Abnormal Pap Smears And HPV

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Papillomaviral Life Cycle

The HPV life cycle is tied to the differentiation of stratified squamous epithelia (Fig. 2). The papillomavirus is thought to gain entry to the basal layer of the epithelium at sites of wounding, attaching to the cell via interaction with an integrin, the candidate papillomavirus cell-surface receptor. In this poorly differentiated cell the viral genome establishes itself as a low copy number nuclear episome. A subset of viral genes (the early genes) are selectively expressed at low levels these genes contribute to the regulated expression of viral genes, viral DNA plasmid replication and cell growth. The initially infected cell is induced to proliferate at a faster rate than the neighboring, uninfected cells, resulting in its clonal expansion and thereby the formation of a papilloma. These events are collectively known as the early or nonproductive stage of the viral life cycle because the infected,

Human Papilloma Virus and EGFlike GFs and Receptor Expression

The human papilloma virus (HPV-16, -18, -33) plays a dominant role in the etiology of cervical carcinogenesis (327,328). The viral proteins, E6 and E7, which are expressed by the high-risk types of HPV, are able to bind to and inactivate the host tumor suppressor proteins p53 and Rb, which normally inhibit cell cycle progression (329,330). Inactiva-tion of p53 and Rb by E6 and E7 leads to dysregulated entry of cells into the S-phase of Approximately 66 of cervical carcinomas and 100 of vulvar condylomas that are the result of HPV-infection express high levels of TGF-a mRNA (325). Because HPV-16 and HPV-18 are associated with approx 60-90 of cervical intraepithelial neoplasias, and since these viruses have a major transforming potential, these data suggest that overexpression of TGF-a may be associated with the early stages of disease after HPV infection. In this context, the E6 and E7 genes are involved in the immortalization and transforming activities of HPV, and the effects of...

Human Papillomavirus Types

Human papillomaviruses (HPVs) are associated with various benign and malignant epithelial proliferative diseases. Over 100 genotypes of HPV are recognized. In vitro studies showed that a group of phylogeneti-cally related mucosal HPV types has oncogenic potential their E6 and E7 proteins interfere with cell cycle regulation by mediating degradation of p53 and pRb proteins, respectively. These oncogenic HPVs, designated high-risk (HR) HPVs, are an important causal factor in carcino-genesis of the uterine cervix. 1 Epidemiological studies have shown that HR-HPVs include types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82 and probably also types 26, 53, and 66. 2 Nononcogenic or low-risk (LR) genital HPVs are phylogenetically distant from the HR-HPVs. They include HPV 6, 11,40, 42, 43, 44, 54, 61, 70, 72, 81, and CP6108. Their E6 and E7 proteins are less competent in interfering with p53 and pRb functions, and they can cause benign proliferations such as condylomata...

The Most Commonly Studied Papillomaviruses

More than 200 PV types exist in humans, and halfofthese have been isolated and formally described. The number of additional PV types in mammals is probably unlimited, although so far only a few dozen have been described. The tremendous diversity of PVs is not such a formidable barrier to understand PV biology as one might fear, as most research was based on only nine HPVs and three PVs from other mammals. Human papillomavirus 1 (HPV-1) induces plantar (foot-sole) warts and HPV-2 common (hand or face) warts. HPV-5 and HPV-8 are associated with epidermodys-plasia verruciformis, a skin neoplasia linked to a genetic risk factor. HPV-6 and HPV-11 cause genital and laryngeal warts. HPV-16, HPV-18, and HPV-31 are the most prominent types causally linked to anogenital and some head and neck carcinomas. Bovine papillomavirus 1 (BPV-1) causes fibropapillomas and BPV-4 mucosal lesions in cattle, and the cottontail rabbit papillomavirus (CRPV) cutaneous lesions in rabbits. Owing to its medical...

Papilloma

Papilloma Eyelid Margin

INTRODUCTION A papilloma is any lesion that is papillomatous in growth pattern that is a smooth, rounded, or pedunculated elevation. The squamous papilloma is a generic term for any papilloma of nonviral origin. Also known as a fibroepithelial polyp, acrochordon, or skin tag, this neoplasm commonly occurs on the eyelid, neck, axilla, and groin. This is a benign tumor of squamous epithelial origin, and this is the most common benign lesion found on the eyelid, representing 15 to 30 of all benign lesions on the lids. It can be seen at any age but occurs most frequently in patients over the age of 30 years. CLINICAL PRESENTATION Papillomas on the eyelid present as small 2 to 3 mm flesh-colored sessile or pedunculated masses. They may be single or multiple. Occasionally they can develop on the palpebral or bulbar conjunctiva. They typically have thickened hyperkeratotic epithelium and may show multiple finger-like projections. On close examination it may be possible to identify a central...

Papillomaviruses HPV

While most lesions are benign, some, especially those caused by HPV-16, -18 and other oncogenic HPV types, may progress to premalignant and malignant lesions. Papillomaviruses are causally associated with cervical cancer, which is diagnosed in 15 000 American women annually and causes approximately 4500 deaths. Types 6 and 11 are responsible for common genital infections and also for recurrent respiratory papillomatosis (RRP), a devastating but rare disease which may be acquired at birth as a result of vaginal delivery by an infected mother. Interferon a (Intron, Aferon) may provide a significant level of efficacy as intralesional therapy for condyloma acuminata (genital warts). Following a course of three times weekly intralesional injection, approximately 40 of IFN recipients achieved a complete response, as opposed to 20 of placebo recipients. As is the case with virtually all HPV therapies, approximately 25 of treated patients developed recurrences. The discomfort of...

Tumor Progression Models For Studying The Epigenetic Lesions Preceding Metastasis

In this model, beginning with normal mouse skin, sequential topical application of different mutagens, such as the polycyclic aromatic hydrocarbon dimethylbenzanthracene (DMBA), and tumor promoting agents, such as 12-0-tetra-decanoylphorbol-13-acetate (TPA), gives rise to a complete spectrum of the stages of tumorigenesis, from premalignant papilloma to highly metastatic tumors with well defined genetic lesions in H-ras or p53 (2-8). The cumulative appearance of DNA methylation aberrations has been widely demonstrated with this model, thus underlining its versatility as a tool for comparative studies of human cancer epigenetics.

Global Dna Methylation Alterations During Mouse Skin Tumor Progression And Metastasis

Interestingly, HPCE reveals that there is a continuous loss of 5-methylcytosine during tumor progression (Figure 1B), with strikingly sharp falls at two points. The first of these occurs in the transition from nontumorigenic (MCA3D cells) to benign papilloma cells (PB and MSCP6) and represents a drop of 25 of the total genomic content in 5-methylcytosine. This loss coincides with the mutational activation of H-ras, exemplifying the synergism between genetic and epigenetic processes on the road to metastasis. The second important hypomethylation event is a loss of around half (54 ) of the total 5-methylcytosine genomic content, which, most importantly, occurs when the transformed cells undergo a phenotypic transition from MSC11B9 epithelial cells to MSC11A5 spindle cells. This morphological change is associated with a striking increase in their tumorigenicity and metastatic potential but the underlying cause is not fully understood.

Obstetriciansgynecologists Obgyns

These health care providers are the ones that most women go to for basic female needs, such as Pap smears, birth control, female infections, and routine pregnancy and delivery. As far as fertility evaluation, the OB GYN is capable of beginning some initial testing and treatment. For example, your OB GYN doctor may order blood tests, perform a laparoscopy, or prescribe a trial of a low-dose fertility medication. The amount of fertility evaluation and treatment that your OB GYN can provide is likely the result of the doctor's own training, interest, and comfort in the field of fertility. However, at some point, if you do not become pregnant from these preliminary methods, you will likely want to see a fertility specialist, the reproductive endocrinologist.

Discharge And Home Healthcare Guidelines

Make sure the patient knows all the postprocedure complications. Provide a phone number to call if any complications occur. Ensure that the patient understands the need for ongoing Pap smears if appropriate. Vaginal cytological studies are recommended at 4-month intervals for 2 years, every 6 months for 3 years, and then annually.

Pelvic Ultrasound Examination

The pelvic ultrasound is almost always performed using a vaginal approach. That's because it allows the doctor to see your internal pelvic organs up close and with great detail and clarity. For this exam, you'll be asked to remove your underwear and recline on the exam table, much as you do for a pelvic or Pap test. You'll have a sheet draped over your lower body for privacy. The lights in the room will be dimmed and a specially shaped vaginal probe transducer will be inserted into your vagina. Prior to insertion, the probe will be covered with a lubricated condom for your safety and comfort. Because the transducer is inside of your vagina and close to your cervix, it is able to transmit clear and detailed images of your uterus, tubes, and ovaries, which are projected on the television-like monitor.

Genome Organization and Expression

All PVs have a double-stranded, circular DNA genome of 7-8 kbp. There is a region of approximately 1 kbp that is called the long control region (LCR), upstream regulatory region (URR), or noncoding region (NCR). This region contains transcriptional enhancers and promoters, the DNA replication origin, and sequences required for genome maintenance (MME minimal maintenance element). The viral promoters are regulated by cellular factors and the viral E2 proteins. In most viruses, the genes are organized in the order LCR-E6-E7-E2 E4-(E5)-SIR-L2-L1, where SIR represents the short intergenic region (see Figure 3). The coding region is divided into the early and late regions. The early region is expressed in the lower, more undifferentiated layers of a papilloma and proteins expressed from this region are designated E1 through E8 (see below). The capsid antigens, L1 and L2, are encoded by the late region and are expressed in the more superficial, differentiated cells of a papilloma. One...

Taxonomy and Evolution

PVs and polyomaviruses share two properties, namely small circular double-stranded DNA genomes and nonenveloped isosahedral capsids. As a consequence, they had once been lumped into one virus family, Papovaviridae. When it became clear that they have different genome organizations and no genomic similarity, they were split into the two families Papillomaviridae and Polyomaviridae. The taxonomy of PVs was built on the comparison of genomes rather than on amplifiable viruses or on serol-ogy, since PVs do not multiply efficiently in cell culture, and since no consistent serology could be established based on natural infections. The genome-based taxonomy of PVs was founded in the 1980s with DNA hybridization data, and was later shifted to nucleotide sequence comparisons. By definition, a PV type is unique when the nucleotide sequence of its L1 gene differs by at least 10 from the L1 sequence of any other PV type. As a consequence, PV types are genotypes and not 'serotypes', although a...

Fibrocystic Breast DRG Category 276

The College of American Pathologists has categorized the types of fibrocystic breast condition according to the associated increased risk for subsequent invasive breast cancer and the particular histologic (microscopic) change that is present. These types include the following no increased risk (nonproliferative changes, including microcysts, adenosis, mild hyperplasia, fibroadenoma, fibrosis, duct, apocrine metaplasia, and gross cysts) slightly increased risk (relative risk, 1.5 to 2 proliferative changes without atypia, including moderate hyperplasia and papilloma) moderately increased risk (relative risk, 4 to 5 proliferative changes with atypia or atypical hyperplasia) and significantly increased risk (relative risk, 8 to 10 ductal and lobular carcinoma in situ).

Clinical manifestation

Occurs on glans penis and scrotum in men, and labia minora, mons veneris, and fourchette in women rare cervical involvement soft, red papules or nodules arising at the site of inoculation lesions eventually ulcerate and produce red, friable, granulo-matous plaques and nodules ulcers with clean, friable bases and distinct, raised, rolled margins autoinoculation results in lesions on adjacent skin occasional hyper-trophic or verrucous plaques, with formation of large, vegetating masses resembling genital warts swelling of the external genitalia in later-stage lesions

Host Range and Viral Propagation

As for the human papilloma viruses, the inability to culture MCV is thought to be due to the need for keratinocytes at a defined stage of differentiation, which is difficult to obtain or sustain in vitro but which is necessary for completion of the uncoating process. In this respect, MCV behaves as a host-dependent conditional lethal mutant.

Taxonomy and Classification

Papillomaviruses belong to the Papovaviridae family of DNA viruses that includes mouse polyoma and the monkey virus, SV40. The family name, 'Papova' is derived from the first two letters of the three principal virus groups, PApilloma, POlyoma, and simian VAcuolating virus (SV40). Based on comparative structural and genetic characteristics, these viruses are considered as two discrete subfamilies Papillomavirus and the Polyomavirus (polyoma, SV40, JC, BK). The members of the Papovaviridae family share a number of properties including a relatively small size, nonenveloped icosahedral capsids, and a double-stranded, covalently closed, supercoiled DNA genome that replicates in the nucleus of infected cells in association with cellular histones. Classification of papillomaviruses into types is based first upon species specificity, and second, upon the degree of relatedness of the viral genomes. For example, six different PV types that infect cattle have been isolated and described. The...

Pathology and Histopathology

BPV-l associated fibropapillomas in cattle occur either singly or as multiple nodules and may reach several centimeters in size. They may appear sessile or pedunculate and lobate, fungiform or verrucate. Other bovine PVs cause flat or filiform teat papillomas and BPV-4 causes alimentary papillomas that can progress to carcinomas. CRPV-induced papillomas occur as multiple, gray or black, well-keratinized Fibropapillomas show a marked proliferation of the underlying fibroblasts within a dense matrix of collagen. Fibroplasia occurs within the first week after infection whereas hyperplasia of the epithelia may not be visible before 4-6 weeks. This long delay in the appearance of epithelial changes is similar to that observed with the strictly epithelial PVs such as CRPV where it may take 3-8 weeks for a papilloma to appear. The PV life cycle is exquisitely attuned to the progressive vertical differentiation that occurs during maturation of the epidermis (see Fig. 3) and the study of the...

Geographic and Seasonal Distribution

HPV infections have a worldwide distribution, as illustrated by skin warts and genital warts, their well-known clinical manifestations. All around the world, HPV5 and HPV16 are the types most frequently associated with EV skin cancers and cervical carcinomas, respectively. Differences in geographic distribution have been noted for some HPV types. A higher prevalence of cervical cancer associated with HPV45 has been reported in Africa, and with HPV52 or HPV58 in China and Japan. HPV13 and HPV32 cause an oral disease mostly restricted to Central and South America, Alaska and Greenland.

Hpv5 X B Rtrx7

Figure 3 Phylogenetic tree of human and animal papillomaviruses based on the amino acid sequence of the L1 protein. (Adapted from Chan SY, Delius H, Halpan AL and Bernard HU (1995) J. Virol 69 3074.) Figure 3 Phylogenetic tree of human and animal papillomaviruses based on the amino acid sequence of the L1 protein. (Adapted from Chan SY, Delius H, Halpan AL and Bernard HU (1995) J. Virol 69 3074.) types 6 and 11 associated with condylomata acuminata, and for HPV types 16,18 and 45 associated with genital cancers. For genital HPVs, the intratype variability does not exceed 2 in the coding region and 5 in the LRR. In contrast, an unusually high degree (about 10 ) of intratypic variability has been observed in the LRR and the E6 and LI genes of HPV5, leading to the identification of three HPV5 subtypes. To what extent this genetic variability affects the biological properties of the viral proteins is still poorly understood. HPV6 variants with short sequence duplications in the regulatory...

Transmission and Tissue Tropism

Epithelial cells or reserve cells of the endocervical glandular epithelium are likely to be susceptible to nonproductive HPV infection, which may result in the development of in situ or invasive adenocarcinomas. Esophageal, laryngeal, tracheobronchial, nasal, conjunctival and urinary epithelia are uncommon sites of infection with the known HPV types. Transmission of cutaneous HPVs occurs through direct contact with an infected tissue or through indirect contact with contaminated objects or surfaces (swimming pools). Genital HPVs are sexually transmitted, as shown by partner tracing and epidemiologic studies. Transmission of HPV6 and 11 by passage through an infected birth canal is probably at the origin of laryngeal papillomatosis of young children. In utero infection with genital or EV-specific HPVs has been recently considered. Indirect transmission of genital HPVs may occur through contaminated fomites or instruments and by laser plumes.

Replicative HPV Life Cycle

Papillomaviral DNA replication is dependent on the host DNA replication machinery (DNA polymerase a primase, DNA polymerase 6 PCNA, replication protein A (RPA) and topoisomerases I and II) and viral proteins, El and E2TA. El is an ATPase-dependent DNA helicase that is thought to assemble the host DNA replication machinery on the viral genome. El binds the viral genome at a specific site positioned at the 3' terminus of the LCR. El also binds to the host DNA pola. E2TA associates with El and is thought to help tether El to the viral genome through its ability to bind ACCN6GGT motifs located nearby to the El DNA binding site. In basal epithelial cells that are nonproductively infected and harbor the viral genome as a nuclear plasmid, DNA synthesis occurs through Cairns (theta) structures and initiates close to or at the DNA binding site for El. The viral genomes replicate on average once per cell cycle. Inheritance of the viral genomes to daughter nuclei requires E2TA, which has been...

Does Ivf Hurt And What Are The Risks

You are typically sedated during the egg retrieval process and again during the embryo transfer process and therefore quite comfortable. Most women say that the procedure is painless and compare it to having a Pap smear. Some women note that after the procedure they have cramping, which usually goes away with rest and a mild pain reliever.

Virus Transmission among Individuals

Portals of virus entry into the body include the skin, respiratory tract, intestinal tract, oropharynx, urogenital tract, and conjunctiva. In some cases, viruses use a particular portal of entry because of particular environmental or host-behavior factors and in other cases because of specific viral ligands and host-cell receptors. In many cases, disruption of normal host-defense mechanisms leads to entry that might otherwise be thwarted for example, papilloma-viruses may enter the deep layers of the skin via abrasions, acid-labile coronaviruses may enter the intestine protected by the buffering capacity of milk, and influenza viruses may enter the lower respiratory tract because a drug has dampened cilial action of the respiratory epithelium.

Surveillance Of Peutzjehgers Patients

Mark's Polyposis Registry, which has been modified by other groups, include the following annual pancreatic ultrasound exams annual pelvic ultrasound exams in females, and testicular ultrasound exams in males biennial upper gastrointestinal endoscopic exams beginning at age 10 biennial colonoscopic exams beginning at age 25 and biennial small bowel X-ray studies starting at age 10. Any gastrointestinal polyps detected should be removed endoscopically and those polyps that cannot be endoscop-ically resected should be removed surgically via laparot-omy with intraoperative endoscopy. 6 In addition, mammography should begin at age 25 and be repeated every 5 years until age 35, then every 2 years until age 50, followed by yearly exams after 50 years of age. Pap smears are recommended every 3 years. 7,32 Family members of PJS patients should be enrolled in surveillance programs if they have clinical evidence of PJS or a detectable STK11 mutation.

Screening versus Diagnostic Tests

Examples of routine population screening currently used in the health care field include Pap smears for women to predict their risk for cervical cancer, mammograms for women to predict their risk for breast cancer, the PPD skin test to predict exposure to tuberculosis mycobacterium (TB) in health care workers, and the prostatic antigen screening (PSA) test for men to predict their risk for prostate cancer.

Cardiovascular Disease

Within the preventive aspects of health care in women, cardiovascular disease should have more attention. The main argument for this statement is the fact that about 40 of women will die from cardiovascular disease and around 20 from malignant disease. In other words, risk factors for cardiovascular disease and blood pressure are more important than a Pap smear.

Common Methods for Generating Immortalized Cell Lines

The most common method for generation of immortalized cell lines is to isolate primary cultures of the cells of interest and then to introduce either SV40 large T antigen (5-7,9,13) or human papilloma virus (8) by in-vitro trans-fection. Since transfection of primary cultures of epithelial cells is relatively inefficient, this approach works well if you can isolate large numbers of cells of interest (5,7,13). It is then necessary to select colonies that have integrated one or more copies of the transgene. In the CF field this approach has been used largely to generate either tracheal (5-8) or bronchial (9) epithelial cell

Future Perspectives

Some two decades ago, only one human virus, EBV, was accepted as a candidate human tumor virus. Since then, the oncogenic potential of human papillomavirus, hepadnavirus and retrovirus has been clearly established. Now it has become evident that virus infections that may result in tumor formation are quite frequent. On a worldwide scale, more than 20 of all malignant tumor forms in females and about 8 of the tumors in males may be the late consequence of a previous virus infection. In most cases, long latency periods of many years or several decades elapse between primary infection by tumor viruses and first symptoms of cancer (Table 1). All human tumor viruses are widespread in the world population. They contribute to tumor disease, mainly by initiation of oncogenesis, but are not sufficient by themselves to cause a tumor. Thus, all human tumor viruses are important risk factors for cancer, but require additional events. This implies that mere proof of an infection with a tumor virus...

Clinical Use of erbBReceptors as Prognostic Factors

In 6 11 normal cervical tissue samples, Goeppinger et al. (371) found strong EGFR staining, using frozen tissues samples from punch biopsies. The staining reaction was confined to the basal and deep parabasal cell layers. Staining was independent of the day of the menstrual cycle, age, or the presence of inflammatory disease. In contrast to the normal epithelium, in all 27 CIN samples (with or without HPV association), homogenous EGFR staining could be observed. In CINs, all dysplastic cells exhibited stronger EGFR staining. No correlation between HPV infection and EGFR staining, localization, or intensity could be found. No EGFR staining could be detected in the more differentiated cell layers of the normal cervical epithelium. This finding suggests that there is an inhibition of EGFR expression in the terminal phase of squamous epithelium cell differentiation.

RNA Virus Vector Systems

Poliovirus, a positive-strand RNA virus, has been used to express a number of foreign genes. Poliovirus vectors expressing epitopes derived from hepatitis A virus, rhinovirus 14, human papillomavirus 16, foot-and-mouth disease virus and HIV have been produced. A poliovirus-HIV chimera has been shown to elicit anti-HIV antibodies in rabbits. Furthermore, this antiserum neutralized a wide range of American and African HIV-1 isolates. The major disadvantage of polio, relative to the negative-strand RNA virus vector systems, is that the systems that have been developed thus far have a limited capacity for foreign sequences.

Effects of Virus Infection on the Host Cell

There are several families of DNA viruses that are the cause of or are associated with tumor induction in animals and cell transformation in cultured cells. These include polyoma-, adeno-, herpes-, papilloma-, hepadna- and poxviruses. In contrast to the RNA viruses, the genes of DNA viruses responsible for transformation are viral in origin and required for virus replication.

Eyelid Lesions and Tissues of Origin

Sweat Gland Disease

Of the benign lesions derived from the epidermis many can look rather similar clinically. Some may remain epidermal in location, but many extend into the underlying dermis. Epidermal lesions include the papilloma, actinic keratosis, seborrheic keratosis, inverted follicular keratosis, ichthyosis, keratoacanthoma, lentigo, milia, molluscum contagiosum, and acquired melanosis. When epidermal cells become buried beneath the surface, keratin can accumulate to form an epidermoid cyst.

Evaluation of Eyelid Lesions

Lesions Definition

From several recent large series looking at the frequency of eyelid lesions benign processes account for approximately 70 to 75 of all lesions, and malignant neoplasms for 25 to 30 (1-5). Among the benign lesions the most frequent diagnoses are squamous papilloma (26 ), nevus (22 ), cysts (20 ), seborrheic keratosis (13 ), vascular lesions (9 ), and neural lesions ( 1 ). The most common malignant tumor on the eyelid is the basal cell carcinoma followed in rapidly descending order by squamous cell carcinoma, sebaceous cell carcinoma, and malignant melanoma. Other rare tumors such as Kaposi's sarcoma, adnexal carcinomas, and Merkel cell tumor are occasionally seen, as are metastatic cancers. One large series of nearly 1100 malignant eyelid tumors from China showed the frequencies of basal cell and sebaceous cell carcinomas to be nearly equal at 38 and 32 , respectively, quite different from the usually quoted values from the Western literature. However, most other studies give the...

Molluscum Contagiosum Dimple Warts

Medical Dermatology Human Figure

Molluscum warts occur characteristically in small children and in young adults, although they may be seen occasionally in any age group. They present as single or grouped papules, and parents will often indicate there was a single lesion present for some time. The incubation period after exposure has been estimated to vary from 14 days to 6 months. Molluscum contagiosum (MC) virus is a member of the poxvirus family and is not related to human papilloma virus, the cause of common verrucous warts.

Sebaceous Cell Carcinoma

Basal Cell Carcinoma Eyelid Margin

DIFFERENTIAL DIAGNOSIS The differential diagnosis includes basal cell carcinoma, squamous cell carcinoma, papilloma, blepharitis, chalazion, ocular cicatricial pemphigoid, cutaneous horns, discoid lupus, pyogenic granulomas, lacrimal sac tumors, and superior limbic keratoconjunctivitis.

Histopathologic Terminology

Granulation Tissue Wound Healing Photos

Koilocytes are vacuolated keratinocytes with eccentrically placed, basophilic, shrunken nuclei surrounded by clear halos. They are found in the upper spinous and granular cell layers of the epidermis in human papillomavirus infections (verruca vulgaris, in the eyelid). Papillomatosis Papillomatosis is characterized histologically by abnormally elongated epidermis and papillary dermis resulting in irregular undulation of the epidermal surface. Papillomatosis is seen most commonly in seborrheic keratosis and verruca vulgaris (shown).

Squamous Cell Carcinoma

Squamous Follicular Keratosis

INTRODUCTION Squamous cell carcinoma is a malignant tumor that most commonly affects elderly, fair-skinned individuals. It arises from keratinocytes of the epidermis. Unlike the more common basal cell carcinoma, squamous cell carcinoma tends to arise in precancerous areas of skin alteration or in areas of skin damaged by chronic sun exposure, ionizing radiation, carcinogens (e.g., arsenic), psoralen plus ultraviolet A (PUVA) therapy for psoriasis, and the human papilloma virus. Intrinsic factors that may contribute to its development include xeroderma pigmentosum, oculocutaneous albinism, and immunodeficiency. Chronic skin dermatoses, inflammation, ulceration, and contracted scars also are associated with the development of this tumor. In fact, scarring of the skin is the most common intrinsic factor leading to this tumor in black patients. Lymphatic spread and perineural invasion are possible. DIFFERENTIAL DIAGNOSIS The differential diagnosis includes basal cell carcinoma, sebaceous...

Erythroplasia of Queyrat

Erythroplasia Queyrat

Arises from squamous epithelial cells of the glans penis or inner lining of prepuce multiple contributing factors including chronic irritation (urine, smegma), inflammation (heat, friction, maceration) and infection (herpes simplex virus infection, human papillomavirus infection) Minimally raised, erythematous plaques, which may be smooth, velvety, scaly, crusted, or verrucous ulceration or distinct papillomatous papules suggest progression to invasive squamous cell carci-

Hysterosalpingogram

The HSG is performed shortly after you have completed your monthly period bleeding. The procedure is usually carried out in a hospital or an outpatient setting where x-ray equipment is available. Some large and well-equipped fertility offices may have this equipment on-site. For the procedure itself, you are placed in the same position as for a Pap test. The doctor places a thin tube into your vagina and threads it up into your cervix. A fluid dye is injected through the tubing while an x-ray of your pelvis is performed. X-ray images follow the contours of your pelvic organs as the dye fills your uterus and up into your fallopian tubes.

Primary Nursing Diagnosis

Treatment depends on the stage of the cancer, the woman's age, and concern for future child-bearing. Preinvasive lesions (CIS) can be treated by conization, cryosurgery, laser surgery, or simple hysterectomy (if the patient's reproductive capacity is not an issue). All conservative treatments require frequent follow-up by Pap tests and colposcopy because a greater level of risk is always present for the woman who has had CIS. A cone-shaped piece of tissue is removed from the cervix after epithelial involvement is clearly outlined as described with the cone biopsy. The cone includes all the abnormal and some normal tissue. Following this procedure, the woman can still have children. The major complication is postoperative bleeding.

Origins of Multistage Theory

In a rarely cited paper, Charles and Luce-Clausen (1942) developed what may be the first quantitative multistage theory. They analyzed observations on skin tumors from mice painted repeatedly with ben-zopyrene. They assumed that benzopyrene causes a mutation rate, u, and that cancer arises by knockout of a single gene following two mutations, one to each of the two alleles. If t is the time since the start of painting with the carcinogen, then the probability of mutation to a single allele is roughly ut, and the probability of two hits to a cell is (ut)2. They assumed that painting affects N cells, so that N(ut)2 cells are transformed, and that the time between the second genetic hit and growth of the transformed cell into an observable papilloma is i.

Mechanisms of Functional Tumor Suppressor Loss

Viral oncoproteins can interact with tumor suppressor gene proteins. The human papillomavirus (HPV) is a small DNA virus that causes warts. Various subtypes of HPV are associated with cervical cancer. The viral transforming protein E7 has the ability to interact with the retinoblastoma protein, thus interfering with the cell cycle checkpoint controlled by the retinoblastoma protein. Similarly, another HPV gene, E6, interacts with the p53 gene, causing the degradation of the p53 protein, thus allowing the cell cycle to go unchecked. see also Apoptosis Breast Cancer Cancer Cell Cycle Chromosomal Aberrations Colon Cancer Oncogenes.

Host Range and Virus Propagation

PVs infect a broad range of vertebrate species and are especially prevalent in mammals. Three PV infections have been described in avian species the genomes of two have been cloned and partially characterized thus far (chaffinch and gray parrot). Papillomatous lesions have also been described in species of amphibians (e.g. newts and salamanders) and reptiles (e.g. snakes, turtles and crocodiles) although a PV etiology has not yet been confirmed. Infection with specific PVs has been confirmed in approximately 50 different mammalian species. One of the hallmark features of PVs is pronounced host specificity with infection being typically restricted to closely related animals of a given family. For example, CRPV naturally infects the cutaneous epithelium of wild cottontail rabbits, and experimental infection of related jackrabbits or snowshoe rabbits will result in the growth of papillomas and production of infectious particles. In contrast, although experimental infection of domestic...

Sexually Transmitted Diseases Introduction

Sexually transmitted diseases (STD) are a diverse group of viral, bacterial, protozoal, and ectoparasitic infections that have a common route of transmission through sexual intercourse. Infectious organisms associated with STDs include Chlamydia trachomatis Neisseria gonorrhoeae bacterial vaginosis, vulvovaginal candidiasis, trichomoniasis syphilis herpes simplex papillomavirus (genital warts) genital herpes and HIV. Infection by each of the above organisms has its own pattern of clinical patterns medications treatments prognosis transmission dynamics host response to infection and patterns of sexual contact.

Viruses Associated with Inhibition or Suppression of Apoptosis

P53 Human papillomavirus E2 Papovaviridae The human papillomavirus (HPV) E6 binds to p53 and prevents its DNA binding and transactivation and or results in the ubiquitin-mediated degradation of p53. The latter occurs in highly oncogenic, high-risk serotypes, such as HPV16 and 18. In these cases, E6 serves to deliver p53 to E6-AP (E6 associated protein), an ubiquitin protein ligase. This, of course, prevents p53-mediated apoptosis due to unregulated cell cycle progression in response to the HPV E7 protein. Simian virus 40 (SV40) large T antigen (LT) binds and inhibits p53, thus preventing apoptosis due to constitutive activation of the cell cycle by LT.

Association of HPVs with Human Cancers

Certain types of HPVs, such as type 16,18, 31 and 33, are associated with human anogenital cancers, and are referred as high-risk HPVs. These cancers include cervical cancers in women and penile cancers in men. The advent of Pap smears, which provide early detection of cervical cancer precursor lesions in women, has led to a significant decrease in deaths due to cervical cancer in countries where there is good access to health care. Nevertheless, cervical cancer remains a leading cause of death by cancer among women. More than 95 of cervical cancers are associated with infection by the sexually transmitted, high-risk anogenital PVs. HPV DNA can be detected in these cancers and cells derived from these cancers. The viral DNA is commonly found to be integrated into the cellular genome. The sites of integration appear relatively random with regard to the host genome, but specific with regard to the viral genome. Integration leads to the disruption of the 3' portion of the viral early...

Transmission and Epidemiology

PV infections are only stable when the pathogen reaches basal layers of an epithelium, for example, in wounds. PV infections result from physical contact between healthy and infected epithelia that peripherally release PV particles (e.g., during desquamation of the skin). As sexual intercourse leads to physical contact between genital epithelia, infections by many HPV types are considered sexually transmitted diseases. Epidemiological data support this mechanistic concept and document a rapid increase of genital PV infections in male and female individuals after commencement of sexual activity. Epidemio-logical evidence also supports the view that the risk to develop cervical carcinomas increases with young age at the start of sexual activity and with the number of sexual partners per lifetime. Additional risk factors are long-term use of anti-ovulants, multiparity, and tobacco smoking. Epidemiology provided a foundation for the concept of 'high-risk' and 'low-risk' HPV types. Both...

Prevention and Control

Treatment of papillomas in animals is not routinely prescribed. Typically the disease is self-limiting although of variable duration. Unlike HPV infection of humans, there is little economic impact resulting from PV-associated disease in animals. Infection of cattle primarily affects the hide with little or no consequence to the quality or harvest of beef. Benign warts or sarcoids in thoroughbred show horses or race horses can however reduce the commercial value of the animals. In contrast however, models of PV infection in animals have seen extensive use in the evaluation of prophylactic and therapeutic modalities prior to human clinical trials against HPV. bacteria. More recent work in which the LI and L2 proteins have been expressed to high levels in insect cells, yeast, or from vaccinia vectors has shown that self-assembly into 'virus-like particles' (VLPs) can occur in the absence of viral DNA. VLPs are currently being evaluated for use in prophylactic vaccination of humans...

Major Molecular Targets of Selected Dietary Chemopreventive Phytochemicals to Induce Apoptosis

Carcinomas in human papilloma virus-16 transgenic mice 84 . Several studies have reported that HIF-2a is upregulated in tumor parenchymal cells and in tumor-associated macrophages (TAM), which are recruited to the hypoxic, avas-cular regions of tumors by growth factors and chemokines resulting in tumor progression 81,85,86 . A number of HIF-regulated angiogenic factors, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), VEGF receptor (VEGFR), IL-8, iNOS, and angiopoietins, are released by macrophages 81,87 . Many of these factors further accelerate inflammatory angiogenic process, thereby triggering tumor growth 88 .

Gender Ethnicracial And Life Span Considerations

Conduct a pelvic examination. Observe the patient's external genitalia for signs of inflammation, bleeding, discharge, or local skin or epithelial changes. Observe the internal genitalia. The normal cervix is pink and nontender, has no lesions, and has a closed os. Cervical tissue with cervical cancer appears as a large reddish growth or deep ulcerating crater before any symptoms are experienced lesions are firm and friable. The Pap smear is done before the bimanual examination. Palpate for motion tenderness of the cervix (Chandelier's sign) a positive Chandelier's sign (pain on movement) usually indicates an infection. Also examine the size, consistency (hardness may reflect invasion by neoplasm), shape, mobility (cervix should be freely movable), tenderness, and presence of masses of the uterus and adnexa. Conduct a rectal exam palpate for abnormalities of contour, motility, and the placement of adjacent structures. Nodular thickenings of the uterosacral and...

Clinical Features of Infection

Genital HPV-associated lesions represent the most commonly diagnosed viral sexually transmitted disease. Condylomata acuminata and Bowenoid papules are found mostly in young adults, on the external genitalia and in the anal region. Condylomata acuminata are soft exophytic proliferations, Bowenoid papules are flat or somewhat elevated, often pigmented, usually multiple. In spite of their usual association with HPV16 and their features of intraepithelial neoplasia, they have a rather benign clinical course, in contrast to solitary lesions of genital Bowen's disease affecting individuals over 50 years. Subclinical macules or papules can be detected on the penis and vulva under magnification, after the application of 5 acetic acid. Anal lesions with a variety of morphological appearance and with features of intraepithelial neoplasia are found at the anorectal junction in HIV-infected males. HPV infection of the cervix results mostly in flat aceto-whitening areas corresponding to low-grade...

Diagnostic Tests

ProbeTec test uses strand displacement amplification 1-13-1 and the GenProbe Aptima test uses transcription-mediated amplification. All three tests amplify the cryptic plasmid which is found in 99 of the clinical isolates. 14 Unfortunately, the Abbott LCx test, which employs the ligase chain reaction, is no longer commercially available. The NAATs are extremely sensitive and can be applied to noninvasive specimens such as first-catch urine and self-administered vaginal swabs. However, NAATS detect dead as well as living organisms and may give false-positive results, particularly in low-prevalence settings, and they are relatively expensive. Liquid Pap smear medium for CT NG collection has also been used with acceptable results. 15 As with all testing, each laboratory must establish an ongoing quality-assurance program to validate the test results. 16 Two nonamplified nucleic acid probe tests are commercially available which can diagnose both C. trachomatis and Neisseria gonorrhoeae...

Replication Cycle

State and is replicated along with cellular DNA in a cell cycle-dependent manner. PV infections are usually long-lived and persistent and these cells must provide a reservoir of infected cells for the overlying virus producing tissue. As the infected cells differentiate and migrate upward to the stratum spinosum, there are changes in viral gene expression and vegetative viral DNA replication begins. Expression of the viral capsid proteins, L1 and L2, is first detected in cells ofthe stratum spinosum and virus-specific cytopathic effects are most pronounced in the stratum granulosum. Virions are assembled in the upper differentiated layers of the papilloma and are found throughout the nuclei, frequently organized into paracrys-talline arrays, in cells which are destined to be sloughed from the epidermis. Viral transcription, translation, and replication are regulated through both positive and negative cellular processes that change during terminal differentiation. In fibropapillomas,...

Virus Propagation

The complete life cycle of PVs requires a stratified, differentiated epithelium because vegetative viral DNA replication and late gene expression can only take place in differentiated keratinocytes. To reproduce this in the laboratory, several xenograft techniques have been developed. Small pieces of epithelial tissue infected with virus and implanted in the renal capsule of an immuno-compromised mouse will produce viral particles. Skin from various species can also be grafted onto immuno-compromised mice and either infected with virus or transfected with viral DNA. The infected xenograft will form a papilloma-like lesion that will produce virion particles. Artificial skin equivalents (organotypic rafts) can also be established in tissue culture from keratino-cytes and fibroblasts of various species. These rafts support the viral life cycle and produce viral particles.

Diagnosis

HPV infections are diagnosed by the detection of a cutaneous or mucosal neoplasia, that is, a wart. Wart-like lesions, condylomata acuminata, can also occur at the cervix under the influence of the low-risk HPV-6 and HPV-11. High-risk HPVs induce flat condylomas which can be diagnosed by visual inspection through a colpo-scope. The traditional diagnosis of cervical PV infections is the Papanicolaou test ('pap test'), a technique developed in the 1950s and predating all knowledge about PVs. The Pap test aims to detect and classify dysplasia by microscopic observation of stained cervical exfoliated cells. Diagnostic criteria include a perinuclear halo (believed to result from accumulation of E4 protein) and nuclear enlargement (a consequence of polyploidies). In recent years, Pap tests have become complemented by DNA diagnostic detection of PVs.

Treatment

The treatment of many benign cutaneous or mucosal PV lesions will typically be a 'wait and see' approach. For those cases where treatment is necessary, surgical procedures can be based on excision by knife, laser, cryotherapy, or caustic substances. The application of concentrated solutions of salicylate is a traditional treatment of common warts, and podophyllin has been used in the treatment of genital warts. Antiviral drugs targeting PVs include interferons and imiquimode. Cervical pre-cancerous lesions are surgically removed by excision of a cone-shaped wedge from the cervix or loop excision of the transformation zone. For information about treatment of malignancies, appropriate handbooks about gynecological oncology, etc., should be consulted.

Genetic Disease

Cancer risk increases with age, as the probability of accumulating mutations in the DNA increases with time. Environmental factors include lifestyle (e.g., smoking), diet (e.g., saturated fats from red meat), and exposure to certain chemicals (e.g., asbestos, benzopyrenes), ionizing radiation (e.g., X-rays, radon gas), ultraviolet radiation (e.g., sun, tanning beds), and certain viruses (e.g., human papillomavirus, Epstein-Barr virus). Heredity also plays a role in oncogenesis, as mutations in certain genes increase the probability of developing certain types of cancer. For instance, women who inherit a mutated copy of the BRCA1 or BRCA2 gene have a greatly increased probability of developing breast cancer at a young age.

Immune Reponse

The immunobiology of HPV infections is far from being fully understood. Strong immune responses are not usually generated because HPVs most often induce latent infection or chronic disease, and productive infection does not lead to host-cell lysis. A major problem has been the unavailability of native HPV antigens, adequate target cell systems and well-characterized assays. In natural infection, humoral responses are essentially directed against conformational epitopes borne by intact viral particles. Low levels of antibodies reacting against HPV1 virions are found in patients with skin warts or in nonselected individuals, with a frequency that varies from 10 to 100 , according to the method used, the age group and the type of warts. Antibodies neutralizing HPV11 infectivity assayed in the nude mouse xenograft system have been detected in patients with genital warts or laryngeal papillomas. Owing to the availability of VLPs and the design of sensitive VLP-based ELISA tests, the...

Shrimp Parvoviruses

IHHNV and HPV are each nonenveloped icosahedral viruses, 22 nm in diameter and containing a linear single-stranded DNA (ssDNA) genome. IHHNV virions have been reported to contain four polypeptides as detected by sodium dodecyl sulfate polyacrylamide gel electro-phoresis (SDS-PAGE) and silver staining (74, 47, 39, and 37.5 kDa). For HPVchin, only one virion structural protein has been observed (54 kDa) but analysis of HPVmon has revealed a doublet protein band (57 kDa major band and 54 kDa minor band). In addition to differences in tissue tropism, the viruses display differences in cytopathology. During HPV infection, cellular lesions correspond to typical densonucleosis in insects with the formation of enlarged, densely stained, and Feulgen-positive nuclei. In IHHNV infections, lesions are discrete, often difficult to detect, and display characteristic eosinophilic intranuclear Cowdry type A inclusion bodies.

Verruca Vulgaris

Verruca Vulgaris Treatment

INTRODUCTION Also known as a viral wart, or a viral papilloma, this lesion is a papilloma caused by an epidermal infection with the human papillomavirus, which is spread by direct contact and fomites. Immunocompromised patients are more susceptible to infection. Verruca vulgaris is more common in children and young adults between the ages of 5 and 20 years. They may occur anywhere on the skin, including the eyelids. Two common variants exist Verruca filiformis or filiform warts (which include the subgroup known as digitate warts) and verruca plana, or flat warts. CLINICAL PRESENTATION These lesions begin as small tan or gray papules that slowly enlarge to become elevated papules with an irregular hyperkeratotic, papillomatous surface. The filiform variety is the most common variety on the face and eyelid, and is distinguished by columnar, hyperkeratotic projections. The digitate variety has several such spikes joined at the base. Lesions along the eyelid margin may induce a mild...

Melanocytic Nevus

Lentigo Maligna Differential Diagnosis

HISTOPATHOLOGY Melanocytic nevi are composed of nevus cells, which are melanocytes that have lost their long dendritic processes. Nevus cells are oval to cuboidal, have clear to pale eosinophilic cytoplasm, and contain a variable amount of melanin. The nevus cells form nests, which often coalesce when they are in the dermis. Melanocytic nevi may have discrete nests of nevus cells at the dermoepidermal junction ( junctional melanocytic nevus ), both at the dermoepidermal junction and within the dermis ( compound melanocytic nevus ), or confined within the dermis ( intradermal melanocytic nevus, shown below). On the eyelid, compound nevi may be papillomatous with a seborrheic keratosis-like appearance to their epidermis. DIFFERENTIAL DIAGNOSIS The differential diagnosis includes lentigo maligna, malignant melanoma, neurofibroma, balloon cell nevus, papilloma, seborrheic keratosis, inverted follicular keratosis, oculodermal melanocytosis, dermatofibroma, pigmented basal cell carcinoma,...

Mri In Brain Tumors

Sbrt Radiation Plans

As the recruitment of vascular networks is crucial for tumor extension and proliferation, vascular morphology is a critical parameter in determining malignant potential. Dynamic blood volume imaging of patients with brain tumors can provide unique information about tumor grade and vascularity that is not appreciated from CT, T2-weighted images, or contrast-enhanced T1-weighted images. TDL can mimic high-grade neoplasms, as both enhance with contrast on T1-weighted imaging and have perilesion edema and variable mass effect and central necrosis (Zagzag et al., 1993). There have been numerous reports of unnecessary surgery and radiation therapy in these patients as a result of the difficulty of diagnosing this process from primary glioma or lymphoma. PWI may play a helpful role in the characterization of these processes, as the vasculature of TDL remains normal in contrast to the neovascular proliferation of tumors (Cha et al, 2001). MRI measurements of CBV have been shown to correlate...

Genital Cancer

Clinical studies, and especially data from molecular biology, suggest that certain types of human papillomavirus (HPV) are of etiological importance for genital cancer. In developing countries, carcinoma of the cervix uteri is the most frequent type of female cancer. HPV DNA can be found in 80-90 of the tumors, and the early genes E6 and E7 are usually expressed. The most prevalent type in epidermoid carcinomas is HPV 16. HPV 18 may be preferentially associated with adenocarcinomas. Other types like HPV 31,33,35,39,45,51,52 or 56 have been detected in a few cases of squamous cell carcinoma each. HPV DNA was also demonstrated in the less prevalent carcinomas of the vulva, the vagina, the penis and the anus HPV 16 is again the most frequent type, followed by HPV 18, HPV 6 and HPV 11. The significantly elevated prevalence of individual HPV types in cancers compared with the normal population led to the concept of HPVs with higher (HPV 16, 18, 45) and lower (HPV 6, 11) carcinogenic...

Benign Tumors

Papilloma Squamous papillomas are uncommon benign tumors, constituting less than 5 of all esophageal neoplasms. These lesions consist of a fibrovascular core with multiple finger-like projections covered by hyperplastic squamous epithelium. They usually occur as solitary lesions ranging from 0.5 to 1.5 cm in size. Most patients are asymptomatic, but some with larger polyps may present with dysphagia. Multiple papillomas may be present in patients with a rare condition known as eso-phageal papillomatosis (2). Papillomas may be recognized on double-contrast esopha-grams as small, sessile polyps with a smooth or slightly lobu-lated contour (Fig. 1) (3). Occasionally, papillomas may be larger and more lobulated, or they may have a bubbly appearance as a result of trapping of barium between the frond-like projections of the tumor (4). Although papillomas are always benign, they cannot be differentiated with certainty from early esophageal cancers on radiographic criteria....

Malignancies

Loss of either the receptor or the ligand resulted in animals devoid of germ cells. In postnatal testes, c-kit has been found to be expressed in Leydig cells and spermatogonia, whereas SCF was expressed in Sertoli cells (Love-land and Schlatt, 1997). Testicular tumors develop from Leydig cells with high frequency in transgenic mice expressing human papilloma virus 16 (HPV16) E6 and E7 oncogenes (Kondoh et al. 1991, 1994). These tumors express both c-kit and SCF, suggesting that an autocrine loop may contribute to the tumorigenesis (Kondoh et al., 1995) associated with cellular loss of functional p53 and the retinoblastoma gene product by association with E6 and E7 (Dyson et al., 1989 Scheffner et al., 1990 Werness et al., 1990). The observation that defective signaling mutants of SCF (Kondoh et al., 1995) or c-kit (Li et al., 1996) inhibited formation of testicular tumors in mice expressing HPV16 E6 and E7 indicates that c-kit activation is pivotal to tumorigenesis in these...

Specific History

Common warts are caused by human papillomavirus infection clinical lesions develop after a latent period of weeks to several months. They have a peak incidence in late childhood and adolescence and then the occurrence sharply declines. They may, however, be found in all age groups. Usually patients will recall a single lesion, which is often interpreted at first as a splinter or thorn.

DNA Tumor Viruses

Human papilloma virus Investigation of the transforming activities of the human papillomaviruses (HPV) is of interest for reasons of medical importance as well as scientific interest. Nearly all human cervical carcinomas are associated with the presence of DNA from either HPV 16 or HPV 18. Completion of the life cycle of the HPVs is unusual in that the early and late stages of the life cycle appear to take place in different stages of epithelial cell differentiation, and complete viral replication takes place only in benign papillomas, or warts. This feature has so far made it impossible to grow the HPVs in culture, a problem that has slowed analysis. However, molecular analysis has been informative. Cervical carcinomas are associated with the presence of the viral genome integrated into the host DNA in a manner that allows for expression of the early region of the viral genome. This region is quite complex, with at least eight open reading frames there is evidence that at least five...

Endometrial Biopsy

The endometrial biopsy is almost always performed in your doctor's office. For the procedure itself, you will be placed in a position very similar to when you are having a Pap test performed. The doctor then inserts a thin plastic strawlike tube through your cervix and into the uterus to obtain a piece of the uterine lining. You may experience some discomfort and cramping during the procedure. You may also have some slight spotting for a few days afterward.

Other Pathogens

BDNA ISH, e.g., could detect about one or two copies of human papillomavirus (HPV) DNA in cervical cancer cell lines and proved to be highly specific in discriminating cells infected with HPV type 16 from those with HPV type 18 DNA. 23 The same technique was subsequently applied to normal and HPV-infected cervical biopsy specimens and the obtained results led to the preliminary interpretation that bDNA ISH, as an adjunct to conventional histopathology, can perhaps improve future diagnostic accuracy at least in cases of HPV-mediated neoplastic disease. 24