In the Name of GOD Screening of Cervical Cancer Pap smear and colposcopy F.Behnamfar Gynecology Oncology Fellow Professor Isfahan University of medical Sciences

Epidemiology and Risk Factors Third most common cancer among women worldwide >85% of cases in developing countries 12,360 new cases and 4020 cancer related deaths in USA,2014 Half of cancers diagnosed in US are late stage and correlate with lack of screening

Squamous denocarcinoma 50-60 million pap tests are performed in the US each year 3.5 million abnormal pap tests and 2.5 million colposcopy each year Burden of cervical cancer extends to recourses of screening

Natural History High risk HPV infection is responsible for cervical cancer - can be detected in 99.7 percent of cervical cancers Eight genotypes responsible for 95% Types 16 and 18 responsible for 70% Types 6 and 11 responsible for 90% of warts

HPV Infection with high-risk strains of HPV and persistence of HPV infection are the most important determinants of progression to cervical cancer

Risk Factors -Early onset of sexual activity – Compared with age at first intercourse of 21 years or older, the risk is approximately 1.5- fold for 18 to 20 years and twofold for younger than 18 years [13] ●Multiple sexual partners – Compared with one partner, the risk is approximately twofold with two partners and threefold with six or more partners [13] ●A high-risk sexual partner (eg, a partner with multiple sexual partners or known HPV infection) ●History of sexually transmitted infections (eg, Chlamydia trachomatis, genital herpes)

Risk Factors History of vulvar or vaginal squamous intraepithelial neoplasia or cancer (HPV infection is also the etiology of most cases of these conditions) Immunosuppression (eg, human immunodeficiency virus infection) Early age at first birth (younger than 20 years old) and increasing parity (3 or more full term births) Low socioeconomic status

Natural History Risk of transmission correlates with lifetime number of sex partners 4-20% even in persons with one partner Up to 50% in young women of US within 36m of start of sexual activity 57% of sexually active adolescents are HPV positive Wart affects only1% of infected women

HPV TESTING Triage Abnormal pap Screening ,co-testing

Pathogenesis Cervical intraepithelial neoplasia (CIN) Slow malignant transformation long latency period for cervical cancer CIN I,II,III Preinvasive dysplasia, depth of involvement and atypicality

George Papanicolaouhe 1883-1962 Greece importance of his work was not recognized until the publication, together with Herbert Frederick Traut (1894–1963), of Diagnosis of Uterine Cancer by the Vaginal Smear in 1943.

Papanicolaou Smear Conventional Thin layer, liquid based (STD tests) Cytology report includes Adequacy General categorization Epithelial cell abnormality Glandular cell abnormality

Abnormal pap smear ASCUS LSIL HSIL

Cytology report includes Adequacy General categorization Epithelial cell abnormality Glandular cell abnormality

Cytologic diagnosis Pap test yeilds cytologic diagnosis Diagnosis of CIN or cervical cancer requiers a tissue sample for histologic diagnosis

Pap Test Screening test rather than diagnostic test Sensitivity and specificity Liquid based/ conventional pap smear Effectiveness No pap in last five years, risk of cervical cancer is threefold 90% risk reduction

Follow up of abnormal cytology ASCUS ASC-H AGC Risk for CIN 2-3 and AIS ,serious precursor of adenocarcinoma LSIL(CIN I- HPV infection) HSIL

HPV test High risk HPV,16-18… Transient Infection Screening triage

Screening Parameters Initial screening Discontinuing screening Frequency of screening Perior hysterectomy HPV Vaccination

Incidence of cervical cancer in different age goups From 2000 to 2004, the United States age- adjusted incidence of cervical cancer in girls under age 20 was 0.1 per 100,000 rising to 1.5 per 100,000 in women age 20 to 24 years ranging from 11.0 to 15.8 per 100,000 for women age 30 to over 85 years.

presentation of cervical cancer Early cervical cancer is frequently asymptomatic, underscoring the importance of screening. Irregular or heavy vaginal bleeding - Postcoital bleeding -Some women present with a vaginal discharge that may be watery, mucoid, or purulent and malodorous. This is a nonspecific finding and may be mistaken for vaginitis or cervicitis.

Advanced disease may present with pelvic or lower back pain, which may radiate along the posterior side of the lower extremities. Bowel or urinary symptoms, such as pressure- related complaints, hematuria, hematochezia, or vaginal passage of urine or stool, are uncommon and suggest advanced disease Post-coital bleeding, which is the most specific presentation of cervical cancer, may also result from cervicitis.

Cervical cancer diagnosis Human papillomavirus (HPV) testing is used in combination with cervical cytology for cervical cancer screening and helps to determine which women with abnormal cytology results require further evaluation However, it does not play a role in the diagnosis of malignancy in women with symptoms or a visible lesion suggestive of cervical cancer

Cervical cancer diagnosis Symptomatic women without a visible lesion and those who have only abnormal cervical cytology should undergo colposcopy with directed biopsy ●Cervical conization is necessary if malignancy is suspected but is not found with directed cervical biopsies

Management of early-stage cervical cancer Conization Hysterectomy Radical Hysterectomy

Advaned cervical cancer Chemoradiation

Vaccination Females —  Vaccination with 9-valent, quadrivalent, or bivalent HPV vaccine provides a direct benefit to female recipients by safely protecting against cancers that can result from persistent HPV infection. This preventive effect is most notable and best studied with cervical cancer, which is one of the most common female cancers worldwide. HPV types 16 and 18, which are targeted by all three HPV vaccines, cause approximately 70 percent of all cervical cancers

Vaccination HPV types 31, 33, 45, 52, and 58, which are additionally targeted by the 9-valent vaccine, cause an additional 20 percent. HPV types 16 and 18 also cause nearly 90 percent of anal cancers and a substantial proportion of vaginal, vulvar, and oropharyngeal cancers. Vaccination with the quadrivalent or 9-valent HPV vaccine also protects against anogenital warts (90 percent of which are caused by HPV types 6 and 11); although they are benign lesions, they are associated with physical and psychological morbidity and have a high rate of treatment failure. The adverse effects of HPV vaccination are generally limited to mild local reactions.

THANKS