Reversing Cervical Dysplasia Naturally

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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...

Classification of Pap Smear Abnormalities

Remember, Pap smear gives information about cervical cytology. Two different systems exist that describe the possible findings of a Pap smear 2. Bethesda system (SIL, squamous intraepithelial lesion) Describes three things (1) the adequacy of the Pap test performed, (2) the degree of abnormality, and (3) a description of the cells

Pap smear report

Conventional Pap smear, liquid based cytology, or other. 5. A description of any ancillary testing or automated review that was performed (eg, human papillomavirus HPV , AutoPap). B. Specimen adequacy. The adequacy of the Pap smear specimen is typically reported as follows. 1. Unsatisfactory. Smears that are unsatisfactory for evaluation may have scanty cellular material or may be obscured by inflammation, blood, or debris so that more than 75 percent of the cells are uninterpretable. Unsatisfactory Pap smears should always be repeated in two to four months. If the cells are obscured by inflammation, an attempt should be made to clear the inflammatory process (eg, treat cervicitis or vaginitis) prior to repeating the smear. 2. Endocervical cells not present. The presence of metaplastic and endocervical cells indicates adequate sampling of the transformation zone of the cervix, the area at risk for neoplasia. Most women without an endocervical...

Laryngeal papilloma

The juvenile form is believed to be acquired during birth from maternal vaginal warts. The condition does not manifest, however, until months or years later when significant papillomata develop. In general, those who present early usually present with airway obstruction, while older children usually present with progressive hoarseness. Treatment is extremely difficult and frequent recurrence is a rule rather than exception. At laryngoscopy, there is usually extensive involvement of the whole larynx simultaneous tracheal and pharyngeal involvement by the papillomata is not uncommon. Repeated CO2 laser therapy offers the best control of the disease. In severe cases, antiviral therapy including interferon therapy may be tried. Although the effectiveness of treatment is unpredictable, spontaneous regression of the papilloma may occur at any age. The adult form typically presents with progressive hoarseness and laryngoscopy, and reveals either a solitary papilloma or multiple but discrete...

Human papillomavirus

The human papillomavirus (HPV) belongs to the family Papovaviridae and up to 100 types have been recognized. The HPVs are naked viruses with a dou-ble-stranded DNA genome. Clinically they cause genital warts or conduloma acuminata affecting the mucosal lining of the genital tract as well as cutaneous sites. Warts are generally benign, self-limiting tumors which may regress spontaneously. All layers of the epithelium are represented in the wart and the basement membrane is not breached. The virus enters one or a few cells in the epithelium (basal germinal layer) presumably through a traumatic process. The virus replicates exclusively in the nucleus and cell growth is stimulated. Several human and animal papillomaviruses are associated with naturally occurring cancers. There is a long latency period with the need for a number of cofactors for the progression of the papillomas to malignancy. This is consistent with a multistep mechanism of carcinogenesis. It is speculated that...

Cervical Dysplasia

Cervical dysplasia and cervical cancer lie on a continuum of conditions. Cervical dysplasia can take one of three paths RISK FACTORS FOR CERVICAL DYSPLASIA AND CERVICAL CANCER Human papillomavirus (HPV) infection 80 of cases Alcohol, 2 to 4 drinks wk, can increase risk of HPV infection. Risk factors for cervical dysplasia LOCATION OF CERVICAL DYSPLASIA TRANSFORMATION ZONE Cervical dysplasia almost always forms at transformation zone. Two things to remember about Pap smear Are the results of a Pap enough to diagnose cervical cancer No-Pap smear only gives cytology. Colposcopy and biopsy are needed for histology, which is necessary for diagnosis, staging, and treatment. PAP SMEAR

Computers Meet Cytometers The Birth of Analytical Flow Cytometry

Recording and storing cell images was a nontrivial task in the 1960s, when mainframe computers occupied entire rooms, required kilowatts of power for both the computer and the mandatory air-conditioning, and cost millions of dollars, for which the buyer received a computer with speed and storage capacity exceeded a thousand-fold by a 2005 model laptop costing under US 1000. Nonetheless, when minicomputers became available in the middle of the decade, there were at least a few groups of analytical cytologists ready to use them. The TICAS system, assembled at the University of Chicago in the late 1960s, interfaced Zeiss's (Oberkochen, Germany) commercial version of the Caspersson microspec-trophotometer to a minicomputer, with the aim of automating interpretation of Pap smears (Wied and Bahr 1970). Around the same time, the promising results obtained with the Cytoanalyzer in attempts to automate reading of Pap smears (Tolles 1955) encouraged executives at the International Business...

Herpes Life Cycle Exam Short Notes

22 Human Papillomavirus Type 31 Life Cycle in HPV-Positive Human Cervical Carcinoma Cells Another common method for detection of DNA viruses is signal amplification-based tests such as the hybrid capture assay (HC Digene, Gaithersburg, MD). HC assays have been used to detect human papillomavirus (HPV), cytomegalovirus (CMV), and hepatitis B virus (HBV) DNA. The HPV HC 2 assay using probe B is capable of detecting 13 carcinogenic types of HPV that include oncogenic HPV16 and HPV18. The potential predictive value of this test was suggested by the observation that about one of every six women with a negative papanicolaou (Pap) test and a positive HPV HC 2 test will develop an abnormal Pap smear within approx 5 yr (4). A comparison of PCR and HC assays for the detection of CMV DNA in different blood compartments showed that there was a significant correlation between the results of HC with whole blood and PCR with peripheral blood lymphocytes (5). The sensitivity of the PCR and HC assays...

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.


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.

Special Considerations

HIV-INFECTED WOMEN In general, there is no need to change the approach to pelvic pain and bleeding in HIV-positive women. Physicians must look for associated infections and complications of chronic illness. The rate of vaginal and pelvic infections as well as cervical dysplasia is high in this cohort of patients. In a cross-sectional survey of 386 women younger than age 50, with and without HIV, neither infection nor immunosuppression affected menstruation or the rate of abnormal vaginal bleeding.21 This was also seen in a study of 85 seropositive women, although the power of the study was low.22

Scheduling your first appointment

Note Obviously, if you're seeing more than one potential GYN, they all can't do testings like Pap smears or mammograms. Your insurance company won't pay for more than one. You can make your first appointment a getting to know you event, with more talk than action. (See Chapter 9 for more on what to expect during your first exam.)

Special circumstances

When an infectious organism is identified, the patient should be contacted to determine if she is symptomatic. Antibiotic therapy is indicated for symptomatic infection. Asymptomatic trichomonas infection should be treated. Most patients with only reactive changes due to inflammation will not have an organism identified on Pap smear. The Pap smear does not need to be repeated unless the patient is HIV positive. D. Management after colposcopy biopsy. Colposcopy biopsy of women with ASC-US will either yield a histologic abnormality (eg, CIN II or III), which should be treated as appropriate or show no abnormal findings. In the latter case, if HPV testing was not performed or showed a low-risk type, then follow-up cytological testing in 12 months is recommended. 1. Management of women who test positive for high-risk HPV types, but have CIN I or less on colposcopy biopsy consists of HPV testing at 12 months postprocedure with repeat colposcopic referral if...

Negative colposcopyendocervical curettage

Occasionally, normal appearing endometrial cells will be reported on a Pap smear. The presence of these cells is reported only in women > 40 years of age. In these cases, endometrial biopsy should be performed. E. Follow-up after treatment. Follow-up Pap smears are recommended every three to four months for the first year after any treatment for dysplasia. Women with cervical dysplasia present at the LEEP or cone margin or in the concomitant endocervical curettage also need follow-up colposcopy with endocervical sampling every six months for one year. Routine surveillance can be resumed if there is no recurrence after the first year. Surveillance consists of Pap smears on a yearly basis for most women and on a twice-yearly basis for high-risk women (ie, HIV positive).

Martin Sapp and Hans Christoph Selinka

This chapter outlines the generation and application of human papillomavirus type 33 (HPV33) pseudovirions. The method describes (1) the construction of vaccinia viruses recombinant for the major and minor HPV capsid proteins, L1 and L2, respectively (2) the transfection of Cos7 cells with a marker plasmid replicating to high copy numbers (3) the expression of L1 and L2 using the vaccinia virus expression system (4) the extraction, purification, and analysis of HPV33 pseudovirions and (5) their use in pseudoinfection assays. These pseudovirions are structurally indistinguishable from native virions and are therefore valuable tools for the study of papillomavirus-cell interactions. The methods described can be adopted for other nonenveloped DNA viruses and may be useful for gene transfer. Key Words Papillomavirus vaccinia virus expression system pseudovirus pseudoinfection HPV capsid protein DNA encapsidation virus-like particle nuclear extract density gradient purification gene...

Background Definition

Sunlight exposure is an established independent risk factor for the development of SCC. SCC arises more commonly in the sun-exposed areas, including the head, neck and arms, but also occurs on the buttocks, genitals and perineum.14 Other risk factors for SCC include older age, male sex, Celtic ancestry, increased sensitivity to sun exposure, increased number of precancerous lesions and immunosuppression.4,15,16 Exposure to oral psoralens, arsenic, cigarette smoking, coal-tar products, UVA photochemotherapy and human papilloma virus have been associated with SCC. Genetic disorders that predispose to SCC include epidermodysplasia verruciformis, albinism and xeroderma pigmentosum.

Cutaneous Manifestations

Intertriginous infections with either Candida or Trichophyton are often seen in patients with HIV and can be diagnosed by microscopic examination of potassium hydroxide preparations of lesion scrapings. Treatment includes topical imidazole creams, such as clotrimazole, miconazole, or ketoconazole. Scabies occurs in about 20 percent of HIV-infected patients, but classic intertriginous lesions are less common. Any patient with a scaly, persistent pruritic eruption should have lesions scraped and examined histologically for scabies mites. Treatment is with permethrin 5 cream or lindane lotion. Human papillomavirus infections occur with increased frequency in immunocompromised patients. Treatment is cosmetic or symptomatic and may include cryotherapy, topical therapy, or laser therapy. Other dermatologic conditions that occur with increased frequency among HIV-infected patients include psoriasis, atopic dermatitis, and alopecia. Referral for dermatologic consultation is appropriate.

Vaccination therapies

Are expressed in a lineage-related manner and are also detected in normal tissue (e.g., MAGE, BAGE, GAGE, NY-ESO-1, SSX) 2) tumor-restricted antigens, which are expressed only on cancer cells (e.g., Melan A MART-1, tyrosinase, gp100, CEA, NY-BR-1, rab 38) 3) unique tumor restricted antigens, including point mutations of normal tumor antigens (e.g., P-catenin, MUM-1, CDK-4, p53, ras) 4) overexpressed antigens of normal tissue (e.g., HER-2 neu, p53, MUC-1) and 5) viral antigens (e.g., human papillomavirus, hepatitis B virus, Epstein-Barr virus).

Choosing how to approach a hysterectomy

Nonetheless, vaginal hysterectomy has advantages. It's an ideal method for removal of the fairly normal-sized uterus for benign conditions like fibroids, adenomyosis (growths in the uterine wall), refractory dysfunctional bleeding, abnormal Pap smears, and prolapse (collapse of the uterus into the vagina through the cervix). And because this surgery involves no large abdominal incisions, recovery is usually quicker than with a laparotomy. Unfortunately, many younger surgeons aren't getting enough exposure to this procedure in training programs, and it's an underused procedure in gynecology today.

Aetiology and risk factors

Warts are caused by HPV, of which there are over 70 different types. Viral warts are most common at sites of trauma such as the hands and feet, and lesions probably result from inoculation of virus into minimally damaged areas of epithelium. Plantar warts are often acquired from common bare-foot areas5 and severe hand warts are an occupational risk for butchers and meat handlers.6 Genital warts are also common and are frequently sexually transmitted they are not discussed in this chapter.

Squamous cell carcinoma complex

This variant of SCC is confined to the epidermis and hair follicles. It is very similar to the human disease termed Bowen's disease. There may be an association with papilloma and FeLV viral infections. The skin lesions are seen in middle-aged and older cats, and include papules, nodules and plaques with crusting and alopecia. An important feature is that haired and pigmented areas are affected. Treatment options may include surgery, although new lesions tend to develop. Retinoids have been recommended, but are expensive, and such therapy should be carefully monitored (Guaguere et al., 1999). Papilloma

Clinical evaluation

Human papillomavirus is the most important factor contributing to the development of cervical intraepithelial neoplasia and cervical cancer. Other epidemiologic risk factors associated with cervical intraepithelial neoplasia and cervical cancer include history of sexual intercourse at an early age, multiple sexual partners, sexually transmitted diseases (including chlamydia), and smoking. Additional risk factors include a male partner or partners who have had multiple sexual partners previous history of squamous dysplasias of the cervix, vagina, or vulva and immunosuppression.

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.

Adjuvant therapy following primary surgery in earlystage carcinoma

Approximately 35 of patients will have persistent or recurrent disease. A common approach includes examinations and Pap tests every 3-4 months for the first 3 years, decreasing to twice yearly in the fourth and fifth years, with and chest X-rays annually for up to 5 years.

Immune response of the host

Sera from animals or humans with a history of infection generally react with papillomavirus capsid proteins. Antibodies to the E7 protein of HPV16 and HPV18 are frequently found in sera of patients with cervical cancer. Similarly, antibody titers against the E2, E6 and E7 proteins have been detected in patients' sera. Infection with the common papillomaviruses of the skin and mucosa often results in a chronic infection. This chronic infection occurs in the immunocompetent host, suggesting that viral antigens are not recognized by the immune system. However, an increased incidence of clinically apparent HPV disease occurs in the immunosuppressed transplant recipient and also in patients with the acquired immune deficiency syndrome (AIDS). These observations indicate that cell-mediated immunity is important in controlling HPV infection. A decrease in the ratio of CD4T (helper) to CD84 (suppressor) T cells has been reported in patients with HPV infection or precancerous cervical...

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.

Leukoplakia and Erythroplakia

Leukoplakia is defined by the World Health Organization as a white patch or plaque that cannot be scraped off or characterized clinically or histopathologically as any other disease.21 Leukoplakia is the most common oral precancer however, only 2 to 4 percent of leukoplakic lesions are carcinoma.22 The prevalence is approximately 20 to 39 per 1000 persons, affecting males twice as frequently as females. Etiology is unknown, but tobacco, alcohol, ultraviolet radiation, candidiasis, human papillomavirus, tertiary syphilis, and trauma have all been implicated. The most common intraoral site involved is the buccal mucosa. Other sites of involvement include the hard and soft palates, maxillary gingiva, and lip mucosa. Biopsy is mandatory for all persistent leukoplakic lesions, yet most demonstrate no dysplastic changes histologically. Leukoplakic lesions of the floor of the mouth, tongue, and vermilion border are most likely associated with malignancy. Lesions demonstrating dysplastic...

Ming Jiang and Jo Milner

The newly discovered phenomenon of RNA interference (RNAi) offers the dual facility of selective viral gene silencing coupled with ease of tailoring to meet genetic variation within the viral genome. Such promise identifies RNAi as an exciting new approach to treat virus-induced diseases, including virus-induced cancers. RNAi can be induced using small interfering RNA (siRNA). Synthetic siRNA targets homologous mRNA for degradation, and this process is highly efficient. Using cervical cancer cells as a model, we demonstrate RNAi for viral oncogenes. Cervical cancer is the second most common cancer in women worldwide and is caused by human papillomavirus (HPV). Silencing of HPV E6 and E7 gene expression was achieved using siRNAs to target the respective viral mRNAs. E6 silencing induced accumulation of cellular p53 protein, transactivation of the cell cycle controlp21 gene, and reduced cell growth. By contrast, E7 silencing induced apoptotic cell death. HPV-negative cells appeared to...

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.

Reproductive Tract Infections

Lyticum, Treponema pallidum, mycoplasmas, human papillomavirus (HPV), herpes simplex virus (HSV). and the gram-negative enteric bacilli. Human immunodeficiency virus (HIV) certainly enters the host by way of the reproductive tract but will not be dealt with here because of its diverse and multiorgan clinical manifestations.

Infections characterized by a minimal or moderate immunologic response

Human papillomaviruses (HPVs) are double-stranded DNA viruses that infect basal epithelial cells. HPVs can be divided into at least 65 genotypes. Human papillomavirus Molluscum contagiosum poxvirus Corynebacterium minutissimum Malassezia furfur Cryptococcus neoformans Cysticercus cellulosae (larval A nongenital HPV lesion of the skin is usually caused uy HPV-l, 2, 3 or 4. In its most common manifestation, HPV infection of the skin presents as verruca vulgaris, the common wart. The immunologic response to HPV infection is poorly understood. A cellular response is undoubtedly important in preventing or limiting infection since individuals deficient in cell-mediated immunity are not only predisposed to HPV infection and dissemination, but also HPV infections in such individuals are often refractory to treatment. Additionally, patients with epidermodysplasia verruciformis, who are congeni-tally susceptible to disseminated HPV infection of the skin, appear to have a specific defect in...

Physiological Functions of atRA

Incidence of spontaneous and carcinogen-induced cancer. Chemopreventive trials in humans show some promise for retinoids in actinic keratoses, oral premalignant lesions, laryngeal leukoplakia, and cervical dysplasia. The US Food and Drug Administration has approved retinoids for acute promyelocytic leukemia and for non-life-threatening diseases, such as cystic acne and psoriasis. Retinoids also provide the active ingredients in agents to treat sun age-damaged skin.

Introduction Clinical Setting

The BK polyoma virus virus was originally isolated from B.K., a Sudanese patient who had distal donor ureteral stenosis months after a living related transplant (9). BK virus is related to JC virus (which also inhabits the human urinary tract) and to simian kidney virus SV-40. These viruses are members of the papovavirus group, which includes the papilloma viruses. The BK virus commonly infects urothelium but rarely causes morbidity in immunocompetent individuals. However, in renal transplant recipients three lesions have been attributed to BK virus hemorrhagic cystitis, ureteral stenosis, and acute interstitial nephritis (10,11). In a prospective study of 48 renal transplant recipients, active polyomavirus (BK or JC) infection was shown in 65 68 of these had intranuclear inclusions in urine cytology (12). Half of infections occurred within the first 3 months after transplantation, but some occurred 2 years or longer afterward. In 26 renal function became impaired at the time of the...

Nature of the tumor antigens

The TSTAs of tumors induced by either the polyoma or the SV40 viruses were the ones first characterized at the molecular level. Both are encoded by genes of the respective viruses, localized to the nucleus and intimately associated with the initiation and maintenance of the neoplastic transformation. An analogous antigen in human neoplasms would provide an optimal target for immunotherapy since its loss is not compatible with a maintained neoplastic pheno-type. It is of great interest, therefore, that most cervical carcinomas are associated with human papillomavirus (HPV) 16, and that the E6 and or E7 genes of HPV-16 encode tumor antigens which can induce a CTL response detected in vitro as well as a CD8 + immune response leading to tumor rejection in animal models. Peptide targets of the CTLs have been identified both in animal models and, more recently, in human cervical carcinomas. Clinical trials with tumor vaccines have been started based on the latter findings.

Prevention of STI condoms other contraceptives

A systematic review and meta-analysis evaluated the relationship between condom use and acquisition of HPV infection, or HPV-associated disease (for example, genital warts or cervical intraepithelial neoplasia). The authors found no convincing evidence for a protective effect associated with condoms.142

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.

Sexually Transmitted Diseases

HUMAN PAPILLOMAVIRUS Human papillomavirus is probably the most common sexually transmitted disease today. HPV-6, -11, and -45 are most commonly associated with condyloma acuminatum, or venereal warts. Although most commonly affecting the anogenital region, oral lesions can occur. Intraorally, the labial and buccal mucosa, palate, tongue, and gingiva are most commonly affected, although any site can be involved. Lesions many be solitary or multiple and are sessile or pedunculated nodules. Treatment is with electrosurgical or laser therapy.1154

BGlandular cell abnormalities

The LSIL category includes changes consistent with human papillomavirus (HPV), mild dysplasia, or CIN I (grade 1 cervical intraepithelial neoplasia). HSIL includes changes consistent with moderate or severe dysplasia, CIN II or III, and carcinoma in situ (CIS). 5. Hyperkeratosis or parakeratosis on an otherwise negative Pap smear is not a marker for significant CIN and may be related to infection or trauma with inflammation, such as from use of a diaphragm. The Pap smear should be repeated in 6 to 12 months. HPV testing with referral to colposcopy if positive for high-risk HPV type if negative for high-risk HPV type, then repeat cytology in 12 months B. Evaluation of ASC-US. Reflex HPV testing is the preferred approach. Reflex testing refers to concurrent collection of cytology and HPV samples with actual testing for HPV only if indicated by cytology results. If liquid-based cytology is used, reflex HPV testing can be performed on the same specimen. 1. Women with a positive test...

Methods for Study Using Tissue Culture Models

The life cycle of human papillomaviruses (HPVs) has been difficult to study in tissue culture owing to its dependence on epithelial differentiation. In this chapter several methods are described to imitate the important steps in the HPV life cycle. Normal human keratinocytes (NHKs) harvested from neonatal foreskins were transfected with HPV type 31 genomes in order to generate stable cell lines containing episomal copies of HPV genomes. HPV-positive keratinocyte cultures were maintained in E medium in the presence of mitomycin C-treated J2 3T3 fibroblast feeders. Finally, the keratinocytes were induced to undergo epithelial differentiation in semisolid medium to provoke viral late functions like genomic amplification and late transcription. The productive life cycle of human papillomaviruses (HPVs) is directly linked to epithelial cell differentiation (1). Infection by papillomaviruses is believed to occur through microtraumas in the epithelium, exposing the basal cells to entry by...

Clinical Features

CONDYLOMATA ACUMINATA Condylomata acuminata, commonly known as anal warts, are caused by a papillomavirus and are probably sexually transmitted in more than 90 percent of cases. They begin as discreet, soft, fleshy growths on the skin of the perianal area as well as on the squamous epithelium of the anal canal. Occasionally, the mucosa of the lower rectum becomes involved. Patients usually first notice the presence of a growth in the perianal areas as well as associated pruritus and varying degrees of anal pain. With time, bleeding and anal discharge become part of the symptom complex. Evaluation of a patient with condyloma acuminata must include ruling out the presence of other STDs. These patients should be referred to an appropriate specialist for definitive treatment. Because cases SYPHILLIS Chancres, the characteristic lesion of primary syphilis, usually manifest themselves at the anal verge or in the anal canal. Rarely will a chancre involve the rectal mucosa, although proctitis...

Ruling out other problems

Doctors can diagnose STDs by taking a blood sample (for syphilis) or a cervical swab (for chlamydia and gonorrhea). If a teen has been sexually active, the speculum may be easier to insert into the vagina than with a teen who isn't sexually active. A Pap test is also necessary if a teen has had intercourse because the test can detect changes in the cervix that may lead to cervical cancer, which the doctor can then treat relatively early and easily.

Therapeutic use of IFNa

Effects, including fever, headache, chills, fatigue, anorexia, leukopenia and thrombocytopenia. Despite their current limitations, IFNs are now well established as useful drugs. IFNa is the most widely used and has received approval in many countries, including Food and Drug Administration (FDA) approval in the US, for several clinical indications. Since 1986 it has been used as a therapy against haii v-cell leukemia. Significant regression of the cancer is observed in more than 90 of patients. Since 1988, IFNa has been successfully used as a therapy against diseases associated with human papillomavirus infection such as juvenile laryngeal papillomatosis and condyloma acuminatum. Since that same year it has also been used in the treatment of Kaposi's sarcoma in patients infected with HIV. Around 30 of the patients who reccive IFNa, however, withdraw from treatment because of side-effects associated with the high IFNa doses. In 1991, IFNa was licensed for the treatment of chronic...

TABLE 1393 Stages of HIV Infection

Early symptomatic infection is characterized by conditions that are more common and more severe in the presence of HIV infection but, by definition, are not AIDS indicator conditions. Examples include thrush, persistent vulvovaginal candidiasis, peripheral neuropathy, cervical dysplasia, recurrent herpes zoster infection, and idiopathic thrombocytopenic purpura. These conditions occur with increased frequency as the CD4 cell count drops below 500 cells pL.

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.

Alternative explanations for the phenomena assigned to the immune surveillance theory

Tumor incidence in immunodeficiency are also entirely plausible. The increased tumor incidence in immunodeficient renal transplant patients is primarily due to an increase in skin cancer (squamous cell carcinoma) and non-Hodgkin lymphoma (the majority being of B cell origin), whereas a substantial increase in the more common cancer types, such as breast cancer, cancer involving the respiratory system, and gastrointestinal cancer, is not observed in these patients. Non-Hodgkin lymphoma and skin cancer in immunodeficiency are associated with a viral etiology (Epstein-Barr virus (EBV) and human papillomavirus (HPV), respectively). It is therefore conceivable either that these viruses are carcinogenic themselves or that the increased frequency of viral infection acts as a cofactor, making the infected cell vulnerable to becoming a tumor cell. With regard to immunosuppression, it should be noted that only parts of the immune system are immunosuppressed (generally the T cell compartment)....

TABLE 1372 Clinical Features of Genital Ulcers

GENITAL WARTS Human papillomaviruses (HPVs) are DNA viruses that cause genital warts by direct transmission. Different genotypes also have been implicated in cervical cancer, but the relationship is far from clear. The warts usually appear after an incubation period of 3 to 4 months and may coalesce to form condylomata acuminata. Although painless, their location or size may cause discomfort.

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.

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.

Thymic peptides as immunoregulators or biological response modifiers

TPs have been used clinically as antiviral agents and in the immunotherapy of cancer. TP5 is a highly effective drug as an antiviral therapy in recurrent herpes simplex, herpes zoster and human papilloma virus infection, reducing the relapse rate. It has also been shown to be a safe and effective adjunct to therapy in patients with severe atopic dermatitis, in which it decreases the release of polymorphonuclear leukocyte-derived inflammatory mediators. TP5 is able to produce consistent clinical and immunological effects in melanoma patients with cutaneous metastases, and is a potentially useful agent in the treatment of a subgroup of patients with Sezarv syndrome.

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

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...

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.

Clinical Findings

Laboratory evaluation in the ED should always include a pregnancy test. The possibility of ectopic pregnancy or septic abortion must be considered, and concurrent pregnancy will affect the treatment for PID. Saline-treated and potassium hydroxide-treated wet preparations of vaginal secretions should be examined for leukorrhea (more than 1 pmn epithelial cell), trichomoniasis, and clue cells. The absence of leukorrhea has been suggested to be a good negative predictor for PID. 13 Endocervical swabs should be sent for culture and can be gram stained for gonococci. DNA probes for gonorrhea and chlamydia are useful, if available. Elevated white blood cell counts, sedimentation rates, and or C-reactive protein support the diagnosis of PID. The syphilis test for rapid plasma reagin should be performed. Patients should be counseled on testing for hepatitis and HIV. HIV-infected women with PID may present with more severe symptoms and more frequent coinfection with Candida and human...

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.


In addition to direct DNA damage, genes involved in DNA repair have been implicated in the pathogenesis of SCC. The p53 gene is mutated in most SCC cases, disabling normal p53 function, which is thought to be critical in suppressing the development of SCC by repairing of UV-damaged DNA.17-20 Keratinocytes with p53 mutations cannot repair the mutations induced by irradiation and subsequently proliferate to develop cancer.17 Furthermore, mice with p53 mutations develop skin tumours more readily. Mutations in p53 can either be acquired (through multiple pathways including human papillomavirus, UV light, carcinogens) or inherited. People with xeroderma pigmentosum have a defective p53 pathway and develop numerous skin cancers they cannot repair mutations induced by irradiation.21

DNA viruses

A number of groups, the hepadana viruses (hepatitis B), papilloma viruses (HPV) and herpes viruses (EBV) are associated with hepatocellular carcinoma, uterine cervical cancer, Burkitt's lymphoma and nasopharyngeal carcinoma, respectively. HPV have small double-stranded circular genomes of DNA which cause benign infective skin warts. They infect basal cells during their proliferative phase which on full differentiation complete the life cycle of the virus. Genital warts, the third commonest form of sexually transmitted disease, are also due to infection by HPV, and are associated with carcinoma of the cervix. Some 30 of all women are infected with HPV and DNA sequences from this have been identified in the majority of cervical carcinomas. Over 70 types of HPV are known to infect genital sites but only a few (predominately types 16 and 18) are associated with neoplasia. Cofactors are smoking, infection by herpes simplex virus and, possibly, oral...


Imiquimod is an immune response modifier. It induces cytokines that promote a TH1 lymphocyte or cell-mediated immune response.43-45 These cytokines include interferon alpha and gamma, and interleukin (IL)-12. In animal studies, imiquimod has demonstrated broad antiviral and antitumor effects that are largely mediated by interferon alfa.44 In humans, imiquimod 5 cream is safe and effective in the treatment of external anogenital warts.47-48 We found six RCTs, summarised in Table 26.7.

Anal Cancer

Anal cancer is rare, accounting for less 5 of large-bowel tumours. Over 80 of anal cancers are squamous cell in origin, however, malignant melanoma may occur in the anal canal. The recognition of a high incidence of squamous cell carcinoma of the anus amongst some homosexual men led to the search for an infective aetiological agent. Risk factors for anal cancer include a history of genital warts and evidence now suggests an association between human papilloma virus types 16, 18, 30, 31 and 33, and anal cancer. It is believed that anal cancer may occur due to progression of anal intraepithelial neoplasia in a manner analogous to intraepithelial carcinoma of the cervix, vulva or vagina.

Nipple Discharge

On the other hand, pathologic nipple discharge is spontaneous, usually unilateral, confined to a single duct, bloody, and associated with a mass. The most common cause of pathologic nipple discharge is intraductal papilloma, followed by duct ectasia (discussed below). 2 While most nipple discharges associated with cancer are bloody, cancer has been shown to be the cause of only 6 percent of cases of bloody discharge. 2

Genital Herpes

Diagnosis is suspected by clinical presentation and confirmed by either culture or polymerase chain reaction, which is extremely sensitive in detecting low concentrations of viral DNA but not yet widely available. The virus can be isolated from vesicle fluid and the base of a wet ulcer. Intact vesicles, if present, should be unroofed and the fluid cultured directly. Scrapings of an ulcer may be taken for a Pap smear or Tzanck preparation. A Tzanck smear stained with either Wright or Giemsa stain is positive if multinucleated giant cells are present, which may be seen in up to 50 percent of cases. Serologic analysis is useful in classifying the initial herpetic episode as primary or nonprimary but is usually not indicated.


Trichomonads are often seen on conventional Papanicolaou smears, but false positive results are not uncommon (30 ). Thus, asymptomatic women with Trichomonas identified on conventional Pap smear should not be treated until the diagnosis is confirmed by wet mount. Treatment of asymptomatic women with trichomonads noted on liquid-based cervical cytology is recommended.

Oral Cancer

Specific etiologic factors play varying roles in oncogenesis. Oral candidiasis, especially in its hyperplastic form, promotes the development of oral squamous cell carcinoma. Immunosuppressive states such as HIV infection slightly increase one's risk of oral cancer, and oncogenic viruses such as human papillomavirus, herpes simplex virus, and various adenoviruses and retroviruses may play some role in the etiology of oral cancer. 1922

Atrophic Vaginitis

During menarche, pregnancy, and lactation and after menopause, the vaginal epithelium lacks the stimulation of estrogen. The maturation of the vaginal and urethra mucosa depends on the presence of estrogen and can be altered by the absence of estrogen or the presence of antiestrogenic factors, such as hormones, drugs, or diseases. Menopause results in a vaginal mucosa that is attenuated, pale, and almost transparent as a result of decreased vascularity. The vagina loses its normal rugae. The squamous epithelium atrophies, the glycogen content of the cells decreases, and the vaginal pH ranges from 5.5 to 7.0. The mucosa is only three or four cells thick and is less resistant to minor trauma and infection. Marked atrophic changes can cause atrophic vaginitis. It is important to distinguish between symptomatic atrophic vaginitis, which is rare, and an atrophic vagina that is a result of physiologic changes of menopause. When symptomatic vaginitis occurs, the vaginal epithelium is thin,...

Polyanionic polymers

Within the viral gp120 that bind to HIV-1 co-receptors on target cells. In addition to their projected potential for blocking sexual transmission of HIV-1, many of the polyanionic polymers have excellent laboratory profiles as potent inhibitors of other STIs such as herpes simplex virus, human papilloma virus, gonorrhea, and Chlamydia. The anticipated performance of these candidate products to block sexual transmission of both HIV-1 and other STIs associated with increased transmission of HIV-1 was a major factor in their advancement to clinical trials.

Plantar Warts

Plantar warts are caused by the human papillomavirus. These warts are fairly common and contagious. They may be painful and are usually found over bony prominences. Single lesions are endophytic and hyperkeratotic. A mother-daughter wart is similar to a single lesion except for a small vesicular satellite lesion. Mosaic warts are often painless, closely grouped, and may coalesce. Diagnosis is usually made clinically. There are many therapeutic options. Treatment is complicated by the fact that many of these lesions will resorb spontaneously within 2 years. These patients may require prolonged treatment in resistant cases and should be referred.3,5

Vulvar Cancer

Vulvar cancer is responsible for only 1 to 4 percent of all gynecologic malignancies and less than 1 percent of all cancers. Approximately 500 women die from vulvar cancer annually in the United States. Seventy-five percent of women diagnosed with vulvar cancer are greater than 55 years of age, with a third of them greater than 75 years of age. The most common histologic type is squamous cell carcinoma (90 percent), followed by melanoma, basal cell carcinoma, adenocarcinoma, sarcoma, Bartholin gland tumors, and metastasis. Luckily, the prognosis is generally good because recognizable symptoms allow for early diagnosis. The most common presenting symptoms include a mass, pruritus, pain, or ulceration (in decreasing order of frequency). The cause for vulvar cancer is still unknown, but there have been associations of vulvar cancers with other cancers of the anogenital tract. Human papillomavirus (HPV) types 16, 18, 31, 35, and 39 have all been suggested as causative factors.

P53 Regulation

Viral proteins can also interact with the p53 protein to affect its activity. For instance, the human papilloma virus (HPV) E6 proteins (type 16 and 18) negatively regulate p53 in a manner similar to Mdm2. The E6 protein binds to a protein complex containing p53, which leads to p53 ubiquitination and subsequent degradation.

Cervical Cancer

Currently, 15,800 new cases of cervical cancer are diagnosed per year. The average age at the time of diagnosis is 54. Risk factors include early coitus, multiple sexual partners, high-risk male partners, smoking, human papillomavirus, and HIV infection (or other immunosuppressive states). The diagnosis of cervical cancer in an HIV-positive patient is now considered an AIDS-identifying illness. Smoking increases the risk of cervical cancer in women by 3.5 times, and even passive smoke increases the risk threefold. Approximately 90 percent of cervical cancers are of squamous histologic type, but adenocarcinoma, which comprises 5 to 10 percent of cervical cancers, is increasing and has a worse prognosis. Cervical cancer, in decreasing order, most often presents with postmenopausal bleeding, abnormal vaginal bleeding, postcoital bleeding, vaginal discharge, pain, or leg swelling. Diagnosis must be made by cervical biopsy. Often, on speculum examination, a mass or ulcerative lesion is...