5 Vaginal & Vulvar Lesions/Cancer Types of HPV>100 Types30-40 typesAnogenital area15-20 typesHigh risk10-15 typesLow riskThe cause of cervical cancer is a sexually transmitted virus, called human papillomavirus. There are many HPV types and only some cause cancer. HPV infections (even high-risk types) usually go away without treatment. Low-risk HPV types can cause genital warts. The high-risk types cause most abnormal pap smears, precancer and cancer of the cervix, vagina, and vulva.HPV 6, 11 cause90% of genital wartsHPV 16, 18 cause70% ofcervical cancerHPV 16, 18 can cause:85% of anal cancers240% of penile cancers235% of throat cancers225% of mouth cancers2HPV 6, 11, 16, 18 can causeVaginal & Vulvar Lesions/Cancer1. Centers for Disease Control and Prevention. Genital HPV infection fact sheet. 2. Centers for Disease Control and Prevention. HPV-Associated Cancers5
6 How does HPV get transmitted? Sexual contactSexual intercourseGenital–genital, manual–genital, oral–genitalGenital HPV infection in virgins is rare, but may result from nonpenetrative sexual contact.Condom use may help reduce the risk, but not fully protective.Nonsexual routesMother to newborn (vertical transmission)Fomites (e.g., undergarments, surgical gloves, biopsy forceps)Hypothesized but not well documented; would be rareMost infected individuals are unaware that they are infected and may unknowingly spread the virus.6
7 How common is HPV?Most men and women who have had sex have been exposed to HPVLifetime risk according to the US Centers for Disease Control for sexually active men and women is at least 50%.This is a very common virus.Studies demonstrate that most sexually active women have had HPV at some time. In fact, HPV infection is so common in women ages 18-29, that current recommendations for screening advice against testing women in this age group.7
8 Risk Factors of HPV Infection WomenYoung age (peak age group 20–24 years of age)Lifetime number of sex partnersEarly age of first sexual intercourseMale partner sexual behaviorSmoking (↓immunity)Oral contraceptive use (sexual behavior)Uncircumcised male partnersMenYoung age (peak age group 25–29 years of age)Lifetime number of sex partnersBeing uncircumcisedSexual partner with CINKey PointThough less documented, risk factors for HPV infection in males seem similar to those in females.BackgroundA number of factors directly or indirectly related to sexual behavior have been associated with increased risk for HPV infection in both men and women. Those consistently relating to infection in women are young age, intercourse at an early age, and sexual behavior, particularly with a higher number of partners.1,2 The sexual behavior of male partners,2 smoking,3 oral contraceptive use,3 and lack of circumcision of male partners4 also appear to increase risk. Risk factors for HPV infection among men are similar to those in women and include young age, number of sex partners, and being uncircumcised.5 HPV infections and HPV-associated penile lesions are frequently found in male sexual partners of women with CIN.6References1. Burk RD, Ho GY, Beardsley L, Lempa M, Peters M, Bierman R. Sexual behavior and partner characteristics are the predominant risk factors for genital human papillomavirus infection in young women. J Infect Dis. 1996;174:679–689.2. Murthy NS, Mathew A. Risk factors for pre-cancerous lesions of the cervix. Eur J Cancer Prev. 2000;9:5–14.3. Winer RL, Lee S-K, Hughes JP, Adam DE, Kiviat NB, Koutsky LA. Genital human papillomavirus infection: Incidence and risk factors in a cohort of female university students. Am J Epidemiol. 2003;157:218–226.4. Schiffman M, Castle PE. Human papillomavirus: Epidemiology and public health. Arch Pathol Lab Med. 2003;127:930–934.5. Svare EI, Kjaer SK, Worm AM, Osterlind A, Meijer CJ, van den Brule AJ. Risk factors for genital HPV DNA in men resemble those found in women: A study of male attendees at a Danish STD clinic. Sex Transm Infect. 2002;78:215–218.6. Bleeker MC, Hogewoning CJ, Voorhorst FJ, van den Brule AJ, Berkhof J, Hesselink AT, Lettink M, Starink TM, Stoof TJ, Snijders PJ, Meijer CJ. HPV-associated flat penile lesions in men of a non-STD hospital population: less frequent and smaller in size than in male sexual partners of women with CIN. Int J Cancer. 2005;113:36-41.8
9 GENITAL WARTS HPV 6, 11 cause 90% of genital warts Cauliflower-like lesionsOften found on the vulva, perineum, perianal area, vagina, cervix, penis and scrotumHPV 6, 11 cause 90% of genital wartsMale perineum area9
10 CERVICAL CANCER Progression from CIN to Cancer Abnormal cell growth in the cervix2nd most common cause of cancer death among womenHPV 16, 18 cause 70% of cervical cancerProgression from CIN to CancerWhere Pap tests are not available for screening, cervical cancer is the number one cancer killer of women. Cervical cancer typically affects women at younger ages than other gynecologic cancers. That’s why we urge all reproductive-age women to educate themselves and to participate in screening.The Pap test has reduced the risk of cancer by early detection of cells destined to become cancer.NormalCIN 1CIN 2CIN 3/AISInvasive Cancer10
11 Disease ProgressionTime after HPV infection3 to 6 months4 to 5 Years9 to 15 YearsPersistent InfectionInitial HPV InfectionCIN 2/3 or AISCervical CancerCIN 1+co-factors(viral, host, environmental)“Cleared” HPV InfectionCIN=Cervical Intraepithelial NeoplasiaAIS=Adenocarcinoma in situThe HPV detected today could have been acquired years agoMany women diagnosed with cervical cancer were likely exposed to HPV during their teens and 20s
12 Cervical Cancer Incidence By Age, Peninsular Malaysia (Per 100,000) 0-910-1920-2930-3940-4950-5960-6970+Age Group0.071.6Age specific cancer incidence per 100,000 populationCervical cancer incidence ratepeak at ages years anddeclined thereafterincrease with age after 30Figure 4: Cervix Uteri Age specific Cancer Incidence per 100,000 population, Peninsular Malaysia 2003Source: 2nd Report of National Cancer Registry Malaysia 2003 (Fig 1.2.3(b))
13 Incidence of Cervical Cancer in Malaysia Cervical cancer is the 2nd most common cancer affecting Malaysian women of reproductive age below 49 years11. Malaysia Cancer Statistics - Data and Figure, Peninsular Malaysia, 200613
14 Cervical Cancer Incidence and Mortality Estimates by Region 2002 estimated cervical cancer incidence and mortality by region1:14,United States/ Canada59,929 29,814Europe61,132 31,314Eastern Asia157,759 86,708Southcentral Asia17,Central America42,538 22,594Southeast AsiaKey PointWorldwide cervical cancer rates are high, particularly in developing countries,and are still unacceptable in developed countries.BackgroundAccording to data obtained from GLOBOCAN 2002, 82% of new cervical cancer cases occur in developing countries.1 As stated by WHO, without screening programs (ie, routine pap smears), “cervical cancer is detected too late and leads to death in almost all cases.”2 However, even in Europe, the United States, or Canada, where most women have access to routine screening, approximately 35,000 women die each year.1ReferencesFerlay J, Bray F, Pisani P, Parkin DM. GLOBOCAN 2002: Cancer incidence, mortality and prevalence worldwide, version 2.0. IARC CancerBase No. 5. Lyon, France: IARC Press; 2004.World Health Organization. State of the art of new vaccines research and development: Initiative for vaccine research. Geneva, Switzerland: World Health Organization; 2003: 1–74.78,896 61,670Africa48,328 21,402South America1,Australia/New Zealand1. Ferlay J, Bray F, Pisani P, Parkin DM. Lyon, France: IARC Press; 2004.
15 VaIN 3 and Vulvar Carcinoma Arising in VIN 3 VAGINAL LESIONS (VaIN*)VaIN 3 and Vulvar Carcinoma Arising in VIN 3VaIN 3Photo courtesy of Dr. J. MonsonegoPhoto courtesy of Dr. R.W. JonesCommonly involves the upper third of the vagina and is often multifocalAverage age of women: 35–50 yearsNo symptoms and difficult to diagnoseSpontaneously clear, but potential to progress to invasive vaginal cancer*VaIN=Vaginal Intraepithelial NeoplasiaCIN=Cervical Intraepithelial NeoplasiaVIN=Vulvar Intraepithelial Neoplasia15
16 VULVAR LESION (VIN*)*VIN=Vulvar Intraepithelial NeoplasiaHPV 16 appears to be the dominant HPV type associated with high-grade VINEstimated 42%–65% of VIN 1 cases are associated with HPV types 6 and 11Most common symptoms include pruritus, pain, soreness, swelling and persistant ulcers.16
17 HPV-Related Disease in Males B&W image is from laryngeal cancer from: other images are from earlier slide kits.1/Lillo/p111/ abstract2/Gross/p35/ col2/¶11/Lillo/p111/ abstract 2/Gross/p40/ col2/¶2Genital wartsPenile intraepithelial neoplasia (PIN) and carcinomaAnal intraepithelial neoplasia (AIN) and carcinomaSome oropharyngeal cancers (tongue, tonsillar, throat and soft palate)1/Lillo/p111/ abstract3/Frisch/p1350/abstract; p 1356/Tab 5; p 1458/col 1/¶11/Lillo/p111/ abstract4/Gillison/ p709/abstract; p712/Tab 11/Lillo/ abstract2/Gross/p35/ col1/¶1Key PointThe disease burden related to HPV infection in males is substantial and includes penile cancer, anal cancer, some oropharyngeal cancers, and genital warts.BackgroundConsiderable laboratory and epidemiologic evidence demonstrates that HPV is a major cause of clinical disease in men as well as women.1,2 Consequences of HPV infection in men include genital warts, penile intraepithelial neoplasia (PIN) and carcinoma, anal intraepithelial neoplasia (AIN) and carcinoma, and a subset of oropharyngeal cancers.High-risk types of HPV (primarily HPV 16 and HPV 18) are present in the majority of anal cancers and in a significant fraction of penile cancers.2,3 High-risk HPV (usually HPV 16) has also been found in some oropharyngeal cancers.4HPV 6 and HPV 11, are known to cause >90% of all cases of genital warts.52/Gross/p 40/ col 2/¶2 3/Frisch/p 1356/Tab 54/Gillison/p 711/col 2/¶2.5/Gissmann/p561/Tab 2HPV = human papillomavirus.ReferencesLillo FB. Human papillomavirus infection and its role in the genesis of dysplastic and neoplastic lesions of the squamous epithelia. New Microbiol. 2005;28:111–118.Gross G, Pfister H. Role of human papillomavirus in penile cancer, penile intraepithelial squamous cell neoplasias and in genital warts. Med Microbiol Immunol. 2004;193:35–44.Frisch M, Glimelius B, van den Brule AJC, et al. Sexually transmitted infection as a cause of anal cancer. N Engl J Med. 1997;337:1350–1358.Gillison ML, Koch WM, Capone RB, et al. Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst. 2000;92:709–720.Gissmann L, Wolnik L, Ikenberg H, Koldovsky U, Schnürch HG, zur Hausen H. Human papillomavirus types 6 and 11 DNA sequences in genital and laryngeal papillomas and in some cervical cancers. Proc Natl Acad Sci U S A. 1983;80:560–563.
18 HPV Disease Prevention Primary**Applicable for males & femalesSecondary**Applicable for females onlyPrevention of any factors that could lead to disease in healthy individualsPrevention by halting the progression of the infection/diseaseModifying lifestyle risksie. tobacco, keep healthy, sexual intercourse >20yrs, condomsVaccinationPap Smear
19 HPV Prophylactic Vaccination: A shift from secondarytoprimary prevention19
20 2 Types of HPV VaccinesQuadrivalent HPV Vaccine which protects against HPV types 6, 11, 16, 18Bivalent HPV Vaccine which protects against HPV 16, 18 onlyKey PointGARDASIL™ is Merck’s quadrivalent HPV L1 virus-like particle (VLP) vaccine. It is produced in recombinant yeast and adsorbed on a proprietary aluminum adjuvant.BackgroundGARDASIL is a non-infectious recombinant, quadrivalent vaccine, prepared from the highly purified VLPs of the recombinant major capsid (L1) protein of HPV types 6, 11, 16, and 18. The L1 proteins are produced by separate fermentations in recombinant Saccharomyces cerevisiae and self-assembled into VLPs.1The VLPs for each type are purified and adsorbed on aluminum-containing adjuvant (amorphous aluminum hydroxyphosphate sulfate). The quadrivalent HPV VLP vaccine is a sterile liquid suspension that is prepared by combining the adsorbed VLPs of each HPV type and additional amounts of the aluminum-containing adjuvant and the final purification buffer.1GARDASIL is a sterile preparation for intramuscular administration. Each 0.5-mL dose contains approximately 20 µg of HPV 6 L1 protein, 40 µg of HPV 11 L1 protein, 40 µg of HPV 16 L1 protein, and 20 µg of HPV 18 L1 protein. Each 0.5-mL dose of the vaccine contains approximately 225 µg of aluminum (as amorphous aluminum hydroxyphosphate sulfate adjuvant).1GARDASIL should be administered intramuscularly as 3 separate 0.5-mL doses at day 1, month 2, and month 6.1GARDASIL is a trademark of Merck & Co., Inc., Whitehouse Station, NJ, USA.Reference1. GARDASIL Prescribing Information. Merck & Co., Inc., Whitehouse Station, NJ, USA..
21 Quadrivalent HPV (HPV 6, 11, 16, 18) Vaccine Protects Against90% of Genital wartscaused by HPV 6 & 1170% of Pre-cancers& cervical cancercaused by HPV 16 & 18Vulvar & vaginal cancercaused byHPV 6, 11, 16 & 18
23 The Right Vaccine for the Right Health Impact GARDASIL [(Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccines] has been demonstrated to prevent more cancers and diseases :98%of cases of cervical cancer related to HPV Types 16 and 1896%of cases of cervical precancerous lesions related to HPV Types 6, 11, 16 and 1899%of cases of genital warts related to HPV Types 6 and 11100%of cases of vaginal and vulvar cancer related to HPV Types 16 and 18
24 91% 83% Adult women (24-45 years old) HPV 6-, 11-, 16-, or 18-related persistent infection, genital warts, vulvar and vaginal lesions, CIN of any grade, AIS and cervical cancer83%HPV 16- or 18-related persistent infection, genital warts, vulvar and vaginal lesions, CIN of any grade, AIS and cervical cancer
25 Is Gardasil for boys/men? Indicated in boys and men 9 to 26 years of age for the prevention of genital warts (condyloma acuminata) caused by HPV types 6 and 11.Is efficacious in reducing the incidence of genital warts related to HPV types 6 and 11 in males relevant to the HPV type(s) 6, 11, 16 and 18
26 Males (18-26 years old)90%efficacious against HPV type 6, 11, 16, 18-related external genital lesions (EGL) – 91% were genital warts89%efficacious against HPV 6 and 11-related genital warts
27 Gardasil - Administration 0-, 2-, 6-month dosing regimenIntramuscular administrationEach 0.5-mL injection volumeFor women from age 9 to 26 years of ageFor boys/men age 9 – 26 years oldIdeally given before first sexual contact, but females who have had sexual activity should still be vaccinatedRegular Pap smear screening still required after vaccination
28 HPV Vaccines – Global Funding Tender with Gardasil (2012) - MALAYSIATo date GARDASIL is available through public funding in 23 countries
29 AUSTRALIA: National Immunization Program April 2007: - target group ongoing target group of year old girls- largely delivered in a school based program women aged up to 26 years- delivered through general practice as a catch up for 2 yearsIn June 2006 the Food and Drug administration approved the use of the HPV vaccine for use in 9-26 year olds, and the Centers for Disease Control and Prevention recommended the vaccine be routinely administered in year olds, and year olds who had not received the vaccine, with 9-10 year olds being vaccinated at the discretion of the parent and providerAust school based uptake 80%29
31 HPV vaccination can help prevent certain HPV-related cancers and most genital warts WPC072010: p1B–DWHO-CCCC: p20A; p21AAdding HPV vaccination to Pap exams comprises a comprehensive approach to cervical cancer prevention1Pap exams are essential, but alone may not be enoughIn a retrospective study of 642 women diagnosed with cervical cancer in a large prepaid health plan between 1988 and 1994:~28% of women diagnosed with cervical cancer had at least one normal Pap exam 6 to 36 months prior to diagnosis.ANDPAPEXAMPATIENTEDUCATIONHPVVACCINATIONSung: p2285A, B, CSung: p2285A3131
32 What have we learned so far? Human Papillomavirus (HPV) can:Affect males & females (at least 50% in a lifetime)Cause cervical cancer, genital warts, vaginal & vulvar cancerBe PREVENTED through:Regular Pap smear screeningVaccinationHPV vaccine can prevent:genital warts in males & femalescervical cancer, vaginal & vulvar cancers in females32
33 Protect Yourself. Protect Your Loved Ones. Now! Cervical cancer & HPV diseases can be prevented. Don’t Wait until it is too late.Protect Yourself. Protect Your Loved Ones. Now!