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Inflammation on Pap smear

Moderate or severe inflammation should be evaluated with a saline preparation, KOH preparation, and gonorrhea and Chlamydia tests. If the source of infection is found, treatment should be provided, and a repeat Pap smear should be done every 6 to 12 months. If no etiology is found, the Pap smear should be repeated in 6 months. (HGSIL) or invasive cancer therefore, persistent inflammation is an indication for colposcopy. 6. Atrophy with inflammation is common in post-menopausal women or in those with estrogen-deficiency states. Atrophy should be treated with vaginal estrogen for 4-6 weeks, then repeat Pap smear.

Human Papilloma Virus

Infections caused by human papillomavirus (HPV) account for 5.5 than 100 types of HPV have been identified in humans. HPV infections can cause genital warts and various benign or malignant neoplasias, or they can be entirely asymptomatic. B. Genital warts occur on the external genitalia and perianal area and can be visible in the vagina, on the cervix, and inside the urethra and anus. External genital warts (EGWs) are usually caused by HPV type 6 and, less commonly, by HPV type 11, both of which are considered low-risk types in that they are unlikely to cause squamous intraepithelial lesions (SIL) or malignancy. Approximately 15 of men and women 1549 years of age have genital warts that can shed HPV DNA. 3. Keratotic warts that have a thick, horny layer, can appear similar to common, non-genital warts, and occur on fully keratinized skin.

Condylomata acuminata

Condylomata acuminata are caused by human papillomaviruses (HPV). They are usually present as genital warts, but other locations (oral) are known to be involved. HIV-infected patients have a higher risk of acquiring genital warts. The typical pathogens, human papillomavirus type 6 or type 11, are not normally considered to be cancerogenic. Although, in both male and female HIV-infected patients, epithelial atypia is seen more often than in uninfected persons. Besides sexual intercourse, transmission of papillomavirus may be possible via smear infection and perhaps through contaminated objects. But the primary risk factor remains the number of sexual partners.

Human Papillomavirus

Carcinomas of the anogenital tract, particularly cancer of the cervix, account for almost 12 of all cancers in women, and so represent the third most frequent gynecological malignancy in the world (44). It is well established that chronic infection of cervical epithelium by human papilloma viruses (HPVs) is necessary for the development of cervical cancer. HPV DNA has been demonstrated in more than 99 of all tumor biopsy specimens, with high-risk HPV16 and HPV18 being most prevalent (45). HPVs are double-stranded DNA viruses that infect basal and suprabasal layers of stratified epithelium. The early genes, which include E1, E2, E4, E5, E6, and E7, code for proteins involved in viral DNA replication, transcriptional control, and cellular transformation. Late genes encode the major viral capsid protein, L1, and a minor capsid protein, L2. It has been demonstrated that E6 and E7 expression is required for the immortilization of primary cells as well as for maintenance of the transformed...

Screening for cervical cancer

Regular Pap smears are recommended for all women who are or have been sexually active and who have a cervix. C. Pap smears should be performed at least every 1 to 3 years. Testing is usually discontinued after age 65 in women who have had regular normal screening tests. Women who have had a hysterectomy, including removal of the cervix for reasons other than cervical cancer or its precursors, do not require Pap testing.

Benign cellular changes

If wet preparation is positive, treat with metronidazole (Flagyl), then continue annual Pap smears. 4. Infection-herpes simplex virus Pap smear has a poor sensitivity, but good specificity, for HSV. Positive smears usually are caused by asymptomatic infection. The patient should be informed of pregnancy risks and the possibility of transmi ssion. Treatment is not necessary, and the Pap should be repeated as for a benign result.

And W Martin Kast PhD

Viruses implicated in the development of human cancer include hepatitis B (HBV) and hepatitis C (HCV) viruses, human papilloma virus (HPV), Epstein-Barr virus (EBV), human T-cell lymphoma virus, and human herpes virus 8. Together they contribute significantly to the total incidence of cancer worldwide. Current work in each of these virus systems seeks to understand the mechanisms of viral action and identify strategies of immune intervention to combat viral infection and subsequent transformation. It is thought that oncogenic proliferation may be instigated by the presence and expression of viral oncogenes, which may be integrated into the host genome. Critical viral genes may also interfere with host genes, resulting in the activation of cellular proto-oncogenes and or the inactivation of anti-oncogenes and their products. Targeting such viral proteins through various vaccination strategies offers both therapeutic and prophylactic strategies against viral induced malignancies. Views...

Management of glandular cell abnormalities

When a Pap smear is performed during menstruation, endometrial cells may be present. However, endometrial cells on a Pap smear performed during the second half of the menstrual cycle or in a post-menopausal patient may indicate the presence of polyps, hyperplasia, or endometrial adenocarcinoma. An endometrial biopsy should be considered in these women.

Oral contraceptives

A careful personal and family medical history (with particular attention to cardiovascular risk factors) and an accurate blood pressure measurement are recommended before the initiation of oral contraceptive pills. A physical examination and a Papanicolaou smear (with screening genital cultures as indicated) are usually performed at the time oral contraceptive pills are initially prescribed. An initial prescription of OCPs can be written before a physical examination and a Pap test are performed in healthy young women.

Other Biological Functions Of Hdac1

In recent years, evidence has emerged that HDAC1 is involved in cellular defense against viral infection. For example, viral transcription mediated by open reading frame 50 (ORF50), an activator of early and late genes in the lytic cycle of the Kaposi's sarcoma-associated herpesvirus, is repressed upon association with HDAC1 (83,84). Furthermore, inhibition of HDAC activity appears to be important for viral infection. For example, Gaml, an early gene product essential for the replication of the avian adenovirus CELO, can interact with HDAC1 and inhibit its enzymatic activity (85). The bovine herpesvirus 1 immediate-early protein (bICPO) has also been shown to associate with HDAC1 and activate transcription by interfering with MAD MAX-dependent transcriptional repression, thereby promoting viral infection in differentiated cells (86). Viral transforming proteins such as the human papillomavirus oncoprotein E7 are also known to interfere with the binding of HDAC1 to pRB, thereby...

Health Issues Affecting Lgbt Populations

Some preliminary studies have suggested that gay men and lesbians may be at increased risk for certain types of cancer (Dean, et al., 2000), though the reasons for these elevated risks are generally due to variables other than sexual behavior. For instance, the higher incidence of breast cancer among lesbians is likely attributable to increased rates of obesity, alcohol consumption, nulliparity and smoking and lower rates of breast cancer screening, gynecological care, and hormone exposure through oral contraceptives (Dean, et al., 2000 Office on Women's Health, 2000). Lesbians are also less likely than heterosexual women to have a Pap test (Aaron, et al., 2001), although no studies have documented higher rates of cervical cancer. Studies have found higher rates of Kaposi's sarcoma, non-Hodgkins lymphoma, Hodgkin's disease, and anal cancer among gay men, but all of these, except anal cancer, have been attributed to increased incidence of HIV AIDS (Dean, et al., 2000 Hessol, et al.,...

Alphavirus Used In Cancer Vaccines

Alphavirus vectors have frequently been applied for vaccine production. In this context, recombinant particles as well as naked nucleic acids have been applied. The proof of concept was originally demonstrated for viral surface proteins known for their potential immunogenicity and capability to induce cytotoxic T-cell (CTL) responses and protection against challenges with lethal viruses (20). Moreover, immunization against tumor challenges has resulted in some promising observations (Table 1). For instance, injection of RNA from an SFV vector expressing bacterial P-galactosidase into mice provided protection against tumor challenges (21). Administration of recombinant SFV particles expressing the P1A gene resulted in protection against P185 tumor challenges in mice (22). The human papilloma virus (HPV) E6 and E7 oncoproteins have been

VSV Gene Therapy and Vaccines

Designed to protect against respiratory syncytial virus (RSV), human papillomavirus (HPV), and viruses associated with acquired immunodeficiency syndrome (AIDS), amongst others (88-91,93-96). In addition, new generations of attenuated, nonpropagat-ing viruses are being developed where the VSV G protein has been deleted. These non-propagating viruses (AG) lacking G, which is essential for infectivity, are generated via helper-cells that supply the VSV G glycoprotein in trans (29,88,97). Budding viruses incorporate the G protein on their surface and are released. Such viruses can infect cells through the highly tropic G protein and commence replication. However, AG progeny viruses, when released from their primary targets, cannot infect other cells because they lack the G protein gene product. In vaccine studies, such viruses have been shown to retain their protective efficacy compared with their wild-type, replication competent counterparts, yet are considerably attenuated (88,97)....

Antioncogenic Properties Of

The antitumor effects of AAV had been initially reported within a few years of identification of the virus itself when it was identified that infection of herpes simplex virus (HSV)-transformed hamster tumor cells with AAV delayed the appearance of palpable tumors and increased the survival time of the animals (70). Since then, several reports have confirmed the inhibition of viral oncogenesis by a variety of DNA viruses, including bovine papillomavirus-1 (71), human papillomavirus (HPV)-16 (72-74), and Epstein-Barr virus (75). Evidence from several reports also suggested that AAV infection might protect against human cervical cancer, in part, by interfering with HPV-induced tumori-genesis (76) although studies of Stickler et al. reported a lack of correlation of between AAV infection and cervical tumorigenesis in a Jamaican population (77).

Squamous Cell Carcinoma

Scribed in women 5, 53, 54, 74, 85, 88, 91, 92 . This may however partly be explained by reporting bias. For instance, vulval squamous cell carcinomas may well be under-reported in association with HS, as this diagnosis was explicitly excluded from Mora's series of squamous cell carcinoma in a black population. Predisposing factors are rarely searched for in the literature. The occurrence of non-skin cancers suggests that general carcinogens such as tobacco may play a role. Some authors have suggested that skin cancers predominate in the perineal region 52, 82 , which raises the possibility of co-carcinogenic factors such as human papilloma virus (HPV) 52, 87, 88 and or past radiotherapy 72, 88 . The presence of these factors and other known carcinogen exposure should reinforce vigilance and encourage physicians to perform a biopsy in any case of suspicious HS lesions.

Strategies Using Nonviral Vectors In Cancer Gene Therapy

Electroporation (66,67), resulting in significantly induced cytokine levels or specific antigen expression. Electroporation has also been used to introduce plasmids that encode antisense RNA against E6 and E7 mRNA to human papilloma virus (HPV) expressing cancer cells, which resulted in a significant inhibition of tumor growth (68). Another approach involved gene gun-mediated delivery of heat-shock protein 70 (Hsp70) linked to the HPV16 E7 tumor antigen gene into antigen presenting cells (APCs). It led to an enhanced E7-specific immune response of lymphocytes after exposure to these transfected APCs (69).

Septal Excision Medial Maxillectomy and Craniofacial Resection Specimens

Most septal excision and medial maxillectomy specimens are for the less extensive or less locally aggressive neoplastic diseases, such as inverted nasal papilloma, olfactory neuroblastoma and even malignant melanoma. They are usually received as multiple fragments of mucosa with underlying bone and or cartilage. In medial maxillectomy specimens, at least the inferior turbinate is included but, depending on tumour location, all turbinates may be represented.

Neoplastic Conditions

Benign tumours squamous cell papilloma commonly occurs on the lips, cheeks and tongue and is often associated with viral warts on the hands. Neurilemmoma, neurofibroma and the granular cell tumour are not infrequently encountered. Lipoma presents as a mucosal polyp, clinically similar to a fibroepithelial polyp. Benign tumours of salivary gland origin arise in the upper lip and in the palate, usually at the junction between the hard and soft palates, the commonest of which is the pleomorphic adenoma. Benign salivary tumours are rare in the tongue and floor of mouth most salivary tumours in the lower parts of the oral cavity are adenocarcinomas. Malignant tumours as at other sites in the upper aerodigestive tract, tobacco and alcohol use are the major risk factors for oral cancers. Their effects are related to dose and duration of use together they have a multiplicative rather than additive effect. Recent interest has focussed on the role of viruses in oral malignancy. Certain forms of...

Chemopreventative Role

Cervical cancer The potential role of folate In the prevention of cervical cancer has been equivocal and results from Intervention studies on cervical cancer have been Inconsistent (Henao et al 2005, Kwanbunjan et al 2005, Sedjo et al 2003). Many of these studies have methodological limitations, Including a lack of Information on high-risk human papillomavirus (HR-HPV) Infection, a risk factor for cervical cancer. This Is notable as folate deficiency may Increase the risk of cervical cancer In Individuals Infected with HR-HPV (Plyathllake et al 2004). The most promising RCT Involved 47 patients taking an OCP who demonstrated mild to moderate Intraepithelial dysplasia. A dose of 10 mg folic acid dally over 3 months resulted In significantly lower biopsy scores In the treatment group and a significant reduction In cytology scores from baseline (Butterworth et al 1982). Other studies have shown that folic acid treatment does not alter the course of disease In patients with...

Kenneth Lundstrom PhD Contents

Alphavirus vectors can infect a broad range of mammalian cells both in cell cultures and in vivo. The presence of the RNA replicon generates extreme RNA levels in infected cells, which is the basis for the very high levels of heterologous gene expression. Application of replication-deficient vectors leads to short-term expression, which makes these vectors highly attractive for cancer gene therapy. Alphaviruses can be used as vaccine vectors for both prophylactic and therapeutic applications. In this context, the P185 tumor antigen and human papilloma virus gene E7, when administered in mice, resulted in protection against tumor challenge and tumor regression in animals with pre-existing tumors. Alphavirus vectors carrying therapeutic or toxic genes used for intratumoral injections have demonstrated efficient tumor regression. For systemic delivery, expression targeting has been obtained by the introduction of targeting sequences in the envelope structure of the virus. Alternatively,...

Risk Factors and Pathogenesis

A number of epidemiologic studies have linked sexual practices and genital viral infections to the development of anal cancer. A case control study in women and heterosexual men demonstrated that the relative risk of anal cancer is highest in those with 10 or more sexual partners or a history of anal warts and sexually transmitted infections (1). Receptive anal sex is a risk factor in both men and women. Smoking increases the risk of anal cancer up to fivefold in premeno-pausal women (2). Human papillomavirus type 16 has been implicated in the pathogenesis of anal intraepithelial neoplasia and invasive anal cancer (3). Whether HIV infection is directly involved in the pathogenesis of anal cancer remains unclear, but HIV infection predisposes to anal papillomavirus infection and an associated increased risk of anal cancer (4,5).

Physical examination

The normal pH level is not usually altered with candidal vaginitis. Microscopic examination of vaginal discharge diluted with saline (wet-mount) and 10 KOH preparations will reveal hyphal forms or budding yeast cells. Some yeast infections are not detected by microscopy because there are relatively few numbers of organisms. Confirmation of candidal vaginiti s by culture is not recommended. Candida on Pap smear is not a sensitive finding because the yeast is a constituent of the normal vaginal flora.

Clinical Presentation

A variety of dysplastic preinvasive lesions, of both squamous and glandular type, are commonly encountered within the cervix. These are usually picked up because of an abnormal cervical smear, performed in the United Kingdom as part of the NHS cervical screening programme. These abnormalities are often associated with and due to infection by human papilloma virus (HPV). Other symptoms related to cervical pathology include watery vaginal discharge and postcoital and intermenstrual bleeding. With advanced cervical tumours invading the bladder or rectum there may be urinary or bowel symptoms. Large tumours can protrude through the external cervical os into the vagina. Small cervical tumours may be asymptomatic. With advanced tumours the ureters can become obstructed with resultant hydronephrosis and renal failure - lymphoedema and deep venous thrombosis may also occur.

Clinical Investigations

This involves looking at the cervix under a special microscope (colposcope) and often taking a biopsy or performing local excision of an abnormal area of cervix (loop or cone biopsy). These areas are identified by their lack of uptake of iodine stain (acetowhite epithelium - AWE) and abnormal surface appearances (e.g., vascular punctation or a mosaic pattern). HPV testing may also be undertaken and involves molecular testing of material taken at a cervical smear. In patients with cervical discharge material may be sent for microbiological investigations. In cases of cervical tumour, radiological investigation, usually in the form of MRI, is carried out for staging purposes.

Cytologic screening

All women should receive screening Pap smears at the onset of sexual activity or at 18 years of age, because strong evidence supports the theory that routine screening with Pap smears will lower the rate of cervical cancer. B. Once three normal annual Pap smears are documented, the interval for continued surveillance with screening Pap smears may be lengthened. Pap smears that suggest invasive disease require further evaluation by colposcopy, colposcopic-directed biopsy and endocervical curettage.

Deficiency Signs And Symptoms

Epidemiological studies have also found an association between low serum carotenoid levels, including lutein and zeaxanthin levels, with all-cause mortality (De Waart et al 2001), the risk of inflammatory polyarthritis (Pattison et al 2005), breast cancer (Tamimi et al 2005), prostate cancer (Jian et al 2005), colon cancer (Nkondjock & Ghadirian 2004), cervical cancer (Garcia-Closas et al 2005, Kim et al 2004), human papilloma virus persistence (Garcia-Closas et al 2005), type 2 diabetes and impaired glucose metabolism (Coyne et al 2005), chronic cholestatic liver diseases (Floreani et al 2000), Alzheimer's disease and vascular dementia (Polidori et al 2004), and low fruit and vegetable consumption (Al-Delaimy et al 2005).

Tumor Induced Changes In Mhc Class I Presentation Of Hostderived Peptides

Additionally, tumors display classical or universal stress responses that are easily identifiable with other disease states, such as viral infection. Indeed, a number of cancers are induced by viral infection by such agents as Epstein Barr Virus and Human Papilloma Viruses. Universal stress induced responses identified in tumor cells include up-regulation of MHC class I, Hsp72, and the NK cell ligands MHC-like MICA and MICB. Interestingly, these common stress induced genes are located within the MHC class I loci of chromosome 6 (Collins, 2004). In addition, many transcriptional regulators and translational regulators are over-expressed by both tumors and virally infected cells, including Stat-1, p68 and eIF4G (Abbas et al., 2000 Bates et al., 2005 Clemens, 2004).

Little Speck in the Brassire

Fig. 12.22 One of the mamillary ducts is quite dilated and obstructed. A filling defect is visible the papilloma has been located. Have you seen the two calcifications in the immediate neighborhood You should be able to make that diagnosis by now -sjsojDau jej Fig. 12.22 One of the mamillary ducts is quite dilated and obstructed. A filling defect is visible the papilloma has been located. Have you seen the two calcifications in the immediate neighborhood You should be able to make that diagnosis by now -sjsojDau jej tion, Hannah is able to gently squeeze some more dark fluid out of the right breast. Together with Dr. Skywang, Hannah calms Mrs. Winnipeg. The reason for these secretions is most likely papillomas, she tells her, and these hardly ever turn malignant. She advises the patient to have a galactography done. For this procedure, the glandular duct in question is cannulated from the nipple with a fine blunt needle and a little contrast is given. Subsequently, a mammogram is...

Extending the Life Span of Muscle Cells

Since the moderate proliferative capacity of primary human skeletal muscle cells is a limiting factor in studies for which large numbers of myoblasts are required, several groups have tried to immortalize human myoblasts, or at least to extend their life span 123-128 . Transfection of human myoblasts with constructs that carry the gene encoding the SV40 large T antigen resulted in an extended life span of these cells while their capacity to differentiate in a nearly physiological manner was more or less well preserved. Expression of the T antigen has been used to immortalize several cell types of human origin 129 . This immortalization depends on the inactivation of tumor suppressor proteins p53, retinoblastoma gene product (RB), and the RB-related proteins p107 andp130 130 . RB, in turn, seems to bind and inactivate MyoD and myogenin, thus inhibiting dedifferentiation of myotubes 131, 132 . Therefore, in myoblasts the expression of the T antigen has to be switched off in order to...

Biological Functions of Rb and E2F

E2F can also be released from E2F Rb complexes by viral oncogenes such as the SV40 large T antigen or by the human papilloma virus E7 protein. The strains of HPV that are associated with cervical cancer encode E7 proteins with the highest affinity and the ability to degrade Rb (Munger, 2002).

Selected Photomicrographs

Cervix-vagina junction, cervical intraepithelial neoplasia, Pap smear (Figure 24-3 see V B 2) Figure 24-3. (A) Diagram of the cervix-vaginal junction. During prepuberty, the ectocervix is covered by nonkerarinized stratified squamous epithelium that is continuous with vaginal epithelium (black area). At puberty, the simple columnar epithelium extends onto the ectocervix. In the adult, exposure of rhc simple columnar epithelium to the acidic (pH) environment ol the vagina induces a squamous metaplasia, forming the transformation zone (dotted area), which is important clinically. Nabothian cysts (NB) may form in the transformation zone. (B) A biopsy of the cervix showing cervical intraepithelial neoplasia (CJN). In certain areas of the stratified squamous epithelium, the regular stratified pattern is lost such that cells near the surface are oriented vertically (arroutt) instead of horizontally. There is a variation of nuclear size and shape. Mitotic figures near the surface can be...

Mutations In The Ube3a Gene

The UBE3A gene had been known to encode the E6-associated protein, a protein interacting with the human papilloma virus, to promote the nonlysosomal degradation of the p53 protein (Huibregtse et al., 1991 Scheffner et al., 1990). The gene encodes an E3 ubiquitin protein ligase that is probably involved in the ubiquitination of a diverse range of proteins (Scheffner et al., 1993 Huibregtse et al., 1993). The UBE3A gene encodes a member of a family of functionally related proteins defined by a conserved C-terminal 350- amino acid ''hect'' domain. Hect E3 proteins appear to be important in substrate recognition and in ubiquitin transfer. RT-PCR experiments provided evidence for several isoforms differing at their N termini. Each of the mRNAs was expressed in all cell lines tested. Additional 5' untranslated exons were also identified (Kishino and Wagstaff, 1998). In fact, at least 16 exons were identified, including six exons that encode the 5' UTR. The gene spans approximately 120 kb,...

Postmenopausal Dyspareunia

As women approach middle-age and menopause, physiological aging, psychosocial factors, and declining levels of endogenously produced sex hormones caused by ovarian senescence can exert significant effects on their sexual response cycle. As such, comprehensive enquiry of dyspareunic pain characteristics and history, climacteric symptoms, as well as changes in sexual functioning, urogenital anatomy, marital partner relations that have occurred are essential in the assessment of post-menopausal dyspareunia. The many anatomical changes, within but not limited to the urogenital region, experienced by aging women (e.g., reduced vaginal and or clitoral size, loss of fat and subcutaneous tissue from the mons pubis, arteriosclerosis) can result in decreased sexual arousal, vaginal dryness, and dyspareunia (23). Dyspareunia may also result from iatrogenic efforts, including pelvic or cervical surgery and radiotherapy, and pharmacotherapy (24). Moreover, it is considered a secondary symptom of...

Division H Of Meiosis

The Papanicolaou test, or Pap smear, which consists of a light microscopic examination of cells obtained painlessly from the vagina and cervix of the uterus, is an important diagnostic test that is of considerable clinical importance in the early diagnosis of cancer of the uterus. The foreign cancerous cells can easily be distinguished from the regular uniform appearance of the epithelial cells.

Get Checked for Cancer

Each year more than 1,500 New Yorkers die of colon cancer, more than 1,200 New York City women die of breast cancer and more than 150 die of cervical cancer (New York City Department of Health and Mental Hygiene, 2004b). Only half of New Yorkers age 50 and older report ever having undergone colon cancer screening via sigmoidoscopy or colonoscopy. One in four women aged 40 and older has not had a mammogram in the past two years, and one in seven women report never having had a Pap smear. Among the activities in which the DOHMH and its partners are engaged are (1) expanding colon cancer screening efforts in high-prevalence neighborhoods through partnerships with public hospitals and the American Cancer Society, including community outreach, professional education and public health detailing activities (2) coordinating citywide resources to expand colon cancer screening capacity, educating the public and health care providers on appropriate colon cancer screening guidelines, and...

Correlation Between Antibody Induction and Tumor Growth Inhibition Increased Survival in Vaccinated Mice

Anti-idiotypic antibodies binding to the antigen-combining site of antitumor antibodies may mimic tumor antigen and induce antitumor immunity (reviewed in ref. 47). By virtue of tumor antigen mimicry, anti-idiotypic antibodies may break immunological tolerance to tumor-associated antigens that are also expressed by normal tissues (47). Wikstrand et al. (48) have recently shown that anti-idiotypic antibodies mimicking mutated epidermal growth factor receptor (EGF-RvIII) can induce EGF-RvIII-specific antibodies in mice, which protect the animals from the growth of established tumors. A recombinant vaccinia virus containing the human papillomavirus E2 protein has been shown to promote tumor regression by stimulating antibody-dependent macrophage-mediated cytotoxicity (49). Augmentation of immunoglobulin (Ig)M titers to sLe(x) and GM3 after immunization with bacille Calmette-Guerin (BCG), or with tumor cells with BCG correlated with retarded tumor growth in mice, whereas increased IgG...

Posttranslational Modifications

P53 was first shown to be ubiquitinated by a cellular factor that associated with the viral E6 protein in papilloma-virus-infected cells (Scheffner et al., 1993). It was later determined to be predominantly degraded through the ubiquitin-proteosomal pathway (Chowdary et al., 1994 Maki et al., 1996). However, in normal cells Mdm2 (Hdm2 in humans hereafter referred to as Mdm2) acts as the predominant regulator of p53 protein levels by implementing its E3 ligase activity on p53 (Haupt et al., 1997 Honda et al., 1997 Kubbutat et al., 1997). Additionally, Mdm2 can inhibit the transactivation ability of p53 (Momand et al., 1992). Maintaining p53 at low levels is critical for cellular homeostasis in unstressed conditions. p53 assists in its

Prospective Cohort Studies

There are also a number of measurable health outcomes that can be monitored to assess needs, evaluate progress and determine the impact of health interventions in urban settings. In the case of illicit drug users, we can examine HIV testing statistics to determine the proportion of individuals that have been tested in the past six months. For those who test HIV positive, the CD4 and viral load measures can also be monitored every three months. We can also look at the uptake of antiretroviral therapy among injection drug users as another good measure of health care coverage (in many urban centers the uptake is sub-optimal due to inadequate services and support). We can analyze the number of annual Pap smears to determine the level of screening in women, and we can examine the number of influenza and pneumococcal vaccinations within specific groups to provide additional measures of primary care uptake.

Adenovirus use in cancer vaccine strategies

Another obvious cancer target can be found in cervical cancers induced by the human papilloma virus (HPV). Approximately 95 of all cervical cancers are caused by HPV infection and subsequent oncogenesis. In these types of cancer, HPV-derived expression of oncogenic proteins (i.e., the E5, E6 and E7 genes) results in the transformation of normal cervical cells. Thus the E6 and E7 are TAAs, potentially allowing for specific induction of immunological effector cells specific for HPV-transformed cervical epithelium. For example, He et al. created both vaccinia virus and E1- Ad-based vectors that both encoded the HPV E6 and E7 genes (13). These constructs were both tested for their ability to induce cancer immunity in both BALB c and C57Bl 6 mice. The results of these studies demonstrated that depending on the strain of mouse model tested, either CD4+ or CD8+ T cells were stimulated by the viral vaccines. The class of immune effector cells elicited resulted in strikingly different...

Analytic Epidemiology

Genital HPV infection more common in HS patients has been repeatedly drawn toward the possible role of hormonal factors 4, 12, 14 . No convincing data are available. In a study of 66 women with HS, 23 had acne and 23 (34.8 ) were significantly obese (body mass index, BMI, > 30 kg m2). Plasma androgens were compared with controls matched for BMI and hirsuteness and no difference was documented 12 . The prevalence of HS has been found to be higher among patients attending a sexually transmitted disease (STD) clinic than in an unselected general population 6 . In principle, a selection bias may explain such a difference. However, an association with chlamydial infections has been also suggested. A case-control study based on patients in a STD clinic was unable to confirm the association with chlamydial infection 15 but, quite unexpectedly, it found a higher prevalence of genital human papilloma virus (HPV) infection among HS cases as compared with controls. The significance of such a...

Vulvar Vestibulitis Syndrome

Vulvar Vestibulitis Treatment

Other factors Many other physically based etiological theories of vulvar vestibulitis exist however, they are based on uncontrolled studies and should be interpreted with caution. These include human papillomavirus infection (57), faulty immune system functioning allergies (6,58), urethral conditions (e.g., interstitial cystitis) (59), vaginismus (46), sexual abuse (44,60), and psychological factors (e.g., somatization disorder) (46). It is important to note that controlled studies of sexual abuse (10,12) show no difference between affected and non-affected women, although a history of depression and physical abuse has been linked to vulvar vestibulitis (8). Furthermore, an increase in pelvic floor muscle tension (61,62) has also been associated with vulvar vestibulitis. Although the tensing of pelvic floor musculature may represent a protective reaction against, or a conditioned response to vulvar pain, this increase in tension is likely to only exacerbate the pain.

Angiogenesis Basic Mechanisms and Role in Head and Neck Squamous Cell Carcinoma

The vast majority (95 ) of head and neck tumors are squamous cell carcinomas (HNSCC), the most common type of cancer affecting the lining of the airways and upper digestive organs. HNSCC comprises a wide variety of epithelial malignant lesions affecting the nasal cavity and paranasal sinuses, nasopharynx, oral cavity, lips, alveolar ridge and retromolar trigone, floor of the mouth, tongue, hard and soft palat, tonsil, pharyngeal wall, larynx, hypopharynx, and salivary glands. Cancer in these locations originates from the cuboidal cells along the basement membrane of the mucosa and usually has profound impairing effects on breathing, speaking, and swallowing. The disease is characterized by local tumor aggressiveness, early recurrence, and high frequency of second primary tumors. Neoplasias of the head and neck region are relatively infrequent in comparison with cancer occurring in the breast, lung, prostate, and colon and represent approximately 5.6 of all tumors....

Genetic Models For Head And Neck Cancer Research

Hpv Promoter

Because the oral cavity is lined by a stratified squamous epithelium, there are certain immediate considerations. This is the incorporation of promoters that have been used predominantly for skin models. These include viral promoters, such as human papillomavirus (HPV) E6 and E7, and cellular promoters, i.e., genes that are associated with basal and suprabasal cells. In the latter context, promoters for keratins 5 and 14 will lead to the targeting of genes to basal cells. Seven hundred base pairs of the 3' downstream sequence was used to drive the expression of an intronless human K14 gene in transgenic mice, and the construct was expressed in a fashion analogous to the endogenous K14 gene in the basal layer of stratified squamous epithelia 64 , Suprabasal promoters include those for keratins 4 and 13 (preferred partners in oral cavity, whereas in skin it is keratins 1 and 10) as well as for involucrin 65 . Six thousand base pairs of the 5' upstream K5 sequence directed proper basal...

Nora A Janjan John M Skibber Miguel A Rodriguez Bigas Christopher Crane Marc E Delclos Edward H Lin and Jaffer A Ajani

Anal cancer is a rare neoplasm, accounting for less than 2 of all cancers of the digestive tract. Despite its rarity, specific risk factors for anal cancer development have been identified. High rates of human papillomavirus (HPV) infection have been observed in anal cancer, and an increased risk of anal HPV infection has been demonstrated in HIV-seropositive patients. An inverse relationship has been shown between the CD4 count and HPV infection. Immunosuppression from other causes, like organ transplantation, increases the risk of anal cancer by a factor of 100. Smoking increases the risk of anal cancer by a factor of 2 to 5 conversely, a prior diagnosis of anal cancer increases the risk of lung cancer by a factor of 2.5.

The Driving Force

Latent viruses associated with certain forms of cancer can also drive CD8+ T cells to senescence, as illustrated by the accumulation of CD8+CD28 T cells with reactivity to the human papilloma virus E7 antigen in cervical cancer patients (Pilch et al., 2002). Other viruses associated with chronic infection, such as Hepatitis C, also seem to elicit expanded populations of CD8+ T cells that lack CD28 expression (Kurokohchi et al., 2003). The common thread in all of these situations is chronic antigenic stimulation, which seems to result in massive cell division of antigen-reactive CD8+ T cells, ultimately causing them to reach what might be considered the endstage of their differentiation pathway, namely replicative senescence. Clearly, most memory T cells encounter their nominal antigen only once or twice over an individual's lifespan, and it is only those CD8+ T cells with reactivity to antigens that are never cleared from the body that have the potential to continue dividing...

Communicable Disease

Elevated risk of various forms of cancer among immigrants groups may be attributable, at least in part, to the significant gaps in health screening utilization by immigrants, including those living in urban areas. It was reported from an analysis of the 2000 National Health Interview Survey that women who had immigrated to the U.S. during the previous 10 years were among those least likely to have had a mammogram within the previous two years or a Pap test within the previous three years (Swan, et al., 2003). Among men and women, recent immigrants were among those least likely to have had a fecal occult blood test or endoscopy within the recommended screening interval. A greater proportion of those surveyed who lived in Metropolitan Statistical Areas (MSAs) had had a mammogram in the two previous years compared to non-MSA residents. (An MSA is defined by the U.S. Office of Management and Budget (OMB) as a county or group of counties with at least one city of 50,000 or by the Census...

Secondary prevention

Secondary prevention includes actions taken to stop or delay the progression of disease. The term is usually applied to measures for the detection of disease at its earliest stage, i.e. in the presymptomatic phase, so that treatment can be started before irreversible pathology is present. The early recognition of hypertension through routine testing (screening) of patients allows treatment during the presymptomatic phase of the illness process. Screening for cervical cancer allows the treatment of cervical dysplasia, a premalignant condition. Other examples include mammography and endoscopy for polyps of the large bowel.

Cancer Treatment

In a RCT, 90 patients with cervical lesions infected with human papilloma virus were given either a capsule containing 200 mg of (-)-epigallocatechin-3-gallate (EGCG) and or an ointment containing 200 mg of polyphenon E to be applied daily (Ahn et al 2003). There was a 69 responder rate when compared with placebo, with the ointment showing the best effects.

Cervical Cancer

About 12,800 women in the United States developed cancer of the uterine cervix each year, and about 4,800 women died of the disease. The incidence of cervical cancer has dramatically decreased from 32 cases per 100,000 women in the 1940s to 8.3 cases per 100,000 women in the 1980s. Women who are at risk for developing cellular abnormalities include those who smoke and those with a history of sexually transmitted diseases, human papillomavirus (HPV) infection, low socioeconomic status, two or more lifetime sexual partners or immunosuppression.

Operative techniques

The incision used should provide maximum exposure of the pelvis and allow thorough evaluation of the upper abdomen. If present, ascites should be aspirated and sent for cytopathologic evaluation. A small amount of heparin should be added to prevent clotting of bloody or mucoid specimens. If ascites is not present, abdominal washings with saline should be obtained from the pericolic gutters, the suprahepatic space, and the pelvis. A Pap test of the diaphragm should be taken.

Vcervix

The Pap smear also may be used to evaluate hormonally a woman in many different clinical situations by establishing a maturation index based on the morphology of 100 cells (Tible 24-3). D. Trichomonas vaginalis is a flagellated protozoan that is sexually transmitted. It produces a vaginitis characterized by an inflammatory Pap smear with numerous neutrophils, strawberry-colored mucosa, and discharge (leukorrhea). Postcoital bleeding is a common complaint. In a wet preparation of the vaginal discharge, the tumbling motility of the organism can be observed. E. Ciardnerella vaginalis is a bacterial infection often associated with Mobiluncus or Bac-lernides. It is not sexually transmitted. It produces a vaginitis characterized by no inflammatory Pap smear, no changes in the mucosa, and discharge. In the sniff test of the vaginal discharge, a drop of potassium hydroxide produces a noticeable fishy, amine-likc smell.

Tumorigenesis

Of keratinocyte and mammary epithelial cells (Neyns et al, 1999 Li et al, 2000). Although c-Jun overexpression in transgenic mice does not result in the development of tumors, c-Jun ablation or its inhibition suppresses tumor progression (Grigoriadis et al, 1993). c-Jun knockout mice have drastically reduced number and size of hepatic tumors (Eferl et al, 2003). c-Jun ablation in the skin of the tumor-prone K5-SOS-F transgenic mice results in less EGF receptor expression in basal keratinocytes and smaller papillomas, and transgenic mice expressing c-Jun TAM67 in the basal keratinocytes escape chemically induced papilloma development (Zenz et al., 2003 Young et al, 1999).

Neoplasm

Although neoplasms are not a cause of acute or chronic pharyngitis, tumors arising in the oropharynx often present with signs and symptoms that most commonly indicate an infectious etiology. Patients treated for infectious pharyngitis, who do not improve, warrant further investigation to identify a possible neoplasm. Common presenting symptoms of oropharyngeal cancer include unilateral sore throat, dysphagia, odynophagia, weight loss, and otalgia. On physical exam, an asymmetric pharyngeal mass is the hallmark clinical finding and warrants further investigation (Fig. 4). The mass may be ulcerative, fungating, or mucosal covered and detectable only by palpation. Cervical adenopathy is present with advanced disease that has metastasized to the locoregional lymph nodes. Risk factors for oropharyngeal cancer include tobacco and alcohol abuse. The human papilloma virus has a role in a subset of oropharyngeal tumors.

Figure 2228

The examination of Pap smears is a valuable diagnostic tool in evaluating the vaginal and cervical mucosae (Fig. 22.29). The superficial epithelial cells are scraped from the mucosa, spread on a glass slide, fixed, and then stained with the Papanicolaou stain (a combination of hematoxylin, orange G, and eosin azure). Examination of the Pap smear provides valuable diagnostic information about the epithelium regarding pathologic changes, response to hormonal changes during the menstrual cycle, and the microbial environment of the vagina. mucosa and vulvar skin known as vulvovaginitis. These pathologic conditions are readily diagnosed with Pap smears. Specific antimicrobial agents (antibiotics, sulfonamides) are used together with nonspecific therapy (acidified 0.1 hexetidine gel) to restore the normal low pH in the vagina and thus prevent the growth of these agents. In addition, cervicovaginal Pap smears are widely used for diagnosis of early cervical cancer as well as endometrial...

Vaccines

AAV vectors are also being examined as potential vehicles for tumor vaccines. In one study, an AAV-based tumor vaccine was developed by constructing a chimeric gene containing a human papillomavirus (HPV) type 16 E7 CTL epitope fused to a heat shock protein. When administered intramuscularly, this vaccine was able to eliminate tumor cells in synge-neic animals in a manner that was dependent on CD4+ and CD8+ cells. This suggests that vaccination with this gene could be a therapeutic treatment for cervical cancer containing HPV-16 E7 (295)

Angiogenesis

The tumour-secreted factors responsible for inducing the switch from unvascularized to pro-angiogenic phenotype are not completely understood. Experiments in transgenic mice bearing spontaneous tumours indicate that only a subset of cells, as few as 4-10 , become angiogenic, and this subpopulation of cells confers increased tumourogenicity on the whole tumour (407, 411-412). In a transgenic mouse tumour model containing the genome of the bovine papilloma virus type 1, the switch to the angiogenic phenotype appeared to be associated with the ability to export basic FGF from the cell (411).

Benign Tumours

Proliferative lesions (radial scar complex sclerosing lesion, intraduct papilloma, nipple adenoma, myoepithelioma) these lesions are due to epithelial proliferations of various complexities which can present as firm palpable masses. Mammography may show parenchymal deformity and foci of microcalcification, thus necessitating cytological assessment. The latter usually shows a highly cellular sample with some degree of nuclear atypia indicating either a core biopsy or local excision. Some of these lesions may harbour DCIS which can only be confirmed or discounted following histological examination.

Chronic Diseases

Smoking rates are extremely high (about 70 ) among homeless people (Connor, et al., 2002). As a result, COPD is a common health problem among older adults. In a study of shelter residents in San Francisco, the prevalence of COPD based on spirometry was 15 , or more than twice the prevalence in the general population (Snyder and Eisner, 2004). Smoking also contributes to the high risk of cancer, especially among homeless single men. In a study from Scotland that adjusted for age and socioeconomic deprivation, the incidence of cancer of the oral cavity and pharynx, larynx, esophagus, and lung in homeless men was 139 , 87 , 61 , and 23 higher than expected, respectively (Lamont, et al., 1997). Homeless people are also less likely to receive recommended cancer screening than the general population among homeless women age 40 and over in Los Angeles County, only 55 had undergone a Pap smear and only 32 had undergone a mammogram within the last year (Chau, et al., 2002). Thus, interventions...