Presentation is loading. Please wait.

Presentation is loading. Please wait.

Virus Description Genus GenusPapovaviridae Morphology Morphology – Naked, icosahedral – 55 nm – 72 capsomeres – 2 capsid proteins including 1 major (L1)

Similar presentations


Presentation on theme: "Virus Description Genus GenusPapovaviridae Morphology Morphology – Naked, icosahedral – 55 nm – 72 capsomeres – 2 capsid proteins including 1 major (L1)"— Presentation transcript:

1 Virus Description Genus GenusPapovaviridae Morphology Morphology – Naked, icosahedral – 55 nm – 72 capsomeres – 2 capsid proteins including 1 major (L1) and 1 minor (L2) – Circular, ds DNA, 8 Kb Established as an episome, but it can integrate into the host DNA

2 Discovery Human papillomas (warts) were linked to a virus in 1907Human papillomas (warts) were linked to a virus in 1907 Papillomavirus was first isolated in rabbits by Richard Shope; thus the first oncogenic strain was discoveredPapillomavirus was first isolated in rabbits by Richard Shope; thus the first oncogenic strain was discovered No further studies were conducted until the 1970’sNo further studies were conducted until the 1970’s Once cervical cancer was linked to HPV, molecular virology allowed these studies to move forthOnce cervical cancer was linked to HPV, molecular virology allowed these studies to move forth Papillomavirus is highly species specificPapillomavirus is highly species specific

3 HPV Genome

4 E1 & E2: Early Viral Protein Expression (Non-structural) E1 major protein E1 major protein – Involved in replication – Exhibits helicase activity – Forms complex, binds sequences at the origin of replication, and recruits polymerases and accessory proteins to mediate replication E2 regulatory protein E2 regulatory protein – For replication and transcription from E6 promoter, as well as DNA packaging – Helps to recruit E1, but also regulates viral transcription from early promoter

5 E4 & E5 The functions of E4 & E5 are not fully understood; however, they may be involved in late viral functions The functions of E4 & E5 are not fully understood; however, they may be involved in late viral functions

6 E6 & E7 E6 & E7 interact with a many cellular proteins; therefore, influencing the outcome of an infection E6 & E7 interact with a many cellular proteins; therefore, influencing the outcome of an infection E7 is responsible for the formation of papillomas E7 is responsible for the formation of papillomas E6 & E7 act as viral oncoproteins of high risk HPVs, but they do not function as such in low risk HPVs E6 & E7 act as viral oncoproteins of high risk HPVs, but they do not function as such in low risk HPVs

7

8 L1& L2 Structural Proteins L1 (Major) and L2 (Minor) are structural proteins that are assembled late and spontaneously to form the icosahedral capsids L1 (Major) and L2 (Minor) are structural proteins that are assembled late and spontaneously to form the icosahedral capsids L1 (Major) makes up 80% of the viral capsid L1 (Major) makes up 80% of the viral capsid

9 Normal Epidermis

10 HPV Replication & Transcription in the Epidermis HPV Replication & Transcription in the Epidermis Infects basal cells of dermal layer (low level of transcription & replication) Infects basal cells of dermal layer (low level of transcription & replication) DNA amplification and capsid proteins made in the upper spinous layer DNA amplification and capsid proteins made in the upper spinous layer Transcription increases in the spinous layer Transcription increases in the spinous layer Squames released at surface to release viral particles Squames released at surface to release viral particles

11 E6 & E7 Work Together as Viral Oncoproteins to Immortalize target cells E6 binds to p53 tumor suppressor via p100 (cellular protein) E6 binds to p53 tumor suppressor via p100 (cellular protein) – Targets p53 leading to degradation and down-regulation of pathways involved in cycle arrest and apoptosis E7 binds to retinoblastoma (RB) tumor suppressor E7 binds to retinoblastoma (RB) tumor suppressor – Represses transcription of genes involved in apoptosis, as well as interferes with cell cycle regulation

12 HPV DNA Map

13 Clinical Aspects of HPV There are approximately 138 HPV strains that have been sequenced There are approximately 138 HPV strains that have been sequenced These include nongenital cutaneous, nongenital mucosal types, and anogenital types (developing around genital area or anal area) These include nongenital cutaneous, nongenital mucosal types, and anogenital types (developing around genital area or anal area) Cancerous types exist in all of these categories Cancerous types exist in all of these categories Low risk types HPV 6 & 11 are the most common low risk genital types Low risk types HPV 6 & 11 are the most common low risk genital types High risk types HPV 16 & 18 are the most common high risk genital types High risk types HPV 16 & 18 are the most common high risk genital types

14 Genital warts (sexually transmittled) Condylomata acuminata - Cauliflowerlike Genital warts -Smooth popular warts Genital Flat warts -Flat warts Bowenoid Papules -Small, elevated Nongenital Warts (non-sexually transmitted) Common warts (non-sexually transmitted) Common warts - Hands, fingers and knees Plantar warts -Feet Flat warts -Hands and face Genital Warts vs. Nongenital Warts

15 Nongenital Mucosal Disease HPV Type Respiratory papillomatosis 6, 11 Squamous cell carcinoma of the lung 6, 11, 16, 18 Laryngeal papilloma 6, 11, 30 Laryngeal carcinoma 16, 18 Maxillary sinus papilloma 57 Squamous cell carcinoma of the sinuses 16, 18 Conjunctival papillomas 6, 11 Conjunctival carcinoma 16 Oral focal epithelial hyperplasia (Heck disease) 13, 32 Oral carcinoma 16, 18 Oral leukoplakia 16, 18 Squamous cell carcinoma of the esophagus 16, 18 Nongenital Mucosal Type

16 Nongenital Mucosal Laryngeal papilloma Conjunctival papillomas

17 Nongenital Cutaneous Disease HPV Type Common warts (verrucae vulgaris) 1, 2, 4, 26, 27, 29, 41, 57, 65 Plantar warts (myrmecias) 1, 2, 4, 63 Flat warts (verrucae plana) 3, 10, 27, 28, 38, 41, 49 Butcher's warts (common warts of people who handle meat, poultry, and fish) 1, 2, 3, 4, 7, 10, 28 Mosaic warts 2, 27, 57 Ungual squamous cell carcinoma 16 Epidermodysplasia verruciformis (benign) 2, 3, 10, 12, 15, 19, 36, 46, 47, 50 Epidermodysplasia verruciformis (malignant or benign) 5, 8, 9, 10, 14, 17, 20, 21, 22, 23, 24, 25, 37, 38 Nonwarty skin lesions 37, 38 Nongenital Types

18 Common & Plantar Warts

19 Intermediate intraepithelial neoplasia 31, 33, 35, 42, 44, 45, 51, 52 High-grade intraepithelial neoplasia 16, 18, 56, 58 Carcinoma of vulva 6, 11, 16, 18 Carcinoma of vagina 16 Carcinoma of cervix 16, 18, 31 Carcinoma of anus 16, 31, 32, 33 Carcinoma in situ of penis (erythroplasia of Queyrat) 16 Carcinoma of penis 16, 18 Anogenital Types

20 Anogenital Disease HPV Type Condylomata acuminata 6, 11, 30, 42, 43, 44, 45, 51, 52, 54 Bowenoid papulosis 16, 18, 34, 39, 42, 45 Bowen disease 16, 18, 31, 34 Giant condylomata (Buschke-Löwenstein tumors) 6, 11 Unspecified intraepithelial neoplasia 30, 34, 39, 40, 53, 57, 59, 61, 62, 64, 66, 67, 68, 69 Low-grade intraepithelial neoplasia 6, 11, 43 Anogenital Types

21 Genital Warts

22 Infection Viral entry may result in a latent infection or can develop within 1-3 months, or may stay undetected for yearsViral entry may result in a latent infection or can develop within 1-3 months, or may stay undetected for years Lesion likely due to clonal expansion of infected cellsLesion likely due to clonal expansion of infected cells Infection can be subclinical or clinicalInfection can be subclinical or clinical

23 Transmission HPV is released from the desquamating superficial keratinocytes of the infected stratified epitheliaHPV is released from the desquamating superficial keratinocytes of the infected stratified epithelia Transmission of cutaneous HPVs occurs through direct contact with infected tissue or through indirect contact with contaminated objects and surfaces such as poolsidesTransmission of cutaneous HPVs occurs through direct contact with infected tissue or through indirect contact with contaminated objects and surfaces such as poolsides Transmission of genital HPV typically occurs through sexual contactTransmission of genital HPV typically occurs through sexual contact

24 HPV & Cervical Disease 99.7 % of cervical cancers99.7 % of cervical cancers are a result of HPV-16 & HPV-18 HPV infection of the cervixHPV infection of the cervix corresponds to low-grade CIN (Cervical intraepithelial Neoplasia) –mostly flat aceto-whitening areas including flat condyloma

25 Progressive Cervical Disease Starts as a benign noninvasive or squamous intraepithelial lesion (SIL) or CINStarts as a benign noninvasive or squamous intraepithelial lesion (SIL) or CIN Most low-grade intraepithelial lesions regress; however, some remain unchangedMost low-grade intraepithelial lesions regress; however, some remain unchanged 10-15% progress to moderate or severe dysplasia; carcinoma in situ10-15% progress to moderate or severe dysplasia; carcinoma in situ High grade CIN may develop into invasive cancer after years or decadesHigh grade CIN may develop into invasive cancer after years or decades –HPV 16, 18, and 45 are the most prevalent detected

26 Cervical Dysplasia

27 Detection Via Molecular Assays Three molecular assays are used to detect HPV in exfoliated cell samples or tissues Signal amplification assay Signal amplification assay – Hybrid Capture 2 assay (only FDA approved assay) Target amplification assays Target amplification assays – PCR & in situ PCR Non-amplified hybridization assays Non-amplified hybridization assays – Dot blot hybridization (DB), Southern transfer hybridization (STH) and in situ hybridiation(ISH)

28 Normal Cells Progress to Dysplasia

29 Moderate Dysplasia to Cancer /

30 Host Immune Response Most encounters of HPV are cleared by the host between 1-2 yearsMost encounters of HPV are cleared by the host between 1-2 years Strong immune response usually is not generatedStrong immune response usually is not generated HPV can be a chronic infectionHPV can be a chronic infection Skin warts generate low levels of antibodiesSkin warts generate low levels of antibodies 50% of IgG found in HPV 6 & 11 genital types50% of IgG found in HPV 6 & 11 genital types IgG and IgA humoral response to HPV 16 associated CIN found in 50-75%IgG and IgA humoral response to HPV 16 associated CIN found in 50-75% Antibodies detected in 15-25% of those with no current infection (most likely indicates past infection)Antibodies detected in 15-25% of those with no current infection (most likely indicates past infection)

31 Host Immune Response Antibodies are rarely detected in patients with pre-malignant cervical lesionsAntibodies are rarely detected in patients with pre-malignant cervical lesions Antibodies detected in 50% of women with late- stage invasive HPV-16 associated with cervical carcinomaAntibodies detected in 50% of women with late- stage invasive HPV-16 associated with cervical carcinoma Cell mediated immunity (CMI) is probably extensively involved in control of the infectionCell mediated immunity (CMI) is probably extensively involved in control of the infection –High incidence of cutaneous and anogenital HPV associated disease is observed among patients with genetic or aquired CMI deficiencies

32 Host Immune Response Immunological and genetic aspects likely to attribute to persistence and progression of CINImmunological and genetic aspects likely to attribute to persistence and progression of CIN –Higher frequency found in HIV infected women Functional alterations of LCs have been shown to correspond with initiation and progression of HPV related cervical diseaseFunctional alterations of LCs have been shown to correspond with initiation and progression of HPV related cervical disease

33 History of HPV Detection 1927 Georges Papanicalaou did research on diagnostic cytology of the cervix 1927 Georges Papanicalaou did research on diagnostic cytology of the cervix 1940s His research was published. First Paps were in Korea 1940s His research was published. First Paps were in Korea 1950s Paps began being used widely 1950s Paps began being used widely 1975 Harold zur Hausen linked HPV with cervical cancer 1975 Harold zur Hausen linked HPV with cervical cancer 1980s His team isolated several genotypes linked to cervical cancer and genital warts 1980s His team isolated several genotypes linked to cervical cancer and genital warts 1999 PCR assay found HPV DNA in 99.7% of cervical cancers studied 1999 PCR assay found HPV DNA in 99.7% of cervical cancers studied

34 Genital HPV Types Only 40 types of HPV infect the genital tract Only 40 types of HPV infect the genital tract Only these types can lead cause carcinoma: Only these types can lead cause carcinoma: – Types 16, 31, 33, 35, 52, 58 – Types 18, 39, 45, 70 (flat – in cervix, create tumors) Infections with certain “high-risk” HPV types can progress to dysphasias or cancer of the cervix, penis, anus, vagina and tonsils. Infections with certain “high-risk” HPV types can progress to dysphasias or cancer of the cervix, penis, anus, vagina and tonsils. Only 1% of HPV infections will progress to cervical cancer. Only 1% of HPV infections will progress to cervical cancer.

35 Prevalence of HPV HPV can show up in women on the cervix and the vulva, inside the surrounding areas of the vagina, and anus. HPV can show up in women on the cervix and the vulva, inside the surrounding areas of the vagina, and anus. It is common for HPV to exhibit no symptoms It is common for HPV to exhibit no symptoms HPV can be acquired and cleared without the person ever knowing that they were infected HPV can be acquired and cleared without the person ever knowing that they were infected HPV is commonly passed unintentionally by people who have no symptoms HPV is commonly passed unintentionally by people who have no symptoms This is one reason why HPV is so common. This is one reason why HPV is so common.

36 Most Women will be Infected HPV infection is estimated to involve 80% of the sexually active population. HPV infection is estimated to involve 80% of the sexually active population. As sexually active people you will probably contract HPV at some point in your life. As sexually active people you will probably contract HPV at some point in your life. 3 of 4 Americans between the ages of 15 and 50 have been infected with HPV at some point. 3 of 4 Americans between the ages of 15 and 50 have been infected with HPV at some point. Your immune system will most likely clear it. Your immune system will most likely clear it. HPV represents the most common sexually transmitted viruses. HPV represents the most common sexually transmitted viruses.

37 UW Students A UW study found that more than 60% of college women became infected over 5 years. A UW study found that more than 60% of college women became infected over 5 years. SOURCE: GRAPH ADAPTED FROM R. L. WINER ET AL., AMERICAN JOURNAL OF EPIDEMIOLOGY 157, 218 (2003)

38 HPV Persistence Most young women clear the virus, but it is unknown how many completely clear it. Most young women clear the virus, but it is unknown how many completely clear it. Some HPV may go into remission after an active period of months or years, but they are not usually fully eliminated. Some HPV may go into remission after an active period of months or years, but they are not usually fully eliminated. – “Active viral infections typically re-emerge from latency during transient or permanent immunodeficiency associated with sunburn, pregnancy, physical and emotional stress, HIV infection and cancer chemotherapy.” (WSDOH) There is no way to tell how long you have been infected or when HPV will express. There is no way to tell how long you have been infected or when HPV will express.

39 Men and HPV Men also harbour and express HPV in the form of penile, perennial and urethral papillomas. Men also harbour and express HPV in the form of penile, perennial and urethral papillomas. Men are much more likely to be carriers and not develop cancer. Men are much more likely to be carriers and not develop cancer. A urethral swab for males to collect exfoliated cells for Pap analysis exists but rarely practiced. A urethral swab for males to collect exfoliated cells for Pap analysis exists but rarely practiced. There is not a FDA approved test for men. There is not a FDA approved test for men. Clinically it is hard to get men in to get tested. Clinically it is hard to get men in to get tested.

40 HPV Infection in the US An estimated 5.5 million people become infected with various types of HPV each year in the U.S.An estimated 5.5 million people become infected with various types of HPV each year in the U.S. An estimated 20 million people are currently infected with at least one HPV type in the U.S.An estimated 20 million people are currently infected with at least one HPV type in the U.S. The “high risk” HPV associated cancers can take years to develop, upwards of 10 to 20 years.The “high risk” HPV associated cancers can take years to develop, upwards of 10 to 20 years. Cervical cancer affects younger women more frequently than most other types of cancer.Cervical cancer affects younger women more frequently than most other types of cancer.

41 Female Invasive Cancer Incidence (Washington State 2001) Source: WSDOH, Wash. Comp. Cancer Control, & American Cancer Society

42 Invasive Cervical Cancer Incidence & Death Source: WSDOH, Wash. Comp. Cancer Control, & American Cancer Society

43 Stage at Diagnosis (WA 2001) Source: WSDOH, Wash. Comp. Cancer Control, & American Cancer Society LocalRegionalDistantUnstaged 11 of 119 die 32 of 67 die 16 of 19 die 5 of 11 die 91%survival 52 % survival 17 % survival 55 % survival Number of cases Total cases = 216 Stage at diagnosis

44 Risk Factors You do not have to have a lot of sex partners to be exposed. You do not have to have a lot of sex partners to be exposed. History of multiple sex partners can increase the number of other sexually transmitted diseases History of multiple sex partners can increase the number of other sexually transmitted diseases Early age at first intercourse Early age at first intercourse Smoking Smoking Diet Diet NO Pap screenings NO Pap screenings

45 Pap Smears Invasive cervical cancer is one of the most preventable types of cancer due to the effectiveness of the Pap test. Invasive cervical cancer is one of the most preventable types of cancer due to the effectiveness of the Pap test. Half of the women who develop cervical cancer have not had regular Pap tests. Half of the women who develop cervical cancer have not had regular Pap tests.

46 Pap Smears The cytological changes associated with HPV infection form the basis of the Papanicolau (Pap) smear screening The cytological changes associated with HPV infection form the basis of the Papanicolau (Pap) smear screening Sampling the cells from the cervix and examining them for signs of malignancy Sampling the cells from the cervix and examining them for signs of malignancy The Pap diagnosis atypical squamous cells of undetermined significance (ASCUS) during cervical screenings The Pap diagnosis atypical squamous cells of undetermined significance (ASCUS) during cervical screenings This diagnosis indicates cell abnormality but is not sufficient for a definitive diagnosis of a squamous intraepithelial lesion This diagnosis indicates cell abnormality but is not sufficient for a definitive diagnosis of a squamous intraepithelial lesion Women who have these abnormalities are referred to get a colposcopic biopsy Women who have these abnormalities are referred to get a colposcopic biopsy

47 Treatments for “high risk” HPV HPV is a long term virus; it is a chronic condition. Procedures target the infected area; treatments do not get rid of the virus. HPV is a long term virus; it is a chronic condition. Procedures target the infected area; treatments do not get rid of the virus. Colposcopic Biopsy – diagnosis for the stage/grade of HPV infection, high grade or low grade Colposcopic Biopsy – diagnosis for the stage/grade of HPV infection, high grade or low grade LEEP (loop electrocautery excision procedure) – cuts out infected site, most common procedure. LEEP (loop electrocautery excision procedure) – cuts out infected site, most common procedure. Laser – burns off infected site Laser – burns off infected site Cryosurgery – freezes off infected siteCryosurgery – freezes off infected site General Surgery – hysterectomy, vulvectomy (in rare cases) General Surgery – hysterectomy, vulvectomy (in rare cases) Natural Products – stress, immune system boosters Natural Products – stress, immune system boosters

48 Referral Guidelines for Women with Abnormal Paps

49 Poverty % population in poverty

50 Race/Ethnicity

51 Additional Risk Factors Women who avoid Pap smearsWomen who avoid Pap smears –Older women or church go'ers –Self-proclaimed virgins and those who pledge abstinence Truth about Abstinence:Truth about Abstinence: –88% of people who take abstinence pledges break them within a year and a half. –Those who pledge abstinence are 1/3 less likely to use a condom when they become sexually active –More likely to participate in risky sex acts

52 US compared to World statistics United States – 14,000 new cases of cervical cancer are diagnosed annually in the U.S. – In the U.S. 4, ,500 women die of cervical cancer each year Worldwide – 600,000 new cases of invasive cervical cancer diagnosed annually worldwide. – Cervical cancer kills 270,000 women worldwide. (2002 statistics) (2002 statistics) Source: Science Magazine (2005). High Hopes and Dilemmas for Cervical Cancer Vaccine, Science Magazine, Volume 308, April 29, 2005.

53 Poorer Countries have > HPV Rates SOURCE: GLOBOCAN 2002, IARC. Science Magazine, Vol. 308, Issue 5722, pages , 29 April 2005

54 Vaccines on the Horizon… SOURCE: Merck and GSK. Science Magazine, Vol. 308, Issue 5722, pages , 29 April 2005

55 Challenges with the Vaccine Vaccine may have little impact on the cases of cervical cancer Vaccine may have little impact on the cases of cervical cancer Access to a provider and preventive screenings/vaccines will still be an issue Access to a provider and preventive screenings/vaccines will still be an issue Poorer countries have a higher need for the vaccine, but wealthier countries will get it 1 st Poorer countries have a higher need for the vaccine, but wealthier countries will get it 1 st

56 Prevention Get regular Pap smears ! Get regular Pap smears ! Don’t smoke Don’t smoke Avoid exposure to HPV – use a condom Avoid exposure to HPV – use a condom Advocate for greater access to preventive screenings for all populations Advocate for greater access to preventive screenings for all populations Live Healthy and Eat Healthy Live Healthy and Eat Healthy

57

58 Nutritional Support for HPV The following are suggested for protection, as well as support for those who are infectedThe following are suggested for protection, as well as support for those who are infected –Vitamin C –Vitamin A & beta-carotene –Folic acid –Pyridoxine (B6) –Selenium –Zinc Correlation has been found between Copper: Zinc ratio (higher copper and lower zinc) in CIN and cancer patients

59 Lactoferrin

60 Therapeutic Use of Lactoferrin Lactoferrin (LF) Lactoferrin (LF) – Iron binding glycoprotein is present in many mucosal secretions including saliva, tears, as well as vaginal and seminal fluids – Found in Human breast milk (HLF) as well as bovine milk (BLF) – Lf exhibits bacterialcidal and fungicidal activity(particularly Candida species) by depriving bacteria and fungus from iron

61 Therapeutic Use of Lactoferrin Lf also exhibits anti-viral activity by inhibiting viral binding to glycosamines such as heparin sulphite; it is hypothesized that heparin sulphite mediates the binding of HPV to the host cell Lf also exhibits anti-viral activity by inhibiting viral binding to glycosamines such as heparin sulphite; it is hypothesized that heparin sulphite mediates the binding of HPV to the host cell Studies have shown that BLF is a better inhibitor than LF and it effectively inhibits HPV-16 Studies have shown that BLF is a better inhibitor than LF and it effectively inhibits HPV-16


Download ppt "Virus Description Genus GenusPapovaviridae Morphology Morphology – Naked, icosahedral – 55 nm – 72 capsomeres – 2 capsid proteins including 1 major (L1)"

Similar presentations


Ads by Google