Cervical cancer
Dr. Shazia Iqbal

OBJECTIVES
 Understand the pathogenesis of lower genital tract
malignancy
 Understand primary prevention of cervical cancer through human
papillomavirus (HPV) vaccinationand cervical screening.
 Understand the diagnosis, International Federation
of Gynecology and Obstetrics (FIGO) staging and management of
premalignant and malignant disease of the Cervix

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

Cervical Cancer
Abnormal cell (Malignant) 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
A major cause of death worldwide
Cervical screening has been shown to reduce both the incidence and the number of deaths
from cervical cancer in higher income countries.
It has been estimated that cervical screening prevents around 5,000 deaths every year in UK
alone.

Human Papillomavirus (HPV)
known to cause warts
Found in many cancers too
Over 100 types identified
Most benign, but 15-20 can cause cancers
Very common
◦ 20,000,000 current cases in US
◦ 6,200,000 new cases annually
◦ 80% of women have HPV by age 50
◦ 50% of college students are infected

Common HPV Types and their effects
HPV Types Lead to:
Low-Risk
High-Risk
HPV 6, 11, 40,
42, 43, 44, 54, 61,
70, 72, 81
HPV 16, 18,
31, 33, 35, 39, 45,
51, 52, 56, 58, 59,
68, 73, 82
Benign cervical changes
Genital warts
Precancer cervical changes
Cervical cancer
Anal and other cancers
1. Cox. Baillière’s Clin Obstet Gynaecol. 1995;9:1.
2. Munoz et al. N Engl J Med. 2003;348:518.

Squamo-columnar junction (SCJ)
Tubular cervix is composed of stromal tissue covered by
squamous epithelium in the vagina (ectocervix)
Columnar epithelium withinthe cervical canal (endocervix).
The endocervix contains many deep folds, called crypts, that are
lined by columnarepithelium. The meeting of the two types of
epithelium is called the squamocolumnar junction (SCJ) and this
is usually on the ectocervix (Figure 16.1).
The position of the SCJ varies throughout life. In children
it lies at the external cervical os, at puberty it extends
outwards onto the ectocervix as the cervix enlarge.

What is transformational zone?
In adult life it returnsto the external cervical os
through the process of metaplasia, which is the
physiological transformation of columnar epithelium to squamous
epithelium.
The so-called ‘transformation zone’ (TZ) is defined as
the area between the original SCJ and the current
SCJ where the epithelium changes from columnar to
squamous epithelium over time. Sometimes the columnar
epithelium is covered by squamous epithelium, leading to
retention of mucus this is called a nabothian follicle
(Figure 16.2).
The TZ is the site where premalignancy and malignancy develop

Human Papillomavirus
 Cancer of cervix 100%
 Cancer of esophagus .
 Cancer of skin .
 Cancer of X,Y,Z…. .
 Cancer of mouth 3%
 Cancer of throat 12%
 Cancer of penis 40%
 Cancer of vulva, vagina 40%
 Cancer of anus 90%
Parkin DM et al. CA Cancer J Clin 2005; 55:74-108.

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
Human Papillomavirus. ACOG Practice Bulletin No. 61. 2005; 105: 905-18.

Regression and progression of CIN
Spontaneous regression of low-grade disease is common and
is likely to occurthrough the patient’s own cell-
mediated immunity.
This is the argument for observational follow-up in patients
with low-grade abnormality. High-gradedisease is less
likely to regress spontaneously and requires treatment,as
there is a risk of progression to cancer.
If left untreated, around 20% of patientswith high-grade
abnormalities develop cancer of the cervix.

Co-factors for HPV Infection
◦ Smoking
◦ HIV infection
◦ Other immune system defect
◦ Pregnancy
◦ Oral contraceptive use
Ferris et al. Modern Colposcopy. 2004.

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.
14
Ferris et al. Modern Colposcopy. 2004: 2-4, 49.
Photo accessed from http://www.cytology-iac.org/Cytopaths/1998/cytoFall98.htm

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
15Cervical Cytology Screening. ACOG Practice Bulletin No. 45. 2003; 102:417-27.

New Liquid Pap Tests
More accurate test
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
16
Linder J. et al. Arch Pathol Lab Med. 1998; 122: 139-144.

Preventing Cervical Cancer
Screening for precancerous changes (and treatment
if problems found)
Vaccination against HPV
19

Cervical Cancer Screening Guidelines
RCOG
First screen 3 years after first intercourse or by age 21
Women aged 25–64, Screen annually with regular Paps or every
3-5 years with liquid-based tests
Stop at 65-70 years with history of negative tests

Colposcopy

NEW! The HPV Vaccine
Gardasil ® (Merck)
Protects against types 16, 18, 6, 11
FDA approved for use
Prevents HPV infection; doesn’t treat
existing infection
Virus-like particles (VLP)
Highly effective
Safe, few serious adverse side effects
Requires 3 injections
Expensive ($360 + administrative fees)

HPV Vaccine
ACOG Recommendations
VACCINATE all females 9-26 years old, regardless of sexual activity
Less potential benefit with increasing age & number of sexual
partners
Special populations – vaccine less effective
Previous abnormal Pap tests or genital warts
Immunocompromised
continue screening with Pap tests!
Human Papillomavirus Vaccination. ACOG Committee Opinion No. 344. 2006; 108: 699-705.

Cervical cancer

Clinical presentaion

Investigations