Cervical cancer is the fourth most common type of cancer in women worldwide. China and India together contributed more than a third of the global cervical cancer burden. Globally, the average age at diagnosis ranges from 44 years to 68 years. The main cause of cervical cancer is infection with Human Papilloma Viruses (HPV), which account for 99% of cervical cancer. There are many different types of HPV and certain strains have a high risk for developing cervical cancer. Risk factors also include having sex at an early age, multiple sexual partners, and poor socio-economic status. One of the most common symptoms of cervical cancer is abnormal vaginal bleeding, but in some cases, there may be no obvious symptoms until the cancer is in its advanced stages.
A Papanicolaou test, also known as Pap smear, can detect this precancerous condition and cancer in the early stage. It is a microscopical examination of cytology specimen retrieved from the cervix. When detected in this stage of development, the disease is completely treatable. The widespread use of cervical screening programs has reduced the incidence of invasive cervical cancer by 50% or more in countries with successful screening programs.
There are two main types of cervical cancer: squamous cell carcinoma and adenocarcinoma. While HPV infection is considered to cause most of the squamous cell carcinomas, adenocarcinomas are only partially associated with such infection.
Squamous cell carcinoma usually develops from a precancerous condition called dysplasia (squamous intraepithelial lesion). It arises in the transitional zone (squamocolumnar junction) of the cervix. A tumor is composed of cells with a variable degree of squamous differentiation, such as keratinization or intercellular bridging. The degree of squamous differentiation and cellular atypia provides the basis for determining if the carcinoma is well, moderately or poorly differentiated but it does not correlate with prognosis. Squamous intraepithelial lesions are defined as the presence of atypical cells confined to epithelium. The degree and distribution of atypia throughout epithelium enable its further classification into low-grade and high-grade squamous intraepithelial lesions (LSIL, HSIL).
Adenocarcinoma is a rare but aggressive form of cervical cancer. It develops from the columnar epithelial cells in mucus-producing glands of the endocervix. It can exhibit different morphology. mucinous, endometrioid, clear cell, serous, gastric, or mesonephric. Gastric and clear cell morphologies are not associated with HPV infection. Adenocarcinoma can also develop from a precursor called adenocarcinoma in situ.
Microscopic diagnosis of cervical cancer is often straightforward and based on morphological features. Poorly differentiated tumors and adenocarcinomas represent diagnostic pitfalls, as it is important to discriminate between cervical tumors and tumors originating in the uterine corpus. Squamous cell carcinomas are positive for cytokeratin 5 and 6, p63 as well as p40. Adenocarcinomas show expression of cytokeratin 7 (KRT7), and, depending on the type, p16, CDX2, CAIX, HNF-1B, CEA, and MUC6. They are almost always negative for hormone receptors (ER, PR). Immunohistochemical staining against p16 and Ki-67 in squamous intraepithelial lesions can be helpful in the diagnosis and grading of such lesions.
Therapy of cervical cancer depends on tumor stage and histological type. In principle, surgery is the main modality, with radiation therapy and chemotherapy reserved for advanced stages. With treatment, 92% of women with localized disease alive 5 years after diagnosis. Only 17% of women with distant disease survive the first five years after the initial diagnosis.
Regular screening and use of anti-HPV vaccine can prevent cervical carcinoma. A vaccine that prevents infection with two high-risk HPV types is available. Studies have shown that the vaccine appears to prevent precancerous lesions and early-stage cervical cancer.