infection plays a pivotal role in the etiology of esophageal squamous cell carcinoma (ESCC). We aim to detect the influence of HPV16 infection on ESCC patient prognosis. Patients and methods Immunohistochemical staining for HPV16 E6 oncoprotein, the low-affinity p75 neurotrophin receptor (p75NTR), and phosphatidylinositol 3-kinase (PI3K) was performed on 103 archived surgical specimens from patients with ESCC and 54 control samples from patients with benign esophageal tumor or inflammatory lesions. All patients were from the Shaan Xi Province, People’s Republic of China. Results HPV16 E6 expression was significantly higher in the ESCC group (P<0.05). HPV16 E6 expression was significantly higher in men than in women (P<0.05). p75NTR expression was higher in those aged >56 years (P<0.05). PI3K expression was higher in those with a more advanced histopathological grade (P<0.05). There was a positive correlation between HPV16 E6 and p75NTR expression (r=0.547, P<0.001) and between p75NTR and PI3K expression (r=0.364, P<0.001). In 100 evaluable patients, the 5-year overall survival (OS) rate was 11%. In patients with ESCC, HPV16 E6 and PI3K expression were negatively correlated with the 3-year OS (P<0.05), 5-year OS (P<0.05), and progression-free survival (P<0.05). Conclusion HPV16 infection likely contributes to the etiology of ESCC patients in Shaan Xi, People’s Republic of China. HPV16 infection status and PI3K expression levels could be useful for predicting prognosis in patients with ESCC. PMID:25784817

  17. Barium inhibits arsenic-mediated apoptotic cell death in human squamous cell carcinoma cells.

    PubMed

    Yajima, Ichiro; Uemura, Noriyuki; Nizam, Saika; Khalequzzaman, Md; Thang, Nguyen D; Kumasaka, Mayuko Y; Akhand, Anwarul A; Shekhar, Hossain U; Nakajima, Tamie; Kato, Masashi

    2012-06-01

    Our fieldwork showed more than 1 μM (145.1 μg/L) barium in about 3 μM (210.7 μg/L) arsenic-polluted drinking well water (n = 72) in cancer-prone areas in Bangladesh, while the mean concentrations of nine other elements in the water were less than 3 μg/L. The types of cancer include squamous cell carcinomas (SCC). We hypothesized that barium modulates arsenic-mediated biological effects, and we examined the effect of barium (1 μM) on arsenic (3 μM)-mediated apoptotic cell death of human HSC-5 and A431 SCC cells in vitro. Arsenic promoted SCC apoptosis with increased reactive oxygen species (ROS) production and JNK1/2 and caspase-3 activation (apoptotic pathway). In contrast, arsenic also inhibited SCC apoptosis with increased NF-κB activity and X-linked inhibitor of apoptosis protein (XIAP) expression level and decreased JNK activity (antiapoptotic pathway). These results suggest that arsenic bidirectionally promotes apoptotic and antiapoptotic pathways in SCC cells. Interestingly, barium in the presence of arsenic increased NF-κB activity and XIAP expression and decreased JNK activity without affecting ROS production, resulting in the inhibition of the arsenic-mediated apoptotic pathway. Since the anticancer effect of arsenic is mainly dependent on cancer apoptosis, barium-mediated inhibition of arsenic-induced apoptosis may promote progression of SCC in patients in Bangladesh who keep drinking barium and arsenic-polluted water after the development of cancer. Thus, we newly showed that barium in the presence of arsenic might inhibit arsenic-mediated cancer apoptosis with the modulation of the balance between arsenic-mediated promotive and suppressive apoptotic pathways.

  18. Bevacizumab enhances the therapeutic efficacy of Irinotecan against human head and neck squamous cell carcinoma xenografts.

    PubMed

    Cao, Shousong; Durrani, Farukh A; Toth, Karoly; Rustum, Youcef M; Seshadri, Mukund

    2011-06-01

    Combining antiangiogenic agents with traditional cytotoxic chemotherapy offers the potential to target both vascular and cellular components of a growing tumor mass. Here, we examined the antitumor activity of the vascular endothelial growth factor antibody, Bevacizumab (Avastin®) in combination with the topoisomerase I inhibitor, Irinotecan (CPT-11) against human head and neck squamous cell carcinoma (HNSCC) xenografts. Bevacizumab was administered daily (at 5 or 20mg/kg) to nude mice bearing FaDu HNSCC xenografts for 28days with the first dose beginning seven days prior to Irinotecan (100mg/kg, weekly × 4). Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and immunohistochemical (IHC) methods were employed to study the antiangiogenic effects of Bevacizumab in vivo. Kinetics of tumor response to treatment was studied by monitoring tumor volume over a 60-day period. DCE-MRI detected a significant reduction in vascular permeability following treatment with Bevacizumab (5mg/kg) while high dose Bevacizumab (20mg/kg) induced significant microvascular damage and tumor necrosis, confirmed by immunohistochemistry (IHC). Irinotecan alone resulted in complete tumor regression (cures) in ∼40% of animals while Bevacizumab alone did not result in any cures. Treatment with Bevacizumab (5mg/kg/day×28days) in combination with Irinotecan (100mg/kg, weekly × 4) was highly effective in inhibiting FaDu tumor growth and resulted in complete tumor regression in 80% of animals. These results demonstrate that long term administration of Bevacizumab effectively modulates chemotherapeutic efficacy against HNSCC xenografts. Further investigation into the therapeutic potential of this combination strategy against HNSCC is warranted.

  19. Human papillomavirus DNA and p16 expression in Japanese patients with oropharyngeal squamous cell carcinoma

    PubMed Central

    Kawakami, Hisato; Okamoto, Isamu; Terao, Kyoichi; Sakai, Kazuko; Suzuki, Minoru; Ueda, Shinya; Tanaka, Kaoru; Kuwata, Kiyoko; Morita, Yume; Ono, Koji; Nishio, Kazuto; Nishimura, Yasumasa; Doi, Katsumi; Nakagawa, Kazuhiko

    2013-01-01

    Human papillomavirus (HPV) is a major etiologic factor for oropharyngeal squamous cell carcinoma (OPSCC). However, little is known about HPV-related OPSCC in Japan. During the study, formalin-fixed, paraffin-embedded OPSCC specimens from Japanese patients were analyzed for HPV DNA by the polymerase chain reaction (PCR) and for the surrogate marker p16 by immuno-histochemistry. For HPV DNA-positive, p16-negative specimens, the methylation status of the p16 gene promoter was examined by methylation-specific PCR. Overall survival was calculated in relation to HPV DNA and p16 status and was subjected to multivariate analysis. OPSCC cell lines were examined for sensitivity to radiation or cisplatin in vitro. The study results showed that tumor specimens from 40 (38%) of the 104 study patients contained HPV DNA, with such positivity being associated with tumors of the tonsils, lymph node metastasis, and nonsmoking. Overall survival was better for OPSCC patients with HPV DNA than for those without it (hazard ratio, 0.214; 95% confidence interval, 0.074–0.614; P = 0.002). Multivariate analysis revealed HPV DNA to be an independent prognostic factor for overall survival (P = 0.015). Expression of p16 was associated with HPV DNA positivity. However, 20% of HPV DNA-positive tumors were negative for p16, with most of these tumors manifesting DNA methylation at the p16 gene promoter. Radiation or cisplatin sensitivity did not differ between OPSCC cell lines positive or negative for HPV DNA. Thus, positivity for HPV DNA identifies a distinct clinical subset of OPSCC with a more favorable outcome in Japanese. PMID:24403267

  20. Human papillomavirus DNA and p16 expression in Japanese patients with oropharyngeal squamous cell carcinoma.

    PubMed

    Kawakami, Hisato; Okamoto, Isamu; Terao, Kyoichi; Sakai, Kazuko; Suzuki, Minoru; Ueda, Shinya; Tanaka, Kaoru; Kuwata, Kiyoko; Morita, Yume; Ono, Koji; Nishio, Kazuto; Nishimura, Yasumasa; Doi, Katsumi; Nakagawa, Kazuhiko

    2013-12-01

    Human papillomavirus (HPV) is a major etiologic factor for oropharyngeal squamous cell carcinoma (OPSCC). However, little is known about HPV-related OPSCC in Japan. During the study, formalin-fixed, paraffin-embedded OPSCC specimens from Japanese patients were analyzed for HPV DNA by the polymerase chain reaction (PCR) and for the surrogate marker p16 by immuno-histochemistry. For HPV DNA-positive, p16-negative specimens, the methylation status of the p16 gene promoter was examined by methylation-specific PCR. Overall survival was calculated in relation to HPV DNA and p16 status and was subjected to multivariate analysis. OPSCC cell lines were examined for sensitivity to radiation or cisplatin in vitro. The study results showed that tumor specimens from 40 (38%) of the 104 study patients contained HPV DNA, with such positivity being associated with tumors of the tonsils, lymph node metastasis, and nonsmoking. Overall survival was better for OPSCC patients with HPV DNA than for those without it (hazard ratio, 0.214; 95% confidence interval, 0.074-0.614; P = 0.002). Multivariate analysis revealed HPV DNA to be an independent prognostic factor for overall survival (P = 0.015). Expression of p16 was associated with HPV DNA positivity. However, 20% of HPV DNA-positive tumors were negative for p16, with most of these tumors manifesting DNA methylation at the p16 gene promoter. Radiation or cisplatin sensitivity did not differ between OPSCC cell lines positive or negative for HPV DNA. Thus, positivity for HPV DNA identifies a distinct clinical subset of OPSCC with a more favorable outcome in Japanese.

  1. Radiosensitization of Oropharyngeal Squamous Cell Carcinoma Cells by Human Papillomavirus 16 Oncoprotein E6*I

    SciTech Connect

    Pang, Ervinna; Delic, Naomi C.; Hong, Angela; Zhang Mei; Rose, Barbara R.; Lyons, J. Guy

    2011-03-01

    Purpose: Patients with oropharyngeal squamous cell carcinoma (OSCC) whose disease is associated with high-risk human papillomavirus (HPV) infection have a significantly better outcome than those with HPV-negative disease, but the reasons for the better outcome are not known. We postulated that they might relate to an ability of HPV proteins to confer a better response to radiotherapy, a commonly used treatment for OSCC. Methods and Materials: We stably expressed the specific splicing-derived isoforms, E6*I and E6*II, or the entire E6 open reading frame (E6total), which gives rise to both full length and E6*I isoforms, in OSCC cell lines. Radiation resistance was measured in clonogenicity assays, p53 activity was measured using transfected reporter genes, and flow cytometry was used to analyze cell cycle and apoptosis. Results: E6*I and E6total sensitized the OSCC cells to irradiation, E6*I giving the greatest degree of radiosensitization (approximately eightfold lower surviving cell fraction at 10 Gy), whereas E6*II had no effect. In contrast to radiosensitivity, E6*I was a weaker inhibitor than E6total of tumor suppressor p53 transactivator activity in the same cells. Flow cytometric analyses showed that irradiated E6*I expressing cells had a much higher G2M:G1 ratio than control cells, indicating that, after G2, cells were diverted from the cell cycle to programmed cell death. Conclusion: This study supports a role for E6*I in the enhanced responsiveness of HPV-positive oropharyngeal carcinomas to p53-independent radiation-induced death.

  2. Primary squamous cell carcinoma of the endometrium unrelated to human papilloma virus: a molecular study.

    PubMed

    Giordano, Giovanna; Pizzi, Silvia; Azzoni, Cinzia; Bottarelli, Lorena; D'Adda, Tiziana

    2013-07-01

    In this paper we report a molecular study of a case of Primary Endometrial Squamous Carcinoma (PESC), in which a Human Papilloma Virus (HPV) infection had been previously excluded by Polymerase Chain Reaction (PCR). The studies performed in an effort to explain the carcinogenesis included immunohistochemical over-expression of p53 and p16 proteins as previously observed in our own papers, plus microsatellite analysis of D10S1765 at 10q23.3 (PTEN) and TP53 at 17p13.1 (P53) as well as the methylation status of the of BRCA1 and p16 promoters using specific PCRs. In this rare malignancy, we found allelic imbalance (AI) at 17p13.1 (P53). Instead, AI at D10S1765 (PTEN) gene was absent. The genetic alteration of p53, with hyper-expression of p53 protein and an absence of abnormalities in the PTEN gene are consistent with the similarities between Uterine Serous Carcinoma (USC) and our case of PESC. The aberrant methylation of both p16 and BCAR1 promoters was not detected in our case. This finding too could imply that ESC is more similar to Uterine Serous Carcinoma than Uterine Endometrioid Carcinoma (UEC). Moreover, the lack of aberrant methylation of p16, which is in accordance with over-expression of p16 immunoreactivity, in the absence of HPV infection may be related to other unknown genetic alterations. In our opinion, it is hard to reach any definite conclusion concerning the carcinogenesis of PESC, because of its rarity and the very few molecular studies reported in the literature. Further studies with more numerous cases and larger molecular analyses are mandatory for this malignancy, to confirm whether it is more closely related to papillary endometrial cancer than to endometrioid carcinoma.

  3. Human Papillomavirus Genotyping and p16(INK4a) Expression in Cervical Lesions: A Combined Test to Avoid Cervical Cancer Progression.

    PubMed

    Zouheir, Yassine; Fechtali, Taoufiq; Elgnaoui, Nadia

    2016-06-01

    Cervical cancer is a major public health problem in Morocco. The cervical cancer has a long precancerous period that provides an opportunity for the screening and treatment. Improving screening tests is a priority goal for the early diagnosis of cervical cancer. This study was conducted to evaluate the combination of p16(INK4a) protein expression, human papillomavirus (HPV) typing, and histopathology for the identification of cervical lesions with high risk to progress to cervical cancer among Moroccan women. A total of 96 cervical biopsies were included in this study. Signal amplification in situ hybridization with biotinylated probes was used to detect HPV. Immunohistochemistry was used to evaluate the expression of p16(INK4a) protein. HPV DNA was detected in 74.0% of the biopsies (71/96). Of the seventy-one positive HPV cases, we detected 67.6% (48/71) of high risk (HR)-HPV (HPV 16 and 18), 24% of low risk-HPV (HPV 6 and 11), 1.4% intermediate risk-HPV (HPV 31, 33, and 35), and 7% coinfections (HPV 6/11 and 16/18). Overexpression of p16(INK4a) protein was observed in 72.9% (70/96) of the biopsies. In addition, p16(INK4a) protein detection was closely correlated with recovery of HR HPV. Our result showed that p16(INK4a) expression level is correlated with HR-HPV status.

  4. Association of Human Papillomavirus 31 DNA Load with Risk of Cervical Intraepithelial Neoplasia Grades 2 and 3

    PubMed Central

    Liu, Xia; Schiffman, Mark; Hulbert, Ayaka; He, Zhonghu; Shen, Zhenping; Koutsky, Laura A.

    2015-01-01

    The association between human papillomavirus 31 (HPV31) DNA loads and the risk of cervical intraepithelial neoplasia grades 2 and 3 (CIN2–3) was evaluated among women enrolled in the atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) triage study (ALTS), who were monitored semiannually over 2 years and who had HPV31 infections detected at ≥1 visit. HPV31 DNA loads in the first HPV31-positive samples and in a random set of the last positive samples from women with ≥2 HPV31-positive visits were measured by a real-time PCR assay. CIN2–3 was histologically confirmed at the same time as the first detection of HPV31 for 88 (16.6%) of 530 women. After adjustment for HPV31 lineages, coinfection with other oncogenic types, and the timing of the first positive detection, the odds ratio (OR) per 1-log-unit increase in viral loads for the risk of a concurrent diagnosis of CIN2–3 was 1.5 (95% confidence interval [CI], 1.2 to 1.9). Of 373 women without CIN2–3 at the first positive visit who had ≥1 later visit, 44 had subsequent diagnoses of CIN2–3. The initial viral loads were associated with CIN2–3 diagnosed within 6 months after the first positive visit (adjusted OR, 1.5 [95% CI, 1.0 to 2.4]) but were unrelated to CIN2–3 diagnosed later. For a random set of 49 women who were tested for viral loads at the first and last positive visits, changes in viral loads were upward and downward among women with and without follow-up CIN2–3 diagnoses, respectively, although the difference was not statistically significant. Results suggest that HPV31 DNA load levels at the first positive visit signal a short-term but not long-term risk of CIN2–3. PMID:26292291

  5. Performance of Self-Collected Cervical Samples in Screening for Future Precancer Using Human Papillomavirus DNA Testing

    PubMed Central

    Hildesheim, Allan; González, Paula; Schiffman, Mark; Rodríguez, Ana Cecilia; Wacholder, Sholom; Jiménez, Silvia; Quint, Wim; Guillen, Diego; Kreimer, Aimée R.; Herrero, Rolando

    2015-01-01

    Background: Self-collected human papillomavirus (HPV) testing could reduce barriers to cervical cancer screening, with performance comparable to clinician-collected specimens. The ability of self-collected specimens to cross-sectionally and prospectively detect precursor lesions was investigated in an HPV vaccine randomized trial in Costa Rica. Methods: In the trial, 7466 women age 18 to 25 years received an HPV16/18 or control vaccine and were followed at least annually for four years. In this secondary analysis, we included all women who provided a self-collected cervicovaginal specimen six months after enrollment (5109 women = full analytical cohort). A subset (615 women = restricted cohort) also had clinician-collected specimens at the six-month postenrollment visit. High-grade squamous intraepithelial lesion or repeat low-grade squamous intraepithelial lesion prompted colposcopic referral throughout the study. HPV testing was performed with SPF10PCR/DEIA/LiPA25. Cross-sectional and prospective sensitivity, specificity, and predictive values were estimated. Results: In the full cohort, one-time HPV testing on self-collected samples detected prevalent CIN2+ with a sensitivity of 88.7% (95% confidence interval [CI] =77.0% to 95.7%) and a specificity of 68.9% (95% CI = 67.6% to 70.1%). For predicting incident CIN2+ in the subsequent four years, sensitivity was 73.9% (95% CI = 65.8% to 81.0%) and specificity 69.4% (95% CI = 68.1% to 70.7%). In the restricted cohort, for incident CIN2+, self-collected HPV was much more sensitive than cytology (80.0% vs 10.0%); relative sensitivity was 0.1 (95% CI = 0.03% to 0.5%). Furthermore, three times more women with normal baseline cytology developed incident CIN2+ than those with negative self-collected HPV. Self-collected and clinician-collected HPV testing had comparable performance. Agreement between self- and clinician-collected samples was 89.7% (kappa = 0.78, McNemar χ2 = 0.62) for carcinogenic HPV types. Conclusions

  6. Cigarette smoking and human papillomavirus in patients with reported cervical cytological abnormality.

    PubMed Central

    Burger, M P; Hollema, H; Gouw, A S; Pieters, W J; Quint, W G

    1993-01-01

    OBJECTIVE--To assess the relation between two risk factors for cervical neoplasia: smoking and infection with oncogenic human papillomavirus. It has been suggested that smoking causes a local immunological defect, which could facilitate the infection and persistence of human papillomavirus. DESIGN--Cross sectional epidemiological study. Completion of a structured questionnaire by the patients, analysis of cervical scrapes for human papillomavirus, and morphological examination of biopsy specimens. SETTING--Outpatient gynaecological clinic. SUBJECTS--181 women with a report of cervical cytological abnormality. MAIN OUTCOME MEASURES--Prevalence of infection with oncogenic human papillomavirus and smoking habits. RESULTS--Oncogenic human papillomavirus was found in the cervix of 26 (41%) of the 63 women who did not smoke, 22 (58%) of the 38 who smoked 1-10 cigarettes a day, 28 (61%) of the 46 who smoked 11-20 cigarettes a day, and 26 (76%) of the 34 who smoked > or = 21 cigarettes a day. The prevalence of the virus thus increased in accordance with the number of cigarettes smoked (p = 0.001). This relation remained after adjustment for age at first intercourse and lifetime number of sexual partners. Of the 63 non-smokers, 23 had previously smoked at least 10 cigarettes a day at some time. Of these 23 women, 14 (61%) had oncogenic human papillomavirus in their cervix. Of the 40 women who had never smoked at least 10 cigarettes a day, 12 (30%) had the virus. The prevalence of oncogenic human papillomavirus in non-smokers therefore depended on previous smoking habits (p = 0.03). CONCLUSION--The dose dependent effect of cigarette smoking on the occurrence of oncogenic human papillomavirus favours a causal relation between these risk factors for cervical neoplasia. PMID:8387842

  7. Human Papillomavirus (HPV) DNA Triage of Women with Atypical Squamous Cells of Undetermined Significance with cobas 4800 HPV and Hybrid Capture 2 Tests for Detection of High-Grade Lesions of the Uterine Cervix

    PubMed Central

    Lapierre, Simon Grandjean; Sauthier, Philippe; Mayrand, Marie-Hélène; Dufresne, Simon; Petignat, Patrick; Provencher, Diane; Drouin, Pierre; Gauthier, Philippe; Dupuis, Marie-Josée; Michon, Bertrand; Ouellet, Stéphan; Hadjeres, Rachid; Ferenczy, Alex; Franco, Eduardo L.

    2012-01-01

    The triage of women with high-risk (HR) human papillomavirus (HPV)-positive smears for atypical squamous cells of undetermined significance (ASC-US) to colposcopy is now an integrated option in clinical guidelines. The performance of cobas 4800 HPV and that of Hybrid Capture 2 (HC2) for HR HPV DNA detection in cervical samples in PreservCyt were compared in 396 women referred to colposcopy for ASC-US. Of these, 316 did not have cervical intraepithelial neoplasia (CIN), 47 had CIN1, 29 had CIN2 or CIN3 (CIN2+), and 4 had CIN of unknown grade. HR HPV was detected in 129 (32.6%) and 149 (37.6%) samples with HC2 and cobas 4800 HPV, respectively (P = 0.15). The clinical sensitivities and specificities for detecting CIN2+ were 89.7% (95% confidence interval [CI], 72.8 to 97.2%) and 66.7% (95% CI, 61.7 to 71.3%) with cobas 4800 HPV and 93.1% (95% CI, 77.0 to 99.2%) and 72.2% (95% CI 67.4 to 76.5%) with HC2. The performance of cobas 4800 HPV was similar to that of HC2 for identifying women with ASC-US who would benefit the most from colposcopy. PMID:22301023

  8. Human papillomavirus and squamous cell cancer of the skin--epidermodysplasia verruciformis-associated human papillomavirus revisited.

    PubMed

    Arnold, Andreas W; Hofbauer, Günther F L

    2012-01-01

    As squamous cell cancer (SCC) is the most common malignancy in organ transplant recipients, a viral etiology has been proposed. Human papillomavirus (HPV) is found more often in organ transplant recipients than in the general population, but its role in cancer development has been debated for years. As a model of susceptibility of HPV the inherited disease epidermodysplasia verruciformis (EV) has been investigated intensively. EV is an autosomal-recessive skin disease leading to multiple flat warts and pityriasis versicolor-like macules in early youth. EV patients are at great risk of developing skin cancer due to a lack of defense against beta HPV. Beta HPV are causally involved in the formation of skin cancer in patients afflicted with EV. Beta HPV has frequently been detected in SCC and its early lesions such as actinic keratoses. Depending on the methods used, a prevalence of 30-90% has been reported for beta HPV for SCC in organ transplant recipients, while this prevalence in the general population is lower, but still considerable at 50%. Epidemiologic studies in the general population seem to suggest that beta HPV plays a role in the formation of SCC, both for invasive and in situ lesions.

  9. DeltaNp63alpha repression of the Notch1 gene supports the proliferative capacity of normal human keratinocytes and cervical cancer cells.

    PubMed

    Yugawa, Takashi; Narisawa-Saito, Mako; Yoshimatsu, Yuki; Haga, Kei; Ohno, Shin-ichi; Egawa, Nagayasu; Fujita, Masatoshi; Kiyono, Tohru

    2010-05-15

    The p53 family member p63 is a master regulator of epithelial development. One of its isoforms, DeltaNp63alpha, is predominantly expressed in the basal cells of stratified epithelia and plays a fundamental role in control of regenerative potential and epithelial integrity. In contrast to p53, p63 is rarely mutated in human cancers, but it is frequently overexpressed in squamous cell carcinomas (SCC). However, its functional relevance to tumorigenesis remains largely unclear. We previously identified the Notch1 gene as a novel transcriptional target of p53. Here, we show that DeltaNp63alpha functions as a transcriptional repressor of the Notch1 gene through the p53-responsive element. Knockdown of p63 caused upregulation of Notch1 expression and marked reduction in proliferation and clonogenicity of both normal human keratinocytes and cervical cancer cell lines overexpressing DeltaNp63alpha. Concomitant silencing of Notch1 significantly rescued this phenotype, indicating the growth defect induced by p63 deficiency to be, at least in part, attributable to Notch1 function. Conversely, overexpression of DeltaNp63alpha decreased basal levels of Notch1, increased proliferative potential of normal human keratinocytes, and inhibited both p53-dependent and p53-independent induction of Notch1 and differentiation markers upon genotoxic stress and serum exposure, respectively. These results suggest that DeltaNp63alpha maintains the self-renewing capacity of normal human keratinocytes and cervical cancer cells partly through transcriptional repression of the Notch1 gene and imply a novel pathogenetical significance of frequently observed overexpression of DeltaNp63alpha together with p53 inactivation in SCCs.

  10. Evaluation of glutathione S-transferase activity in human buccal epithelial dysplasias and squamous cell carcinomas.

    PubMed

    Chen, Y K; Lin, L M

    1997-06-01

    Glutathione S-transferase (GST) activity and amount of GST alpha, mu and pi isoforms were measured in 40 patients with histopathologically confirmed oral epithelial dysplasia (OED) and squamous cell carcinoma of buccal mucosa. The results were compared with those of normal mucosa in an equal number of age- and sex-matched healthy controls. Mean total GST activities were significantly elevated from normal buccal mucosa for mild OED, moderate OED, severe OED and squamous cell carcinoma. GST activity of value approximating 100 nmol/min/mg distinguished between normal and dysplasia, and of value about 400 nmol/min/mg delineated between dysplasia and squamous cell carcinoma were observed. GST pi was the predominant class in both the diseased and normal buccal mucosa examined. This class pi GST was present at an intracellular concentration, which was significantly higher in diseased buccal mucosa than in normal buccal mucosa. These results indicated that pi class GST was the major form of this enzyme in the cytosolic fraction of oral mucosa. The severity of OED related to squamous cell carcinoma development seemed to increase concomitantly with an increase in the level of this enzyme. Further studies will validate the role of GST pi estimation in predicting the potential malignancy of OED.

  11. Human papillomavirus and p53 mutations in head and neck squamous cell carcinoma among Japanese population.

    PubMed

    Maruyama, Hiromi; Yasui, Toshimichi; Ishikawa-Fujiwara, Tomoko; Morii, Eiichi; Yamamoto, Yoshifumi; Yoshii, Tadashi; Takenaka, Yukinori; Nakahara, Susumu; Todo, Takeshi; Hongyo, Tadashi; Inohara, Hidenori

    2014-04-01

    We aimed to reveal the prevalence and pattern of human papillomavirus (HPV) infection and p53 mutations among Japanese head and neck squamous cell carcinoma (HNSCC) patients in relation to clinicopathological parameters. Human papillomavirus DNA and p53 mutations were examined in 493 HNSCCs and its subset of 283 HNSCCs. Oropharyngeal carcinoma was more frequently HPV-positive than non-oropharyngeal carcinoma (34.4% vs 3.6%, P < 0.001), and HPV16 accounted for 91.1% of HPV-positive tumors. In oropharyngeal carcinoma, which showed an increasing trend of HPV prevalence over time (P < 0.001), HPV infection was inversely correlated with tobacco smoking, alcohol drinking, p53 mutations, and a disruptive mutation (P = 0.003, <0.001, <0.001, and <0.001, respectively). The prevalence of p53 mutations differed significantly between virus-unrelated HNSCC and virus-related HNSCC consisting of nasopharyngeal and HPV-positive oropharyngeal carcinomas (48.3% vs 7.1%, P < 0.001). Although p53 mutations were associated with tobacco smoking and alcohol drinking, this association disappeared in virus-unrelated HNSCC. A disruptive mutation was never found in virus-related HNSCC, whereas it was independently associated with primary site, such as the oropharynx and hypopharynx (P = 0.01 and 0.03, respectively), in virus-unrelated HNSCC. Moreover, in virus-unrelated HNSCC, G:C to T:A transversions were more frequent in ever-smokers than in never-smokers (P = 0.04), whereas G:C to A:T transitions at CpG sites were less frequent in ever-smokers than in never-smokers (P = 0.04). In conclusion, HNSCC is etiologically classified into virus-related and virus-unrelated subgroups. In virus-related HNSCC, p53 mutations are uncommon with the absence of a disruptive mutation, whereas in virus-unrelated HNSCC, p53 mutations are common, and disruptive mutagenesis of p53 is related with oropharyngeal and hypopharyngeal carcinoma.

  12. Altered epigenetic regulation of homeobox genes in human oral squamous cell carcinoma cells

    SciTech Connect

    Marcinkiewicz, Katarzyna M.; Gudas, Lorraine J.

    2014-01-01

    To gain insight into oral squamous cell carcinogenesis, we performed deep sequencing (RNAseq) of non-tumorigenic human OKF6-TERT1R and tumorigenic SCC-9 cells. Numerous homeobox genes are differentially expressed between OKF6-TERT1R and SCC-9 cells. Data from Oncomine, a cancer microarray database, also show that homeobox (HOX) genes are dysregulated in oral SCC patients. The activity of Polycomb repressive complexes (PRC), which causes epigenetic modifications, and retinoic acid (RA) signaling can control HOX gene transcription. HOXB7, HOXC10, HOXC13, and HOXD8 transcripts are higher in SCC-9 than in OKF6-TERT1R cells; using ChIP (chromatin immunoprecipitation) we detected PRC2 protein SUZ12 and the epigenetic H3K27me3 mark on histone H3 at these genes in OKF6-TERT1R, but not in SCC-9 cells. In contrast, IRX1, IRX4, SIX2 and TSHZ3 transcripts are lower in SCC-9 than in OKF6-TERT1R cells. We detected SUZ12 and the H3K27me3 mark at these genes in SCC-9, but not in OKF6-TERT1R cells. SUZ12 depletion increased HOXB7, HOXC10, HOXC13, and HOXD8 transcript levels and decreased the proliferation of OKF6-TERT1R cells. Transcriptional responses to RA are attenuated in SCC-9 versus OKF6-TERT1R cells. SUZ12 and H3K27me3 levels were not altered by RA at these HOX genes in SCC-9 and OKF6-TERT1R cells. We conclude that altered activity of PRC2 is associated with dysregulation of homeobox gene expression in human SCC cells, and that this dysregulation potentially plays a role in the neoplastic transformation of oral keratinocytes. - Highlights: • RNAseq elucidates differences between non-tumorigenic and tumorigenic oral keratinocytes. • Changes in HOX mRNA in SCC-9 vs. OKF6-TERT1R cells are a result of altered epigenetic regulation. • RNAseq shows that retinoic acid (RA) influences gene expression in both OKF6-TERT1R and SCC-9 cells.

  13. [Chromosomal instability in carcinogenesis of cervical cancer.

    PubMed

    de Los Santos-Munive, Victoria; Alonso-Avelino, Juan Angel

    2013-01-01

    In order to spot common chromosomal imbalances in early and late lesions of cervical cancer that might be used as progression biomarkers, we made a search of literature in PubMed from 1996 to 2011. The medical subject headings employed were chromosomal alterations, loss of heterozygosis, cervical cancer, cervical tumorigenesis, chromosomal aberrations, cervical intraepithelial neoplasm and low-grade squamous intraepithelial lesion. The common chromosomal imbalances were gains in 8q24 (77.7 %), 20q13 (66.9 %), 3q26 (47.1 %), Xp22 (43.8 %), and 5p15 (60 %), principally. On the other hand, integration of the high-risk human papillomavirus genome into the host chromosome has been associated with the development of neoplasia, but the chromosomal imbalances seem to precede and promote such integration. Chromosomal imbalances in 8q24, 20q13, 3q21-26 and 5p15-Xp22, determined by fluorescent in situ hybridization assay or comparative genomic hybridization assay for early detection of the presence of high-risk human papillomavirus, are promising markers of cervical cancer progression.

  14. Prevalence of adeno-associated virus and human papillomavirus DNA in Iranian women with and without cervical cancer.

    PubMed

    Shafiei-Jandaghi, Nazanin Zahra; Yavarian, Jila; Faghihloo, Ebrahim; Ghavami, Nastaran; Yousefi Ghalejoogh, Zohreh; Kiani, Seyed Jalal; Shatizadeh Malekshahi, Somayeh; Shahsiah, Reza; Jahanzad, Eisa; Hosseini, Mostafa; Mokhtari Azad, Talat

    2017-02-24

    There is plenty of substantial evidence to support anti-tumor activity of viruses. Adeno-associated virus (AAV) may interact with human papillomavirus (HPV) to modify the risk of cervical neoplasia. The seroprevalence of AAV among women with cervical cancer has been reported to be lower than healthy ones. In spite of this finding, detection of AAV DNA in cervical biopsies does not entirely support the inverse association between AAV seropositivity and cervical cancer. This association is still controversial and requires more thorough evaluation in different countries. The aim of this case-control study was to find the prevalence of AAV and HPV DNA sequences in Iranian women with and without cervical cancer to assess the probable association of AAV infection and cervical cancer. In this study, paraffin-embedded tissue samples of 61 cervical cancer cases and 50 healthy controls (HCs) were investigated for AAV and HPV DNA by semi-nested and nested PCRs respectively. AAV DNA was detected in 7 cases (14%) of HCs and 9 specimens (14.8%) of case group. According to the branching in the phylogenetic tree, AAV2 was the only type detected in this study. Moreover, HPV DNA was detected in 8 cases (16%) of HCs and 44 specimens (72.13%) of case group. In conclusion, a low proportion of cervical biopsies from Iranian women contained AAV-2 genome. No significant difference in correlation between HPV and cervical cancer in presence or absence of AAV genome in cervix was found.

  15. Prediction of high-grade cervical intraepithelial neoplasia in cytologically normal women by human papillomavirusesting

    PubMed Central

    Carozzi, F; Ronco, G; Confortini, M; Noferini, D; Maddau, C; Ciatto, S; Segnan, N

    2000-01-01

    Human papillomavirus (HPV) testing has been suggested for primary screening of cervical cancer. Prediction of future high-grade cervical lesions is crucial for effectiveness and cost. We performed a case control study in a retrospective cohort of women with at least two cervical smears, all but the last one being negative, from the organized cervical screening programme in Florence, Italy. We searched for high-risk HPV in all previous, archival, smears from cases (new histologically confirmed cervical intraepithelial neoplasia (CIN) grade II or worse) and in one previous smear from each control (last smear cytologically normal, matched by age and interval (latency) from last smear). We applied polymerase chain reaction (PCR), and the b-globin gene was used as a DNA preservation marker. High-risk HPV was identified in 71/92 (77.17%) previous smears from 79 cases and 17/332 controls (5.12%). The odds ratio (OR) was 63.76 (95% CI 30.57–132.96). Among cases the proportion of HPV-positive smears declined slightly with increasing latency. Among cases, HPV was found in 81.24% (95% CI 69.93–88.96%) of smears with latency < 4 years and in 67.80% (95% CI 47.72–82.93%) of those taken at longer intervals, up to 6 years. These findings suggest that testing for high-risk HPV allows predicting 80% of CINII/III 3 years before the cytological diagnosis and two thirds 6 years before. They also suggest that testing women negative for high-risk HPV at longer interval and strictly following-up women who are HPV positive could be an effective strategy for cervical cancer screening. © 2000 Cancer Research Campaign http://www.bjcancer.com PMID:11076654

  16. Cytotoxic effect and induction of apoptosis in human cervical cancer cells by Antrodia camphorata.

    PubMed

    Yang, Pei-Yu; Hu, Dan-Ning; Liu, Fu-Shing

    2013-01-01

    Antrodia camphorata is a Chinese herb indigenous to Taiwan. Previous reports demonstrated that it could induce apoptosis in some cancer cells. The purpose of this study was to investigate the apoptotic effect of the crude extract of A. camphorata in cervical cancer cells. Two human cervical cancer cell lines, HeLa and C-33A, were treated with extract of A. camphorata (10-1000 μg/mL). We found that A. camphorata extract was cytotoxic to both cervical cancer cells in a dose- and time-dependent manner as examined by MTT assay. Treatment with A. camphorata extract at 400 μg/mL induced a 2.3- and 4.4-fold increase in oligonucleosome formation from the cleaved chromosomal DNA in HeLa and C-33A cells, respectively. A. camphorata extract also activated caspase-3, -8, and -9 activities and increased the cytosolic level of cytochrome c in both cell lines as the dosage increased. Furthermore, A. camphorata extract increased expressions of Bak, Bad and Bim, while decreasing expressions of Bcl-2 and Bcl-xL of the Bcl-2 family proteins in HeLa and C-33A cells. The expression of IAP proteins, XIAP and survivin, was also decreased in both cervical cancer cells after treatment with A. camphorata. Our in vitro study suggests that A. camphorata is cytotoxic to cervical cancer cells through both extrinsic and intrinsic apoptotic mechanisms. It could be used as a novel phytotherapeutic agent or auxiliary therapy in the treatment of cervical cancer.

  17. LncRNA expression profile of ΔNp63α in cervical squamous cancers and its suppressive effects on LIF expression.

    PubMed

    Qian, Lili; Xu, Fei; Wang, Xiaolin; Jiang, Ming; Wang, Juan; Song, Weiguo; Wu, Dabao; Shen, Zhen; Feng, Dingqing; Ling, Bin; Cheng, Yong; Xiao, Weihua; Shan, Ge; Zhou, Ying

    2017-04-06

    We aim to determine the lncRNA targets of ΔNp63α in cervical cancer and molecular programs in cancerous differentiation. Different profiles of the lncRNAs were assayed and validated in overexpressing p63 SiHa cells (SiHa/ΔNp63α) and the control cell lines (SiHa/pCon). ENST00000422259, ENST00000447565 (Lnc-LIF-AS) and ENST00000469965, together with their related antisense mRNA DPYD (dihydropyrimidine dehydrogenase, a pyrimidine catabolic pathway gene), LIF (leukemia inhibitor factor) and FLNC (filamin C) were all notably differentially expressed in both ΔNp63α overexpression cells and knockdown cells. Here, we illustrated that ΔNp63α can inhibit the levels of LIF mRNA by direct transcription regulation and decrease LIF mRNA stability by suppressing the expression of Lnc-LIF-AS. An inverse interaction of LIF and ΔNp63α expression was as well validated in clinical samples of cervical cancer, and high level of LIF in cervical cancers was related with poor patient survival. The decrease of ΔNp63α also attenuated the differentiation of cervical cancerous cells. Suggesting that ΔNp63α may be form a complex network in regulation cervical cancerous differentiation.

  18. Claudin-5, -7, and -18 suppress proliferation mediated by inhibition of phosphorylation of Akt in human lung squamous cell carcinoma.

    PubMed

    Akizuki, Risa; Shimobaba, Shun; Matsunaga, Toshiyuki; Endo, Satoshi; Ikari, Akira

    2017-02-01

    Abnormal expression of claudin (CLDN) subtypes has been reported in various solid cancers. However, it is unknown which subtype plays a key role in the regulation of proliferation in cancer cells. The expression of CLDN3-5, 7, and 18 in human lung squamous carcinoma tissues was lower than that in normal tissue. Here, we examined which combination of exogenous CLDNs expression inhibits proliferation and the molecular mechanism using human lung squamous RERF-LC-AI cells. Real-time polymerase chain reaction and western blotting showed that CLDN3-5, 7, and 18 are little expressed in RERF-LC-AI cells. In the exogenously transfected cells, CLDN5, 7, and 18 were distributed in the cell-cell contact areas concomitant with ZO-1, a tight junctional scaffolding protein, whereas CLDN3 and 4 were not. Cell proliferation was individually and additively suppressed by CLDN5, 7, and 18. The expression of these CLDNs showed no cytotoxicity compared with mock cells. CLDN5, 7, and 18 increased p21 and decreased cyclin D1, resulting in the suppression of cell cycle G1-S transition. The expression of these CLDNs inhibited phosphorylation of Akt without affecting phosphorylated ERK1/2. Furthermore, these CLDNs inhibited the nuclear localization of Akt and its association with 3-phosphoinositide-dependent protein kinase-1 (PDK1). The suppression of G1-S transition caused by CLDN5, 7, and 18 was rescued by the expression of constitutively active-Akt. We suggest that the reduction of CLDN5, 7, and 18 expression loses the suppressive ability of interaction between PDK1 and Akt and causes sustained phosphorylation of Akt, resulting in the disordered proliferation in lung squamous carcinoma cells.

  19. Human leukocyte antigen (HLA)-G and cervical cancer immunoediting: a candidate molecule for therapeutic intervention and prognostic biomarker?

    PubMed

    Gimenes, Fabrícia; Teixeira, Jorge Juarez Vieira; de Abreu, André Luelsdorf Pimenta; Souza, Raquel Pantarotto; Pereira, Monalisa Wolski; da Silva, Vânia Ramos Sela; Bôer, Cinthia Gandolfi; Maria-Engler, Silvya Stuchi; Bonini, Marcelo Gialluisi; Borelli, Sueli Donizete; Consolaro, Márcia Edilaine Lopes

    2014-12-01

    While persistent infection with oncogenic types of human Papillomavirus (HPV) is required for cervical epithelial cell transformation and cervical carcinogenesis, HPV infection alone is not sufficient to induce tumorigenesis. Only a minor fraction of HPV infections produce high-grade lesions and cervical cancer, suggesting complex host-virus interactions. Based on its pronounced immunoinhibitory properties, human leukocyte antigen (HLA)-G has been proposed as a possible prognostic biomarker and therapeutic target relevant in a wide variety of cancers and viral infections, but to date remains underexplored in cervical cancer. Given the possible influence of HLA-G on the clinical course of HPV infection, cervical lesions and cancer progression, a better understanding of HLA-G involvement in cervical carcinogenesis might contribute to two aspects of fundamental importance: 1. Characterization of a novel diagnostic/prognostic biomarker to identify cervical cancer and to monitor disease stage, critical for patient screening; 2. Identification of HLA-G-driven immune mechanisms involved in lesion development and cancer progression, leading to the development of strategies for modulating HLA-G expression for treatment purposes. Thus, this systematic review explores the potential involvement of HLA-G protein expression and polymorphisms in cervical carcinogenesis.

  20. Prevalence and genotyping of high risk human papillomavirus in cervical cancer samples from Punjab, Pakistan.

    PubMed

    Siddiqa, Abida; Zainab, Maidah; Qadri, Ishtiaq; Bhatti, Muhammad Faraz; Parish, Joanna L

    2014-07-17

    Cervical cancer is the third most common cause of cancer-related death in women worldwide. Infection with high-risk human papillomavirus (HPV) is established as the cause of cervical carcinoma, therefore, high risk HPV detection may have prognostic significance for the women who are at increased risk of disease progression. The paucity of data on the incidence of cervical cancer in Pakistan makes it difficult to determine disease burden. Even less information is available regarding the prevalent HPV strains in cervical specimens collected from this region. Cervical cancer is a neglected disease in Pakistan in terms of screening, prevention, and vaccination. Identification and accurate genotyping of the virus burden in cancer specimens is important to inform intervention policies for future management of HPV associated disease and to potentially stratify patients dependent on HPV status. In this study, detection and genotyping of HPV types 16 and 18 from 77 cervical specimens were carried out. Consensus primers GP5+/GP6+, which detect 44 genital HPV types, and type specific primers (TS16 and TS18) were used in conjunction with newly designed type specific primers. Using a combination of these methods of detection, a total of 94.81% (95% CI ±4.95) of cervical lesions were positive for HPV. Single infections of HPV16 were detected in 24.68% (95% CI ±9.63) of total samples and HPV18 was found in 25.97% (95% CI ±9.79) samples. Interestingly, a high proportion of samples (40.26%, 95% CI ±10.95) was positive for both HPV16 and 18, indicating a higher incidence of co-infection than previously reported for similar ethnic regions. The HPV genotype of 3.90% of HPV positive samples remained undetected, although these samples were positive with the GP5+/GP6+ primer set indicating infection with an HPV type other than 16 or 18. These data indicate that the overall incidence of high risk HPV infection in cervical cancer and intraepithelial neoplasia specimens in Punjab

  1. Improving the Utilization of Human Papillomavirus and Cervical Cytology Co-testing for Cervical Cancer Screening in an Obstetrics and Gynecology Resident Clinic.

    PubMed

    Yoshino, Kurt; Karimoto, Maxine; Marzo, Christina; Kaneshiro, Bliss; Hiraoka, Mark

    2015-08-01

    Human Papillomavirus (HPV) testing in combination with cervical cytology (HPV co-testing) has been recommended for cervical cancer screening for women 30 to 65 years of age. In several studies, HPV co-testing increased sensitivity for detecting high grade dysplasia and resulted in cost-savings. This retrospective cohort study assessed the prevalence of HPV co-testing in an obstetrics and gynecology resident clinic before and after a brief educational intervention which was designed to reinforce current cervical cancer screening recommendations. The intervention consisted of a short presentation that was given to all residents and medical assistants in October 2011. The proportion of women age 30-65 years of age who had cervical cancer screening with HPV co-testing as compared to cervical cytology alone was compared before and after the intervention using chi-square tests. The goal of the intervention was to increase the percentage of patients receiving co-testing from 0.5% to 7.8%. Each arm (pre- and post-intervention) required 130 subjects to achieve 80% power with a significance of P = .05. No significant differences in demographics including age, insurance type, and cytology were noted. HPV co-testing increased from 0% to 55% (P < .001). Of the 72 subjects who had co-testing, 58 (80%) will not need cervical cancer screening for another 5 years. HPV co-testing represents an underutilized cervical cancer screening modality for women 30 years and older. This brief educational intervention, adaptable to any clinical setting, significatnly increased co-testing at the clinical site.

  2. The Aetiological Role of Human Papillomavirus in Oesophageal Squamous Cell Carcinoma: A Meta-Analysis

    PubMed Central

    Liyanage, Surabhi S.; Rahman, Bayzidur; Ridda, Iman; Newall, Anthony T.; Tabrizi, Sepehr N.; Garland, Suzanne M.; Segelov, Eva; Seale, Holly; Crowe, Philip J.; Moa, Aye; MacIntyre, C. Raina

    2013-01-01

    Background The aetiological role of human papillomavirus (HPV) in oesophageal squamous cell carcinoma (OSCC) has been widely researched for more than three decades, with conflicting findings. In the absence of a large, adequately powered single case-control study, a meta-analysis of all available case-control studies is the most rigorous way of identifying any potential association between HPV and OSCC. We present the first global meta-analysis of case-control studies investigating the role of HPV in OSCC. Methods Case-control studies investigating OSCC tissue for presence of HPV DNA were identified. 21 case-control studies analyzing a total of 1223 cases and 1415 controls, met our inclusion criteria. HPV detection rates were tabulated for each study and all studies were assessed for quality. The random effects method was used to pool the odds ratios (OR). Results From all OSCC specimens included in this meta-analysis, 35% (426/1223) were positive for HPV DNA. The pooled OR for an HPV-OSCC association was 3.04 (95% CI 2.20 to 4.20). Meta-regression analysis did not find a significant association between OR and any of the quality domains. Influence analysis was non-significant for the effect of individual studies on the pooled estimate. Studies conducted in countries with low to medium OSCC incidence showed a stronger relationship (OR 4.65, 95% CI 2.47 to 8.76) than regions of high OSCC incidence (OR 2.65, 95% CI 1.80 to 3.91). Conclusions Uncertainty around the aetiological role of HPV in OSCC is due largely to the small number and scale of appropriately designed studies. Our meta-analysis of these studies suggests that HPV increases the risk of OSCC three-fold. This study provides the strongest evidence to date of an HPV-OSCC association. The importance of these findings is that prophylactic vaccination could be of public health benefit in prevention of OSCC in countries with high OSCC incidence. PMID:23894436

  3. Macrophages Modulate Migration and Invasion of Human Tongue Squamous Cell Carcinoma

    PubMed Central

    Pirilä, Emma; Väyrynen, Otto; Sundquist, Elias; Päkkilä, Kaisa; Nyberg, Pia; Nurmenniemi, Sini; Pääkkönen, Virve; Pesonen, Paula; Dayan, Dan; Vered, Marilena; Uhlin-Hansen, Lars; Salo, Tuula

    2015-01-01

    Oral tongue squamous cell carcinoma (OTSCC) has a high mortality rate and the incidence is rising worldwide. Despite advances in treatment, the disease lacks specific prognostic markers and treatment modality. The spreading of OTSCC is dependent on the tumor microenvironment and involves tumor-associated macrophages (TAMs). Although the presence of TAMs is associated with poor prognosis in OTSCC, the specific mechanisms underlying this are still unknown. The aim here was to investigate the effect of macrophages (Mfs) on HSC-3 tongue carcinoma cells and NF-kappaB activity. We polarized THP-1 cells to M1 (inflammatory), M2 (TAM-like) and R848 (imidazoquinoline-treated) type Mfs. We then investigated the effect of Mfs on HSC-3 cell migration and NF-kappaB activity, cytokine production and invasion using several different in vitro migration models, a human 3D tissue invasion model, antibody arrays, confocal microscopy, immunohistochemistry and a mouse invasion model. We found that in co-culture studies all types of Mfs fused with HSC-3 cells, a process which was partially due to efferocytosis. HSC-3 cells induced expression of epidermal growth factor and transforming growth factor-beta in co-cultures with M2 Mfs. Direct cell-cell contact between M2 Mfs and HSC-3 cells induced migration and invasion of HSC-3 cells while M1 Mfs reduced HSC-3 cell invasion. M2 Mfs had an excess of NF-kappaB p50 subunit and a lack of p65 subunits both in the presence and absence of HSC-3 cells, indicating dysregulation and pro-tumorigenic NF-kappaB activation. TAM-like cells were abundantly present in close vicinity to carcinoma cells in OTSCC patient samples. We conclude that M2 Mfs/TAMs have an important role in OTSCC regulating adhesion, migration, invasion and cytokine production of carcinoma cells favouring tumor growth. These results demonstrate that OTSCC patients could benefit from therapies targeting TAMs, polarizing TAM-like M2 Mfs to inflammatory macrophages and modulating NF

  4. Combining metformin and nelfinavir exhibits synergistic effects against the growth of human cervical cancer cells and xenograft in nude mice

    PubMed Central

    Xia, Chenglai; Chen, Ruihong; Chen, Jinman; Qi, Qianqian; Pan, Yanbin; Du, Lanying; Xiao, Guohong; Jiang, Shibo

    2017-01-01

    Human cervical cancer is the fourth most common carcinoma in women worldwide. However, the emergence of drug resistance calls for continuously developing new anticancer drugs and combination chemotherapy regimens. The present study aimed to investigate the anti-cervical cancer effects of metformin, a first-line therapeutic drug for type 2 diabetes mellitus, and nelfinavir, an HIV protease inhibitor, when used alone or in combination. We found that both metformin and nelfinavir, when used alone, were moderately effective in inhibiting proliferation, inducing apoptosis and suppressing migration and invasion of human cervical cell lines HeLa, SiHa and CaSki. When used in combination, these two drugs acted synergistically to inhibit the growth of human cervical cancer cells in vitro and cervical cancer cell xenograft in vivo in nude mice, and suppress cervical cancer cell migration and invasion. The protein expression of phosphoinositide 3-kinase catalytic subunit PI3K(p110α), which can promote tumor growth, was remarkably downregulated, while the tumor suppressor proteins p53 and p21 were substantially upregulated following the combinational treatment in vitro and in vivo. These results suggest that clinical use of metformin and nelfinavir in combination is expected to have synergistic antitumor efficacy and significant potential for the treatment of human cervical cancer. PMID:28252027

  5. Wnt-11 overexpression promoting the invasion of cervical cancer cells.

    PubMed

    Wei, Heng; Wang, Ning; Zhang, Yao; Wang, Shizhuo; Pang, Xiaoao; Zhang, Shulan

    2016-09-01

    Wnt-11 is a positive regulator of the Wnt signaling pathway, which plays a crucial role in carcinogenesis. However, Wnt-11 expression in cervical cancer has not been well investigated. The aim of this study was to investigate the role of Wnt-11 in cervical tumor proliferation and invasion. This study examined 24 normal cervical squamous epithelia, 29 cervical intraepithelial neoplasia (CIN), and 78 cervical cancer samples. The expression of Wnt-11 was investigated by immunohistochemistry and quantitative reverse transcription-polymerase chain reaction analysis. The expression of the high-risk human papilloma virus (HR-HPV) E6 oncoprotein was also investigated by immunohistochemistry. In addition, the expression of Wnt-11, HR-HPV E6, JNK-1, phosphorylated JNK-1(P-JNK1), and β-catenin was examined by western blot analysis following Wnt-11 knockdown or overexpression in HeLa or SiHa cells, respectively. The promotion of cervical cancer cell proliferation and invasion was investigated using the cell counting kit-8 and Matrigel invasion assay, respectively. Wnt-11 and HR-HPV E6 expression increased in a manner that corresponded with the progression of cervical cancer and was significantly correlated with the International Federation of Gynecology and Obstetrics cancer stage, lymph node metastasis, tumor size, and HPV infection. Wnt-11 protein expression was positively associated with HR-HPV E6 protein expression in all 78 cervical cancer samples (P < 0.001). Furthermore, Wnt-11 was positively associated with P-JNK1 expression and promoted cervical cancer cell proliferation and invasion. These observations suggest that the increased Wnt-11 expression observed in cervical cancer cells may lead to the phosphorylation and activation of JNK-1 and significantly promote tumor cell proliferation and cell migration/invasion through activation of the Wnt/JNK pathway. Consequently, Wnt-11 may serve as a novel target for cervical cancer therapy.

  6. Distribution of Carcinogenic Human Papillomavirus Genotypes and Association to Cervical Lesions among Women in Fez (Morocco)

    PubMed Central

    Souho, Tiatou; El Fatemi, Hinde; Karim, Safae; El Rhazi, Karima; Bouchikhi, Chahrazed; Banani, Abdelaziz; Melhouf, Moulay Abdelilah; Benlemlih, Mohamed; Bennani, Bahia

    2016-01-01

    Objectives To determine the distribution of cervical high-risk human papillomavirus genotypes and their association to cellular abnormalities in women from Fez and its neighborhood. Methods Women attending the Hassan II University Hospital for cervical pap smears were recruited after an informed consent. Interviews and two cervical samples were performed for each woman. Cervical samples were used for cytological analysis and HPV DNA detection. HPV was typed using a method based on multiplex PCR with fluorescently labeled specific primers followed by capillary electrophoresis. The study was approved by the ethics committee of the Faculty of Medicine and Pharmacy of Fez. Results The HPV prevalence in the studied population was 43.1% and the most prevalent types were HPV 53 (23 cases); HPV 16 (20 cases); HPV 35 (18 cases); HPV 51 (10 cases) and HPV 56 (7 cases). From the 619 confirmed pap smears, 20% were abnormal. The cytological abnormalities were significantly associated to HPV infection, women age, number of pregnancies and parity (p < 0.05). Conclusion More attention should be given to HPV in Morocco because it represents an important public health concern. The distribution of carcinogenic HPV types in the studied population is different from the data in other regions but epidemiological studies in other Moroccan regions are required. PMID:26731415

  7. From Human Papillomavirus (HPV) Detection to Cervical Cancer Prevention in Clinical Practice

    PubMed Central

    Lee, Sin Hang; Vigliotti, Jessica S.; Vigliotti, Veronica S.; Jones, William

    2014-01-01

    The newly gained knowledge of the viral etiology in cervical carcinogenesis has prompted industrial interests in developing virology-based tools for cervical cancer prevention. Due to the long incubation period from viral infection to developing an invasive cancer, a process whose outcome is influenced by numerous life-style and genetic factors, the true efficacy of the genotype-specific human papillomavirus (HPV) vaccines in cervical cancer prevention cannot be determined for another 30 years. Most HPV DNA test kits designed to replace the traditional Papanicolaou (Pap) smears for precancer detection lack the analytical sensitivity and specificity to comprehensively detect all potentially carcinogenic HPVs and to perform reliable genotyping. The authors implemented the classic nested PCR and Sanger DNA-sequencing technology for routine HPV testing. The results showed a true negative HPV PCR invariably indicates the absence of precancerous cells in the cytology samples. However, 80.5% of single positive HPV-16 tests and 97.3% of single positive HPV-18 tests were associated with a negative or a largely self-reversible Pap cytology. Routine sensitive and reliable HPV type-specific or perhaps even variant-specific methods are needed to address the issues of persistence of HPV infection if a virology-based primary cervical screen is used to replace the Pap cytology screening paradigm. PMID:25279452

  8. Integration of human papillomavirus vaccination and cervical cancer screening in Latin America and the Caribbean.

    PubMed

    Franco, Eduardo L; Tsu, Vivien; Herrero, Rolando; Lazcano-Ponce, Eduardo; Hildesheim, Allan; Muñoz, Nubia; Murillo, Raul; Sánchez, Gloria Ines; Andrus, Jon Kim

    2008-08-19

    Despite substantial efforts to control cervical cancer by screening, most Latin American and Caribbean countries continue to experience incidence rates of this disease that are much higher than those of other Western countries. The implementation of universal human papillomavirus (HPV) vaccination for young adolescent women is the best prospect for changing this situation. Even though there are financial challenges to overcome to implement such a policy, there is broad political support in the region for adopting universal HPV vaccination. The costs of implementing this policy could be largely alleviated by changing cervical cancer control practices that rely on inefficient use of resources presently allocated to cytology screening. In view of the strong evidence base concerning cervical cancer prevention technologies in the region and the expected impact of vaccination on the performance of cytology, we propose a reformulation of cervical cancer screening policies to be based on HPV testing using validated methods followed by cytologic triage. This approach would serve as the central component of a system that plays the dual role of providing screening and surveillance as integrated and complementary activities sharing centralized resources and coordination.

  9. Cervical and crown outline analysis of worn Neanderthal and modern human lower second deciduous molars.

    PubMed

    Benazzi, Stefano; Fornai, Cinzia; Buti, Laura; Toussaint, Michel; Mallegni, Francesco; Ricci, Stefano; Gruppioni, Giorgio; Weber, Gerhard W; Condemi, Silvana; Ronchitelli, Annamaria

    2012-12-01

    Despite the general increase in digital techniques for dental morphometric analyses, only a few methods are available to study worn teeth. Moreover, permanent dentitions are studied much more frequently than deciduous teeth. In this study, we address both issues by providing a taxonomic classification of Neanderthal and modern human (MH) lower second deciduous molars (dm(2) s) through the analysis of crown and cervical outlines. Crown and cervical outlines were obtained from a three-dimensional (3D) digital sample of uniformly oriented dm(2) s. Both outlines were centered on the centroid of their area and represented by 16 pseudolandmarks obtained by equiangularly spaced radial vectors out of the centroid. We removed size information from the oriented and centered outlines with a uniform scaling of the pseudolandmark configurations to unit Centroid Size. Group shape variation was evaluated separately for the dm(2) crown and cervical outlines through a shape-space principal component (PC) analysis. Finally, quadratic discriminant analysis of a subset of PCs was used to classify the specimens. Our results demonstrate that both outlines successfully separate the two groups. Neanderthals showed a buccodistal expansion and convex lingual outline shape, whilst MHs have buccodistal reduction and straight lingual outline shape. Therefore, we confirmed that the cervical outline represents an effective parameter for distinguishing between the two taxa when dealing with worn or damaged dm(2) s.

  10. Developing a prognostic micro-RNA signature for human cervical carcinoma.

    PubMed

    How, Christine; Pintilie, Melania; Bruce, Jeff P; Hui, Angela B Y; Clarke, Blaise A; Wong, Philip; Yin, Shaoming; Yan, Rui; Waggott, Daryl; Boutros, Paul C; Fyles, Anthony; Hedley, David W; Hill, Richard P; Milosevic, Michael; Liu, Fei-Fei

    2015-01-01

    Cervical cancer remains the third most frequently diagnosed and fourth leading cause of cancer death in women worldwide. We sought to develop a micro-RNA signature that was prognostic for disease-free survival, which could potentially allow tailoring of treatment for cervical cancer patients. A candidate prognostic 9-micro-RNA signature set was identified in the training set of 79 frozen specimens. However, three different approaches to validate this signature in an independent cohort of 87 patients with formalin-fixed paraffin-embedded (FFPE) specimens, were unsuccessful. There are several challenges and considerations associated with developing a prognostic micro-RNA signature for cervical cancer, namely: tumour heterogeneity, lack of concordance between frozen and FFPE specimens, and platform selection for global micro-RNA expression profiling in this disease. Our observations provide an important cautionary tale for future miRNA signature studies for cervical cancer, which can also be potentially applicable to miRNA profiling studies involving other types of human malignancies.

  11. Cell membrane softening in human breast and cervical cancer cells

    NASA Astrophysics Data System (ADS)

    Händel, Chris; Schmidt, B. U. Sebastian; Schiller, Jürgen; Dietrich, Undine; Möhn, Till; Kießling, Tobias R.; Pawlizak, Steve; Fritsch, Anatol W.; Horn, Lars-Christian; Briest, Susanne; Höckel, Michael; Zink, Mareike; Käs, Josef A.

    2015-08-01

    Biomechanical properties are key to many cellular functions such as cell division and cell motility and thus are crucial in the development and understanding of several diseases, for instance cancer. The mechanics of the cellular cytoskeleton have been extensively characterized in cells and artificial systems. The rigidity of the plasma membrane, with the exception of red blood cells, is unknown and membrane rigidity measurements only exist for vesicles composed of a few synthetic lipids. In this study, thermal fluctuations of giant plasma membrane vesicles (GPMVs) directly derived from the plasma membranes of primary breast and cervical cells, as well as breast cell lines, are analyzed. Cell blebs or GPMVs were studied via thermal membrane fluctuations and mass spectrometry. It will be shown that cancer cell membranes are significantly softer than their non-malignant counterparts. This can be attributed to a loss of fluid raft forming lipids in malignant cells. These results indicate that the reduction of membrane rigidity promotes aggressive blebbing motion in invasive cancer cells.

  12. Expression of the WT1 gene -KTS domain isoforms suppresses the invasive ability of human lung squamous cell carcinoma cells.

    PubMed

    Moriya, Shogo; Takiguchi, Masaki; Seki, Naohiko

    2008-02-01

    Although the WT1 gene was originally isolated as a tumor suppressor gene from Wilms' tumor, oncogenic roles for WT1 have been reported in several tumors. Here, we present new findings of high levels of WT1 expression associated with the suppression of lymph node metastasis in patients with human lung squamous cell carcinoma (SCC). We investigated the effect of down-regulated WT1 gene expression on the invasive phenotype of the SCC cell line RERF-LC-AI. Invasive ability was enhanced in WT1-specific siRNA-transfected cells, and a WT1 target gene p21(Waf1/Cip1) was isolated by comprehensive gene expression analysis. As several isoforms are produced from the WT1 gene, we isolated eight major WT1 isoforms from a cDNA library and cloned each variant into an expression vector. Luciferase reporter assays revealed that p21(Waf1/Cip1) expression was enhanced only by the WT1 cDNA variants that included a three-amino acid deletion (-KTS). Our results suggested that the -KTS-containing variants of WT1 are directly involved in the regulation of p21(Waf1/Cip1) expression and the subsequent suppression of lymph node metastasis in human lung squamous cell carcinoma.

  13. Cucurbitacin E as Inducer of Cell Death and Apoptosis in Human Oral Squamous Cell Carcinoma Cell Line SAS

    PubMed Central

    Hung, Chao-Ming; Chang, Chi-Chang; Lin, Chen-Wei; Ko, Shun-Yao; Hsu, Yi-Chiang

    2013-01-01

    Human oral squamous cell carcinoma (OSCC) is a common form of malignant cancer, for which radiotherapy or chemotherapy are the main treatment methods. Cucurbitacin E (CuE) is a natural compound previously shown to be an antifeedant as well as a potent chemopreventive agent against several types of cancer. The present study investigates anti-proliferation (using MTT assay, CuE demonstrated cytotoxic activity against SAS cell with IC50 values at 3.69 μM) and induced apoptosis of human oral squamous cell carcinoma SAS cells after 24 h treatment with CuE. Mitochondrial membrane potential (MMP) and caspase activity were studied and our results indicate that CuE inhibits cell proliferation as well as the activation of apoptois in SAS cells. Both effects increased in proportion to the dosage of CuE and apoptosis was induced via mitochondria- and caspase-dependent pathways. CuE can induce cell death by a mechanism that is not dependent on apoptosis induction, and thus represents a promising anticancer agent for prevention and treatment of OSCC. PMID:23965977

  14. Cucurbitacin E as inducer of cell death and apoptosis in human oral squamous cell carcinoma cell line SAS.

    PubMed

    Hung, Chao-Ming; Chang, Chi-Chang; Lin, Chen-Wei; Ko, Shun-Yao; Hsu, Yi-Chiang

    2013-08-20

    Human oral squamous cell carcinoma (OSCC) is a common form of malignant cancer, for which radiotherapy or chemotherapy are the main treatment methods. Cucurbitacin E (CuE) is a natural compound previously shown to be an antifeedant as well as a potent chemopreventive agent against several types of cancer. The present study investigates anti-proliferation (using MTT assay, CuE demonstrated cytotoxic activity against SAS cell with IC50 values at 3.69 µM) and induced apoptosis of human oral squamous cell carcinoma SAS cells after 24 h treatment with CuE. Mitochondrial membrane potential (MMP) and caspase activity were studied and our results indicate that CuE inhibits cell proliferation as well as the activation of apoptois in SAS cells. Both effects increased in proportion to the dosage of CuE and apoptosis was induced via mitochondria- and caspase-dependent pathways. CuE can induce cell death by a mechanism that is not dependent on apoptosis induction, and thus represents a promising anticancer agent for prevention and treatment of OSCC.

  15. [Human papillomavirus and cervical cancer in México: a constant struggle].

    PubMed

    Torres-Poveda, Kirvis; Madrid-Marina, Vicente

    2015-01-01

    Given that human papillomavirus and cervical cancer are a health problem in México, since they affect women of reproductive age and have a negative impact on our society, it is crucial to prevent those diseases and to raise awareness among physicians who deal with their clinical and therapeutic management. That is the reason why we show three Original contributions and 13 Current themes in this supplement of the Revista Médica del Instituto Mexicano del Seguro Social.

  16. Global Inequalities in Cervical Cancer Incidence and Mortality are Linked to Deprivation, Low Socioeconomic Status, and Human Development

    PubMed Central

    Singh, Gopal K.; Azuine, Romuladus E.; Siahpush, Mohammad

    2012-01-01

    Objectives This study examined global inequalities in cervical cancer incidence and mortality rates as a function of cross-national variations in the Human Development Index (HDI), socioeconomic factors, Gender Inequality Index (GII), and healthcare expenditure. Methods Age-adjusted incidence and mortality rates were calculated for women in 184 countries using the 2008 GLOBOCAN database, and incidence and mortality trends were analyzed using the WHO cancer mortality database. Log-linear regression was used to model annual trends, while OLS and Poisson regression models were used to estimate the impact of socioeconomic and human development factors on incidence and mortality rates. Results Cervical cancer incidence and mortality rates varied widely, with many African countries such as Guinea, Zambia, Comoros, Tanzania, and Malawi having at least 10-to-20-fold higher rates than several West Asian, Middle East, and European countries, including Iran, Saudi Arabia, Syria, Egypt, and Switzerland. HDI, GII, poverty rate, health expenditure per capita, urbanization, and literacy rate were all significantly related to cervical cancer incidence and mortality, with HDI and poverty rate each explaining >52% of the global variance in mortality. Both incidence and mortality rates increased in relation to lower human development and higher gender inequality levels. A 0.2 unit increase in HDI was associated with a 20% decrease in cervical cancer risk and a 33% decrease in cervical cancer mortality risk. The risk of a cervical cancer diagnosis increased by 24% and of cervical cancer death by 42% for a 0.2 unit increase in GII. Higher health expenditure levels were independently associated with decreased incidence and mortality risks. Conclusions and Public Health Implications Global inequalities in cervical cancer are clearly linked to disparities in human development, social inequality, and living standards. Reductions in cervical cancer rates are achievable by reducing

  17. Doxycycline inhibits proliferation and induces apoptosis of both human papillomavirus positive and negative cervical cancer cell lines.

    PubMed

    Zhao, Yan; Wang, Xinyu; Li, Lei; Li, Changzhong

    2016-05-01

    The clinical management of cervical cancer remains a challenge and the development of new treatment strategies merits attention. However, the discovery and development of novel compounds can be a long and labourious process. Drug repositioning may circumvent this process and facilitate the rapid translation of hypothesis-driven science into the clinics. In this work, we show that a FDA-approved antibiotic, doxycycline, effectively targets human papillomavirus (HPV) positive and negative cervical cancer cells in vitro and in vivo. Doxycycline significantly inhibits proliferation of a panel of cervical cancer cell lines. It also induces apoptosis of cervical cancer cells in a time- and dose-dependent manner. In addition, the apoptosis induced by doxycycline is through caspase-dependent pathway. Mechanism studies demonstrate that doxycycline affects oxygen consumption rate, glycolysis, and reduces ATP levels in cervical cancer cells. In HeLa xenograft mouse model, doxycycline significantly inhibits growth of tumour. Our in vitro and in vivo data clearly demonstrate the inhibitory effects of doxycycline on the growth and survival of cervical cancer cells. Our work provides the evidence that doxycycline can be repurposed for the treatment of cervical cancer and targeting energy metabolism may represent a potential therapeutic strategy for cervical cancer.

  18. Role of IL-10 and TGF-β1 in local immunosuppression in HPV-associated cervical neoplasia

    PubMed Central

    Torres-Poveda, Kirvis; Bahena-Román, Margarita; Madrid-González, Claudia; Burguete-García, Ana I; Bermúdez-Morales, Víctor Hugo; Peralta-Zaragoza, Oscar; Madrid-Marina, Vicente

    2014-01-01

    Cervical cancer is a worldwide disease that constitutes a significant public health problem, especially in developing countries, not only due to its high incidence but also because the most affected population comprises women who belong to marginalized socio-economic classes. Clinical and molecular research has identified immunological impairment in squamous intraepithelial cervical lesions and cervical cancer patients. Human Papillomavirus (HPV) has several mechanisms for avoiding the immune system: it down-regulates the expression of interferon and upregulates interleukin (IL)-10 and transforming growth factor (TGF)-β1 to produce a local immunosuppressive environment, which, along with altered tumor surface antigens, forms an immunosuppressive network that inhibits the antitumor immune response. In this review we analyzed the available data on several deregulated cellular immune functions in patients with NIC I, NIC II and NIC III and cervical cancer. The effects of immunosuppressive cytokines on innate immune response, T-cell activation and cellular factors that promote tumor cell proliferation in cervical cancer patients are summarized. We discuss the functional consequences of HPV E2, E6, and E7 protein interactions with IL-10 and TGF-β1 promoters in the induction of these cytokines and postulate its effect on the cellular immune response in squamous intraepithelial cervical lesions and cervical cancer patients. This review provides a comprehensive picture of the immunological functions of IL-10 and TGF-β1 in response to HPV in humans. PMID:25302175

  19. Antibodies against high-risk human papillomavirus proteins as markers for invasive cervical cancer.

    PubMed

    Combes, Jean-Damien; Pawlita, Michael; Waterboer, Tim; Hammouda, Doudja; Rajkumar, Thangarajan; Vanhems, Philippe; Snijders, Peter; Herrero, Rolando; Franceschi, Silvia; Clifford, Gary

    2014-11-15

    Different human papillomavirus (HPV) genes are expressed during the various phases of the HPV life cycle and may elicit immune responses in the process towards malignancy. To evaluate their association with cervical cancer, antibodies against proteins from HPV16 (L1, E1, E2, E4, E6 and E7) and HPV18/31/33/35/45/52/58 (L1, E6 and E7) were measured in serum of 307 invasive cervical cancer cases and 327 controls from Algeria and India. Antibody response was evaluated using a glutathione S-transferase-based multiplex serology assay and HPV DNA detected from exfoliated cervical cells using a GP5+/6+-mediated PCR assay. Among HPV16 DNA-positive cases, seroprevalence of HPV16 antibodies ranged from 16% for HPV16 E1 to 50% for HPV16 E6 and all were significantly higher than controls. Seroprevalence of E6, E7 and L1 antibodies for HPV18 and for at least one of HPV31/33/35/45/52/58 were also higher in cases positive for DNA of the corresponding type (50% and 30% for E6 of HPV18 and HPV31/33/35/45/52/58 combined, respectively). E6 and E7 antibodies were rarely found in controls, but cross-reactivity was evident among cancer cases positive for DNA of closely phylogenetically-related HPV types. E6 or E7 antibodies against any of the eight HPV types were detected in 66.1% of all cervical cancer cases, as compared to 10.1% of controls. E6, and to a lesser extent E7, antibodies appear to be specific markers of HPV-related malignancy. However, even among cases positive for the same type of HPV DNA, approximately one-third of cervical cancer cases show no detectable immune response to either E6 or E7.

  20. The caspase 3-dependent apoptotic effect of pycnogenol in human oral squamous cell carcinoma HSC-3 cells

    PubMed Central

    Yang, In-Hyoung; Shin, Ji-Ae; Kim, Lee-Han; Kwon, Ki Han; Cho, Sung-Dae

    2016-01-01

    In the present study, the apoptotic effect of pycnogenol and its molecular mechanism in human oral squamous cell carcinoma HSC-3 cells were investigated. Pycnogenol significantly inhibited the viability of HSC-3 cells and suppressed neoplastic cell transformation in HSC-3 cells and TPA-treated JB6 cells. It caused caspase-dependent apoptosis evidenced by the increase in cleaved poly (ADP-ribose) polymerase and caspase 3 in a dose-dependent manner. Pycnogenol increased Bak protein by enhancing its protein stability whereas other Bcl-2 family members were not altered. In addition, the treatment with pycnogenol led to the production of reactive oxygen species and N-acetyl-l-cysteine almost blocked pycnogenol-induced reactive oxygen species generation. Taken together, these findings suggest that pycnogenol may be a potential candidate for the chemoprevention or chemotherapy of human oral cancer. PMID:26798196

  1. The caspase 3-dependent apoptotic effect of pycnogenol in human oral squamous cell carcinoma HSC-3 cells.

    PubMed

    Yang, In-Hyoung; Shin, Ji-Ae; Kim, Lee-Han; Kwon, Ki Han; Cho, Sung-Dae

    2016-01-01

    In the present study, the apoptotic effect of pycnogenol and its molecular mechanism in human oral squamous cell carcinoma HSC-3 cells were investigated. Pycnogenol significantly inhibited the viability of HSC-3 cells and suppressed neoplastic cell transformation in HSC-3 cells and TPA-treated JB6 cells. It caused caspase-dependent apoptosis evidenced by the increase in cleaved poly (ADP-ribose) polymerase and caspase 3 in a dose-dependent manner. Pycnogenol increased Bak protein by enhancing its protein stability whereas other Bcl-2 family members were not altered. In addition, the treatment with pycnogenol led to the production of reactive oxygen species and N-acetyl-l-cysteine almost blocked pycnogenol-induced reactive oxygen species generation. Taken together, these findings suggest that pycnogenol may be a potential candidate for the chemoprevention or chemotherapy of human oral cancer.

  2. [Etiology and pathogenesis of precancerous lesions and invasive cervical carcinoma].

    PubMed

    Panjković, Milana; Ivković-Kapicl, Tatjana

    2008-01-01

    Cervical cancer is the second most common gynecological malignancy in the world. Human papilloma virus (HPV) infection is the leading ethiologic agent in the development of premalignant and malignant cervical diseases. HPV is a member of the Papovaviridae family and until now over 100 types have been recognized There are two types of viral infection: latent and productive. Virus induced oncogenesis is the result of interaction between virus oncoproteins E6 and E7 and tumor supresor host genes p53 and Rb. Many cofactors such as immunosuppression, early sexual relationship, multiple sexual partners, other sexualy transsmited infections and smoking are contributing factors of the precancerous and invasive cervical lesions. According to the oncogenic potential HPV are divided into three groups: low, intermediate and high oncogenic risk viruses. Molecular technics which are used for the virus detection are: In situ hibridisation, Hyybrid capture test and polymerasa chain reaction. Human papilloma virus testing has an important role in the follow up and treatment of women with "atypical squamous cells of unknown significant" changes in cervical smears and low-grade squamous intraepithelial lesions, changes in punch biopsy.

  3. Antiproliferative and Apoptosis-inducing Effect of exo-Protoporphyrin IX based Sonodynamic Therapy on Human Oral Squamous Cell Carcinoma

    PubMed Central

    Lv, Yanhong; Zheng, Jinhua; Zhou, Qi; Jia, Limin; Wang, Chunying; Liu, Nian; Zhao, Hong; Ji, Hang; Li, Baoxin; Cao, Wenwu

    2017-01-01

    Sonodynamic therapy (SDT) is an innovative modality for cancer treatment. But the biological effect of SDT on oral squamous cell carcinoma has not been studied. Our previous study has shown that endo-Protoporphyrin IX based SDT (ALA-SDT) could induce apoptosis in human tongue squamous carcinoma SAS cells through mitochondrial pathway. Herein, we investigated the effect of exo- Protoporphyrin based SDT (PpIX-SDT) on SAS cells in vitro and in vivo. We demonstrated that PpIX-SDT increased the ratio of cells in the G2/M phase and induced 3–4 times more cell apoptosis compared to sonocation alone. PpIX-SDT caused cell membrane damage prior to mitochondria damage and upregulated the expression of Fas and Fas L, while the effect was suppressed if cells were pre-treated with p53 inhibitor. Additionally, we examined the SDT-induced cell apoptosis in two cell lines with different p53 status. The increases of p53 expression and apoptosis rate in wild-type p53 SAS cells were found in the SDT group, while p53-mutated HSC-3 cells did not show such increase. Our data suggest that PpIX-SDT suppress the proliferation of SAS cells via arresting cell cycle at G2/M phase and activating the extrinsic Fas-mediated membrane receptor pathway to induce apoptosis, which is regulated by p53. PMID:28102324

  4. Decrease of miR-146a is associated with the aggressiveness of human oral squamous cell carcinoma

    PubMed Central

    Shi, Zonggao; Johnson, Jeffrey J.; Jiang, Rong; Liu, Yueying; Stack, M. Sharon

    2015-01-01

    With the aim to identify microRNAs that may contribute to oral squamous cell carcinoma (OSCC) progression, we compared the microRNA expression profiles of two related cell lines that form tumors with differential aggressiveness. A panel of 28 microRNAs was found to be more than 1.5-fold altered, among which miR-146a was the most significantly changed (-4.6-fold). Loss of miR-146a expression was validated in human high-grade tumors, while normal oral mucosa retained expression, using fluorescence in situ hybridization on a tissue microarray. Restoration of miR-146a in SCC25 and UMSCC1 cells decreased in vitro invasive activity, suppressed tumor growth in vivo, and decreased the incidence of UMSCC1 lung metastasis. The transcription factor Sox2 was found to be a putative target of miR-146a. In conclusion, the loss or decrease of miR-146a is a new feature that is associated with more aggressive behavior in oral squamous carcinoma. PMID:26159827

  5. [High-risk human papilloma virus associated oropharynx squamous cell carcinomas: clinical, biological implications and therapeutical perspectives].

    PubMed

    Guihard, S; Jung, A-C; Noël, G

    2012-02-01

    The infection of the head and neck epithelium by high-risk human papillomaviruses (HPV) is a risk factor for cancer onset and development. The incidence of HPV-related head and neck squamous cell carcinoma is currently increasing. These lesions display distinct clinical features. HPV positive patients are often younger and have a smaller history of tobacco smoking and alcohol drinking, but have a history of virus-transmitting sex practices. HPV-related tumours are mainly found in the oropharynx, are more associated to a local lymph node invasion and display a poorly differentiated morphology. Despite these more aggressive features, HPV-positive head and neck squamous cell carcinomas correlate with an improved local control, disease-free and global survival. It is thought that HPV-driven specific biologic abnormalities underlie higher tumour sensitivity to chemotherapeutic drugs and ionizing radiations. The expression of the HPV E6 and E7 oncoproteins induce cell transformation by interfering with cell signalling pathways involved in apoptosis, cell cycle, angiogenesis and induce the overexpression of the CDKN2A gene. Therefore, alternative treatments based on therapies targeting these pathways in combination with radiation dose de-escalation could be proposed to HPV-positive patients, if they are properly and reliably identified.

  6. Effect and mechanism of RUNX3 gene on biological characteristics of human esophageal squamous cell carcinoma (ESCC).

    PubMed

    Chen, Huaxia; Wang, Zhou; Wang, Shuai; Zhang, Zhiping; Shi, Shanshan

    2015-01-01

    The aim of this study was to investigate the role of RUNX3 in esophageal squamous cell carcinoma (ESCC) cells biological behavior and the relationship between the expression of RUNX3 and MMP-9, TIMP-1, ICAM-1. RUNX3 levels in 90 esophageal squamous cell carcinoma specimens using immunohistochemical staining to examine the correlation between RUNX3 expression and clinical stage of ESCC. Furthermore, the role of RUNX3 in ESCC progression was evaluated in vitro by siRNA-mediated knockdown of RUNX3 or lentivirus-mediated over-expression of RUNX3 in ESCC cell lines. The expression and activities of MMP-9, TIMP-1, and ICAM-1 were analyzed. We found decreased expression of RUNX3 in ESCC tissue to be significantly related to T stage of tumor (p < 0.01). In vitro, knockdown of RUNX3 in Eca9706 cells resulted in promoting cell growth, migration, and invasion. Additionally, MMP-9 and ICAM-1 were upregulated in RUNX3-knockdown cells. Notably, RUNX3 over-expression in Kyse150 cells could significantly decrease MMP-9 and ICAM-1. Tumorigenesis in vivo was significantly determined. The study indicates that low expression of RUNX3 in human ESCC tissue is significantly correlated with progression. Restoration of RUNX3 expression significantly inhibits ESCC cells migration, invasion, and tumorigenesis, which may be caused by RUNX3's interaction with MMP-9 and ICAM-1; RUNX3 may be a potential therapeutic target for ESCC.

  7. HPV-related squamous neoplasia of the lower anogenital tract: an update and review of recent guidelines.

    PubMed

    Maniar, Kruti P; Nayar, Ritu

    2014-09-01

    Squamous cell carcinomas of the lower anogenital tract that are related to human papillomavirus (HPV) infection represent a significant disease burden worldwide. The diagnosis and management of their noninvasive precursors has been the subject of extensive study and debate over several decades, accompanied by an evolving understanding of HPV biology. Recent new consensus recommendations for the pathologic diagnosis of these precursor lesions were published in 2012, the result of the Lower Anogenital Squamous Terminology project cosponsored by the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology. Most salient among the new guidelines are the recommendation to switch to a 2-tiered nomenclature (high-grade squamous intraepithelial lesion and low-grade squamous intraepithelial lesion) rather than the traditional 3-tiered "intraepithelial neoplasia" terminology, and the recommendation to expand use of the immunohistochemical marker p16 to distinguish between low-grade squamous intraepithelial lesion and high-grade squamous intraepithelial lesion/intraepithelial neoplasia 2. The goals of the project were to align diagnostic terminology with our knowledge of HPV biology, increase reproducibility, consolidate diverse systems of nomenclature, and ultimately better determine a patient's true cancer risk. The clinical guidelines for screening and management of cervical intraepithelial neoplasia have also been recently updated, most notably with a lengthening of screening intervals. In this review, we focus on the new guidelines put forth for pathologic diagnosis of HPV-related anogenital neoplasia, with discussion of the evidence behind them and their potential implications. We also provide an update on relevant biomarkers, clinical recommendations, and the newest developments relating to cervical neoplasia.

  8. Inhibiting the cytoplasmic location of HMGB1 reverses cisplatin resistance in human cervical cancer cells.

    PubMed

    Xia, Jiyi; Yu, Xiaolan; Song, Xueqin; Li, Gang; Mao, Xiguang; Zhang, Yujiao

    2017-01-01

    Cervical cancer is the fourth most common malignancy in women worldwide, and resistance to chemotherapy drugs is the biggest obstacle in the treatment of cervical cancers. In the present study, the molecular mechanisms underlying cisplatin resistance in human cervical cancer cells were investigated. When human cervical cancer cells were treated with 10 µg/ml of cisplatin for 24 and 48 h, high mobility group box 1 (HMGB1) protein expression levels significantly increased in a time‑dependent manner. Comparisons between cisplatin‑sensitive HeLa cells and cisplatin‑resistant HeLa/DDP cells revealed higher levels of HMGB1 in HeLa/DDP cells than in HeLa cells. Additionally, the half maximal inhibitory concentration (IC50) value for cisplatin in HeLa/DDP cells was 5.3‑fold that in HeLa cells. Analysis of the distribution of cellular components revealed that HMGB1 translocation from the nucleus to cytoplasm contributed to cisplatin resistance. This was further confirmed by demonstration that ethyl pyruvate treatment suppressed the cytoplasmic translocation of HMGB1, resulting in inhibition of HeLa cell proliferation. Furthermore, endogenous HMGB1 was inhibited with HMGB1‑specific short hairpin (sh)RNA, and MTT assay results showed that interference with HMGB1 expression reduced cell viability and potentially reversed cisplatin resistance in HeLa cells. Transfection with HMGB1 shRNA was demonstrated to induce cell apoptosis in HeLa cells, as detected by FACS analysis. In addition, administration of recombinant HMGB1 protein in HeLa cells promoted cell autophagy, mediated by the phosphorylation of extracellular signal‑regulated kinase 1/2. Thus, cytoplasmic HMGB1 translocation and HMGB1‑induced cell autophagy are proposed to contribute to cisplatin resistance by inhibiting apoptosis of cervical cancer cells. HMGB1 could, therefore, represent a novel therapeutic target for, and a diagnostic marker of, chemotherapy resistant cervical cancers.

  9. Anticancer Effect of Ursodeoxycholic Acid in Human Oral Squamous Carcinoma HSC-3 Cells through the Caspases.

    PubMed

    Pang, Liang; Zhao, Xin; Liu, Weiwei; Deng, Jiang; Tan, Xiaotong; Qiu, Lihua

    2015-05-05

    Bear bile was used as a traditional medicine or tonic in East Asia, and ursodeoxycholic acid (UDCA) is the most important compound in bear bile. Further, synthetic UDCA is also used in modern medicine and nutrition; therefore, its further functional effects warrant research, in vitro methods could be used for the fundamental research of its anticancer effects. In this study, the apoptotic effects of UDCA in human oral squamous carcinoma HSC-3 cells through the activation of caspases were observed by the experimental methods of MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) assay, DAPI (4',6-diamidino-2-phenylindole) staining, flow cytometry analysis, RT-PCR (reverse transcription-polymerase chain reaction) assay and Western blot assay after HSC-3 cells were treated by different concentrations of UDCA. With 0 to 400 μg/mL UDCA treatment, UDCA had strong growth inhibitory effects in HSC-3 cells, but had almost no effect in HOK normal oral cells. At concentrations of 100, 200 and 400 μg/mL, UDCA could induce apoptosis compared to untreated control HSC-3 cells. Treatment of 400 μg/mL UDCA could induce more apoptotic cancer cells than 100 and 200 μg/mL treatment; the sub-G1 DNA content of 400 μg/mL UDCA treated cancer cells was 41.3% versus 10.6% (100 μg/mL) and 22.4% (200 μg/mL). After different concentrations of UDCA treatment, the mRNA and protein expressions of caspase-3, caspase-8, caspase-9, Bax, Fas/FasL (Fas ligand), TRAIL (TNF-related apoptosis-inducing ligand), DR4 (death receptor 4) and DR5 (death receptor 5) were increased in HSC-3 cells, and mRNA and protein expressions of Bcl-2 (B-cell lymphoma 2), Bcl-xL (B-cell lymphoma-extra large), XIAP (X-linked inhibitor of apoptosis protein), cIAP-1 (cellular inhibitor of apoptosis 1), cIAP-2 (cellular inhibitor of apoptosis 2) and survival were decreased. Meanwhile, at the highest concentration of 400 μg/mL, caspase-3, caspase-8, caspase-9, Bax, Fas/FasL, TRAIL, DR4, DR5, and Iκ

  10. Adenosine uptake is the major effector of extracellular ATP toxicity in human cervical cancer cells

    PubMed Central

    Mello, Paola de Andrade; Filippi-Chiela, Eduardo Cremonese; Nascimento, Jéssica; Beckenkamp, Aline; Santana, Danielle Bertodo; Kipper, Franciele; Casali, Emerson André; Nejar Bruno, Alessandra; Paccez, Juliano Domiraci; Zerbini, Luiz Fernando; Wink, Marcia Rosângela; Lenz, Guido; Buffon, Andréia

    2014-01-01

    In cervical cancer, HPV infection and disruption of mechanisms involving cell growth, differentiation, and apoptosis are strictly linked with tumor progression and invasion. Tumor microenvironment is ATP and adenosine rich, suggesting a role for purinergic signaling in cancer cell growth and death. Here we investigate the effect of extracellular ATP on human cervical cancer cells. We find that extracellular ATP itself has a small cytotoxic effect, whereas adenosine formed from ATP degradation by ectonucleotidases is the main factor responsible for apoptosis induction. The level of P2×7 receptor seemed to define the main cytotoxic mechanism triggered by ATP, since ATP itself eliminated a small subpopulation of cells that express high P2×7 levels, probably through its activation. Corroborating these data, blockage or knockdown of P2×7 only slightly reduced ATP cytotoxicity. On the other hand, cell viability was almost totally recovered with dipyridamole, an adenosine transporter inhibitor. Moreover, ATP-induced apoptosis and signaling—p53 increase, AMPK activation, and PARP cleavage—as well as autophagy induction were also inhibited by dipyridamole. In addition, inhibition of adenosine conversion into AMP also blocked cell death, indicating that metabolization of intracellular adenosine originating from extracellular ATP is responsible for the main effects of the latter in human cervical cancer cells. PMID:25103241

  11. Differential effects of lipid fractions from silver carp brain on human cervical carcinoma cells in vitro.

    PubMed

    Wang, Caixia; Xia, Wenshui; Jiang, Qixing; Xu, Yanshun; Yu, Peipei

    2014-09-01

    Previous research has revealed that n3 polyunsaturated fatty acids (PUFAs) exhibit anticancer activities. Lipids from a fish brain contain substantial n3 PUFAs. However, no research has been conducted on the action and mechanism of their potent anticancer activities. In this study, total lipids (TLs) from silver carp brain were isolated into polar lipids (PLs) and neutral lipids (NLs), and the anticancer potential of the lipid fractions (LFs) was investigated using the human cervical carcinoma HeLa cell line. LFs effectively inhibited the cell proliferation of HeLa cells in a time- and dose-dependent manner by cell cycle arrest at the S stage and by inducing apoptosis. Further analyses indicated that the loss of mitochondrial membrane potential could be one of mechanisms of apoptosis induced by LFs. Among the TLs, PLs have proven to be more effective in inducing cervical carcinoma cell death than NLs. This work will play a role in promoting lipids from silver carp brain as a potential preventive and therapeutic agent against human cervical carcinoma.

  12. Stat3 induces oncogenic Skp2 expression in human cervical carcinoma cells

    SciTech Connect

    Huang, Hanhui; Zhao, Wenrong; Yang, Dan

    2012-02-03

    Highlights: Black-Right-Pointing-Pointer Upregulation of Skp2 by IL-6 or Stat3 activation. Black-Right-Pointing-Pointer Stat3 activates Skp2 expression through bound to its promoter region. Black-Right-Pointing-Pointer Stat3 activates Skp2 expression through recruitment of P300. Black-Right-Pointing-Pointer Stat3 activation decreases the P27 stability. -- Abstract: Dysregulated Skp2 function promotes cell proliferation, which is consistent with observations of Skp2 over-expression in many types of human cancers, including cervical carcinoma (CC). However, the molecular mechanisms underlying elevated Skp2 expression have not been fully explored. Interleukin-6 (IL-6) induced Stat3 activation is viewed as crucial for multiple tumor growth and metastasis. Here, we demonstrate that Skp2 is a direct transcriptional target of Stat3 in the human cervical carcinoma cells. Our data show that IL-6 administration or transfection of a constitutively activated Stat3 in HeLa cells activates Skp2 mRNA transcription. Using luciferase reporter and ChIP assays, we show that Stat3 binds to the promoter region of Skp2 and promotes its activity through recruiting P300. As a result of the increase of Skp2 expression, endogenous p27 protein levels are markedly decreased. Thus, our results suggest a previously unknown Stat3-Skp2 molecular network controlling cervical carcinoma development.

  13. Cure of urinary bladder functions in severe (95%) motoric complete cervical spinal cord injury in human.

    PubMed

    Schalow, G

    2010-01-01

    Severe cervical Spinal Cord Injury (SCI) leads to quadriplegia, and autonomic dysfunctions. Bladder/bowel continence, cardiovascular performance, and breathing are impaired besides movements. Even though there are no fully restorative treatments for SCI, I report about a patient, who suffered a severe cervical, motoric complete SCI, in whom urinary bladder functions were fully repaired by functional and structural repair (limited regeneration of the cord) upon 2.5 years of Coordination Dynamics Therapy (CDT). On the repair of the blood circulation (no occurrence of pressure ulcers any more), breathing and motor functions was reported earlier. The mechanism that underlies this important repair of urinary bladder functions is the learning transfer from movements to bladder functions. The human bladder repair is analyzed at the neuron level, the collective variable level (System Theory of Pattern Formation), the movement, and the clinical diagnostic level.

  14. Human papillomavirus infection, vaccination, and cervical cancer communication: the protection dilemma faced by women in southern Appalachia.

    PubMed

    Hutson, Sadie P; Dorgan, Kelly A; Duvall, Kathryn L; Garrett, Linda H

    2011-11-30

    Human papillomavirus is the most frequently occurring sexually transmitted infection and has been recognized as the necessary cause of cervical cancer. Understanding the shift in public awareness caused by recent changes to cervical prevention is critical to addressing cervical cancer disparities in Appalachia. Since the human papillomavirus vaccine was approved for prevention, little data have been collected regarding human papillomavirus risk assessment and vaccine perceptions among Appalachian women. The purpose of the authors in this study was to investigate communication and cultural issues via a social scripting framework that could influence human papillomavirus vaccine uptake among southern Appalachian women; and explore participants' perceptions of human papillomavirus, cervical cancer, and the vaccine. A qualitative, descriptive design was employed to examine these issues in eight counties in northeast Tennessee and southwest Virginia. Thirty-nine women aged 18-49 years participated in a single individual interview or focus group session from October 2007 through August 2008. Interview and focus group data were audio-taped and transcribed verbatim. Two major themes emerged from the data: the human papillomavirus vaccine protection dilemma and spheres of silence surrounding the human papillomavirus vaccine protection dilemma. Study findings suggested areas for future research and may assist healthcare professionals in approaching southern Appalachian women as they make decisions regarding cervical cancer prevention.

  15. Cervical Microbiome and Cytokine Profile at Various Stages of Cervical Cancer: A Pilot Study

    PubMed Central

    Bahena-Román, Margarita; Téllez-Sosa, Juan; Martínez-Barnetche, Jesús; Cortina-Ceballos, Bernardo; López-Estrada, Guillermina; Delgado-Romero, Karina; Burguete-García, Ana I.; Cantú, David; García-Carrancá, Alejandro; Madrid-Marina, Vicente

    2016-01-01

    Cervical cancer (CC) is caused by high-risk human papillomavirus persistence due to the immunosuppressive tumor microenvironment mediated by cytokines. Vaginal microbiota determines the presence of certain cytokines locally. We assessed the association between cervical microbiota diversity and the histopathological diagnosis of each stage of CC, and we evaluated mRNA cervical expression levels of IL-4, IL-6, IL-10, TGF-β1, TNF-α and IFN-γ across the histopathological diagnosis and specific bacterial clusters. We determined the cervical microbiota by high throughput sequencing of 16S rDNA amplicons and classified it in community state types (CST). Mean difference analyses between alpha-diversity and histopathological diagnosis were carried out, as well as a β-diversity analysis within the histological diagnosis. Cervical cytokine mRNA expression was analyzed across the CSTs and the histopathological diagnoses. We found a significant difference in microbiota's diversity in NCL-HPV negative women vs those with squamous intraepithelial lesions (SIL) and CC(p = 0.006, p = 0.036).When β-diversity was evaluated, the CC samples showed the highest variation within groups (p<0.0006) and the largest distance compared to NCL-HPV negative ones (p<0.00001). The predominant bacteria in women with normal cytology were L. crispatus and L. iners, whereas for SIL, it was Sneathia spp. and for CC, Fusobacterium spp. We found higher median cervical levels of IL-4 and TGF-β1 mRNA in the CST dominated by Fusobacterium spp. These results suggest that the cervical microbiota may be implicated in cervical cancer pathology. Further cohort studies are needed to validate these findings. PMID:27115350

  16. American Cancer Society Guideline for human papillomavirus (HPV) vaccine use to prevent cervical cancer and its precursors.

    PubMed

    Saslow, Debbie; Castle, Philip E; Cox, J Thomas; Davey, Diane D; Einstein, Mark H; Ferris, Daron G; Goldie, Sue J; Harper, Diane M; Kinney, Walter; Moscicki, Anna-Barbara; Noller, Kenneth L; Wheeler, Cosette M; Ades, Terri; Andrews, Kimberly S; Doroshenk, Mary K; Kahn, Kelly Green; Schmidt, Christy; Shafey, Omar; Smith, Robert A; Partridge, Edward E; Garcia, Francisco

    2007-01-01

    The American Cancer Society (ACS) has developed guidelines for the use of the prophylactic human papillomavirus (HPV) vaccine for the prevention of cervical intraepithelial neoplasia and cervical cancer. These recommendations are based on a formal review of the available evidence. They address the use of prophylactic HPV vaccines, including who should be vaccinated and at what age, as well as a summary of policy and implementation issues. Implications for screening are also discussed.

  17. Comparison of Xpert(®) HPV and Hybrid Capture(®) 2 DNA Test™ for detection of high-risk HPV infection in cervical atypical squamous cells of undetermined significance.

    PubMed

    Rabaan, Ali A; Taylor, Donald R; Dawamneh, Mohammed F; Al-Tawfiq, Jaffar A

    This study compares Xpert(®) HPV and Hybrid Capture(®) 2 High-Risk HPV DNA Test™ (hc2) for the detection of high-risk HPV infection in cervical smears. Papanicolaou smears with atypical squamous cells of undetermined significance (ASC-US) constituted the study specimens. Of the 168 ASC-US samples, 134 (79.8%) were from Saudi patients. The hc2 test was positive in 33 (19.6%) of the total patients, 20% among Saudi patients, and 17.6% among non-Saudi patients. Xpert(®) HPV produced positive results in 30 (17.8%) of the samples. The overall concordance rate between the two tests was 98.2%, and the positive concordance rate was 91%. There were three samples tested positive by hc2 that tested negative by Xpert(®) HPV. HPV 16, HPV 18/45 and HPV other types were the most common types. Both tests have a reasonable positive concordance rate, although hc2 detected more cases than Xpert(®) HPV. Xpert(®) HPV provides a viable alternative to the hc2 test with similar detection results for samples with ASC-US.

  18. Analysis of the entire HLA region in susceptibility for cervical cancer: a comprehensive study

    PubMed Central

    Zoodsma, M; Nolte, I; Schipper, M; Oosterom, E; van der Steege, G; de Vries, E G E; te Meerman, G J; van der Zee, A G J

    2005-01-01

    Background: Infection with human papillomavirus (HPV) is the main cause of cervical cancer and its precursor lesion, cervical intraepithelial neoplasia (CIN). Variability in host immunogenetic background is important in determining the overall cellular immune response to HPV infections. Objective: To determine whether the HLA-DQ or HLA-DR genes, or others in their vicinity, are associated with cervical cancer. Methods: Markers covering the entire HLA region were genotyped in a large sample of CIN and cervical cancer patients and in controls (311 CIN, 695 cervical cancer, 115 family controls, and 586 unrelated controls). Results: Two markers were associated with susceptibility to cervical neoplasia, G511525 and MICA. G511525, close to the region containing the HLA-DQ and HLA-DR genes, was most strongly associated, showing a decrease in frequency of allele 221 from 6.7% to 3.3% in patients with squamous cell cancer (SCC). An association was found for MICA (allele 184) with SCC (odds ratio (OR) = 1.31 (95% confidence interval, 1.13 to 1.53); homozygotes, OR = 1.48 (1.06 to 2.06)). No associations were observed with adenocarcinoma or CIN. Conclusions: There is an association of the region containing the HLA-DQ and HLA-DR genes with the risk of developing squamous cell carcinoma. An increased risk was observed for carriers of allele 184 at the MICA locus, in particular for homozygotes, suggesting a recessive effect. PMID:16061555

  19. Lobaplatin arrests cell cycle progression, induces apoptosis and alters the proteome in human cervical cancer cell Line CaSki.

    PubMed

    Li, Xiaoqin; Ran, Li; Fang, Wen; Wang, Donghong

    2014-04-01

    Cervical cancer is one of the most common gynecologic tumors. There is an upward trend in the incidence. The objective of this research was to explore the effect of lobaplatin on cervical cancer CaSki cells proliferation, cell cycle and apoptosis and analysis of the differential expressed proteins of CaSki cells after exposed to lobaplatin. Our findings have shown that lobaplatin inhibits cell proliferations in human cervical cancer CaSki cells in dose- and time-dependent manner. Flow cytometry assay confirmed that lobaplatin affected cervical cancer cell survival by blocking cell cycle progression in S phase and G0/G1 phase and inducing apoptosis in dose- and time-dependent manner. Lobaplatin treatment reduced polypyrimidine tract-binding protein 2, ribose-phosphate pyrophosphokinase, hypothetical protein, terminal uridylyltransferase 7, ubiquitin specific protease 16 and heterogeneous nuclear ribonucleoprotein A2/B1 expression and increase zinc finger protein 91, zinc finger protein, C-X-C motif chemokine 10 precursor, stromal cell protein and laminin subunit alpha-4 expression. Some of the differentially expressed proteins may be associated with antitumor effect of lobaplatin. Lobaplatin showed a good antitumour activity in in vitro models of human cervical cancer cells. These results indicate that lobaplatin could be an effective chemotherapeutic agent in human cervical cancer treatment by inducing apoptosis, cell cycle arrest and changing many kinds of protein molecule expression level.

  20. Cervical vertebral motions and biomechanical responses to direct loading of human head.

    PubMed

    Ono, Koshiro; Kaneoka, Koji; Hattori, Shinichiro; Ujihashi, Sadayuki; Takhounts, Eric G; Haffner, Mark P; Eppinger, Rolf H

    2003-06-01

    There is little known data characterizing the biomechanical responses of the human head and neck under direct head loading conditions. However, the evaluation of the appropriateness of current crash test dummy head-neck systems is easily accomplished. Such an effort, using experimental means, generates and provides characterizations of human head-neck response to several direct head loading conditions. Low-level impact loads were applied to the head and face of volunteers and dummies. The resultant forces and moments at the occipital condyle were calculated. For the volunteers, activation of the neck musculature was determined using electromyography (EMG). In addition, cervical vertebral motions of the volunteers have been taken by means of X-ray cineradiography. The Ethics Committee of Tsukuba University approved the protocol of the experiments in advance. External force of about 210 N was applied to the head and face of five volunteers with an average age of 25 for the duration of 100 msec or so, via a strap at one of four locations in various directions: (1) an upward load applied to the chin, (2) a rearward load applied to the chin without facial mask, (3) a rearward load applied to the chin with the facial mask, and (4) a rearward load applied to the forehead. The same impact force as those for the human volunteers was also applied to HY-III, THOR, and BioRID. We found that cervical vertebral motions differ markedly according to the difference in impact loading condition. Some particular characteristics are also found, such as the flexion or extension of the upper cervical vertebrae (C0, C1, and C2) or middle cervical vertebrae (C3-C4), showing that the modes of cervical vertebral motions are markedly different among the different loading conditions. We also found that the biofidelity of dummies to neck response characteristics of the volunteers at the low-level impact loads is in the order of BioRID, THOR, and HY-III. It is relevant in this regard that the

  1. CLDN1 expression in cervical cancer cells is related to tumor invasion and metastasis

    PubMed Central

    Wang, Xiao-li; Hu, Zheng; Zhu, Da; Ding, Wen-cheng; Liu, Dan; Li, Ke-zhen; Ma, Ding; Wang, Hui

    2016-01-01

    Even though infection with human papillomaviruses (HPV) is very important, it is not the sole cause of cervical cancer. Because it is known that genetic variations that result from HPV infection are probably the most important causes of cervical cancer, we used human whole genome array comparative genomic hybridization to detect the copy number variations of genes in cervical squamous cell carcinoma. The results of the array were validated by PCR, FISH and immunohistochemistry. We find that the copy number and protein expression of claudin-1 (CLDN1) increase with the progression of cervical cancer. The strong positive staining of CLDN1 in the cervical lymph node metastasis group received a significantly higher score than the staining in the group with no lymph node metastasis of cervical cancer tissues. The overexpression of CLDN1 in SiHa cells can increase anti-apoptosis ability and promote invasive ability of these cells accompanied by a decrease in expression of the epithelial marker E-cadherin as well as an increase in the expression of the mesenchymal marker vimentin. CLDN1 induces the epithelial-mesenchymal transition (EMT) through its interaction with SNAI1. Furthermore, we demonstrate that CLDN1 overexpression has significant effects on the growth and metastasis of xenografted tumors in athymic mice. These data suggest that CLDN1 promotes invasion and metastasis in cervical cancer cells via the expression of EMT/invasion-related genes. Therefore, CLDN1 could be a potential therapeutic target for the treatment of cervical cancer. PMID:27974683

  2. Lack of association between serum 25-hydroxyvitamin D levels and cervical human papillomavirus infection in systemic lupus erythematosus.

    PubMed

    García-Carrasco, M; Mendoza-Pinto, C; Munguía-Realpozo, P; Rodríguez-Gallegos, A; Vallejo-Ruiz, V; Muñoz-Guarneros, M; Méndez-Martínez, S; Soto-Santillán, P; Pezzat-Said, E; Reyes-Leyva, J; López-Colombo, A; Ruiz-Argüelles, A; Cervera, R

    2015-05-01

    Our objective was to evaluate whether vitamin D deficiency is associated with cervical human papilloma virus (HPV) infection in women with SLE. This is a cross-sectional study of 67 women with SLE. A structured questionnaire was administered to ascertain the possible risk factors associated with cervical HPV infection. A gynaecological evaluation and cervical cytology screening were made. HPV detection and genotyping was made by PCR and linear array assay. Serum 25 hydroxyvitamin D levels were quantified by chemiluminescence immunoassay. Mean age and disease duration were 44.8 ± 10.6 and 42.5 ± 11.8 years, respectively. Demographic characteristics were similar in patients with and without deficiency (<20 ng/ml and ≥20 ng/ml). There were 28.4% of women with cervical HPV infection and 68.4% had high-risk HPV infections. Patients with 25 hydroxyvitamin D levels <20 ng/ml had a higher prevalence of cervical HPV infection than those with levels ≥20 ng/ml (30.7% vs. 25.8%; p = 0.72). We found no significant difference when high-risk HPV infection was evaluated (36.8% vs. 31.5%; p = 0.73). In conclusion, women with SLE have a high prevalence of vitamin D deficiency and cervical HPV infection. However, we found no association between vitamin D deficiency and cervical HPV.

  3. O-linked N-acetylglucosamine transferase promotes cervical cancer tumorigenesis through human papillomaviruses E6 and E7 oncogenes

    PubMed Central

    Kang, Min Young; Park, Jeongsook; Lee, Dong Hoon; Roh, Gu Seob; Kim, Hyun Joon; Kang, Sang Soo; Cho, Gyeong Jae; Park, Ji Kwon; Cho, Jin Won; Shin, Jeong Kyu; Choi, Wan Sung

    2016-01-01

    O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) increases O-GlcNAc modification (O-GlcNAcylation), and transcriptional co-regulator host cell factor 1 (HCF-1) is one of OGT targets. High-risk Human Papillomaviruses (HPVs) encode E6 and E7 oncoproteins, which promote cervical cancer. Here, we tested whether O-GlcNAc modification of HCF-1 affects HPV E6 and E7 expressions and tumorigenesis of cervical cancer. We found that depleting OGT with OGT-specific shRNA significantly decreased levels of E6 and E7 oncoproteins, and cervical cancer tumorigenesis, while OGT overexpression greatly increased levels of E6 and E7 oncoproteins. Notably, OGT overexpression caused dose-dependent increases in the transcriptional activity of E6 and E7, and this activity was decreased when HCF-1 was depleted with HCF-1-specific siRNA. Moreover, OGT depletion reduced proliferation, invasion, and metastasis in cervical cancer cells. Further, high glucose enhanced the interaction between OGT and HCF-1, paralleling increased levels of E6 and E7 in cervical cancer cells. Most importantly, we found that reducing OGT in HeLa cells caused decreased tumor growth in vivo. These findings identify OGT as a novel cellular factor involved in E6 and E7 expressions and cervical cancer tumorigenesis, suggesting that targeting OGT in cervical cancer may have potential therapeutic benefit. PMID:27331873

  4. O-linked N-acetylglucosamine transferase promotes cervical cancer tumorigenesis through human papillomaviruses E6 and E7 oncogenes.

    PubMed

    Kim, Minjun; Kim, Yoon Sook; Kim, Hwajin; Kang, Min Young; Park, Jeongsook; Lee, Dong Hoon; Roh, Gu Seob; Kim, Hyun Joon; Kang, Sang Soo; Cho, Gyeong Jae; Park, Ji Kwon; Cho, Jin Won; Shin, Jeong Kyu; Choi, Wan Sung

    2016-07-12

    O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) increases O-GlcNAc modification (O-GlcNAcylation), and transcriptional co-regulator host cell factor 1 (HCF-1) is one of OGT targets. High-risk Human Papillomaviruses (HPVs) encode E6 and E7 oncoproteins, which promote cervical cancer. Here, we tested whether O-GlcNAc modification of HCF-1 affects HPV E6 and E7 expressions and tumorigenesis of cervical cancer. We found that depleting OGT with OGT-specific shRNA significantly decreased levels of E6 and E7 oncoproteins, and cervical cancer tumorigenesis, while OGT overexpression greatly increased levels of E6 and E7 oncoproteins. Notably, OGT overexpression caused dose-dependent increases in the transcriptional activity of E6 and E7, and this activity was decreased when HCF-1 was depleted with HCF-1-specific siRNA. Moreover, OGT depletion reduced proliferation, invasion, and metastasis in cervical cancer cells. Further, high glucose enhanced the interaction between OGT and HCF-1, paralleling increased levels of E6 and E7 in cervical cancer cells. Most importantly, we found that reducing OGT in HeLa cells caused decreased tumor growth in vivo. These findings identify OGT as a novel cellular factor involved in E6 and E7 expressions and cervical cancer tumorigenesis, suggesting that targeting OGT in cervical cancer may have potential therapeutic benefit.

  5. Role of human papillomavirus in oral squamous cell carcinoma and oral potentially malignant disorders: A review of the literature

    PubMed Central

    Gupta, Shikha; Gupta, Sunita

    2015-01-01

    Human papillomaviruses (HPVs) are epitheliotropic viruses with an affinity for keratinocytes and are principally found in the anogenital tract, urethra, skin, larynx, tracheobronchial and oral mucosa. On the basis of high, but variable frequency of HPV in oral squamous cell carcinoma (OSCC), malignant potential of HPV infection has been hypothesized but not definitely confirmed. The aim of this review was to highlight the genomic structure and possible mechanism of infection and carcinogenesis by HPV in the oral mucosa and to review the frequency of HPV prevalence in OSCC and oral potentially malignant disorders. A computer database search was performed through the use of PubMed from 1994 to 2014. Search keywords used were: HPV and oral cancer, HPV and oral leukoplakia, HPV and oral lichen planus, HPV and OSCC, HPV and verrucous carcinoma, HPV and proliferative verrucous leukoplakia, HPV and oral papilloma. PMID:26097339

  6. The transmembrane channel-like protein family and human papillomaviruses: Insights into epidermodysplasia verruciformis and progression to squamous cell carcinoma.

    PubMed

    Horton, Jaime S; Stokes, Alexander J

    2014-01-01

    Epidermodysplasia verruciformis (EV) is a rare genodermatosis characterized by increased sensitivity to infection by the β-subtype of human papillomaviruses (β-HPVs), causing persistent, tinea versicolor-like dermal lesions. In a majority of affected individuals, these macular lesions progress to invasive cutaneous squamous cell carcinoma (CSCC) in sun-exposed areas. While mutations in transmembrane channel-like 6 (TMC6 / EVER1) and 8 (TMC8 / EVER2) have been causally linked to EV, their molecular functions are unclear. It is likely that their protective effects involve regulation of the β-HPV life cycle, host keratinocyte apoptosis vs. survival balance and/or T-cell interaction with infected host cells.

  7. Proteomic analysis of cellular response induced by boron neutron capture reaction in human squamous cell carcinoma SAS cells.

    PubMed

    Sato, Akira; Itoh, Tasuku; Imamichi, Shoji; Kikuhara, Sota; Fujimori, Hiroaki; Hirai, Takahisa; Saito, Soichiro; Sakurai, Yoshinori; Tanaka, Hiroki; Nakamura, Hiroyuki; Suzuki, Minoru; Murakami, Yasufumi; Baiseitov, Diaz; Berikkhanova, Kulzhan; Zhumadilov, Zhaxybay; Imahori, Yoshio; Itami, Jun; Ono, Koji; Masunaga, Shinichiro; Masutani, Mitsuko

    2015-12-01

    To understand the mechanism of cell death induced by boron neutron capture reaction (BNCR), we performed proteome analyses of human squamous tumor SAS cells after BNCR. Cells were irradiated with thermal neutron beam at KUR after incubation under boronophenylalanine (BPA)(+) and BPA(-) conditions. BNCR mainly induced typical apoptosis in SAS cells 24h post-irradiation. Proteomic analysis in SAS cells suggested that proteins functioning in endoplasmic reticulum, DNA repair, and RNA processing showed dynamic changes at early phase after BNCR and could be involved in the regulation of cellular response to BNCR. We found that the BNCR induces fragments of endoplasmic reticulum-localized lymphoid-restricted protein (LRMP). The fragmentation of LRMP was also observed in the rat tumor graft model 20 hours after BNCT treatment carried out at the National Nuclear Center of the Republic of Kazakhstan. These data suggest that dynamic changes of LRMP could be involved during cellular response to BNCR.

  8. C6-pyridinium ceramide sensitizes SCC17B human head and neck squamous cell carcinoma cells to photodynamic therapy

    PubMed Central

    Boppana, Nithin B.; Stochaj, Ursula; Kodiha, Mohamed; Bielawska, Alicja; Bielawski, Jacek; Pierce, Jason S.; Korbelik, Mladen; Separovic, Duska

    2015-01-01

    Combining photodynamic therapy (PDT)1 with another anticancer treatment modality is an important strategy for improved efficacy. PDT with Pc4, a silicon phthalocyanine photosensitizer, was combined with C6-pyridinium ceramide (LCL29) to determine their potential to promote death of SCC17B human head and neck squamous cell carcinoma cells. PDT+LCL29-induced enhanced cell death was inhibited by zVAD-fmk, a pan-caspase inhibitor, and fumonisin B1 (FB), a ceramide synthase inhibitor. Quantitative confocal microscopy showed that combining PDT with LCL29 enhanced FB-sensitive ceramide accumulation in the mitochondria. Furthermore, PDT+LCL29 induced enhanced FB-sensitive redistribution of cytochrome c and caspase-3 activation. Overall, the data indicate that PDT+LCL29 enhanced cell death via FB-sensitive, mitochondrial ceramide accumulation and apoptosis. PMID:25635908

  9. C6-pyridinium ceramide sensitizes SCC17B human head and neck squamous cell carcinoma cells to photodynamic therapy.

    PubMed

    Boppana, Nithin B; Stochaj, Ursula; Kodiha, Mohamed; Bielawska, Alicja; Bielawski, Jacek; Pierce, Jason S; Korbelik, Mladen; Separovic, Duska

    2015-02-01

    Combining photodynamic therapy (PDT) with another anticancer treatment modality is an important strategy for improved efficacy. PDT with Pc4, a silicon phthalocyanine photosensitizer, was combined with C6-pyridinium ceramide (LCL29) to determine their potential to promote death of SCC17B human head and neck squamous cell carcinoma cells. PDT+LCL29-induced enhanced cell death was inhibited by zVAD-fmk, a pan-caspase inhibitor, and fumonisin B1 (FB), a ceramide synthase inhibitor. Quantitative confocal microscopy showed that combining PDT with LCL29 enhanced FB-sensitive ceramide accumulation in the mitochondria. Furthermore, PDT+LCL29 induced enhanced FB-sensitive redistribution of cytochrome c and caspase-3 activation. Overall, the data indicate that PDT+LCL29 enhanced cell death via FB-sensitive, mitochondrial ceramide accumulation and apoptosis.

  10. Screening and identification of distant metastasis-related differentially expressed genes in human squamous cell lung carcinoma.

    PubMed

    Wang, Na; Zhou, Fachen; Xiong, Hai; Du, Sha; Ma, Jianwei; Okai, Issac; Wang, Jian; Suo, Jing; Hao, Lihong; Song, Yang; Hu, Jun; Shao, Shujuan

    2012-05-01

    Distant metastasis is one of the leading causes of lung cancer death. Detecting the early-stage molecular alternations in primary tumors, such as gene expression differences, provides a "prognostic" value to the precaution of tumor metastasis. The aim of this article is to screen and identify the metastasis-related genes in human squamous cell lung carcinoma. Primary tumor tissues of nine patients with subsequent metastasis and eight patients without metastasis were selected to perform the gene microarray experiment. GO and pathway analyses were used to determine the differentially expressed genes. Two identified genes were further validated by real-time quantitative reverse transcription polymerase chain reaction (PCR) (real-time qRT-PCR). Two hundred and thirty-eight differentially expressed genes were detected in gene chip experiment, including 51 up-regulated genes and 187 down-regulated genes. These genes were involved in several cellular processes, including cell adhesion, cell cycle regulation, and apoptosis. GO analysis showed that the differentially expressed genes participated in a wide ranging of metastasis-related processes, including extracellular region and regulation of liquid surface tension. In addition, pathway analysis demonstrated that the differentially expressed genes were enriched in pathways related to cell cycle and Wnt signaling. Real-time qRT-PCR validation experiment of LCN2 and PDZK1IP1 showed a consistent up-regulation in the metastasis group. The metastasis of human squamous cell lung carcinoma is a complex process that is regulated by multiple gene alternations on the expression levels. The 238 differentially expressed genes identified in this study presumably contain a core set of genes involved in tumor metastasis. The real-time qRT-PCR results of PDZK1IP1 and LCN2 validated the reliability of this gene microarray experiment.

  11. Human Papillomavirus (HPV) Type Distribution in Females with Abnormal Cervical Cytology. A Correlation with Histological Study

    PubMed Central

    Cobo, Fernando; Concha, Ángel; Ortiz, Marta

    2009-01-01

    The aim of this study was to determine human papillomavirus (HPV) types distribution in cervical preneoplasic lesions in a Southern Spanish population and their relationship between HPV type and grade of histopathological abnormality. Finally, 232 cervical samples from 135 women with previous cytological abnormalities were included in this study. Colposcopy studies and biopsies were performed. Haematoxylin-eosin stained slides were observed and detection of HPV DNA in cervical swabs was carried out with use of a polymerase chain reaction and microarrays technology. The relationship between the presence of HPV infection and diagnostic variables was evaluated. HPV 16 was the most common type followed by HPV 58, 51, 33 and 31. However, the two HPV types targeted in the prophylactic vaccines such as HPV type 16 and 18 were detected in only 37 (21.2%) and 2 (1.1%) cases respectively. Thirty-three (18.9%) of samples were infected with multiple types, the majority of them with two types. In addition, during the follow-up of patients many changes in type distribution were observed. Several studies will be necessary in order to evaluate the HPV type distribution for therapeutically and prophylactic purposes such as vaccine treatment. Also, because of the differences obtained depending of use of various DNA technologies, the performance of some comparative studies of the different methods from detection of HPV would be advisable in a high population of patients and with the most homogeneous conditions possible. PMID:19750125

  12. Amygdalin induces apoptosis in human cervical cancer cell line HeLa cells.

    PubMed

    Chen, Yu; Ma, Jinshu; Wang, Fang; Hu, Jie; Cui, Ai; Wei, Chengguo; Yang, Qing; Li, Fan

    2013-02-01

    Amygdalin, a naturally occurring substance, has been suggested to be efficacious as an anticancer substance. The effect of amygdalin on cervical cancer cells has never been studied. In this study, we found that the viability of human cervical cancer HeLa cell line was significantly inhibited by amygdalin. 4,6-Diamino-2-phenyl indole (DAPI) staining showed that amygdalin-treated HeLa cells developed typical apoptotic changes. The development of apoptosis in the amygdalin-treated HeLa cells were confirmed by double staining of amygdalin-treated HeLa cells with annexin V-FITC and propidium iodide (PI) along with increase in caspase-3 activity in these cells. Further studies indicated that antiapoptotic protein Bcl-2 was downregulated whereas proapoptotic Bax protein was upregulated in the amygdalin-treated HeLa cells implying involvement of the intrinsic pathway of apoptosis. In vivo, amygdalin administration inhibited the growth of HeLa cell xenografts through a mechanism of apoptosis. The results in the present study suggest that amygdalin may offer a new therapeutic option for patients with cervical cancer.

  13. Achieving effective cervical screening coverage in South Africa through human resources and health systems development.

    PubMed

    Kawonga, Mary; Fonn, Sharon

    2008-11-01

    South Africa's cervical screening policy recommends three free Pap smears at ten-year intervals for all women over 30 years of age, aiming to achieve 70% coverage by 2010 by targeting the age group most at risk of developing pre-cancerous cervical lesions. Attaining wide coverage requires an adequate supply of motivated and supported public sector health workers with appropriate training and skills, working in a functional health system. Given the dearth of doctors in South Africa, professional nurses were tasked with performing the bulk of Pap smears at primary care level. Coverage remains sub-optimal and a significant proportion of women with precursor lesions do not receive treatment. Further, health system strengthening - essential for cytology-based screening - has not happened. Research to evaluate alternative screening technologies has proliferated in recent years, but regrettably, strengthening of the health system required to make the new technology work has not received similar attention. Using the South African experience, this article argues that technological interventions and innovations alone are not sufficient to improve cervical screening programmes. Task-shifting is limited unless other human resource concerns (e.g. training, increasing demands on personnel, attrition, and skills mix) are concurrently addressed within a comprehensive workforce development strategy, alongside work to make the health care delivery system functional.

  14. Human papillomavirus prevalence, cervical abnormalities and risk factors among female sex workers in Lima, Peru

    PubMed Central

    Brown, B; Blas, M M; Cabral, A; Byraiah, G; Guerra-Giraldez, C; Sarabia-Vega, V; Carcamo, C; Gravitt, P E; Halsey, N A

    2015-01-01

    Summary Female sex workers (FSWs) are at high risk of human papillomavirus (HPV) infection. Questionnaires were administered to 200 FSWs aged 18–26 years in Lima, Peru, to gather risk behaviours, and cervical swab samples were collected for Pap smears and HPV DNA testing as part of a longitudinal study. Participants reported a median of 120 clients in the past month, and 99.2% reported using condoms with clients. The prevalence of any HPV in cervical samples was 66.8%; 34 (17.1%) participants had prevalent HPV 16 or 18, and 92 (46.2%) had one or more oncogenic types. Fifteen women had abnormal Pap smears, 13 of which were HPV DNA positive. Fewer years since first sex was associated with oncogenic HPV prevalence in a model adjusted for previous sexually transmitted infection (STI) status and condom use with partners (prevalence ratio = 0.77, 95% confidence interval [CI] = 0.60–0.97). Our data confirm the high rates of HPV transmission among FSWs in Peru, highlighting the need for early and effective strategies to prevent cervical cancer. PMID:22581946

  15. Human papillomavirus prevalence, cervical abnormalities and risk factors among female sex workers in Lima, Peru.

    PubMed

    Brown, B; Blas, M M; Cabral, A; Byraiah, G; Guerra-Giraldez, C; Sarabia-Vega, V; Carcamo, C; Gravitt, P E; Halsey, N A

    2012-04-01

    Female sex workers (FSWs) are at high risk of human papillomavirus (HPV) infection. Questionnaires were administered to 200 FSWs aged 18-26 years in Lima, Peru, to gather risk behaviours, and cervical swab samples were collected for Pap smears and HPV DNA testing as part of a longitudinal study. Participants reported a median of 120 clients in the past month, and 99.2% reported using condoms with clients. The prevalence of any HPV in cervical samples was 66.8%; 34 (17.1%) participants had prevalent HPV 16 or 18, and 92 (46.2%) had one or more oncogenic types. Fifteen women had abnormal Pap smears, 13 of which were HPV DNA positive. Fewer years since first sex was associated with oncogenic HPV prevalence in a model adjusted for previous sexually transmitted infection (STI) status and condom use with partners (prevalence ratio = 0.77, 95% confidence interval [CI] = 0.60-0.97). Our data confirm the high rates of HPV transmission among FSWs in Peru, highlighting the need for early and effective strategies to prevent cervical cancer.

  16. Human papillomavirus types 16 and 18 and the prognosis of patients with stage I cervical cancer

    PubMed Central

    de Araújo Catão Zampronha, Rossana; Freitas-Junior, Ruffo; Murta, Eddie Fernando Candido; Michelin, Márcia Antoniazi; Barbaresco, Aline Almeida; Adad, Sheila Jorge; de Oliveira, Amaurillo Monteiro; Rassi, Amanda B.; Oton, Glória Jabur Bittar

    2013-01-01

    OBJECTIVE: This study sought to evaluate the prevalence of human papillomavirus (HPV) types 16 and 18 in women with clinical stage IB cervical cancer treated by radical hysterectomy with pelvic lymphadenectomy as well as to establish a correlation between HPV type and cancer prognosis. METHODS: A single-center cohort study was conducted with 86 patients who had undergone radical hysterectomy for stage I cervical cancer. Prognostic factors and the presence of HPV 16 and 18 were analyzed using a polymerase chain reaction assay. A univariate analysis using Kaplan-Meier curves was conducted to estimate survival. RESULTS: The prevalence of HPV 16 in the study group was 65.3%, and the prevalence of HPV 18 was 33.3%. The prevalence of infection with both viruses was 26.9%. Overall survival at 5 years was 91% among women with HPV 18 and 96% among those without this virus type (p = 0.133). Among the women with HPV 16, the overall survival was 94%, whereas this rate was 96% among those without this virus type (p = 0.663). Disease-free survival was unaffected by the presence of HPV type 16 or 18. CONCLUSION: In the present study, despite the high prevalence of HPV types 16 and 18, the presence of these virus types did not affect the prognosis of patients with stage I cervical cancer who underwent radical hysterectomy. PMID:23778490

  17. Human papillomavirus infection and immunohistochemical p16(INK4a) expression as predictors of outcome in penile squamous cell carcinomas.

    PubMed

    Bezerra, Stephania M; Chaux, Alcides; Ball, Mark W; Faraj, Sheila F; Munari, Enrico; Gonzalez-Roibon, Nilda; Sharma, Rajni; Bivalacqua, Trinity J; Burnett, Arthur L; Netto, George J

    2015-04-01

    Approximately 50% of penile squamous cell carcinomas (SCC) are associated with high-risk human papillomavirus (HR-HPV) infection. We evaluated the correlation of p16(INK4a) expression and HR-HPV with clinicopathological features and outcome in a cohort of patients with penile SCC. Two tissue microarrays were constructed from 53 invasive penile SCC at our hospital. p16(INK4a) expression was assessed by immunohistochemistry (CINtec Kit). High-risk human papillomavirus status was assessed by in situ hybridization (INFORM HPV III family 16 probe B cocktail). High-risk human papillomavirus was detected in 8 cases (15%), and p16(INK4a) overexpression was found in 23 cases (44%). Both markers showed a significant association with histologic subtype (P = .017 and P = .01, respectively) and lymphovascular invasion (P = .015 and P = .015, respectively). Regarding outcome analyses, neither HPV infection nor p16(INK4a) overexpression significantly predicted overall survival or cancer-specific survival using Cox proportional hazards regression model. High-risk human papillomavirus positivity and p16(INK4a) overexpression were significantly associated with histologic subtype and presence of lymphovascular invasion. Human papillomavirus status was not predictive of outcome in our cohort.

  18. Prevalence of Human Papillomavirus Type 58 in Women With or Without Cervical Lesions in Northeast Brazil

    PubMed Central

    Fernandes, JV; Carvalho, MGF; de Fernandes, TAAM; Araújo, JMG; Azevedo, PRM; Azevedo, JCV; Meissner, RV

    2013-01-01

    Background: Human papillomavirus (HPV) has been recognized as a necessary, but not sufficient, cause of cervical cancer. Aim: In this study, we investigated the prevalence of HPV and the genotype distribution in women from Natal, North-East Brazil, with normal cytology and with cervical lesions of different degrees. Subjects and Methods: Included in this study were 110 women with a normal cytology and 315 with a previous history of cervical cytological abnormalities. The patients were enrolled between January 2005 and December 2008. The cytopathological analyzes were performed by the Pap smear exam, and the pre-malignant and maligant lesions were confirmed based on the histopathological analysis. The presence of HPV was detected by polymerase chain reaction with genotyping by dot blot hybridization. All the data were included in a database, using the software SPSS, Version 10.0 (Chicago Il, USA). Results: Overall HPV prevalence was 65.2% (277/425), with 85.9% (238/277) single and 14.1% (39/277) multiple infection. The most prevalent HPV types were HPVs 16, 58, 18, 31, and 45. HPV 16 was the most prevalent genotype, independently of the health status of patients. HPV 58 was the second most prevalent type in women with normal cytology and in those who had mild or moderate dysplasia. HPV 58 presented equal prevalence to HPV 18 in patients with severe dysplasia. However, it was less prevalent than HPV 18 in women with cervical cancer. Conclusions: The results show a high prevalence of HPV 58, especially in women with mild and moderate dysplasia, revealing the high-frequency circulation of this genotype of HPV in the local population. This finding suggests the need to include this genotype in future HPV vaccines targeting women in this region. PMID:24379999

  19. Use of primary high-risk human papillomavirus testing for cervical cancer screening: interim clinical guidance.

    PubMed

    Huh, Warner K; Ault, Kevin A; Chelmow, David; Davey, Diane D; Goulart, Robert A; Garcia, Francisco A R; Kinney, Walter K; Massad, L Stewart; Mayeaux, Edward J; Saslow, Debbie; Schiffman, Mark; Wentzensen, Nicolas; Lawson, Herschel W; Einstein, Mark H

    2015-02-01

    In 2011, the American Cancer Society, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology updated screening guidelines for the early detection of cervical cancer and its precursors. Recommended screening strategies were cytology or cotesting (cytology in combination with high-risk human papillomavirus [hrHPV] testing). These guidelines also addressed the use of hrHPV testing alone as a primary screening approach, which was not recommended for use at that time. There is now a growing body of evidence for screening with primary hrHPV testing, including a prospective U.S.-based registration study. Thirteen experts, including representatives from the Society of Gynecologic Oncology, the American Society for Colposcopy and Cervical Pathology, the American College of Obstetricians and Gynecologists, the American Cancer Society, the American Society of Cytopathology, the College of American Pathologists, and the American Society for Clinical Pathology, convened to provide interim guidance for primary hrHPV screening. This guidance panel was specifically triggered by an application to the U.S. Food and Drug Administration (FDA) for a currently marketed HPV test to be labeled for the additional indication of primary cervical cancer screening. Guidance was based on literature review and review of data from the FDA registration study, supplemented by expert opinion. This document aims to provide information for health care providers who are interested in primary hrHPV testing and an overview of the potential advantages and disadvantages of this strategy for screening as well as to highlight areas in need of further investigation.

  20. RBBP6: a potential biomarker of apoptosis induction in human cervical cancer cell lines

    PubMed Central

    Moela, Pontsho; Motadi, Lesetja Raymond

    2016-01-01

    Overexpression of RBBP6 in cancers of the colon, lung, and esophagus makes it a potential target in anticancer therapy. This is especially important because RBBP6 associates with the tumor suppressor gene p53, the inactivation of which has been linked to over 50% of all cancer types. However, the expression of RBBP6 in cancer and its interaction with p53 are yet to be understood in order to determine whether or not RBBP6 is cancer promoting and therefore a potential biomarker. In this study, we manipulated RBBP6 expression levels followed by treatment with either camptothecin or γ-aminobutyric acid in cervical cancer cells to induce apoptosis or cell cycle arrest. We began by staining human cervical cancer tissue sections with anti-RBBP6 monoclonal antibody to evaluate the extent of expression of RBBP6 in patients’ specimens. We followed on with silencing the overexpression of RBBP6 and treatment with anticancer agents to evaluate how the specimens respond to combinational therapy. Apoptosis induction was evaluated through confocal microscope, and flow cytometry using annexin V staining, and also by checking the mitochondrial and caspase-3/7 activity. Cell cycle arrest was evaluated using flow cytometry through staining with propidium iodide. RBBP6 was highly expressed in cervical cancer tissue sections that were in stage II or III of development. Silencing RBBP6 followed by treatment with γ-aminobutyric acid and camptothecin seems to sensitize cells to apoptosis induction rather than cell cycle arrest. Overexpression of RBBP6 seems to promote S-phase in cell cycle and cell proliferation. These results predict a proliferative role of RBBP6 in cancer progression rather than as a cancer-causing gene. Furthermore, sensitization of cells to camptothecin-induced apoptosis by RBBP6 targeting suggests a promising tool for halting cervical cancer progression. PMID:27536134

  1. [Cost effectiveness of human papilloma virus testing in cervical cancer screening: a literature review].

    PubMed

    Mejía, Aurelio; Salas, Walter

    2008-03-01

    Human papilloma virus DNA testing may improve the cost effectiveness of cervical cancer screening programs. However, the circumstances to get this improvement are not the same between countries. The objective of this paper is to evaluate the cost effectiveness of introducing human papilloma virus testing in the current screening practice both in developed and developing countries. We conducted a review of published articles since January 2000 until December 2006 related to the cost effectiveness of introducing human papilloma virus testing in cervical cancer screening programs. A total of 17 original researches and six reviews were analyzed. Human papilloma virus testing is cost effective in developed countries only if it is a complementary test to Pap test and used to determine the management of women with atypical squamus cells of undetermined significance, the interval among tests is increased more than two years and it is performed in women over 30 years. On the other hand, developing countries should establish first organized screening programs and guarantee full coverage and access to diagnosis and treatment.

  2. Trials and projects on cervical cancer and human papillomavirus prevention in sub-Saharan Africa.

    PubMed

    Adefuye, Peter O; Broutet, Nathalie J; de Sanjosé, Silvia; Denny, Lynette A

    2013-12-29

    Cervical cancer is the leading cause of cancer morbidity and mortality in women in sub-Saharan Africa (SSA), accounting for about 50,000 deaths annually. Until recently, cytology was the gold standard for screening and prevention of cervical cancer. This method of screening has not been successful in SSA due to a lack of human, financial and material resources and poor health care infrastructure. It is estimated that less than 5% of at risk women have ever being screened. In the past two decades alternative approaches to cytology for cervical cancer screening have been evaluated in low- and medium-income countries. Visual inspection with acetic acid (VIA) and/or Lugol's iodine (VILI) have been shown to have adequate sensitivity, although low specificity, in a number of cross-sectional research and demonstration projects. Visual inspection methods require minimal resources, are technologically accessible, and are feasible for screening for precancerous lesions. Linking screening with VIA/VILI to treatment with cryotherapy may enable screening and treatment to take place in one visit, but this is likely to result in large numbers of women being subjected to unnecessary treatment. A number of studies have shown that cryotherapy is not associated with significant side effects or complications and is well tolerated. Creating the infrastructure for screening of older women is considered desirable, despite the limitations of visual inspection methods as screening tests. Understanding the role of human papillomavirus (HPV) infection in the etiology of cervical cancer and the discovery of HPV rapid test kits, as well as the development of vaccines against the HPV oncogenic types, have created new opportunities for prevention of cervical cancer. Trials and projects have established (and are still ongoing) the feasibility of using these molecular tests for screening. The ultimate in prevention method is primary prevention, offered by the advent of prophylactic vaccines

  3. Crinane alkaloids of the amaryllidaceae with cytotoxic effects in human cervical adenocarcinoma (HeLa) cells.

    PubMed

    Nair, Jerald J; Rárová, Lucie; Strnad, Miroslav; Bastida, Jaume; Cheesman, Lee; van Staden, Johannes

    2014-04-01

    The family Amaryllidaceae has a long history of usage in the traditional medicinal practices of the indigenous peoples of South Africa, with three of its species known to be used for cancer treatment. Furthermore, the Amaryllidaceae is widely recognized for its unique alkaloid constituents, several of which exhibit potent and selective cytotoxic activities. In this study, several crinane alkaloids derived from local Amaryllidaceae species were examined for cytotoxic effects against the human cervical adenocarcinoma cell line, of which distichamine was the most potent (IC50 2.2 microM).

  4. Carbonic anhydrase IX (CA-IX) and human papillomavirus (HPV) as diagnostic biomarkers of cervical dysplasia/neoplasia in women with a cytologic diagnosis of atypical glandular cells (AGC): a Gynecologic Oncology Group (GOG) Study

    PubMed Central

    Liao, Shu-Yuan; Rodgers, William H.; Kauderer, James; Bonfiglio, Thomas A.; Walker, Joan L.; Darcy, Kathleen M.; Carter, Randy; Hatae, Masayuji; Levine, Lyuba; Spirtos, Nick M; Stanbridge, Eric J.

    2009-01-01

    High-risk human papillomavirus (H-HPV) infection is strongly linked to cervical neoplasia but its role in detecting glandular lesions is unclear. In the cervix, carbonic anhydrase IX (CA-IX) is expressed in cervical neoplasia, but rarely in the benign cervix. The diagnostic utility of these biomarkers was evaluated in women with a cytologic diagnosis of atypical glandular cells (AGC). H-HPV was detected using Hybrid Capture 2 (HC2) in liquid based cytology and CA-IX immunoreactivity was studied on conventional Pap smears. Of 403 patients, 111 (28%) were positive for significant cervical lesions (SCLs) including CIN2, CIN3, adenocarcinoma in situ or invasive carcinoma. CA-IX testing alone (n=403) had a sensitivity of 75%, 95%, or 65% for SCLs, significant glandular lesions (GLs) or squamous lesions (SLs), respectively, with a specificity of 88%, and a false negative rate (FNR defined as one minus negative predictive value) of 10%. Testing for H-HPV (n=122) had a sensitivity of 97%, 100%, or 96% for SCLs, GLs or SLs, respectively, with a specificity of 87%, and a FNRof 1%. The combination of CA-IX and H-HPV testing (n=122), collectively, had the same sensitivity, specificity and FNR for SCLs, GLs or SLs as H-HPV testing alone. The conclusions of this study are that both H-HPV and CA-IX testing are useful diagnostic markers for GLs. However, H-HPV testing is a better diagnostic marker for SLs. The combination of CA-IX with H-HPV testing does not improve the diagnostic accuracy for cervical neoplasia in women with AGC diagnosis over that of H-HPV testing alone. PMID:19670419

  5. Carbonic anhydrase IX and human papillomavirus as diagnostic biomarkers of cervical dysplasia/neoplasia in women with a cytologic diagnosis of atypical glandular cells: a Gynecologic Oncology Group study in United States.

    PubMed

    Liao, Shu-Yuan; Rodgers, William H; Kauderer, James; Bonfiglio, Thomas A; Walker, Joan L; Darcy, Kathleen M; Carter, Randy; Hatae, Masayuji; Levine, Lyuba; Spirtos, Nick M; Stanbridge, Eric J

    2009-11-15

    High-risk human papillomavirus (H-HPV) infection is strongly linked to cervical neoplasia, but its role in detecting glandular lesions (GLs) is unclear. In the cervix, carbonic anhydrase IX (CA-IX) is expressed in cervical neoplasia, but rarely in the benign cervix. The diagnostic utility of these biomarkers was evaluated in women with a cytologic diagnosis of atypical glandular cells (AGC). H-HPV was detected using hybrid capture 2 (HC2) in liquid-based cytology, and CA-IX immunoreactivity was studied on conventional Pap smears. Of 403 patients, 111 (28%) were positive for significant cervical lesions (SCLs) including CIN2, CIN3, adenocarcinoma in situ or invasive carcinoma. CA-IX testing alone (n = 403) had a sensitivity of 75, 95 or 65% for SCLs, significant GLs or squamous lesions (SLs), respectively, with a specificity of 88% and a false negative rate (FNR defined as 1 minus negative predictive value) of 10%. Testing for H-HPV (n = 122) had a sensitivity of 97, 100 or 96% for SCLs, GLs or SLs, respectively, with a specificity of 87% and a FNR of 1%. The combination of CA-IX and H-HPV testing (n = 122), collectively, had the same sensitivity, specificity and FNR for SCLs, GLs or SLs as H-HPV testing alone. The conclusions of our study are that both H-HPV and CA-IX testing are useful diagnostic markers for GLs. However, H-HPV testing is a better diagnostic marker for SLs. The combination of CA-IX with H-HPV testing does not improve the diagnostic accuracy for cervical neoplasia in women with AGC diagnosis over that of H-HPV testing alone.

  6. Mitomycin C in combination with radiotherapy as a potent inhibitor of tumour cell repopulation in a human squamous cell carcinoma

    PubMed Central

    Budach, W; Paulsen, F; Welz, S; Classen, J; Scheithauer, H; Marini, P; Belka, C; Bamberg, M

    2002-01-01

    The potential of Mitomycin C in combination with fractionated irradiation to inhibit tumour cell repopulation of a fast growing squamous cell carcinoma after fractionated radiotherapy was investigated in vivo. A rapidly growing human squamous cell carcinoma (FaDudd) was used for the study. For experiments, NMRI (nu/nu) mice with subcutaneously growing tumours were randomly allocated to no treatment, Mitomycin C, fractionated irradiation (ambient: 11x4.5 Gy in 15 days), or fractionated irradiation combined with Mitomycin C. Graded top up doses (clamped blood flow: 0–57 Gy) were given at day 16, 23, 30 or 37. End point of the study was the time to local tumour progression. Data were examined by multiple regression analysis (Cox). Mitomycin C alone resulted in a median time to local tumour progression of 23 (95% confidence limits: 17–43) days, fractionated irradiation in 31 (25–35) days and combined Mitomycin C plus fractionated irradiation in 65 (58–73) days (P=0.02). Mitomycin C decreased the relative risk of local recurrence by 94% (P<<0.001) equivalent to 31.7 Gy top up dose. Repopulation accounted for 1.33 (0.95–1.72) Gy per day top up dose after fractionated irradiation alone and for 0.68 (0.13–1.22) Gy per day after fractionated irradiation+Mitomycin C (P=0.018). Mitomycin C significantly reduces the risk of local recurrence and inhibits tumour cell repopulation in combination with fractionated irradiation in vivo in the tested tumour model. British Journal of Cancer (2002) 86, 470–476. DOI: 10.1038/sj/bjc/6600081 www.bjcancer.com © 2002 The Cancer Research Campaign PMID:11875717

  7. Human papillomavirus as prognostic marker with rising prevalence in neck squamous cell carcinoma of unknown primary: A retrospective multicentre study.

    PubMed

    Schroeder, Lea; Boscolo-Rizzo, Paolo; Dal Cin, Elisa; Romeo, Salvatore; Baboci, Lorena; Dyckhoff, Gerhard; Hess, Jochen; Lucena-Porcel, Carlota; Byl, Anne; Becker, Nikolaus; Alemany, Laia; Castellsagué, Xavier; Quer, Miquel; León, Xavier; Wiesenfarth, Manuel; Pawlita, Michael; Holzinger, Dana

    2017-03-01

    Patients with neck squamous cell carcinomas of unknown primary tumour (NSCCUP) present with lymph node metastasis without evidence for a primary tumour. Most patients undergo an aggressive multimodal treatment, which induces severe, potentially unnecessary toxicity. Primary tumours of NSCCUP can be hidden in the oropharynx. Human papillomavirus (HPV) is causally involved in a subgroup of oropharyngeal squamous cell carcinomas (OPSCC) associated with early lymph node metastasis and good prognosis. Detection of markers for HPV transformation in NSCCUP could allow focussing on the oropharynx in primary tumour search and could be of value for choice and extent of treatment. In a retrospective multicentre study (Germany, Italy and Spain), we analysed metastatic lymph nodes from 180 NSCCUP patients for the presence of HPV DNA, HPV E6*I mRNA and cellular p16(INK4a) overexpression, a surrogate marker for HPV-induced transformation. HPV status, defined as positivity for viral mRNA with at least one additional marker, was correlated with clinical parameters and survival outcome. A substantial proportion (16%) of NSCCUP were HPV-driven, mainly by HPV16 (89%). HPV prevalence increased with year of diagnosis from 9% during 1998-2004 to 23% during 2005-2014 (p = 0.007). HPV-driven NSCCUP had significantly better overall and progression-free survival rates (p ≤ 0.008). Based on this survival benefit, it is contended that HPV RNA status should be included in NSCCUP diagnosis and in therapeutic decision-making. Deintensification of radiation in patients with HPV-driven NSCCUP, while concurrently concentrating on the oropharynx appears to be a promising therapeutic strategy, the efficacy of which should be assessed in prospective trials. To our knowledge, this is the largest study on HPV in NSCCUP.

  8. Prevalence and clinical features of human papillomavirus in head and neck squamous cell carcinoma in Okinawa, southern Japan.

    PubMed

    Deng, Zeyi; Hasegawa, Masahiro; Matayoshi, Sen; Kiyuna, Asanori; Yamashita, Yukashi; Maeda, Hiroyuki; Suzuki, Mikio

    2011-11-01

    Previous studies from Okinawa, a subtropical island in southern Japan, demonstrated a higher prevalence of human papillomavirus (HPV) in oral carcinoma and a higher incidence of oral and pharyngeal carcinoma than those for mainland Japan. The present study aims to investigate epidemiologic and clinical features of HPV in head and neck squamous cell carcinoma (HNSCC) in Okinawa. A total of 150 DNA samples from 150 Okinawan patients with head and neck squamous cell carcinoma (HNSCC) were screened for HPV sequences by PCR using three consensus primer sets, and HPV types were determined by direct sequencing. The samples were consisted of 46 cases from the hypopharynx, 44 from the oropharynx, 16 from the larynx, 25 from the oral cavity, 10 from the maxillary sinus, and 9 from the nasopharynx. HPV DNA was detected in 45 (30.0%) HNSCCs, and HPV-16 was identified in 86.7% of positive specimens. The highest prevalence of the HPV sequence was found in oropharyngeal carcinomas (50.0%), especially in tonsillar cancer (63.6%). Multivariate analysis showed that oropharyngeal carcinoma (P = 0.002; OR = 5.34; 95% CI = 1.83-15.58), oral cavity carcinoma (P = 0.012; OR = 4.94; 95% CI = 1.43-17.10), and histological poor differentiation (P = 0.011; OR = 4.25; 95% CI = 1.39-13.04) each independently increased the prevalence of HPV infection. The present study reveals that patients with HNSCC, e.g., oropharyngeal and oral cavity carcinomas, in Okinawa have relatively high HPV-16 positive rates and low HPV-18 positive rates comparing with mainland Japan.

  9. Application of covariance images and PCA to study the stages of dysplasia in human cervical tissues

    NASA Astrophysics Data System (ADS)

    Jagtap, Jaidip; Mozumder, Meghdoot; Shukla, Prashant; Pandey, Kiran; Agarwal, Asha; Pradhan, Asima

    2011-08-01

    Mueller Matrix has the potential to extract vital information regarding subtle morphological changes that appear in human tissue in the early stages of cancer. In this report we have analyzed data of Muller Matrix imaging obtained from human cervical tissue. The depolarization power quantifies the increase in density of cells in epithelium layer during the progress of dysplasia. The early changes in dysplasia seen in the breakdown of ordered collagen fiber of the stromal region result in changes in birefringence property. The retardance parameter of Mueller Matrix decomposition displays these changes quantitatively. Analysis of retardance images performed on measurements obtained from the stromal region shows significant differences to discriminate dysplasia from normal tissue, where histopathology fails to diagnose. Further, the covariance map of depolarization power and their highest eigenvector from the epithelial layer are able to grade the two different stages of dysplastic conditions, grade I (GD1) and grade II (GD2) in human cervical tissue. This study can improve sensitivity of detection in clinics as a supplementary technique to histopathology.

  10. Application of covariance images and PCA to study the stages of dysplasia in human cervical tissues

    NASA Astrophysics Data System (ADS)

    Jagtap, Jaidip; Mozumder, Meghdoot; Shukla, Prashant; Pandey, Kiran; Agarwal, Asha; Pradhan, Asima

    2010-12-01

    Mueller Matrix has the potential to extract vital information regarding subtle morphological changes that appear in human tissue in the early stages of cancer. In this report we have analyzed data of Muller Matrix imaging obtained from human cervical tissue. The depolarization power quantifies the increase in density of cells in epithelium layer during the progress of dysplasia. The early changes in dysplasia seen in the breakdown of ordered collagen fiber of the stromal region result in changes in birefringence property. The retardance parameter of Mueller Matrix decomposition displays these changes quantitatively. Analysis of retardance images performed on measurements obtained from the stromal region shows significant differences to discriminate dysplasia from normal tissue, where histopathology fails to diagnose. Further, the covariance map of depolarization power and their highest eigenvector from the epithelial layer are able to grade the two different stages of dysplastic conditions, grade I (GD1) and grade II (GD2) in human cervical tissue. This study can improve sensitivity of detection in clinics as a supplementary technique to histopathology.

  11. Neurochemical profile of the human cervical spinal cord determined by MRS.

    PubMed

    Hock, Andreas; Wilm, Bertram; Zandomeneghi, Giorgia; Ampanozi, Garyfalia; Franckenberg, Sabine; Zoelch, Niklaus; Wyss, Patrik Oliver; De Zanche, Nicola; Nordmeyer-Maßner, Jurek; Kraemer, Thomas; Thali, Michael; Ernst, Matthias; Kollias, Spyros; Henning, Anke

    2016-10-01

    MRS enables insight into the chemical composition of central nervous system tissue. However, technical challenges degrade the data quality when applied to the human spinal cord. Therefore, to date detection of only the most prominent metabolite resonances has been reported in the healthy human spinal cord. The aim of this investigation is to provide an extended metabolic profile including neurotransmitters and antioxidants in addition to metabolites involved in the energy and membrane metabolism of the human cervical spinal cord in vivo. To achieve this, data quality was improved by using a custom-made, cervical detector array together with constructive averaging of a high number of echo signals, which is enabled by the metabolite cycling technique at 3T. In addition, the improved spinal cord spectra were extensively cross-validated, in vivo, post-mortem in situ and ex vivo. Reliable identification of up to nine metabolites was achieved in group analyses for the first time. Distinct features of the spinal cord neurochemical profile, in comparison with the brain neurotransmission system, include decreased concentrations of the sum of glutamate and glutamate and increased concentrations of aspartate, γ-amino-butyric acid, scyllo-inositol and the sum of myo-inositol and glycine.

  12. Inhibition of antiviral drug cidofovir on proliferation of human papillomavirus-infected cervical cancer cells

    PubMed Central

    Yang, Jing; Dai, Lv-Xia; Chen, Ming; Li, Bei; Ding, Nana; Li, Gang; Liu, Yan-Qing; Li, Ming-Yuan; Wang, Bao-Ning; Shi, Xin-Li; Tan, Hua-Bing

    2016-01-01

    In order to evaluate the potential application value of cidofovir (CDV) in the prevention of human papillomavirus (HPV) infection and treatment of cervical cancer, the inhibitory effect of CDV on the proliferation of HPV 18-positive HeLa cells in cervical cancer was preliminarily investigated, using cisplatin (DDP) as a positive control. An MTT assay was used to analyze the effects of CDV and DDP on HeLa cell proliferation. In addition, clone formation assay and Giemsa staining were used to examine the extent of HeLa cell apoptosis caused by CDV and DDP. Flow cytometry was also used to detect the shape and size of apoptotic cells following propidium iodide staining, while western blot analysis identified the expression levels of of E6 and p53 proteins in HeLa cells. A cell climbing immunofluorescence technique was used to locate the subcellular position of p53 in HeLa cells. The results demonstrated that CDV and DDP inhibited the proliferation of HeLa cells in a concentration- and time-dependent manner. Flow cytometry showed that CDV and DDP treatments resulted in cell arrest in the S-phase, and triggered programmed cell death. Furthermore, western blot analysis revealed that CDV and DDP inhibited E6 protein expression and activated p53 expression in HeLa cells. Finally, the immunofluorescence results indicated that CDV and DDP inhibited the nuclear export of p53 by E6 protein, which is required for degradation of endogenous p53 by MDM2 and human papilloma virus E6. In conclusion, CDV and DDP inhibited HeLa cell proliferation in a concentration- and time-dependent manner, reduced the expression of E6 protein, and reinstated p53 protein activity. Thus, CDV regulates cell cycle arrest and apoptosis, and may be a potential cervical cancer therapeutic strategy. PMID:27882102

  13. Ginsenoside-Rg5 induces apoptosis and DNA damage in human cervical cancer cells

    PubMed Central

    LIANG, LI-DAN; HE, TAO; DU, TING-WEI; FAN, YONG-GANG; CHEN, DIAN-SEN; WANG, YAN

    2015-01-01

    Panax ginseng is traditionally used as a remedy for cancer, inflammation, stress and aging, and ginsenoside-Rg5 is a major bioactive constituent of steamed ginseng. The present study aimed to evaluate whether ginsenoside-Rg5 had any marked cytotoxic, apoptotic or DNA-damaging effects in human cervical cancer cells. Five human cervical cancer cell lines (HeLa, MS751, C33A, Me180 and HT-3) were used to investigate the cytotoxicity of ginsenoside-Rg5 using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Additionally, the effects of ginsenoside-Rg5 on the apoptosis of HeLa and MS751 cells were detected using DNA ladder assays and flow cytometry. DNA damage was assessed in the HeLa and MS751 cells using alkaline comet assays and by detection of γH2AX focus formation. The HeLa and MS751 cells were significantly more sensitive to ginsenoside-Rg5 treatment compared with the C-33A, HT-3 and Me180 cells. As expected, ginsenoside-Rg5 induced significant concentration- and time-dependent increases in apoptosis. In addition, ginsenoside-Rg5 induced significant concentration-dependent increases in the level of DNA damage compared with the negative control. Consistent with the comet assay data, the percentage of γH2AX-positive HeLa and MS751 cells also revealed that ginsenoside-Rg5 caused DNA double-strands to break in a concentration-dependent manner. In conclusion, ginsenoside-Rg5 had marked genotoxic effects in the HeLa and MS751 cells and, thus, demonstrates potential as a genotoxic or cytotoxic drug for the treatment of cervical cancer. PMID:25355274

  14. Structural and Ultrastructural Analysis of the Cervical Discs of Young and Elderly Humans.

    PubMed

    Fontes, Ricardo Braganca de Vasconcellos; Baptista, Josemberg Silva; Rabbani, Said Rahnamaye; Traynelis, Vincent C; Liberti, Edson Aparecido

    2015-01-01

    Several studies describing the ultrastructure and extracellular matrix (ECM) of intervertebral discs (IVDs) involve animal models and specimens obtained from symptomatic individuals during surgery for degenerative disease or scoliosis, which may not necessarily correlate to changes secondary to normal aging in humans. These changes may also be segment-specific based on different load patterns throughout life. Our objective was to describe the ECM and collagen profile of cervical IVDs in young (G1 - <35 years) and elderly (G2 - >65 years) presumably-asymptomatic individuals. Thirty cervical discs per group were obtained during autopsies of presumably-asymptomatic individuals. IVDs were analyzed with MRI, a morphological grading scale, light microscopy, scanning electron microscopy (SEM) and immunohistochemistry (IHC) for collagen types I, II, III, IV, V, VI, IX and X. Macroscopic degenerative features such as loss of annulus-nucleus distinction and fissures were found in both groups and significantly more severe in G2 as expected. MRI could not detect all morphological changes when compared even with simple morphological inspection. The loose fibrocartilaginous G1 matrix was replaced by a denser ECM in G2 with predominantly cartilaginous characteristics, chondrocyte clusters and absent elastic fibers. SEM demonstrated persistence of an identifiable nucleus and Sharpey-type insertion of cervical annulus fibers even in highly-degenerated G2 specimens. All collagen types were detected in every disc sector except for collagen X, with the largest area stained by collagens II and IV. Collagen detection was significantly decreased in G2: although significant intradiscal differences were rare, changes may occur faster or earlier in the posterior annulus. These results demonstrate an extensive modification of the ECM with maintenance of basic ultrastructural features despite severe macroscopic degeneration. Collagen analysis supports there is not a "pathologic" collagen type

  15. Inhibition of antiviral drug cidofovir on proliferation of human papillomavirus-infected cervical cancer cells.

    PubMed

    Yang, Jing; Dai, Lv-Xia; Chen, Ming; Li, Bei; Ding, Nana; Li, Gang; Liu, Yan-Qing; Li, Ming-Yuan; Wang, Bao-Ning; Shi, Xin-Li; Tan, Hua-Bing

    2016-11-01

    In order to evaluate the potential application value of cidofovir (CDV) in the prevention of human papillomavirus (HPV) infection and treatment of cervical cancer, the inhibitory effect of CDV on the proliferation of HPV 18-positive HeLa cells in cervical cancer was preliminarily investigated, using cisplatin (DDP) as a positive control. An MTT assay was used to analyze the effects of CDV and DDP on HeLa cell proliferation. In addition, clone formation assay and Giemsa staining were used to examine the extent of HeLa cell apoptosis caused by CDV and DDP. Flow cytometry was also used to detect the shape and size of apoptotic cells following propidium iodide staining, while western blot analysis identified the expression levels of of E6 and p53 proteins in HeLa cells. A cell climbing immunofluorescence technique was used to locate the subcellular position of p53 in HeLa cells. The results demonstrated that CDV and DDP inhibited the proliferation of HeLa cells in a concentration- and time-dependent manner. Flow cytometry showed that CDV and DDP treatments resulted in cell arrest in the S-phase, and triggered programmed cell death. Furthermore, western blot analysis revealed that CDV and DDP inhibited E6 protein expression and activated p53 expression in HeLa cells. Finally, the immunofluorescence results indicated that CDV and DDP inhibited the nuclear export of p53 by E6 protein, which is required for degradation of endogenous p53 by MDM2 and human papilloma virus E6. In conclusion, CDV and DDP inhibited HeLa cell proliferation in a concentration- and time-dependent manner, reduced the expression of E6 protein, and reinstated p53 protein activity. Thus, CDV regulates cell cycle arrest and apoptosis, and may be a potential cervical cancer therapeutic strategy.

  16. Time trends of human papillomavirus types in invasive cervical cancer, from 1940 to 2007.

    PubMed

    Alemany, Laia; de Sanjosé, Silvia; Tous, Sara; Quint, Wim; Vallejos, Carlos; Shin, Hai-Rim; Bravo, Luis E; Alonso, Patricia; Lima, Marcus A; Guimerà, Núria; Klaustermeier, Joellen; Llombart-Bosch, Antonio; Kasamatsu, Elena; Tatti, Silvio A; Felix, Ana; Molina, Carla; Velasco, Julio; Lloveras, Belen; Clavero, Omar; Lerma, Enrique; Laco, Jan; Bravo, Ignacio G; Guarch, Rosa; Pelayo, Adela; Ordi, Jaume; Andújar, Miguel; Sanchez, Gloria I; Castellsagué, Xavier; Muñoz, Nubia; Bosch, F Xavier

    2014-07-01

    Contribution over time of human papillomavirus (HPV) types in human cancers has been poorly documented. Such data is fundamental to measure current HPV vaccines impact in the years to come. We estimated the HPV type-specific distribution in a large international series of invasive cervical cancer (ICC) over 70 years prior to vaccination. Paraffin embedded ICC cases diagnosed between 1940 and 2007 were retrieved from eleven countries in Central-South America, Asia and Europe. Included countries reported to have low-medium cervical cancer screening uptake. Information on age at and year of diagnosis was collected from medical records. After histological confirmation, HPV DNA detection was performed by SPF-10/DEIA/LiPA25 (version1). Logistic regression models were used for estimating the adjusted relative contributions (RC) of HPV16 and of HPV18 over time. Among 4,771 HPV DNA positive ICC cases, HPV16 and HPV18 were the two most common HPVs in all the decades with no statistically significant variations of their adjusted-RC from 1940-59 to 2000-07 (HPV16-from 61.5 to 62.1%, and HPV18-from 6.9 to 7.2%). As well, the RC of other HPV types did not varied over time. In the stratified analysis by histology, HPV16 adjusted-RC significantly increased across decades in adenocarcinomas. Regarding age, cases associated to either HPV16, 18 or 45 were younger than those with other HPV types in all the evaluated decades. The observed stability on the HPV type distribution predicts a high and stable impact of HPV vaccination in reducing the cervical cancer burden in future vaccinated generations.

  17. Cloning of monomeric human papillomavirus type 16 DNA integrated within cell DNA from a cervical carcinoma

    SciTech Connect

    Matsukura, T.; Kanda, T.; Furuno, A.; Yoshikawa, H.; Kawana, T.; Yoshiike, K.

    1986-06-01

    The authors have molecularly cloned and characterized monomeric human papillomavirus type 16 DNA with flanking cell DNA sequences from a cervical carcinoma. Determination of nucleotide sequence around the junctions of human papillomavirus and cell DNAs revealed that at the site of integration within cell DNA the cloned viral DNA had a deletion between nucleotides 1284 and 4471 (numbering system from K. Seedorf, G. Kraemmer, M. Duerst, S. Suhai, and W.G. Roewkamp), which includes the greater part of E1 gene and the entire E2 gene. In the remaining part of the E1 gene, three guanines were found at the location where two guanines at nucleotides 1137 and 1138 have been recorded. This additional guanine shifted the reading frame and erased an interruption in the E1 gene. The data strongly suggest that, like other papillomaviruses, human papillomavirus type 16 has an uninterrupted E1 gene.

  18. HLA-DP is the cervical cancer susceptibility loci among women infected by high-risk human papillomavirus: potential implication for triage of human papillomavirus-positive women.

    PubMed

    Jia, Meiqun; Han, Jing; Hang, Dong; Jiang, Jie; Wang, Minjie; Wei, Baojun; Dai, Juncheng; Zhang, Kai; Guo, Lanwei; Qi, Jun; Ma, Hongxia; Shi, Jufang; Ren, Jiansong; Hu, Zhibin; Dai, Min; Li, Ni

    2016-06-01

    Given that only a small proportion of women infected by high-risk human papillomavirus (hrHPV) develop cervical cancer, it's important to identify biomarkers for distinguishing women with hrHPV positivity who might develop cervical cancer from the transient infections. In this study, we hypothesized that human leukocyte antigens (HLA) susceptibility alleles might contribute to cervical cancer risk among females infected by hrHPV, and interact with hrHPV types. A case-control study with 593 cervical cancer cases and 407 controls (all hrHPV positive) was conducted to evaluate the effect of eight HLA-related single-nucleotide polymorphisms (SNPs) and their interactions with hrHPV types on the risk of cervical cancer. Three HLA-DP SNPs (rs4282438, rs3117027, and rs3077) were found to be significantly associated with risk of cervical cancer (rs4282438: odds ratio (OR) = 0.72, 95 % confidence interval (CI) = 0.56-0.93; rs3117027: OR = 1.41, 95 % CI = 1.10-1.83; and rs3077: OR = 1.37, 95 % CI = 1.04-1.80) among women infected with hrHPV. An additive interaction between HPV16 and rs4282438 for cervical cancer risk was also found (P for interaction = 0.002). Compared with subjects carrying variant genotypes (GG/TG) and non-HPV16 infections, those carrying wild-type genotype (TT) of rs4282438 and HPV16 positive had a 5.22-fold increased risk of cervical cancer (95 % CI = 3.39-8.04). Our study supported that certain HLA-DP alleles in concert with HPV16 could have a predisposition for cervical cancer development, which may be translated for triage of hrHPV-positive women.

  19. Cell density governs the ability of human bronchial epithelial cells to recognize serum and transforming growth factor beta-1 as squamous differentiation-inducing agents.

    PubMed Central

    Ke, Y.; Gerwin, B. I.; Ruskie, S. E.; Pfeifer, A. M.; Harris, C. C.; Lechner, J. F.

    1990-01-01

    Sparse (75 to 2000 cells/cm2) density cultures of normal human bronchial epithelial cells uniformly undergo terminal squamous differentiation when incubated in medium containing serum (fetal bovine serum [FBS]) or transforming growth factor beta-1 (TGF-beta 1). It was found that the cell density of the culture affects the probability that a cell will respond to these differentiation-inducing agents. Thus whereas irreversible inhibition of DNA synthesis occurs in sparse cell-density cultures within 24 hours after exposure, only a transient (less than 36 hours) depression in DNA synthesis was seen in high (more than 10,000 cells/cm2) density cultures. In addition, although phase microscopic image analysis revealed that virtually all of the cells displayed a squamous morphology within 1 hour after exposure to FBS or TGF-beta 1, observations made 48 to 72 hours later showed the presence of clusters of small prolate spheroid-shaped cells surrounded by many involucrin-positive squamous-appearing cells. Only the small cells were capable of DNA synthesis and cell division as determined by autoradiography and time-lapse photomicrographic images. These replicating cells immediately undergo squamous differentiation if they are subcultured and reinoculated at low cell density and incubated in medium supplemented with FBS or TGF-beta 1. Therefore the probability that a human bronchial epithelial cell will be refractive to FBS- or TGF-beta 1 induced terminal squamous differentiation is solely a function of the cell density of the culture. Images Figure 7 Figure 8 Figure 9 PMID:2221015

  20. Nuclear expression of Rac1 in cervical premalignant lesions and cervical cancer cells

    PubMed Central

    2012-01-01

    Background Abnormal expression of Rho-GTPases has been reported in several human cancers. However, the expression of these proteins in cervical cancer has been poorly investigated. In this study we analyzed the expression of the GTPases Rac1, RhoA, Cdc42, and the Rho-GEFs, Tiam1 and beta-Pix, in cervical pre-malignant lesions and cervical cancer cell lines. Methods Protein expression was analyzed by immunochemistry on 102 cervical paraffin-embedded biopsies: 20 without Squamous Intraepithelial Lesions (SIL), 51 Low- grade SIL, and 31 High-grade SIL; and in cervical cancer cell lines C33A and SiHa, and non-tumorigenic HaCat cells. Nuclear localization of Rac1 in HaCat, C33A and SiHa cells was assessed by cellular fractionation and Western blotting, in the presence or not of a chemical Rac1 inhibitor (NSC23766). Results Immunoreacivity for Rac1, RhoA, Tiam1 and beta-Pix was stronger in L-SIL and H-SIL, compared to samples without SIL, and it was significantly associated with the histological diagnosis. Nuclear expression of Rac1 was observed in 52.9% L-SIL and 48.4% H-SIL, but not in samples without SIL. Rac1 was found in the nucleus of C33A and SiHa cells but not in HaCat cells. Chemical inhibition of Rac1 resulted in reduced cell proliferation in HaCat, C33A and SiHa cells. Conclusion Rac1 is expressed in the nucleus of epithelial cells in SILs and cervical cancer cell lines, and chemical inhibition of Rac1 reduces cellular proliferation. Further studies are needed to better understand the role of Rho-GTPases in cervical cancer progression. PMID:22443139

  1. Overexpression of Ribosomal RNA in the Development of Human Cervical Cancer Is Associated with rDNA Promoter Hypomethylation

    PubMed Central

    Zhou, Hong; Wang, Yapei; Lv, Qiongying; Zhang, Juan; Wang, Qing; Gao, Fei; Hou, Haoli; Zhang, Hao; Zhang, Wei; Li, Lijia

    2016-01-01

    The ribosomal RNA (rRNA) gene encodes rRNA for protein synthesis. Aberrant expression of the rRNA gene has been generally observed in tumor cells and levels of its promoter methylation as an epigenetic regulator affect rRNA gene transcription. The possible relationship between expression and promoter methylation of rDNA has not been examined in human clinical cervical cancer. Here we investigate rRNA gene expression by quantitative real time PCR, and promoter methylation levels by HpaII/MspI digestion and sodium bisulfite sequencing in the development of human cervical cancer. We find that indeed rRNA levels are elevated in most of cervical intraepithelial neoplasia (CIN) specimens as compared with non-cancer tissues. The rDNA promoter region in cervical intraepithelial neoplasia (CIN) tissues reveals significant hypomethylation at cytosines in the context of CpG dinucleotides, accompanied with rDNA chromatin decondensation. Furthermore treatment of HeLa cells with the methylation inhibitor drug 5-aza-2’-deoxycytidine (DAC) demonstrates the negative correlation between the expression of 45S rDNA and the methylation level in the rDNA promoter region. These data suggest that a decrease in rDNA promoter methylation levels can result in an increase of rRNA synthesis in the development of human cervical cancer. PMID:27695092

  2. Oxidative Stress Triggered by Apigenin Induces Apoptosis in a Comprehensive Panel of Human Cervical Cancer-Derived Cell Lines

    PubMed Central

    Souza, Raquel P.; Gimenes, Fabrícia; Ratti, Bianca A.; Kaplum, Vanessa; Bruschi, Marcos L.; Nakamura, Celso V.; Maria-Engler, Silvya S.

    2017-01-01

    Recently, the cytotoxic effects of apigenin (4′,5,7-trihydroxyflavone), particularly its marked inhibition of cancer cell viability both in vitro and in vivo, have attracted the attention of the anticancer drug discovery field. Despite this, there are few studies of apigenin in cervical cancer, and these studies have mostly been conducted using HeLa cells. To evaluate the possibility of apigenin as a new therapeutic candidate for cervical cancer, we evaluated its cytotoxic effects in a comprehensive panel of human cervical cancer-derived cell lines including HeLa (human papillomavirus/HPV 18-positive), SiHa (HPV 16-positive), CaSki (HPV 16 and HPV 18-positive), and C33A (HPV-negative) cells in comparison to a nontumorigenic spontaneously immortalized human epithelial cell line (HaCaT). Our results demonstrated that apigenin had a selective cytotoxic effect and could induce apoptosis in all cervical cancer cell lines which were positively marked with Annexin V, but not in HaCaT (control cells). Additionally, apigenin was able to induce mitochondrial redox impairment, once it increased ROS levels and H2O2, decreased the Δψm, and increased LPO. Still, apigenin was able to inhibit migration and invasion of cancer cells. Thus, apigenin appears to be a promising new candidate as an anticancer drug for cervical cancer induced by different HPV genotypes. PMID:28191273

  3. Human papilloma virus-dependent HMGA1 expression is a relevant step in cervical carcinogenesis.

    PubMed

    Mellone, Massimiliano; Rinaldi, Christian; Massimi, Isabella; Petroni, Marialaura; Veschi, Veronica; Talora, Claudio; Truffa, Silvia; Stabile, Helena; Frati, Luigi; Screpanti, Isabella; Gulino, Alberto; Giannini, Giuseppe

    2008-08-01

    HMGA1 is a member of a small family of architectural transcription factors involved in the coordinate assembly of multiprotein complexes referred to as enhanceosomes. In addition to their role in cell proliferation, differentiation, and development, high-mobility group proteins of the A type (HMGA) family members behave as transforming protoncogenes either in vitro or in animal models. Recent reports indicated that HMGA1 might counteract p53 pathway and provided an interesting hint on the mechanisms determining HMGA's transforming potential. HMGA1 expression is deregulated in a very large array of human tumors, including cervical cancer, but very limited information is available on the molecular mechanisms leading to HMGA1 deregulation in cancer cells. Here, we report that HMGA1 expression is sustained by human papilloma virus (HPV) E6/E7 proteins in cervical cancer, as demonstrated by either E6/E7 overexpression or by repression through RNA interference. Knocking down HMGA1 expression by means of RNA interference, we also showed that it is involved in cell proliferation and contributes to p53 inactivation in this type of neoplasia. Finally, we show that HMGA1 is necessary for the full expression of HPV18 E6 and E7 oncoproteins thus establishing a positive autoregulatory loop between HPV E6/E7 and HMGA1 expression.

  4. Anticancer properties of extracts from Opuntia humifusa against human cervical carcinoma cells.

    PubMed

    Hahm, Sahng-Wook; Park, Jieun; Oh, Se-Yeong; Lee, Chul-Won; Park, Kun-Young; Kim, Hyunggee; Son, Yong-Suk

    2015-01-01

    In this study, we found that the total polyphenol and ascorbic acid levels in the fruit of Opuntia humifusa are higher than those in other parts of the plant. We further hypothesized that antioxidants in O. humifusa might affect the growth or survival of cancer cells. Hexane extracts of seeds and ethyl acetate extracts of fruits and stems significantly suppressed the proliferation of HeLa cervical carcinoma cells, but did not affect the proliferation of normal human BJ fibroblasts. Additionally, the extracts of O. humifusa induced G1 phase arrest in HeLa cells. The O. humifusa extracts reduced the levels of G1 phase-associated cyclin D1, cyclin-dependent kinase 4 (Cdk4), and phosphorylated retinoblastoma proteins. Moreover, p21(WAF1/Cip1) and p53 expression significantly increased after treatment. We examined the effects of ethyl acetate extracts of O. humifusa fruit (OHF) on HeLa cells xenograft tumor growth. OHF treatment significantly reduced tumor volume and this decrease was correlated with decreased Cdk4 and cyclin D1 expression. Furthermore, flavonoids, trans Taxifolin, and dihydrokaempferol, were isolated from OHF. Thus, this extract may be a promising candidate for treating human cervical carcinoma.

  5. Human Papilloma Virus-Dependent HMGA1 Expression Is a Relevant Step in Cervical Carcinogenesis1

    PubMed Central

    Mellone, Massimiliano; Rinaldi, Christian; Massimi, Isabella; Petroni, Marialaura; Veschi, Veronica; Talora, Claudio; Truffa, Silvia; Stabile, Helena; Frati, Luigi; Screpanti, Isabella; Gulino, Alberto; Giannini, Giuseppe

    2008-01-01

    HMGA1 is a member of a small family of architectural transcription factors involved in the coordinate assembly of multiprotein complexes referred to as enhanceosomes. In addition to their role in cell proliferation, differentiation, and development, high-mobility group proteins of the A type (HMGA) family members behave as transforming protoncogenes either in vitro or in animal models. Recent reports indicated that HMGA1 might counteract p53 pathway and provided an interesting hint on the mechanisms determining HMGA's transforming potential. HMGA1 expression is deregulated in a very large array of human tumors, including cervical cancer, but very limited information is available on the molecular mechanisms leading to HMGA1 deregulation in cancer cells. Here, we report that HMGA1 expression is sustained by human papilloma virus (HPV) E6/E7 proteins in cervical cancer, as demonstrated by either E6/E7 overexpression or by repression through RNA interference. Knocking down HMGA1 expression by means of RNA interference, we also showed that it is involved in cell proliferation and contributes to p53 inactivation in this type of neoplasia. Finally, we show that HMGA1 is necessary for the full expression of HPV18 E6 and E7 oncoproteins thus establishing a positive autoregulatory loop between HPV E6/E7 and HMGA1 expression. PMID:18670638

  6. The role of human papillomavirus in the pathogenesis of head & neck squamous cell carcinoma: an overview

    PubMed Central

    2011-01-01

    Cancer statistics report an increased incidence of OSCC and OPSCC around the world. Though improvements in screening and early diagnosis have dramatically reduced the incidence of this neoplasm in recent years, the 5-year-disease-free survival, is still poor, specially for oropharyngeal cancer, despite the great scientific and financial efforts. Recently, several papers showed that HPV may be involved at least in the pathogenesis of a subgroup of oral and cervical SCC, leading to distinct molecular characteristics compared with HPV-negative ones. Nevertheless, OPSCCs associated with HPV infection seem to show a better prognosis and affect younger patients (< 40 yrs.), especially females. Therefore, there is the need to properly assess oropharyngeal SCC subgroups: 1) not HPV associated/classic oral SCC: less responsive to anticancer drugs: needs novel post-surgical treatment; 2) HPV associated/oral SCC: needs several management options and suitable "target" therapy against the virus, and/or immune-stimulating therapy. Further issues are: 1) the disclosure of putative targets for more efficient molecular therapy, which may work as cervical cancer post-surgical treatment, in anticipation of the effects of "global prevention" performed by WHO anti-HPV vaccination programs; 2) careful identification of precancerous lesions in both sites; dysplasia is currently treated by excisional or ablative procedures, which don't consider the concept of field carcinogenesis. In fact, it is probable that near or far from an excised precancerous lesion new foci of cell transformation may exist, which are not yet macroscopically evident, but, if detected, would put the patient into a high risk subgroup. Comparing findings reported in the recent literature, the data of this state of the art about HPV might add useful informations concerning oropharyngeal carcinogenesis. Moreover, our review would be useful in order to define novel perspectives of treatment choice for Head & Neck cancer

  7. Novel drug discovery system for cancer stem cells in human squamous cell carcinoma of the esophagus.

    PubMed

    Kano, Yoshihiro; Konno, Masamitsu; Kawamoto, Koichi; Tamari, Keisuke; Hayashi, Kazuhiko; Fukusumi, Takahito; Satoh, Taroh; Tanaka, Shinji; Ogawa, Kazuhiko; Mori, Masaki; Doki, Yuichiro; Ishii, Hideshi

    2014-03-01

    Cancer stem cells (CSCs) have been identified in several tumor tissues. Since CSCs are resistant to cancer therapies, including chemotherapy and radiation therapy, and can even remain after therapies, tumor tissue often regrows and relapses. Thus, identification of CSCs and treatment targeting CSCs are required to treat tumor tissues. Reportedly, a fluorescent vector consisting of fluorescein ZsGreen fused to the carboxyl-terminal region of ornithine decarboxylase (cODC) was used to detect CSCs or therapy-resistant cancer cells in tumor tissues of the brain, pancreas and liver. Cells transfected with the fluorescent vector can express a fluorescein fused to cODC and become fluorescent only when the fusion protein is accumulated. In the present study, CSCs or therapy-resistant cancer cells were identified with the fluorescent vector in esophageal squamous cell carcinoma. The use of this fluorescent vector in drug screening enabled the detection of three drugs, AKT inhibitor XI, ERK inhibitor II and JAK inhibitor I, which target malignant CSCs.

  8. Inhibitory effect of berberine on human skin squamous cell carcinoma A431 cells.

    PubMed

    Li, D X; Zhang, J; Zhang, Y; Zhao, P W; Yang, L M

    2015-09-08

    Berberine (BBR) is a natural alkaloid with significant anti-tumor activity against many types of cancer cells. In this study, we investigated the molecular mechanisms employed by BBR to repress the proliferation and growth of skin squamous cell carcinoma A431 cells. Berberine was reported to inhibit the proliferation of A431 cells in a dose- and time-dependent manner and was observed to induce a series of biochemical events, including the loss of mitochondrial membrane potential, release of cytochrome-c to cytosol, induction of proteins of the Bcl-2 family and caspases, and the cleavage of poly(ADP)-ribose polymerase. This suggested its ability to induce apoptosis. The results of a wound healing test revealed that berberine inhibited the migration of A431 cells. Ezrin was transfected into A431 cells by RNA interference. The level of expression of Ezrin in the transfected A431 cells was observed to decrease with berberine treatment, which suggested that berberine might inhibit the invasion of A431 cells through Ezrin. The results of this study demonstrated that berberine could potentially inhibit proliferation, induce apoptosis, and inhibit the invasion of A431 cells.

  9. Tropomyosin-1 acts as a potential tumor suppressor in human oral squamous cell carcinoma

    PubMed Central

    Pan, Hao; Gu, Liqun; Liu, Binjie; Li, Yiping; Wang, Yuehong; Bai, Xinna; Li, Long; Wang, Baisheng; Peng, Qian; Yao, Zhigang; Tang, Zhangui

    2017-01-01

    It is widely accepted that oral squamous cell carcinoma (OSCC) is a major contributor to the incidence and mortality of neck and head cancer. Tropomyosin-1 (TPM1), which is expressed at a low level, has been considered a prominent tumor-suppressing gene in a variety of solid tumors, although the precise mechanism of the TPM1 gene in OSCC progression remains unknown. We found that TPM1 expression levels decreased in OSCC patients and OSCC cell lines. The overall and cancer-specific survival of patients who exhibited low TPM1 levels were inferior to those of patients who had high TPM1 levels. It was also found that OSCC patients who suffered from disease stageⅠ-Ⅱ were more likely to have an up-regulated TPM1 expression level, and OSCC patients with lymph node metastasis had a higher probability of exhibiting reduced TPM1 expression. We show that overexpression of TPM1 can promote cell apoptosis and inhibit migration. Our results suggest that TPM1 can suppress tumors in OSCC, and the TPM1 expression level is related to OSCC patient prognosis. PMID:28182650

  10. Tropomyosin-1 acts as a potential tumor suppressor in human oral squamous cell carcinoma.

    PubMed

    Pan, Hao; Gu, Liqun; Liu, Binjie; Li, Yiping; Wang, Yuehong; Bai, Xinna; Li, Long; Wang, Baisheng; Peng, Qian; Yao, Zhigang; Tang, Zhangui

    2017-01-01

    It is widely accepted that oral squamous cell carcinoma (OSCC) is a major contributor to the incidence and mortality of neck and head cancer. Tropomyosin-1 (TPM1), which is expressed at a low level, has been considered a prominent tumor-suppressing gene in a variety of solid tumors, although the precise mechanism of the TPM1 gene in OSCC progression remains unknown. We found that TPM1 expression levels decreased in OSCC patients and OSCC cell lines. The overall and cancer-specific survival of patients who exhibited low TPM1 levels were inferior to those of patients who had high TPM1 levels. It was also found that OSCC patients who suffered from disease stageⅠ-Ⅱ were more likely to have an up-regulated TPM1 expression level, and OSCC patients with lymph node metastasis had a higher probability of exhibiting reduced TPM1 expression. We show that overexpression of TPM1 can promote cell apoptosis and inhibit migration. Our results suggest that TPM1 can suppress tumors in OSCC, and the TPM1 expression level is related to OSCC patient prognosis.

  11. Aberrant Expression Profile of Long Noncoding RNA in Human Sinonasal Squamous Cell Carcinoma by Microarray Analysis

    PubMed Central

    Meng, Ling-zhao; Sun, Jing-wu; Yang, Fan

    2016-01-01

    Objectives. This study aimed to identify aberrantly expressed long noncoding RNAs (lncRNAs) profile of sinonasal squamous cell carcinoma (SSCC) and explore their potential functions. Methods. We investigated lncRNA and mRNA expression in SSCC and paired adjacent noncancerous tissues obtained from 6 patients with microarrays. Gene ontology (GO) analysis and pathway analysis were utilized to investigate the gene function. Gene signal-network and lncRNA-mRNA network were depicted. Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to validate 5 lncRNAs in a second set of paired SSCC and adjacent noncancerous tissues obtained from 22 additional patients. Results. We identified significantly differentially expressed lncRNAs (n = 3146) and mRNAs (n = 2208) in SSCC relative to noncancerous tissues. The GO annotation indicated that there are some core gene products that may be attributed to the progress of SSCC. The pathway analysis identified many pathways associated with cancer. The results of lncRNA-mRNA network and gene signal-network implied some core lncRNAs/mRNAs might play important roles in SSCC pathogenesis. The results of qRT-PCR showed that all of the 5 lncRNAs were differentially expressed and consistent with the microarray results. Conclusion. Our study is the first screening and analysis of lncRNAs expression profile in SSCC and may offer new insights into pathogenesis of this disease. PMID:28044124

  12. Infrastructure requirements for human papillomavirus vaccination and cervical cancer screening in sub-Saharan Africa.

    PubMed

    Sankaranarayanan, Rengaswamy; Anorlu, Rose; Sangwa-Lugoma, Ghislain; Denny, Lynette A

    2013-12-29

    The availability of both human papillomavirus (HPV) vaccination and alternative screening tests has greatly improved the prospects of cervical cancer prevention in sub-Saharan African (SSA) countries. The inclusion of HPV vaccine in the portfolio of new vaccines offered by the Gobal Alliance for Vaccines and Immunization (GAVI) to GAVI-eligible countries has vastly improved the chances of introducing HPV vaccination. Further investments to improve vaccine storage, distribution and delivery infrastructure and human resources of the Extended Programme of Immunization will substantially contribute to the faster introduction of HPV vaccination in SSA countries through both school- and campaign-based approaches. Alternative methods to cytology for the prevention of cervical cancer through the early detection and treatment of cervical cancer precursors have been extensively evaluated in the past 15 years, in Africa as well as in other low-resource settings. Visual inspection with 3-5% dilute acetic acid (VIA) and HPV testing are the two alternative screening methods that have been most studied, in both cross-sectional and randomised clinical trials. VIA is particularly suitable to low-resource settings; however, its efficacy in reducing cervical cancer is likely to be significantly lower than HPV testing. The introduction of VIA screening programmes will help develop the infrastructure that will, in turn, facilitate the introduction of affordable HPV testing in future. Links with the existing HIV/AIDS control programmes is another strategy to improve the infrastructure and screening services in SSA. Infrastructural requirements for an integrated approach aiming to vaccinate single-year cohorts of girls in the 9-13 years age-range and to screen women over 30 years of age using VIA or affordable rapid HPV tests are outlined in this manuscript. This article forms part of a regional report entitled "Comprehensive Control of HPV Infections and Related Diseases in the Sub

  13. Cervical lymph node metastases of squamous cell carcinoma of unknown origin: the diagnostic value of FDG PET/CT and clinical outcome.

    PubMed

    Dale, Einar; Moan, Jon M; Osnes, Terje A; Bogsrud, Trond V

    2017-02-01

    FDG PET/CT is perceived as a valuable diagnostic tool in addition to the standard diagnostic workup for patients with isolated neck lymph nodes of squamous cell carcinoma of unknown primary (SCCUP). For patients with SCCUP intended for primary radiotherapy, we hypothesize that the previously reported FDG PET/CT detection rates are too high. From 2008 to 2015, 30 SCCUP patients were examined with FDG PET/CT. The objective of the FDG PET/CT examination was twofold: (1) improve the radiotherapy target definition, and (2) identify the primary cancer. Before the FDG PET/CT, the patients had been through a standard workup consisting of CT of the neck and chest, examination with flexible endoscopy with patient awake, panendoscopy and examination under general anesthesia, tonsillectomy and sometimes blind sampling biopsies, and MRI (floor of the mouth). All FDG PET/CTs were performed applying a flat table, head support and fixation mask as part of the radiotherapy treatment planning. Diagnostic CT with contrast was an integrated part of the PET/CT examination. Only 1/30 patients (cancer of the vallecula) had their primary cancer detected by FDG PET/CT. In addition, a non-biopsied patient with high uptake in the ipsilateral palatine tonsil was included, giving a detection rate of ≤7 % (95 % CI 2-21 %). In this retrospective study, we found that the FDG PET/CT detection rate of the primary for SCCUP patients is lower than previously reported. It is questionable whether FDG PET/CT is necessary for these patients when improved, advanced workup is available.

  14. Novel cell-surface peptides specific to human oral squamous cell carcinoma using an E. coli peptide display library.

    PubMed

    Kawai, Noriko; Asaumi, Junichi; Murakami, Jun; Wakasa, Toru; Kuroda, Masahiro; Hisatomi, Miki; Unetsubo, Teruhisa; Maki, Yuu; Matsuzaki, Hidenobu; Yanagi, Yoshinonu; Konouchi, Hironobu

    2007-04-01

    We attempted to find a specific antigen of oral squamous cell carcinoma (SCC) cells that could be safely applied to gene therapy in the conservative clinical treatment of oral cancer. We performed subtraction using normal human keratinocyte cells, followed by selection using four oral SCC cell lines. We isolated three clones from poorly differentiated SCC cells and four from well-differentiated SCC cells. These seven clones adsorbed to the oral SCC cells at rates 10-100 times those of normal human keratinocyte cells. The three clones from the poorly differentiated SCC cells showed the same peptide sequence (LAPRTHP). Of the four clones from the well-differentiated SCC cells, three showed the same peptide sequence (FGTLPGT) and the fourth showed a different one (VTPNSTP). Each peptide sequence may recognize the material that exists specifically on the oral SCC cell cortex. We can expect applications not only for tumor-targeting treatment using a gene therapy virus vector but also for diagnosis using, as a tumor marker, the peculiar SCC surface material that these peptides recognize.

  15. XPC silencing in normal human keratinocytes triggers metabolic alterations that drive the formation of squamous cell carcinomas

    PubMed Central

    Rezvani, Hamid Reza; Kim, Arianna L.; Rossignol, Rodrigue; Ali, Nsrein; Daly, Meaghan; Mahfouf, Walid; Bellance, Nadège; Taïeb, Alain; de Verneuil, Hubert; Mazurier, Frédéric; Bickers, David R.

    2010-01-01

    DNA damage is a well-known initiator of tumorigenesis. Studies have shown that most cancer cells rely on aerobic glycolysis for their bioenergetics. We sought to identify a molecular link between genomic mutations and metabolic alterations in neoplastic transformation. We took advantage of the intrinsic genomic instability arising in xeroderma pigmentosum C (XPC). The XPC protein plays a key role in recognizing DNA damage in nucleotide excision repair, and patients with XPC deficiency have increased incidence of skin cancer and other malignancies. In cultured human keratinocytes, we showed that lentivirus-mediated knockdown of XPC reduced mitochondrial oxidative phosphorylation and increased glycolysis, recapitulating cancer cell metabolism. Accumulation of unrepaired DNA following XPC silencing increased DNA-dependent protein kinase activity, which subsequently activated AKT1 and NADPH oxidase-1 (NOX1), resulting in ROS production and accumulation of specific deletions in mitochondrial DNA (mtDNA) over time. Subcutaneous injection of XPC-deficient keratinocytes into immunodeficient mice led to squamous cell carcinoma formation, demonstrating the tumorigenic potential of transduced cells. Conversely, simultaneous knockdown of either NOX1 or AKT1 blocked the neoplastic transformation induced by XPC silencing. Our results demonstrate that genomic instability resulting from XPC silencing results in activation of AKT1 and subsequently NOX1 to induce ROS generation, mtDNA deletions, and neoplastic transformation in human keratinocytes. PMID:21123941

  16. Decreased microRNA-143 expression and its tumor suppressive function in human oral squamous cell carcinoma.

    PubMed

    Ni, Z Y; Lin, F O; Liu, D F; Xiao, J

    2015-06-26

    MicroRNA-143 serves as a tumor suppressor in many human malignancies. However, its involvement in oral squamous cell carcinoma (OSCC) is still unclear. In this study, we investigated the effects of miR-143 in OSCC tumorigenesis and development. Using real-time quantitative reverse transcription-polymerase chain reaction, we detected miR-143 expression in 109 pairs of human OSCC and adjacent noncancerous tissues. The associations between miR-143 expression and clinicopathological factors and prognosis of OSCC patients were also statistically analyzed. Further, the effects of miR-143 on the biological behavior of OSCC cells were investigated. miR-143 expression was significantly downregulated in OSCC tissue samples and cell lines. Decreased miR-143 expression was significantly associated with advanced T classifications, positive N classification, advanced TNM stage, and shorter overall survival. In addition, upregulation of miR-143 in Tca8113 cells reduced cell proliferation, invasion, and migration, as well as promoted cell apoptosis in vitro. These findings validate the clinical significance of miR-143 in OSCC and reveal that it may be an intrinsic regulator of tumor progression and a potential prognostic factor for this disease.

  17. XPC silencing in normal human keratinocytes triggers metabolic alterations that drive the formation of squamous cell carcinomas.

    PubMed

    Rezvani, Hamid Reza; Kim, Arianna L; Rossignol, Rodrigue; Ali, Nsrein; Daly, Meaghan; Mahfouf, Walid; Bellance, Nadège; Taïeb, Alain; de Verneuil, Hubert; Mazurier, Frédéric; Bickers, David R

    2011-01-01

    DNA damage is a well-known initiator of tumorigenesis. Studies have shown that most cancer cells rely on aerobic glycolysis for their bioenergetics. We sought to identify a molecular link between genomic mutations and metabolic alterations in neoplastic transformation. We took advantage of the intrinsic genomic instability arising in xeroderma pigmentosum C (XPC). The XPC protein plays a key role in recognizing DNA damage in nucleotide excision repair, and patients with XPC deficiency have increased incidence of skin cancer and other malignancies. In cultured human keratinocytes, we showed that lentivirus-mediated knockdown of XPC reduced mitochondrial oxidative phosphorylation and increased glycolysis, recapitulating cancer cell metabolism. Accumulation of unrepaired DNA following XPC silencing increased DNA-dependent protein kinase activity, which subsequently activated AKT1 and NADPH oxidase-1 (NOX1), resulting in ROS production and accumulation of specific deletions in mitochondrial DNA (mtDNA) over time. Subcutaneous injection of XPC-deficient keratinocytes into immunodeficient mice led to squamous cell carcinoma formation, demonstrating the tumorigenic potential of transduced cells. Conversely, simultaneous knockdown of either NOX1 or AKT1 blocked the neoplastic transformation induced by XPC silencing. Our results demonstrate that genomic instability resulting from XPC silencing results in activation of AKT1 and subsequently NOX1 to induce ROS generation, mtDNA deletions, and neoplastic transformation in human