Page 14 - Screening for Cervical Cancer: Systematic Evidence Review

Chapter I. Introduction

genital condylomata or warts, squamous cell carcinomas of the genital tract including vaginal

and vulvar cancers, and cervical cancer. More than 70 strains or types of HPV have been

classified. For instance, HPV Types 6 and 11 cause warts; other types have oncogenic

properties.

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The best characterized types associated with cervical cancer are Types 16 and 18.
These are officially recognized by the International Agency for Research on Cancer (IARC) and

the World Health Organization (WHO) as carcinogenic infectious agents. The primary

difference between “oncogenic” and “non-oncogenic” virus is the interaction of two viral genes,

E6 and E7, that influence cell cycle control mechanisms. Oncogenic E6 and E7 gene products

can “cripple” a normal cell’s ability to control cell proliferation, which in some instances leads to

cancer.

HPV is a necessary but not sufficient precursor of squamous cell carcinoma of the cervix.

Among women without cervical cytology abnormalities at baseline, those with high-risk HPV

types have a relative risk of developing high-grade cervical lesions (CIN 2 - 3, CIS) that is 58- to

71-fold higher than the risk for those without detectable HPV. 19,20

The natural history of HPV acquisition, clearance, persistence, and possible re-infection

is complex. To promote cervical cancer abnormalities, the virus must become integrated into the

host genomic DNA. This event, which is essential for cancer progression, appears to be rare. In

the absence of viral integration, the normal viral lifecycle produces morphologic changes in the

cervical epithelium characteristic of low-grade dysplasia (LSIL). With viral integration, the

oncogenic effect of the E6 and E7 proteins is enhanced and cellular changes characteristic of

high-grade dysplasia and ultimately cancer are observed. 21,22

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