Introduction to HPV Infection & Cervical Cancer Disease GardasilTM Essential Training Package for HPV Vaccine Introduction Module 1 Introduction to HPV Infection & Cervical Cancer Disease GardasilTM

Learning objectives At the end of the module, you will have learned to: Explain the incidence & mortality of cervical cancer globally and regionally Explain the cause of most cases of cervical cancer Explain HPV transmission and disease progression Discuss symptoms, prevention and treatment of cervical cancer Duration 45’

Key Issues What is cervical cancer, its incidence & its mortality? 1 What causes cervical cancer? 2 How does HPV infection lead to cervical cancer? 3 What are the risk factors for cervical cancer? 4 Explain to the participants the key issues raised in this module: 1. What cervical cancer is and its mortality 2. The cause of most cases of cervical cancer 3. Explain HPV transmission and disease progression 4. The risk factors for pre-cancer lesions and cervical cancer 5. Symptoms, treatment and prevention of cervical cancer What are the symptoms, treatment and prevention of cervical cancer? 5

Global Burden of Cervical Cancer The second most common cancer in women Every year: 530,000 new cases diagnosed 275,000 deaths Over 85% in developing countries By 2050: one million cases 90% in developing countries Let’s begin by sharing what you know or have heard about cervical cancer. Let me explain what the magnitude of cervical cancer is: Cervical cancer remains the second most common cancer in women in developing countries. Cervical cancer affects an estimated 530,000 women each year and leads to 275,000 deaths, over 85% in developing countries. By 2050, it is estimated that one million women worldwide will be diagnosed with cervical cancer (every year) and 90% of those who die from cervical cancer reside in developing countries. The highest incidence and mortality rates are in sub-Saharan Africa; Latin America and the Caribbean; and South and Southeast Asia. Source: HPV vaccine introduction into national immunization programmes: Information for programme managers and health workers. WHO 2013 Comprehensive cervical cancer prevention and control: a healthier future for girls and women. Guidance Note. WHO 2013

Introduction Let’s begin by looking at the estimated cervical cancer mortality rate worldwide. Data are available from IARC, the International Agency for Research on Cancer (IARC is part of WHO) - the most current available IARC data come from 2012. Overall, the mortality rate or case fatality ratio is 50% - this means 50 of 100 women diagnosed with cervical cancer (every year) die from it.

What is cervical cancer? The cervix is the lower part of uterus (womb) Cervical cancer is the uncontrolled growth of abnormal cells in the cervix, which usually starts on the surface Cervical cancer is invasive, which means it can grow deep into the cervix and uterus It can spread to other parts of the body (metastasize) in some cases Cervix is the lower part of uterus (womb) Cervical cancer is the uncontrolled growth of abnormal cells in the cervix Cervical cancer occurs when the cells in the cervix begin to grow and replicate in an abnormal and uncontrolled way. The uncontrolled growth usually starts in the surface cells at the outer part of the cervix Invasive cancer means that the cancer affects the deeper tissues of the cervix Cervical cancer can also spread to other parts of the body. This spread is called metastasis. Cervical cancer usually spreads by direct invasion of neighboring tissues to involve the bladder, the vagina, or the rectum and later involve the intestines, ureters, liver, and kidneys

What causes cervical cancer? Human papillomavirus (HPV) is the main cause of cervical cancer HPV is a common virus, which is Easily spread by skin-to-skin contact during sexual activity with another infected person HPV types 16 and 18 are associated with about 70% of all cervical cancer cases Risk factors for HPV infection and cervical cancer: Early sexual intercourse Multiple sexual partners Tobacco use Certain Human papillomarvirus (HPV) types cause cancer including cervical, vulvar, vaginal, penile, anal, and oropharyngeal (base of the tongue, tonsils and back of throat) cancers There are many different types of HPV, and many do not cause problems. However, infection with certain types of HPV can lead to Cervical cancer (HPV types 16 and 18 cause over 70 percent of cervical cancer cases) and other types can cause genital warts Human Papillomavirus 7

Symptoms of advanced cervical cancer HPV infection is often asymptomatic Symptoms appear after cancer reaches an advanced stage Main symptoms include: Irregular vaginal bleeding or bleeding after sexual intercourse Back, leg or pelvic pain Fatigue, weight loss, loss of appetite Vaginal discomfort or odorous discharge Single swollen leg More severe symptoms (usually more advanced): Severe anaemia Renal failure Fistulae Lymphoedema HPV infection is often asymptomatic. Symptoms of cervical cancer tend to appear only after the cancer has reached an advanced stage and may include: Irregular, intermenstrual or abnormal vaginal bleeding after sexual intercourse Back, leg, or pelvic pain, Fatigue, weight loss, loss of appetite Vaginal discomfort or odorous discharge which may be pale, watery, pink, brown, or bloody Single swollen leg More severe symptoms may arise at more advanced stages including more severe anaemia, renal failure, fistulae, and lymphoedema Human papillomavirus

World Health Organization How does HPV infection lead to cervical cancer? 28 November 2018 28 November, 2018 Graph A: Cervical cancer begins with infection of cells on the surface of the cervix. Most HPV infections clear up spontaneously, but a small percentage of women infected with oncogenic (cancer-causing) HPV types develop persistent infections, and this can lead to precancerous changes or lesions. Some lesions resolve spontaneously, but others progress to invasive cervical cancer Progress from infection to precancer and cancer is slow (15-20 years or more); so cervical cancer is most often found in women of middle age. Because of this long period of progression, there are good opportunities to identify and treat early stages of the disease—either HPV infections or precancerous lesions. If lesions are treated early, success rates are very high and invasive cancer typically does not develop In women with immune suppression, such as women with untreated HIV infection, progression of HPV infection to precancer and cancer can be rapid, sometimes resulting in cervical cancer in women still in their 20’s HPV infections (short-lived or persistent) do not show symptoms, so women must be screened periodically to determine if a persistent infection has occurred or if lesions have developed 9

Over what timespan does Cervical cancer develop? Graph B: The prevalence curves are not drawn to scale. The graph shows age-related prevalence of HPV infections (pink), precancer (blue), and cervical cancer (green). Most people become HPV infected shortly after they become sexually active It takes 15 – 20 years to develop into cancer in women with normal immune systems. It can take only 5-10 years in women with abnormal immune systems, such as those with untreated HIV infection Cervical cancer screening should start around 30 years of age (in women with normal immune systems) so that most precancerous lesions can be detected and treated, before cancer develops This graph also shows us why we should vaccinate early – administering HPV vaccine in girls who are 9-13 years old allows them to be protected from HPV infection before they are exposed to the virus and before the high-risk period where HPV infection prevalence is highest

Prevention and Treatment World Health Organization 28 November 2018 HPV vaccination prevents 95% of HPV infections with types 16 & 18 The WHO Comprehensive Approach to Cervical Cancer Prevention and Control includes primary prevention, secondary prevention and tertiary prevention. The most effective national strategies for prevention and control contain a combination of primary, secondary, and tertiary prevention which - due to its breadth of activities - calls for cross-disciplinary coordination HPV vaccination offers the earliest opportunity to prevent cervical cancer before a girl is even infected. HPV vaccines prevent over 95% of HPV infections caused by HPV types 16 and 18, and may have some cross-protection against other less common HPV types which cause cervical cancer Tobacco use is a risk factor for cervical cancer and people often start using tobacco during adolescence. This age group is therefore an important window of opportunity for prevention Safe sexual practices, including delay in onset of sexual activity, reduce the risk of HPV infection. Therefore sexuality education is another component of cervical cancer prevention (such as through the promotion of condom use)

Key messages (1/2) Cervical cancer is the 2nd most common cancer in women Cervical cancer affects an estimated 528,000 women each year and leads to 266,000 deaths (2012) over 85% of affected women live in developing countries Cervical cancer is caused by persistent infection with certain types of HPV virus – types 16 &18 cause most cervical cancers HPV viruses are common and spread easily by skin-to- skin contact during sexual activity Cervical cancer remains the second most common cancer in women Cervical cancer affects an estimated 528,000 women each year and leads to 266,000 deaths (2012), over 85% in developing countries Almost all cervical cancers are caused by the human papillomavirus (HPV). Persistent infection with specific types of HPV (most frequently, types 16 and 18) may lead to precancerous lesions HPV is a common virus that is easily spread by skin-to-skin contact during sexual activity with another infected person 12

Key messages (2/2) Risk factors for HPV infection and cervical cancer are: early sexual intercourse, multiple sexual partners tobacco use Progress from infection to pre-cancerous lesions and cancer is slow but can be rapid in women with immune suppression Symptoms of cervical cancer tend to appear only after the cancer has reached an advanced stage HPV vaccines prevent over 95% of infections from HPV types 16 & 18 Risk factors associated with HPV infection and cervical cancer are early sexual intercourse, multiple sexual partners, and tobacco use Progress from infection to precancer and cancer is slow (15-20 years or more) but can be rapid in women with weak immune suppression HPV infection is often asymptomatic. Symptoms of cervical cancer tend to appear only after the cancer has reached an advanced stage HPV types 16 and 18 cause 70% of cervical cancer and HPV vaccines prevent over 95% of HPV infections caused by HPV types 16 and 18 . HPV vaccines may have some cross-protection against other less common HPV types that cause cervical cancer 13

End of module for your attention! Thank you This is the end of the module, thank you for your attention!

References Comprehensive cervical cancer prevention and control: a healthier future for girls and women. Guidance Note. WHO 2013 HPV vaccine introduction into national immunization programmes: Information for programme managers and health workers. WHO 2013