HPV Infection and Cervical Cancer Prevention

CERVICAL ANATOMY
The cervix is the narrow, fibromuscular neck that makes up the lower portion of the uterus. The endocervix is the cervical canal, and the ectocervix extends inferiorly into the vagina.⁷ The internal os is the opening of the cervix into the uterus, and the external os is the opening of the cervix into the vagina. The endocervix is lined with glandular columnar epithelium. This tissue can extend beyond the external os onto the ectocervix, and when this occurs it is known as cervical ectopy.¹⁶ The surface of the cervix lying between the glandular tissue and the vaginal wall is comprised of stratified nonkeratinizing squamous epithelium.⁷ The squamocolumnar junction (SCJ) is defined as the location where the squamous and glandular cells meet.¹⁷ Adjacent to the SCJ is the transformation zone, an area vulnerable to HPV infection where glandular cells are actively undergoing squamous metaplasia.¹⁷

The location of the SCJ varies depending on age and hormonal changes. In prepubertal females, the SCJ is close to the external os, but in women of reproductive age, the SCJ moves away from the external os onto the surface of the ectocervix. This change in the location of the SCJ occurs due to increased estrogen levels following menarche, which cause the endocervical canal to elongate.^7,17 A satisfactory Pap smear for cervical cytology includes cells from the transformation zone, as well as the ectocervix and endocervix.

HUMAN PAPILLOMAVIRUS
The human papillomavirus is a nonenveloped, double-stranded DNA virus that is known to cause abnormalities in skin cells. This virus is predominantly spread through sexual contact via skin-to-skin transmission. There are more than 100 known subtypes in the HPV family, of which 40 subtypes have been recognized to cause genital tract disease. Of these 40 subtypes, 15 have been identified to be oncogenic.^9,18,19

HPV subtypes are separated into low-risk and high-risk categories (see Table 2^5,7,18). The low-risk subtypes cause either no cellular change, low-grade intraepithelial neoplasia, or condyloma. The high-risk subtypes are associated with the development of CIN and cancer. Of the 15 high-risk subtypes, HPV-16 and HPV-18 are the most oncogenic, followed by HPV-31 and HPV-45. HPV-16 is implicated in up to 70% of cervical cancers, HPV-18 in up to 20%, and HPV-31 and HPV-45 in up to 10%.^5,9,20 Of the low-risk HPV subtypes, HPV-6 and HPV-11 cause 90% of condyloma infections.^16,21

After HPV infection is contracted, the virus migrates into the squamous epithelial mucosa of the cervix, where it is capable of altering cells and causing the development of precancerous properties. This typically happens within the transformation zone, which is vulnerable to HPV infection.¹⁷ Depending on the state of the host’s immune system, many of these HPV infections clear without intervention. It is estimated that approximately 70% of HPV infections resolve spontaneously within one year, and 90% resolve within two years.⁵ HPV infections that persist beyond two years are more likely to lead to the development of CIN and, ultimately, cervical cancer, if left untreated.²² There is an association between genetic amplification (extra copies) of gene 3q26 and progression of CIN to cervical cancer, but ultimately a high-risk HPV subtype must be involved for cervical cancer to develop.²³

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