Life-time risk (%) for cervical cancer USA 0,83 Scandinavia 1,01 India 2,22 South Amerika 5,31 5.8 West Asia 7.4 East Asia 7.4 Australia/N. Zeal. 7.7 North America 9.0 North Europe 10.0 West Europe 10.7 South Europe 12.1 North Africa 14.5 East Europe 18.7 South East Asia 26.2 South Cent. Asia 28.0 Central Africa 28.6 South America 29.3 West Africa 30.6 Central. America 38.2 South Africa 42.7 East Africa
Incidence of Cervical Cancer per 100,000 Females in Arab World < 4.0 4.0 – 7.9 8.0 – 11.9 12.0 – 15.9 ≥ 16.0 Algeria Map produced by Prof. Inas Elattar Pakistan Pakistan Morocco Afghanistan Palestine Bahrain Iran Iraq Sudan Somalia Libya Egypt Saudi Arabia Oman Yemen UAE Jordan Qatar Kuwait Syria Lebanon Djibouti
Two key reasons : 1. The vast majority of women still know little about cervical cancer or what they should do to prevent it. 2. Many countries have ineffective prevention programmes or no prevention programmes at all.
As the consequence, a high proportion of cervical cancer is diagnosed when already advanced and metastatic, leading to low probability of cure and high mortality rates . 85% Cervical Cancer: Groote Schuur Hospital, 1984 – 2000 (n = 3098)
Every 2 minutes , one women dies of cervical cancer !
HPV infe c tion Low-grade changes High-grade lesions Cancer 300 milion s 30 milion s 10 milion s 0. 5 milion s HPV E6, E7 Cellular changes Many years 8-15 HPV infe ction Parkin DM, Bray F, Ferlay J, Pisani P. CA Cancer J Clin. 2005;55:74–108 World Health Organization. Geneva, Switzerland: World Health Organization; 1999:1–22. Number of cases 0.15% ! Estimated World Burden of HPV-related Disease and Diagnoses
Is it possible ? Preven tion of Cervical Cancer
Natural history of cervical cancer and prevention Precancerous lesion Invasive disease Normal Cervix Persistent infection with HR types HPV Clearance Progression Initial HPV infection
Most patients with early stage cervical cancer are treated by either radical surgery or radical radiotherapy. Both treatment modalities have proven to be equally effective . Landoni et al : Lancet 1997 350 535- 540
Parametrial involvement 5/799 (0.63%) The incidence of parametrial tumor involvement in early invasive cervical cancer Stegman M et al. Gynecol Oncol, 2007; 105:475-480
T y p e II I T ype II Types of hysterectomy- Piver 40% Magrina, 1995 0.8% Urinary dysfunction 7% 1.1% Thromboembolism 0.3% 0.5% Deaths 1% 0.3% Digestive fistulas 4.8% 0.3% Urinary fistulas Type III Type II Complication
Adjuvant therapy in early cervical cancer For adjuvant irradiation - High risk, negative nodes - Positive nodes (1-3) - Poorly differentiated or undiferentiated tumor (G3) - LVSI (lympho-vascular space invasion) - Primary tumor > 3cm (tumor-cervix volume > 3cm ) - Endocervical invasion (barrel shaped ) - Inadequate surgery - Insufficient HP report For adjuvant chemo-irradiation - Positive resection margins - Involvement of parametria - Residual tumor
Postoperative pelvic radiation in patients with nodal metastases has been the standard approach. It increases local control, but not the overall survival , due to inability of adjuvant pelvic irradiation to influence distant metastases
An overall survival benefit has been shown for concurrent chemo-radiation therapy .
The survival of patients that had bulky nodes removed has been significantly improved compared to those who had not the nodes resected (31% vs 6%) Hacker et al. Int. J Gynecol Cancer, 1995;5: 250-256 1. KiKim et al. Gynecol Oncol, 1998; 69: 243-7
Standard treatment for advanced stage Cervical Cancer has been Radiation
External beam radiotherapy using Linear accelerator
Four field technique to the central pelvis
Parametrial or side wall boosts controversial
Doses between 45 and 52 Gy in 25/30 fractions
All fields being treated daily
Preferably with no interval or gap
Low or intermediate dose 24 to 28 Gy, single insertion
High dose 14Gy/2 fractions, 18 Gy/3, 24 Gy/4 up to 30/5
Extended-field radiotherapy is the standard part of treatment achieving the long-term survival of 30-40% for stage Ib patients with positive PALN. Consistent benefit of concurrent chemo-radiation with Cis-platin based chemotrerapy incorporated in extended-field irradiation.
Systemic Chemotherapy in Treatment of Cervical Cancer
Neoadjuvant to Surgery
Neoadjuvant to Radiation
Post operative adjuvant or maintenance?
Chemotherapy for Cervix Cancer 1999 : the year the world changed !
Neo-adjuvant chemotherapy followed by radical surgery has emerged as a possible alternative to conventional chemo-radiation, which may improve a survival in patients with stage Ib2 disease Benedetti -Panici P.J Clin Oncol, 2002; 20: 179-188 Tierney J. Eur J Cancer, 2003; 39: 2470-2486 14%