Introduction
Cervical intraepithelial neoplasia (CIN) describes the premalignant dysplasia of the cervical
epithelium, most commonly at the squamocolumnar junction, driven by infection with the human
papillomavirus (HPV). Over time, it may progress to cervical cancer, requiring chemoradiation
and potential surgery.1
Cervical cancer is a common and highly preventable cancer.
This article has been written for medical students to understand the presentation and
management of CIN and cervical cancer, as well as methods of prevention.
Epidemiology
Cervical cancer is the 4th most common female cancer worldwide, with an annual incidence
of 604,000 and mortality of 342,000 in 2020.2 HPV-16 and HPV-18 contribute to over 70% of
cervical cancer. Other high-risk types include 31, 33, 35, 45, 52 and 58, which account for an
additional 20% of cervical cancers.3
In the UK, cervical cancer is the 14th most common cancer among women of all ages, and the
2nd most common cancer among women aged 15-44. There are around 3,200 new cases and
850 deaths every year. Around 50% of cervical cancer occurs under the age of 45, with the
incidence rising from the age of 15, peaking at 30-34 before decreasing with age (Figure 1).4
Figure 1. Cervical cancer average annual
incidence and mortality between 2016 and 2018 in the United Kingdom. Produced from national
data.4
You might also be interested in our surgical flashcard collection which contains over 500
flashcards that cover key surgical topics.
Aetiology
Almost all CIN and cervical cancer is driven by infection with HPV. High-risk types include
HPV-16 and HPV-18, which contribute to over 70% of cervical cancer and 31, 33, 35, 45, 52
and 58, which account for an additional 20% of cervical cancers.3
, Anatomy5
The cervix is an anatomical region which facilitates the passage of sperm into the uterine cavity
and maintains sterility of the upper female reproductive tract.
The cervix is composed of two regions: the endocervical canal, and the ectocervix.
The endocervical canal is lined by mucus-secreting simple columnar epithelium and ends
at a narrowing called the internal os, which marks the beginning of the uterine cavity.
The ectocervix is the distal part of the cervix which projects into the vagina and is lined by
stratified squamous non-keratinised epithelium which is resistant to the low pH of the
vagina. The external os marks the transition from the ectocervix to the endocervical canal.
The squamocolumnar junction (SCJ) marks the location where the squamous epithelium of
the ectocervix and columnar epithelium of the endocervix meet. When the columnar epithelium
of the endocervix is exposed to the acidic environment in the vagina, it undergoes squamous
metaplasia.
During this process, the original SCJ everts from its original position onto the ectocervix; the
area between the original SCJ and the new SCJ is known as the transformation zone.
Figure 2. Anatomy of the cervix. The
transformation zone is shown in blue. Adapted from Cancer Research UK.6
Pathophysiology and carcinogenesis7
Microtrauma to the epithelial cells of the transformation zone provides HPV with access to
basal keratinocytes. HPV infects these cells with its surface proteins and uses its E6 and E7
oncoproteins to inhibit the tumour suppressors p53 and pRb, resulting in uncontrolled
cellular proliferation.
The ensuing accumulation of mutations results in pre-malignant cellular abnormalities,
named cervical intraepithelial neoplasia (CIN). Eventually, CIN can progress to invasive
carcinomas (figure 3).
80% of cervical cancers are squamous cell carcinomas of the epithelial lining of the
ectocervix.
20% of cervical cancers are adenocarcinomas of the glands within the lining of the cervix.
More information on the HPV life cycle can be found here.
Cervical intraepithelial neoplasia (CIN) describes the premalignant dysplasia of the cervical
epithelium, most commonly at the squamocolumnar junction, driven by infection with the human
papillomavirus (HPV). Over time, it may progress to cervical cancer, requiring chemoradiation
and potential surgery.1
Cervical cancer is a common and highly preventable cancer.
This article has been written for medical students to understand the presentation and
management of CIN and cervical cancer, as well as methods of prevention.
Epidemiology
Cervical cancer is the 4th most common female cancer worldwide, with an annual incidence
of 604,000 and mortality of 342,000 in 2020.2 HPV-16 and HPV-18 contribute to over 70% of
cervical cancer. Other high-risk types include 31, 33, 35, 45, 52 and 58, which account for an
additional 20% of cervical cancers.3
In the UK, cervical cancer is the 14th most common cancer among women of all ages, and the
2nd most common cancer among women aged 15-44. There are around 3,200 new cases and
850 deaths every year. Around 50% of cervical cancer occurs under the age of 45, with the
incidence rising from the age of 15, peaking at 30-34 before decreasing with age (Figure 1).4
Figure 1. Cervical cancer average annual
incidence and mortality between 2016 and 2018 in the United Kingdom. Produced from national
data.4
You might also be interested in our surgical flashcard collection which contains over 500
flashcards that cover key surgical topics.
Aetiology
Almost all CIN and cervical cancer is driven by infection with HPV. High-risk types include
HPV-16 and HPV-18, which contribute to over 70% of cervical cancer and 31, 33, 35, 45, 52
and 58, which account for an additional 20% of cervical cancers.3
, Anatomy5
The cervix is an anatomical region which facilitates the passage of sperm into the uterine cavity
and maintains sterility of the upper female reproductive tract.
The cervix is composed of two regions: the endocervical canal, and the ectocervix.
The endocervical canal is lined by mucus-secreting simple columnar epithelium and ends
at a narrowing called the internal os, which marks the beginning of the uterine cavity.
The ectocervix is the distal part of the cervix which projects into the vagina and is lined by
stratified squamous non-keratinised epithelium which is resistant to the low pH of the
vagina. The external os marks the transition from the ectocervix to the endocervical canal.
The squamocolumnar junction (SCJ) marks the location where the squamous epithelium of
the ectocervix and columnar epithelium of the endocervix meet. When the columnar epithelium
of the endocervix is exposed to the acidic environment in the vagina, it undergoes squamous
metaplasia.
During this process, the original SCJ everts from its original position onto the ectocervix; the
area between the original SCJ and the new SCJ is known as the transformation zone.
Figure 2. Anatomy of the cervix. The
transformation zone is shown in blue. Adapted from Cancer Research UK.6
Pathophysiology and carcinogenesis7
Microtrauma to the epithelial cells of the transformation zone provides HPV with access to
basal keratinocytes. HPV infects these cells with its surface proteins and uses its E6 and E7
oncoproteins to inhibit the tumour suppressors p53 and pRb, resulting in uncontrolled
cellular proliferation.
The ensuing accumulation of mutations results in pre-malignant cellular abnormalities,
named cervical intraepithelial neoplasia (CIN). Eventually, CIN can progress to invasive
carcinomas (figure 3).
80% of cervical cancers are squamous cell carcinomas of the epithelial lining of the
ectocervix.
20% of cervical cancers are adenocarcinomas of the glands within the lining of the cervix.
More information on the HPV life cycle can be found here.
