Cervical Cancer and HPVCervical Cancer and HPV

Z Mike Chirenje MD FRCOGZ Mike Chirenje MD FRCOGUniversity of Zimbabwe, Department of University of Zimbabwe, Department of

Obstetrics and Gynecology, Harare, Obstetrics and Gynecology, Harare, Zimbabwe Zimbabwe

• Summary from (Chirenje ZM, HIV and Cancer Summary from (Chirenje ZM, HIV and Cancer of the cervix, in: of the cervix, in: Best Practice & ResearchBest Practice & Research, , Clinical Obstetrics and Gynaecology. Vol. 19, Clinical Obstetrics and Gynaecology. Vol. 19, No. 2, pp. 269 – 276: April 2005, London UK).No. 2, pp. 269 – 276: April 2005, London UK).

Cancer Burden WorldwideCancer Burden Worldwide

• In 1985 it was estimated that there were In 1985 it was estimated that there were approximately 7.6 million new cases of cancer approximately 7.6 million new cases of cancer diagnosed throughout the world (Parkin DM diagnosed throughout the world (Parkin DM et al., Int. J. Cancer, 1993) .et al., Int. J. Cancer, 1993) .

• Half of the cases occurred in womenHalf of the cases occurred in women• Distribution of cancer is highest in breast Distribution of cancer is highest in breast

followed by cervixfollowed by cervix• In Africa cervical cancer carries the highest In Africa cervical cancer carries the highest

burden occurring in 20-30% cancers among burden occurring in 20-30% cancers among women (compared to 4-6% in high income women (compared to 4-6% in high income countries) countries)

Cancer Burden in Women Cancer Burden in Women

Cancer Burden in Women Cancer Burden in Women

• 471,000 new cases diagnosed in 2000 of 471,000 new cases diagnosed in 2000 of which 80% were in the developing worldwhich 80% were in the developing world

• Close to 300,000 women die from cervical Close to 300,000 women die from cervical cancer worldwide every yearcancer worldwide every year

• Peak incidence for cervical cancer worldwide Peak incidence for cervical cancer worldwide is late 40s to early 50sis late 40s to early 50s

Cervical Cancer BurdenCervical Cancer Burden by Country Income by Country Income

Majority of cervical cancer cases are in low income countries Majority of cervical cancer cases are in low income countries Possible target populations: Developing countries: 52.5 million girls Possible target populations: Developing countries: 52.5 million girls

High-income countries: 6.5 million girlsHigh-income countries: 6.5 million girls

Source: 2002 Globocan data and PATH staff estimatesSource: 2002 Globocan data and PATH staff estimates

Country Grouping Estimated Cases, 2002

Percent Share

Low income countries of which: India

264,931(132,082)

54%(27%)

Lower middle income 112,232 23%

Upper middle income 60,223 12%

High Income 54,402 11%

Total 491,788 100%

Estimates of the Number of Cases Estimates of the Number of Cases and Incidence of Cervical Cancer, and Incidence of Cervical Cancer, 20022002

Magnitude of Cervical Cancer Problem Magnitude of Cervical Cancer Problem in Zimbabwean women:in Zimbabwean women:

Female cancers registered in 2002 by site:Female cancers registered in 2002 by site:• Cervix uteri (771)Cervix uteri (771) 25.9%25.9%• Kaposi sarcoma (478)Kaposi sarcoma (478) 16.1% 16.1%• Breast (304)Breast (304) 10.2%10.2%• Ovary (74)Ovary (74) 2.5%2.5%• Cervix corpus (40)Cervix corpus (40) 1.3%1.3%Zimbabwe cancer Registry (2006).Zimbabwe cancer Registry (2006).• Therefore 1 in every 4 women diagnosed to have Therefore 1 in every 4 women diagnosed to have

cancer had cervical cancer.cancer had cervical cancer.

• Cervical cancer is often slow growing, with Cervical cancer is often slow growing, with progressive generalised wasting for several months progressive generalised wasting for several months that creates difficult home care in low resources.that creates difficult home care in low resources.

• Family members complain about the unbearable Family members complain about the unbearable smell that is socially embarrassing and impossible to smell that is socially embarrassing and impossible to eradicate (unresponsive to antibiotics).eradicate (unresponsive to antibiotics).

Epidemiology and Treatment of Epidemiology and Treatment of Cervical Cancer :Cervical Cancer :

• Survival of cervical cancer patients after treatment in Survival of cervical cancer patients after treatment in a study by Zimbabwe cancer registry demonstrated a study by Zimbabwe cancer registry demonstrated that only 26.8% were alive after 3 years (Chokunonga that only 26.8% were alive after 3 years (Chokunonga et. al. Int. J. Cancer, 2003).et. al. Int. J. Cancer, 2003).

• The peak age for ICC is 46 years resulting in major The peak age for ICC is 46 years resulting in major catastrophic loss for immediate family, community catastrophic loss for immediate family, community and national economic loss.and national economic loss.

Epidemiology and Treatment of Epidemiology and Treatment of Cervical Cancer :Cervical Cancer :

• Majority (63.3%) are from rural communities Majority (63.3%) are from rural communities (Chirenje et. al 2000) where a typical 46 year old (Chirenje et. al 2000) where a typical 46 year old woman has 3 to 4 children (oldest 16 years youngest woman has 3 to 4 children (oldest 16 years youngest 8 years of age) left behind as young orphans.8 years of age) left behind as young orphans.

• Majority (80%) present at FIGO > stage 2bMajority (80%) present at FIGO > stage 2b• Psychological effect on nurses/doctors results in Psychological effect on nurses/doctors results in

withdrawal/depression symptoms.withdrawal/depression symptoms.

Epidemiology and Treatment of Epidemiology and Treatment of Cervical Cancer :Cervical Cancer :

• One of the earliest observations in cancer One of the earliest observations in cancer epidemiology was that cancer of the uterine epidemiology was that cancer of the uterine cervix cervix rarelyrarely occurred among celibate nuns occurred among celibate nuns (Rigoni-Stern, 1842). Rigoni-Stern D.A, Fatti (Rigoni-Stern, 1842). Rigoni-Stern D.A, Fatti statistici relativi alle mallattie cancrose. statistici relativi alle mallattie cancrose. Giovnali per servire ai progressi della Giovnali per servire ai progressi della Patologia e della Terapeutica (1842); 2: 507 – Patologia e della Terapeutica (1842); 2: 507 – 517.517.

Cervical Cancer Overview Cervical Cancer Overview

Role of Screening in advent of HPV Role of Screening in advent of HPV VaccinesVaccines

• The role of oncogenic HPV has been The role of oncogenic HPV has been establishes as necessary cause of ICC and its establishes as necessary cause of ICC and its precursor (CIN)precursor (CIN)

• Over 100 different genotypes identified of Over 100 different genotypes identified of which 40 detected in anogenital area which 40 detected in anogenital area

•HPV and Cervical Specific LessionsHPV and Cervical Specific Lessions

HPV infections are among the most HPV infections are among the most common sexually transmitted infections common sexually transmitted infections among adults.among adults.

HR DNA is age dependant (peak age late HR DNA is age dependant (peak age late 20’s) with rates of 15 – 20% and drops 20’s) with rates of 15 – 20% and drops significantly to 2-6% by mid thirties when significantly to 2-6% by mid thirties when the age specific incidence rates (ASIR) of the age specific incidence rates (ASIR) of ICC are peaking up.ICC are peaking up.

HPV EpidemiologyHPV Epidemiology

• Evidence from several African studies Evidence from several African studies demonstrate prevalence of multiple HPV demonstrate prevalence of multiple HPV types among women with normal cytology, types among women with normal cytology, abnormal cytology, CIN 2/3 (up to 50% HPV abnormal cytology, CIN 2/3 (up to 50% HPV types 16, 18) and ICC ( up to 70 % HPV types types 16, 18) and ICC ( up to 70 % HPV types 16, 18).16, 18).

PersistencePersistence of HR HPV infection of HR HPV infection (16,18,26,31, (16,18,26,31, 33,35,39,45,51,52,53,56,58,59,66,68,73 33,35,39,45,51,52,53,56,58,59,66,68,73 and 82) is necessary for and 82) is necessary for development, development, maintenance maintenance andand progression progression of CIN the of CIN the known precursor for ICC.known precursor for ICC.

Persistence of HPV DNA from types Persistence of HPV DNA from types 16, 18, 16, 18, 4545 and and 3131 are found in 99.7% of all ICC. are found in 99.7% of all ICC.

Studies over the past 15 years have Studies over the past 15 years have

conclusively established that conclusively established that

oncogenic HPV types (16, 18, 31, 45) oncogenic HPV types (16, 18, 31, 45)

are aetiologically linked to CIN III and are aetiologically linked to CIN III and

invasive cervical cancer. (Womach invasive cervical cancer. (Womach

SD, Chirenje ZM, et al, BJOG 107(1) SD, Chirenje ZM, et al, BJOG 107(1)

33-38, Int.J. Cancer 2000. 85, 206 - 33-38, Int.J. Cancer 2000. 85, 206 -

210210

Most squamous cell cancers of the Most squamous cell cancers of the

cervix develop from CIN over a long cervix develop from CIN over a long

latency period.latency period.

• Summary from (Chirenje ZM, HIV and Cancer Summary from (Chirenje ZM, HIV and Cancer of the cervix, in: of the cervix, in: Best Practice & ResearchBest Practice & Research, , Clinical Obstetrics and Gynaecology. Vol. 19, Clinical Obstetrics and Gynaecology. Vol. 19, No. 2, pp. 269 – 276: April 2005, London UK).No. 2, pp. 269 – 276: April 2005, London UK).

Practice PointsPractice Points

• HIV-positive women have 2 to 12 fold higher risk of HIV-positive women have 2 to 12 fold higher risk of CIN lesions compared with HIV-negative women.CIN lesions compared with HIV-negative women.

• HIV positive women should be offered cervical HIV positive women should be offered cervical cytology screening, referral for colposcopy and cytology screening, referral for colposcopy and follow-up with 6-monthly cervical cytology follow-up with 6-monthly cervical cytology surveillance.surveillance.

• Treatment of CIN lesions in HIV-positive Treatment of CIN lesions in HIV-positive women has high recurrence rates, women has high recurrence rates, irrespective of treatment modality irrespective of treatment modality (Chirenje ZM et al, J. Lower Gen. Tract. (Chirenje ZM et al, J. Lower Gen. Tract. Disease 2003).Disease 2003).