1. Cervical Cancer & HPV

2. Presentation Overview
Cervical cancer Cause: Human Papilloma Virus (HPV)
“Natural history”
Treatment
Preventing cervical cancer
Avoiding exposure to HPV
Current screening guidelines
The new HPV vaccines

3. Cervical Cancer
Abnormal cell growth on cervix (lowest part of the uterus)
Caused by HPV infection, especially during the first years after puberty
Pre-cancerous changes long before invasive cancer develops
Rarely fatal in this country
A major cause of death worldwide

4. Human Papillomavirus (HPV)
Long known to cause warts
Found in many cancers too
Over 100 types identified
Most benign, but can cause cancers
Key Point
There are many different types of HPV; of the 15–20 oncogenic types, HPV 16 and HPV 18 account for the majority of cervical cancers.
The disease burden is large. HPV is very prevalent, especially among young sexually active teens and adults.
Background
Papillomaviruses such as HPV are nonenveloped, double-stranded DNA viruses. More than 100 HPV types have been detected, with >80 types sequenced and classified. Approximately 30–40 types of HPV are anogenital, of which 15–20 types are oncogenic. HPV Types 16 and 18 are oncogenic and account for about two thirds of all cervical cancers. HPV Types 6 and 11 are nononcogenic and are associated with external anogenital warts and RRP.
References
1. Schiffman M, Castle PE. Human papillomavirus: Epidemiology and public health. Arch Pathol Lab Med. 2003;127:930–934.
2. Wiley DJ, Douglas J, Beutner K, et al. External genital warts: Diagnosis, treatment, and prevention. Clin Infect Dis. 2002;35(suppl 2):S210–S224.

5. HPV & Cervical Cancer HPV recognized as the underlying cause of
cervical cancer since 1996
The causal role of human papillomavirus in all cancers of the cervix has been firmly established biologically and epidemiologically.
Reference: Munoz, N. et al. “HPV in the etiology of human cancer.” Vaccine 24S3 2006;24S3: 1-10.

6. Common HPV Types and their effects
Lead to:
HPV 6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 81
Benign cervical changes
Genital warts
Low-Risk
Precancer cervical changes
Cervical cancer
Anal and other cancers
High-Risk
HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, 82
Low-risk HPV types, such as types 6 and 11, most commonly cause benign low-grade cervical changes and genital warts.
Types 16 and 18 and other “high-risk” HPV types are the most common cause of low-grade cervical cell abnormalities, and almost exclusively cause high-grade cervical cell abnormalities that are precursors to invasive cervical cancer and other lower genital tract malignancies including vulvar, vaginal, penile and anal cancer.
The large IARC study of cervical cancers around the world demonstrated that over 90% of all of cervical cancers were associated with high-risk types of HPV
Irrespective of geographical area
43% to 65% of the cancers were associated with HPV 16
8% to 31% were associated with HPV 18.
Taken together, HPV 16 and 18 accounted for approximately two-thirds of all invasive cancers from all geographic areas.
References:
1. Cox. Baillière’s Clin Obstet Gynaecol. 1995;9:1. 2. Munoz et al. N Engl J Med. 2003;348:518.
1. Cox. Baillière’s Clin Obstet Gynaecol. 1995;9:1. 2. Munoz et al. N Engl J Med. 2003;348:518.

7. Natural History of HPV Infections
Sexually transmitted
Usually no symptoms
No treatment for HPV infection before symptoms
Immune system clears most cases; some persist
HPV present in >99% of cervical cancers
High risk types (16, 18) associated with cancer
Low risk types (6, 11) are associated with genital warts
All can cause abnormal Pap tests
Genital HPV is transmitted sexually. Transmission occurs through contact with infected genital skin, mucous membranes, or body fluids from a partner with either overt or subclinical HPV infection. Other modes include oro-genital, manual-genital, and nonpenetrative genital-genital contact.
Covering infected areas with a latex condom provides theoretical protection from infection. Areas not covered by condom can transmit HPV infection.
Infrequently transmitted in the neonatal period, although published studies are conflicting.
Most HPV infections are transient and are cleared by the immune system
70-90% will clear within 1-2 years
Persistent HPV viral infections may lead to cancer and its precursors
No treatment for HPV infection but cervical changes and warts CAN be treated
Reference: Human Papillomavirus. ACOG Practice Bulletin No. 61. American College of Obstetricians and Gynecologists. Obstet Gynecol 2005; 105:
Human Papillomavirus. ACOG Practice Bulletin No ; 105:

8. Co-factors for HPV Infection
Smoking
HIV infection
Other immune system defect
Pregnancy
Oral contraceptive use
Co-factors to HPV in cervical carcinogenesis may act in at least 3 ways:
By influencing the acquisition of HPV infection (OCPs, multiparity)
By increasing the risk of HPV persistence (HIV, immunosuppresion)
By increasing the risk of progression from HPV infection to CIN 2,3 and cancer (smoking, multiparity)
Cigarette smoking is a significant and independent risk factor for the development of CIN3 and SCC of cervix, increasing RR 2-5 fold. Risk increases with increased intensity and duration of smoking. Mechanism is likely that tobacco containing carcinogens promote neoplastic progression in HPV infected cells.
HIV and other immunosupression cause an inability to clear HPV, increasing susceptibility to HPV and oncogenicity.
Multiparity has been found to be associated with both cervical cancer and CIN3 with risk rising with increased number of pregnancies. Effect is independent of sexual behavior and socioeconomic variables. Pregnancy-induced alterations in nutritional status, the effects of hormones on the cervix or on HPV expression, increased susceptibility to potential mutagens or effect of trauma at delivery are proposed mechanisms.
OCP use conveys a measurable increase in risk for SCC. The strongest evidence comes from an IARC multicenter case-control study demonstrating only a moderate association with cancer risk. Mechanism appears to be the physiologic effects such as eversion of the columnar epithelium, thus activating HPV-vulnerable immature squamous metaplasia.
Reference: Ferris et al. Modern Colposcopy. 2004: 2-4,
Ferris et al. Modern Colposcopy

9. HPV Infections: Summary
Most people are infected by HPV at some time
Immune system usually clears HPV, but not always
Persistent low-risk HPV can lead to genital warts
Persistent high-risk HPV can lead to pre-cancer
Long persistence of HPV can lead to cancer
In summary
Most will get HPV at some time during their lifetime
Most, even with high-risk HPV, will clear or permanently suppress the virus.
However, some do not.
It is persistence of high-risk HPV that can lead to true pre-cancer
Long persistence of high-risk HPV and HPV-induced CIN3 are necessary for the accumulation of random mutations that lead to cancer.
Cancer
HPV

10. Preventing Cervical Cancer
Screening for precancerous changes (and treatment if problems found)
Vaccination against HPV

11. History of the Conventional Pap Smear
Developed by Dr. George N. Papanicolaou in 1940’s
Most common cancer screening test
Key part of annual gynecologic examination
Has greatly reduced cervical cancer mortality in U.S.
Primary cervical cancer screening essentially began with the introduction of the Pap Smear.
Introduced in the 1940’s, by Dr. George N. Papanicolaou, the pap smear eventually became the standard screening test for cervical cancer and pre-malignant lesions.
The Pap test is based on a relatively simple principle. Cells from squamous epithelium exfoliate over time. Thus, the cells removed for cytologic examination represent epithelial cells, normal or abnormal, found at the surface.
Widespread use of the pap smear has decreased cervical cancer deaths by 70%.
Reference: Ferris et al. Modern Colposcopy. 2004: 2-4, 49.
Ferris et al. Modern Colposcopy. 2004: 2-4, 49.
Photo accessed from

12. Screening with the Conventional Pap Smear
Widely available
Inexpensive
But not perfect
Screening test – not diagnostic
7-10% of women need further evaluation
Low sensitivity – need regular repeats
Cervical cytology screening is, in many respects, the ideal screening test.
Cervical cancer has a defined premalignant phase of many years, which allows repeated tests to significantly reduce the impact of individual false-negative test results.
Cervical cytology is inexpensive and is readily accepted among American women.
However, cervical cytology, is not a diagnostic test. The sensitivity of the pap smear is low (ranges from 47-85%) and the specificity is high (95-98%).
Reference: Cervical Cytology Screening. ACOG Practice Bulletin No ; 102:
Cervical Cytology Screening. ACOG Practice Bulletin No ; 102:

13. New Liquid Pap Tests More accurate test Screening needed less often
Thin, uniform layer of cells
Screening errors reduced by half
Screening needed less often
Can test for HPV with same specimen if abnormal cells found
Expensive
In 1996, the FDA approved the first of two currently available liquid-based thin-layer cytology preparations for cervical screening.
Liquid-based thin-layer cervical cytology was introduced to help reduce the potential sampling errors. The Thin-Prep method appears to have increased sensitivity for detecting cancer precursor lesions over the conventional method, but the degree to which sensitivity is increased is unknown. The reported increase in sensitivity may make this method especially useful in women who are screened infrequently (fewer false negatives).
The difference in specificity between the liquid-based and conventional tests has not been determined. Although an increase in sensitivity will permit earlier detection of cancer precursor lesions, any decrease in specificity can result in increased cost and morbidity from false-positive diagnoses.
Both the conventional test and the liquid-based thin-layer test can be effective in population screening.
Providers selecting a cervical cytology method should consider the screening history of their patient, the cost of the test, and the possible effects of false-negative or false-positive results.
Reference: ACOG Practice Bulletin. Cervical Cytology Screening. 2003; 45:1-11.
Linder J. et al. Arch Pathol Lab Med. 1998; 122:

14. Cervical Cancer Screening Guidelines
First screen 3 years after first intercourse or by age 21
Screen annually with regular Paps or every 2 years with liquid-based tests
After three normal tests, can go to every three years
Stop at years with history of negative tests
Still need annual check-ups
The next several slides will review the newest guidelines for cervical cancer screening from the American Cancer Society, the United States Preventive Services Task Force and the American College of Obstetricians and Gynecologists.
These guidelines specifically state how often screening should be done, when to initiate screening and when screening can be discontinued.
Reference: Cervical Cytology Screening. ACOG Practice Bulletin No ; 102:
Cervical Cytology Screening. ACOG Practice Bulletin No ; 102:

15. Cervical cancer

16. Introduction
Cancer of the cervix is the most common female genital cancer in developing countries every year about 500,000 women , acquire the disease and 75% are from frame developing countries.
About 300,000 women also die from the disease annually and of these 75% are from developing countries

17. Incidence
4-6 % of female genital cancers.

18. Age
40-50 years old

19. Risk factors and aetiology
Coitus at young age: <16 years old increased risk by 50%
Number of sexual partners: 6 sexual partners or more increase risk by 14.2 folds.
Smoking
Smoking for> 12 years increase the risk by 12.7 folds.
Male related risk factors:
number of the partners previous sexual relationships is relevant .
cervical cancer risk increased if partners has penile cancer (circumcision)
Previous wife with cervical cancer.
Previous CIN
Poor uptake of screening program.
Long term use of the contraceptive pill increase the risk due to increasing exposure to seminal fluids.
Barrier method decrease the risk (condan)
Immuno suppresion risk increased with immuno suppressed renal transplant patients and in HIV positive women.
HPV (Human papilloma virus ) infection mainly 16,18
the main aetiological is infection with subtypes of HPV (16,18)
Low socioecomic class of
Coitus at young age: <16 years old increased risk by 50%
Number of sexual partners: 6 sexual partners or more increase risk by 14.2 folds.
Smoking
Smoking for> 12 years increase the risk by 12.7 folds.
Male related risk factors:
number of the partners previous sexual relationships is relevant .
cervical cancer risk increased if partners has penile cancer (circumcision)
Previous wife with cervical cancer.
Previous CIN
Poor uptake of screening program.
Long term use of the contraceptive pill increase the risk due to increasing exposure to seminal fluids.
Barrier method decrease the risk (condan)
Immuno suppresion risk increased with immuno suppressed renal transplant patients and in HIV positive women.
HPV (Human papilloma virus ) infection mainly 16,18
the main aetiological is infection with subtypes of HPV (16,18)
Low socioecomic class of
Coitus at young age: <16 years old increased risk by 50%
Number of sexual partners: 6 sexual partners or more increase risk by 14.2 folds.
Smoking
Smoking for> 12 years increase the risk by 12.7 folds.
Male related risk factors:
number of the partners previous sexual relationships is relevant .
cervical cancer risk increased if partners has penile cancer (circumcision)
Previous wife with cervical cancer.
Previous CIN
Poor uptake of screening program.
Long term use of the contraceptive pill increase the risk due to increasing exposure to seminal fluids.
Barrier method decrease the risk (condan)
Immuno suppresion risk increased with immuno suppressed renal transplant patients and in HIV positive women.
HPV (Human papilloma virus ) infection mainly 16,18
the main aetiological is infection with subtypes of HPV (16,18)
Low socioecomic class of
Coitus at young age: <16 years old increased risk by 50%
Number of sexual partners: 6 sexual partners or more increase risk by 14.2 folds.
Smoking
Smoking for> 12 years increase the risk by 12.7 folds.
Male related risk factors:
number of the partners previous sexual relationships is relevant .
cervical cancer risk increased if partners has penile cancer (circumcision)
Previous wife with cervical cancer.
Previous CIN
Poor uptake of screening program.
Long term use of the contraceptive pill increase the risk due to increasing exposure to seminal fluids.
Barrier method decrease the risk (condan)
Immuno suppresion risk increased with immuno suppressed renal transplant patients and in HIV positive women.
HPV (Human papilloma virus ) infection mainly 16,18
the main aetiological is infection with subtypes of HPV (16,18)
Low socioecomic class of
Coitus at young age: <16 years old increased risk by 50%
Number of sexual partners: 6 sexual partners or more increase risk by 14.2 folds.
Smoking
Smoking for> 12 years increase the risk by 12.7 folds.
Male related risk factors:
number of the partners previous sexual relationships is relevant .
cervical cancer risk increased if partners has penile cancer (circumcision)
Previous wife with cervical cancer.
Previous CIN
Poor uptake of screening program.
Long term use of the contraceptive pill increase the risk due to increasing exposure to seminal fluids.
Barrier method decrease the risk (condan)
Immuno suppresion risk increased with immuno suppressed renal transplant patients and in HIV positive women.
HPV (Human papilloma virus ) infection mainly 16,18
the main aetiological is infection with subtypes of HPV (16,18)
Low socioecomic class of
Coitus at young age: <16 years old increased risk by 50%
Number of sexual partners: 6 sexual partners or more increase risk by 14.2 folds.
Smoking
Smoking for> 12 years increase the risk by 12.7 folds.
Male related risk factors:
number of the partners previous sexual relationships is relevant .
cervical cancer risk increased if partners has penile cancer (circumcision)
Previous wife with cervical cancer.
Previous CIN
Poor uptake of screening program.
Long term use of the contraceptive pill increase the risk due to increasing exposure to seminal fluids.
Barrier method decrease the risk (condan)
Immuno suppresion risk increased with immuno suppressed renal transplant patients and in HIV positive women.
HPV (Human papilloma virus ) infection mainly 16,18
the main aetiological is infection with subtypes of HPV (16,18)
Low socioecomic class of
Coitus at young age: <16 years old increased risk by 50%
Number of sexual partners: 6 sexual partners or more increase risk by 14.2 folds.
Smoking
Smoking for> 12 years increase the risk by 12.7 folds.
Male related risk factors:
number of the partners previous sexual relationships is relevant .
cervical cancer risk increased if partners has penile cancer (circumcision)
Previous wife with cervical cancer.
Previous CIN
Poor uptake of screening program.
Long term use of the contraceptive pill increase the risk due to increasing exposure to seminal fluids.
Barrier method decrease the risk (condan)
Immuno suppresion risk increased with immuno suppressed renal transplant patients and in HIV positive women.
HPV (Human papilloma virus ) infection mainly 16,18
the main aetiological is infection with subtypes of HPV (16,18)
Low socioecomic class of
Coitus at young age: <16 years old increased risk by 50%
Number of sexual partners: 6 sexual partners or more increase risk by 14.2 folds.
Smoking
Smoking for> 12 years increase the risk by 12.7 folds.
Male related risk factors:
number of the partners previous sexual relationships is relevant .
cervical cancer risk increased if partners has penile cancer (circumcision)
Previous wife with cervical cancer.
Previous CIN
Poor uptake of screening program.
Long term use of the contraceptive pill increase the risk due to increasing exposure to seminal fluids.
Barrier method decrease the risk (condan)
Immuno suppresion risk increased with immuno suppressed renal transplant patients and in HIV positive women.
HPV (Human papilloma virus ) infection mainly 16,18
the main aetiological is infection with subtypes of HPV (16,18)
Low socioecomic class of
Coitus at young age: <16 years old increased risk by 50%
Number of sexual partners: 6 sexual partners or more increase risk by 14.2 folds.
Smoking
Smoking for> 12 years increase the risk by 12.7 folds.
Male related risk factors:
number of the partners previous sexual relationships is relevant .
cervical cancer risk increased if partners has penile cancer (circumcision)
Previous wife with cervical cancer.
Previous CIN
Poor uptake of screening program.
Long term use of the contraceptive pill increase the risk due to increasing exposure to seminal fluids.
Barrier method decrease the risk (condan)
Immuno suppresion risk increased with immuno suppressed renal transplant patients and in HIV positive women.
HPV (Human papilloma virus ) infection mainly 16,18
the main aetiological is infection with subtypes of HPV (16,18)
Low socioecomic class of
Coitus at young age: <16 years old increased risk by 50%
Number of sexual partners: 6 sexual partners or more increase risk by 14.2 folds.
Smoking
Smoking for> 12 years increase the risk by 12.7 folds.
Male related risk factors:
number of the partners previous sexual relationships is relevant .
cervical cancer risk increased if partners has penile cancer (circumcision)
Previous wife with cervical cancer.
Previous CIN
Poor uptake of screening program.
Long term use of the contraceptive pill increase the risk due to increasing exposure to seminal fluids.
Barrier method decrease the risk (condan)
Immuno suppresion risk increased with immuno suppressed renal transplant patients and in HIV positive women.
HPV (Human papilloma virus ) infection mainly 16,18
the main aetiological is infection with subtypes of HPV (16,18)
Low socioecomic class of
Coitus at young age: <16 years old increased risk by 50%
Number of sexual partners: 6 sexual partners or more increase risk by 14.2 folds.
Smoking
Smoking for> 12 years increase the risk by 12.7 folds.
Male related risk factors:
number of the partners previous sexual relationships is relevant .
cervical cancer risk increased if partners has penile cancer (circumcision)
Previous wife with cervical cancer.
Previous CIN
Poor uptake of screening program.
Long term use of the contraceptive pill increase the risk due to increasing exposure to seminal fluids.
Barrier method decrease the risk (condan)
Immuno suppresion risk increased with immuno suppressed renal transplant patients and in HIV positive women.
HPV (Human papilloma virus ) infection mainly 16,18
the main aetiological is infection with subtypes of HPV (16,18)
Low socioecomic class of
Coitus at young age: <16 years old increased risk by 50%
Number of sexual partners: 6 sexual partners or more increase risk by 14.2 folds.
Smoking
Smoking for> 12 years increase the risk by 12.7 folds.
Male related risk factors:
number of the partners previous sexual relationships is relevant .
cervical cancer risk increased if partners has penile cancer (circumcision)
Previous wife with cervical cancer.
Previous CIN
Poor uptake of screening program.
Long term use of the contraceptive pill increase the risk due to increasing exposure to seminal fluids.
Barrier method decrease the risk (condan)
Immuno suppresion risk increased with immuno suppressed renal transplant patients and in HIV positive women.
HPV (Human papilloma virus ) infection mainly 16,18
the main aetiological is infection with subtypes of HPV (16,18)
Low socioecomic class of
Coitus at young age: <16 years old increased risk by 50%
Number of sexual partners: 6 sexual partners or more increase risk by 14.2 folds.
Smoking
Smoking for> 12 years increase the risk by 12.7 folds.
Male related risk factors:
number of the partners previous sexual relationships is relevant .
cervical cancer risk increased if partners has penile cancer (circumcision)
Previous wife with cervical cancer.
Previous CIN
Poor uptake of screening program.
Long term use of the contraceptive pill increase the risk due to increasing exposure to seminal fluids.
Barrier method decrease the risk (condan)
Immuno suppresion risk increased with immuno suppressed renal transplant patients and in HIV positive women.
HPV (Human papilloma virus ) infection mainly 16,18
the main aetiological is infection with subtypes of HPV (16,18)
Low socioecomic class of
Coitus at young age: <16 years old increased risk by 50%
Number of sexual partners: 6 sexual partners or more increase risk by 14.2 folds.
Smoking
Smoking for> 12 years increase the risk by 12.7 folds.
Male related risk factors:
number of the partners previous sexual relationships is relevant .
cervical cancer risk increased if partners has penile cancer (circumcision)
Previous wife with cervical cancer.
Previous CIN
Poor uptake of screening program.
Long term use of the contraceptive pill increase the risk due to increasing exposure to seminal fluids.
Barrier method decrease the risk (condan)
Immuno suppresion risk increased with immuno suppressed renal transplant patients and in HIV positive women.
HPV (Human papilloma virus ) infection mainly 16,18
the main aetiological is infection with subtypes of HPV (16,18)
Low socioecomic class of
Coitus at young age: <16 years old increased risk by 50%
Number of sexual partners: 6 sexual partners or more increase risk by 14.2 folds.
Smoking
Smoking for> 12 years increase the risk by 12.7 folds.
Male related risk factors:
number of the partners previous sexual relationships is relevant .
cervical cancer risk increased if partners has penile cancer (circumcision)
Previous wife with cervical cancer.
Previous CIN
Poor uptake of screening program.
Long term use of the contraceptive pill increase the risk due to increasing exposure to seminal fluids.
Barrier method decrease the risk (condan)
Immuno suppresion risk increased with immuno suppressed renal transplant patients and in HIV positive women.
HPV (Human papilloma virus ) infection mainly 16,18
the main aetiological is infection with subtypes of HPV (16,18)
Low socioecomic class of
Coitus at young age: <16 years old increased risk by 50%
Number of sexual partners: 6 sexual partners or more increase risk by 14.2 folds.
Smoking
Smoking for> 12 years increase the risk by 12.7 folds.
Male related risk factors:
number of the partners previous sexual relationships is relevant .
cervical cancer risk increased if partners has penile cancer (circumcision)
Previous wife with cervical cancer.
Previous CIN
Poor uptake of screening program.
Long term use of the contraceptive pill increase the risk due to increasing exposure to seminal fluids.
Barrier method decrease the risk (condan)
Immuno suppresion risk increased with immuno suppressed renal transplant patients and in HIV positive women.
HPV (Human papilloma virus ) infection mainly 16,18
the main aetiological is infection with subtypes of HPV (16,18)
Low socioecomic class of
Coitus at young age: <16 years old increased risk by 50%
Number of sexual partners: 6 sexual partners or more increase risk by 14.2 folds.
Smoking
Smoking for> 12 years increase the risk by 12.7 folds.
Male related risk factors:
number of the partners previous sexual relationships is relevant .
cervical cancer risk increased if partners has penile cancer (circumcision)
Previous wife with cervical cancer.
Previous CIN
Poor uptake of screening program.
Long term use of the contraceptive pill increase the risk due to increasing exposure to seminal fluids.
Barrier method decrease the risk (condan)
Immuno suppresion risk increased with immuno suppressed renal transplant patients and in HIV positive women.
HPV (Human papilloma virus ) infection mainly 16,18
the main aetiological is infection with subtypes of HPV (16,18)
Low socioecomic class of
Coitus at young age: <16 years old increased risk by 50%
Number of sexual partners: 6 sexual partners or more increase risk by 14.2 folds.
Smoking
Smoking for> 12 years increase the risk by 12.7 folds.
Male related risk factors:
number of the partners previous sexual relationships is relevant .
cervical cancer risk increased if partners has penile cancer (circumcision)
Previous wife with cervical cancer.
Previous CIN
Poor uptake of screening program.
Long term use of the contraceptive pill increase the risk due to increasing exposure to seminal fluids.
Barrier method decrease the risk (condan)
Immuno suppresion risk increased with immuno suppressed renal transplant patients and in HIV positive women.
HPV (Human papilloma virus ) infection mainly 16,18
the main aetiological is infection with subtypes of HPV (16,18)
Low socioecomic class of
Coitus at young age: <16 years old increased risk by 50%
Number of sexual partners: 6 sexual partners or more increase risk by 14.2 folds.
Smoking
Smoking for> 12 years increase the risk by 12.7 folds.
Male related risk factors:
number of the partners previous sexual relationships is relevant .
cervical cancer risk increased if partners has penile cancer (circumcision)
Previous wife with cervical cancer.
Previous CIN
Poor uptake of screening program.
Long term use of the contraceptive pill increase the risk due to increasing exposure to seminal fluids.
Barrier method decrease the risk (condan)
Immuno suppresion risk increased with immuno suppressed renal transplant patients and in HIV positive women.
HPV (Human papilloma virus ) infection mainly 16,18
the main aetiological is infection with subtypes of HPV (16,18)
Low socioecomic class of

20. Type of patient: Multiparous. Low socioeconomic class. Poor hygiene.
Prostitutes.
Low incidence in Muslims and Jews.

21. Predisposing factors:
Cervical dysplasia.
(Cervical intraepithelial neoplasia)
CIN III / CARCINOMA IN SITU
THE LESION PROCEEDS THE INVASION BY YEARS

25. Symptoms: Early symptoms Late symptoms - None.
- Thin, watery, blood tinged vaginal discharge frequently goes unrecognized by the patient.
- Abnormal vaginal bleeding
Intermenstrual
Postcoital
Perimenopausal
Postmenopausal
- Blood stained foul vaginal discharge.
- Pain, leg oedema.
- Urinary and rectal symptoms
dysuria
haematuria
rectal bleeding
constipation
haemorrhoids
- Uraemia

26. Pathology type
Squamous cell carcinoma- 90%.
Adenocarcinoma- 10%.

27. Types of growth
Exophytic: is like cauliflower filling up the vaginal vualt.
Endophytic: it appears as hard mass with a good deal of induration.
Ulcerative: an ulcer in the cervix.

28. DIAGNOSIS 1- History. Many women are a symptomatic .
Presented with abnormal routine cx smear
Complain of abnormal vaginal bleeding
I M bleeding
post coital bleeding
perimenopausal bleeding
postmenopausal bleeding
blood stain vaginal discharge

29. 2- Examination:
Mainly vaginal examination using cuscu’s speculem nothing is found in early stage .
Mass ,ulcerating fungating in the cervix
P/V P/R is very helful.

30. Preoperative evaluation
Review her history.
General examination:
Anaemia.
Lymphadenopathy-Supraclavicular LN.
Renal area.
Liver or any palpable mass.
Oedema.
Laboratory tests:
CBC, LFT, RFT, Urine analysis.
Tumour markers.
Chest X- ray, abdominal X- ray, IVU.
CAT, MRI, if necessary.
Ultrasound.
Lymphography, if necessary.

31. Staging Best to follow FIGO system. Examination under anaesthesia.
Bimanual palpation.
P/V, P/R.
Cervical biopsy, uterine biopsy.
Cystoscopy, Proctoscopy, if necessary.

33. STAGES OF CANCER CERVIX
Once cancer cervix is found (diagnosed), more tests will be done to find out if the cancer cells have spread to other parts of the body. This testing is called staging.
TO PLAN TREATMENT, A DOCTOR NEEDS TO KNOW THE STAGE OF THE DISEASE.

39. SPREAD: Direct Lymphatic Dissemination (late) - Uteruq. - Vagina.
- Parametrium.
- Bladder and rectum.
A- primary node:
parametrial.
Paracervical.
Vesicovaginal.
Rectovaginal.
Hypogastric.
Obturator and external iliac
B-Secondary nodes:
Common iliac
Sacral
Vaginal
Paraaortic
Inguinal.
- parametrial spread causes obstruction of the ureters, many deaths occur due to uraemia.
- Obstruction to the cervical canal results in pyometria.

40. DIFFERENTIAL DIAGNOSIS
Cervical ectropion.
Cervical tuberculosis.
Cervical syphilis, Schistosomiasis, and Choriocarcinoma are rare causes.

41. TREATMENT Surgical. Radiotherapy. Radiotherapy & Surgery.
Radiotherapy and Chemotherapy followed by Surgery.
Palliative treatment.

42. The choice of treatment will depend on
Fitness of the patients
Age of the patients
Stage of disease.
Type of lesion
Experience and the resources avalible.

43. Surgical procedure
The classic surgical procedure is the wertheim’s hystrectomy for stage Ib,IIa, and some cases of IIb in young and fat patient

44. Werthemeim’s hystrectomy
Total abdominal hystrectomy including the parametrium.
Pelvic lymphadenectomy
3 cm vaginal cuff
The original operation conserved the ovaries ,since squamouss cell carcinoma does not spread dirctly to the ovaries.
Oophorectomy should be performed in cases of adenocarcinoma as there is 5-10% of ovarian metastosis

45. Surgery offers several advantage
It allows presentation of the ovaries (radiotherapy will destroythem).
There is better chance of preserving sexual function.
(vaginal stonosis occur in up 85% of irradiates.
Psychological feeling of removing the disease from the body .
More accute staging and prognsis

46. COMPLICATIONS OF SURGERY
Haemorrhage: primary or secondary.
Injury to the bladder, uerters.
Bladder dysfunction.
Fistula.
Lymphocele.
Shortening of the vagina.

47. INDICATIONS OF P/O XRT FOLLOWING WERTHEIM’S HYSTERECTOMY (STAGE I , IIa):
Positive pelvic lymph nodes.
Tumour close to resection margins and/or parametrial extension.

48. Radiotherapy Stage IIb and III Radical Radiotherapy
External irradiation (Teletherapy).
Intracavitary radiation (Brachytherapy).
In some cases of stage IIa or b radio and chemotherapy to be given then followed by simple hysterectomy

49. Palliative therapy For stage IV – individualized therapy.
Some suitable for palliative XRT ( usually intracavitary Caesium).
Some suitable for extensive surgery.
Some suitable for chemotherapy.
Good nursing care.
Analgesia-must be used in sufficient amount to pain (Codein sulfate, Pethidine, Morphine, Diamorphine).
Antiemetic if necessary.
IV drip, entral, and parentral feeding.
Urinary Catheterization.
Other measures for symptom relief.

50. PROGNOSIS Depends on: Age of the patient. Fitness of the patient.
Stage of the disease.
Type of the tumour.
Adequacy of treatment.

51. THE OVERALL 5 YEARS SURVIVAL FOLLOWING THERAPY:
Stage I %
Stage II %
Stage III %
Stage IV %

52. MANAGEMENT OF RECURRENT DISEASE
1. Local recurrence:
Radiation – if not used.
Pelvic exenturation.
2. Distant disease
Chemotherapy.

53. Endometrial carcinoma

54. Endometrial carcinoma is the fifth leading cancer in the women worldwide. In developed countries it’s the most common gynaecological cancer but in developing countries it’s surpassed by cervical cancer.

55. Age groups: Mean age of presentation is 56 years. 75% after menopause
Age groups: Mean age of presentation is 56 years . 75% after menopause. 20% perimenopausal. 5% before age of 40. Aetiology: a- indiscriminate use of oestrogen. b- un opposed oestrogen. c- Theca granulosa cell tumours.

56. Prediposing factors: Atypical adenomatous hyperplasia (complex atypical ) –25% ( %) to progress to cancer Type of patient: Nullipara or low parity Middle or upper social class Overweight and obese patients Early menarche and late menopause

57. Associated factors:
Diabetes or abnormal glucose tolerance test.
Hypertension.
Fibroids.
Polycystic ovarian syndrome.
Infertility, Arthritis, and Thyroid disease.
Use of TAMOXIFEN.
Previous pelvic irradiation.
Positive family history of breast, ovarian, and to lesser extent colon cancer.

58. Protective factors: Smoking. Use of oral contraceptive
Protective factors: Smoking ! Use of oral contraceptive. Use of progesterone.

59. Pathology: Adenocarcinoma % Adenoacanthoma(adeno + squamous metaplasia) % Adenosquamous carcinoma % Clear cell carcinoma % Papillary adenocarcinoma % Secretory carcinoma % Mixed type ~

60. Spread :
Invasion through the myometrium and by filling the uterine cavity.
Invasion to the cervix with subsequent lymphatic spread involving the iliac and para-aortic nodes.
From upper uterus may spread to round ligament to the deep inguinal nodes.
In advanced cases, the blood-stream spread may carry to the lungs, liver, and to the bone.

61. Diagnosis and assessement:
A-History:
postmenopausal bleeding or staining( this symptom should be assumed to be caused by carcinoma of the endometrium until proved otherwise), only 10% of PMB have endometrial carcinoma.
Perimenopausal menstrual irregularities.
Blood stained vaginal discharge.
Heavy and irregular vaginal bleeding.

62. Diagnosis and assessement:
B-Examination:
physical examination of the patient with endometrial carcinoma is frequently entirely normal, it should include palpation of supraclavicular and inguinal lymph nodes, abdominal palpation might be difficult due to obesity.
Gynaecological examination:
inspection of vulva, vaginal skin in suburethral area
and cervix.
Bimanual vaginal examination assesses uterine size, and mobility, state of parametria and adnexa.
Bimanual recto-vaginal examination.

63. Diagnosis and assessement:
C-Investigation:
CBC.
Liver function test.
Renal function test.
Chest X ray.
Cytology brush from lower cervical canal and posterior fornix to analyze the cells.
Endometrial sampling :-

64. Endometrial sampling :-
ONE sample for histology: - Piplle - Vabra - Jet suction - Other Two Examination under anaesthesia and D&C. Three Hysteroscopy & biopsy. -ultrasound for endometrial thickness, myometrial invasion and lymph nodes. -MRI – to assess site, thickness, and myomtrial invasion for staging. -proctoscopy and / or sigmoidoscopy, cystoscopy, and bone scan for some exceptional cases, when there is a clinical suspicion of metastasis.

65. Patient completely relaxed Requires anaesthesia
Method
Advantage
Disadvantage
Endometrial biopsy
Outpatient procedure
Well tolerated
Blind sample
Not always possible
D&C
Patient completely relaxed
Requires anaesthesia
USS
Painless
Reasonable resolution
Available at outpatient
Endometrial thickness
measured
endometrium not actually visualized and no histology
Hysteroscopy
Direct visualization
Guided biopsy possible
Can be outpatient procedure
Invasive
Can be painful

67. Stage I: Carcinoma confined to the corpus I a – tumour limited to endometrium. I b – invasion of less than ½ of myometrium. I c – invasion of more than ½ of myometrium.

68. Histopathology : Degree of differentiation
Histopathology : Degree of differentiation. G1= 5% or less of non-squamous or non-morular solid growth pattern. G2= 6-50% of a non-squamous or non-morular solid growth pattern. G3= more than 50% of a non-squamous or non-morular solid growth Pattern.

69. Prognostic factors included in final surgical staging:
Histologic type (pathology).
Histologic differentiation.
Stage of disease.
Depth of myometrial invasion.
Result of peritoneal wash.
Lymph node metastasis.
Adnexal metastasis.
Other (capillary- like space involvement, tumour size, hormonal receptors!).
Ploidy and growth factors.
Age and body morphology.

70. TREATMENT:
The mainstay of treatment for endometrial carcinoma is an extrafascial total abdominal hysterectomy and bilateral sapingo-oopherectomy, peritoneal washing, and ?lymph node biopsy. (TAH+BSO+PW+?LNB ).
The role of preoperative radiotherapy has become controversial with the introduction of the new (FIGO) staging system. Preoperative radiotherapy will severely affect the surgicopathological staging.

71. ONCE STAGING IS PERFORMED.
l-For stage I, Gl Adenocarcinoma:
-Total abdominal hysterectomy, bilateral salpingo-oopherectomy and peritoneal wash.
-In some cases of stage I the uterus is enlarged- and an extended hysterectomy and BSO and removing a cuff of vagina is indicated.

72. Indications for post operative radiotherapy:
-Moderate or poor differentiation(G2,G3).
-Other histological type than adenocarcinoma as papillary or clear cell carcinoma.
-Invasion of myometrium of> 1/2.
-Positive peritoneal wash.
-Positive lymph nodes.

73. 2-stage II adenocarcinoma:
- WERTHEIM'S HYSTERECTOMY- which includes removal of the upper half of the vagina, pelvic lymphadenectomy and para-aortic lymph node sampling is best for surgically fit patients.
This is not always possible as the patient, usually very old, obese, hypertensive, diabetic and high risk for extensive surgery.
-if surgery is not possible- radiotherapy is chosen, to the whole pelvis in 5 ~ weeks, in some cases additional of extrafascial hysterectomy 6 weeks after pelvic irradiation and intracavity brachytherapy may improve survival.
N.B- in those patients in whom spread to the cervix is occult, with the diagnosis being made on hysteroscopy or endocervical curettage, management should be identical to those patients with high risk stage I disease.

74. 3-stage III adenocarcinoma:
-If the disease confined to the pelvis (parametrial extension or vaginal involvement) radiotherapy is the treatment of choice, and should be given as in a manner similar to stage 11
-When there is clinical spread to the adnexae a laparatomy should still be undertaken to define accurately the extent of the disease, and to remove as much tumour as possible. Following removal of the pelvic disease, omentectomy, lymphadenectomy should be performed together with multiple peritoneal biopsies. If the disease is central - notfixed to side wall, and the patient suitable for surgery there is possibility for pelvic exenturation

75. 4-stage IV adenocarcinoma:
management needs to be individualized with the primary aim being
control of tumour growth, so:
-palliative surgery.
-Radiotherapy.
-Cytotoxic drugs.
-Hormonal therapy
May all be required. Rarely limited surgery to stop the bleeding as palliative procedure is carried out.

76. Radiotherapy may be used as :
1- An adjuvant to surgery - as in stage I disease.
2- Radical treatment for stage ILIII.
3- Palliative therapy as for stage IV.
Usually external radiation followed by intracavitary radiation.
*adjuvant hormonal therapy:
-Medroxyprogesterone acetate ( mg daily)
- Gn RH analogues
The rule of chemotherapy is limited
- Anthracycline.
-Doxorubine.
- platinum drugs
All are effective drugs can be used in a single course.

77. Summary of treatment Consult expert advice.
patients with low risk stage I disease i.e. well differentiated, only superficially invasive, may be treated with a total abdominal hysterectomy and bilateral salpingo-oophorectomy
patients with high risk stage I disease i.e. poorly differentiated, deeply invasive, are treated as above with additionally, post-operative radiotherapy. This management approach reduces the risk of local recurrence from 20 to 5%
stage II disease is managed as for high risk stage I
stages III and IV - which fortunately, are rare - are managed on an individualised basis. Surgery is rarely employed. Progestogen therapy may be helpful. Chemotherapy may occasionally be used in metastatic disease