1. Cervical cancer

2. Epidemiology Cervical cancer is the 5 th most common cancer in women worldwide In some parts of Africa, South America and South Eastern Asia is the second most common cancer after breast cancer Cervical cancer is the most common cancer for women in Central America and Southern Africa.

4. Risk factors I. Environmental HPV=main risk factor Smoking AIDS Diabetes (high glucose levels) Daughters of women who had used DES (diethylstilbestrol) to prevent miscarriages (~1950- 1970) (although it doesn’t decrease the risk of miscarriage) II. Genetic -there is sometimes familial aggregation of the disease

5. Human Papilloma Virus =“human wart virus”

6. Classification More than 150 subtypes of HPV 1.High risk: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, 82 -16 and 18 present in ~70% of cervical cancers 2. Probably high risk: 26, 53, 66 3. Low risk: 6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 81

9. Vulvar cancer

10. Anal canal cancer

11. Oral cavity, oropharyngeal, nasopharyngeal and esophageal cancer

12. Discovery 2008 Nobel-prize in medicine: Harald zur Hausen: HPV causes cervical cancer (1977).

13. Incidence of infection 80% of women will be infected with at least one subtype of HPV during their life, but the immune system eliminates the infection in most of the cases In some cases the infection will be chronic and leads to dysplasia (a premalignant condition) and later to cancer The time from infection to cancer is usually long (10- 15 years), but it can be shorter, especially in younger women Plus younger women eliminate the infection less frequently

14. Histology Squamous cell carcinoma (80-90%) Adenocarcinoma of the cervix-more rare and not related to HPV infection

15. Routes of spread Local extension: vagina, parametria, rectum, bladder, uterine corpus

16. Lymphatic spread

17. Metastases Para-aortic lymph nodes-potentially curable Other non-regional lymph nodes: supraclavicular, neck Lung Rarely: bone, liver

18. Symptoms Vaginal hemorrhage -postcoital -intermenstrual (metrorrhagia) - heavy and prolonged menstrual bleeding (menorrhagia) -in menopause (metrorrhagia) Leucorrhea Pelvic pain Urinary symptoms: hematuria Rectal symptoms: rectorrhagia, obstruction Lumbar pain: para-aortic metastases or hydronephrosis

19. Diagnosis Pelvic examination Biopsy Pelvi-abdominal CT/MRI/PET-CT Rectal symptoms=> rectoscopy Hematuria=> cystoscopy Chest radiography General work-up Laparoscopic lymphatic staging-if available

20. Treatment Stage IA=tumor not seen by the naked eye and diagnosed only microscopically a)Total hysterectomy b)Younger patients: conization for fertility preservation c)Brachytherapy

21. Treatment Stage IB-IIA-tumor seen by the naked eye, but not extending to the parametria a) Total hysterectomy and bilateral salpingo- oophorectomy (TH+BSO) plus pelvic lymphadenectomy + adjuvant RT b) Exclusive radio- chemotherapy

22. Treatment Stage IIB-IVA-tumors extending at least to the parametria or the lower third of the vagina a)Exclusive radio- chemotherapy b)Radio-chemotherapy followed by surgery

23. Radiotherapy External beam radiotherapy Brachytherapy a)Intracavitary b)Interstitial

27. Vaccines Cervarix: 16, 18 Silgard = Gardasil: 6, 11, 16, 18

28. When is ideal to vaccinate? Before the first sexual contact. (Furthermore girls age 10-14 develop the strongest immunity.) But can vaccinate at any age, because of the low probability to have been infected with all subtypes (6, 11, 16, 18).

29. How many people have been vaccinated to date? Over 30 000 000. How many adult women have been vaccinated in Romania? Over 35 000. How many girls were vaccinated in RO during the 2008-2009 school campaign? Over 10 000. No serious side effects. (Medical events after vaccination couldn’t be linked with the vaccination.) => Vaccine appears to be safe.

30. Screening for cervical cancer Cervical cytology = Pap smear -cells from the cervix are removed with a swab Starting at 3 yrs from first vaginal intercourse Yearly Women aged 70 may discontinue screening if during the last 10 years did not have abnormal cytology

31. Questions What are the risk factors for cervical cancer? What are the symptoms of cervical cancer? What are the treatment options for cervical cancer? How should be cervical cancer screened for?