Cervical Cancer Vaccination

Cervical cancer is malignant neoplasm of the cervix uteri or cervical area. It may present with vaginal bleeding but symptoms may be absent until the cancer is in its advanced stages. Treatment consists of surgery (including local excision ) in early stages and chemotherapy and radiotherapy in advanced stages of the disease.

Pap smear screening can identify potentially precancerous changes. Treatment of high grade changes can prevent the development of cancer. In developed countries, the widespread use of cervical screening programs has reduced the incidence of invasive cervical cancer by 50% or more.

Human papillomavirus (HPV) infection is a necessary factor in the development of nearly all cases of cervical cancer. HPV vaccine effective against the two strains of HPV that cause the most cervical cancer has been licensed in the U.S. and the EU. These two HPV strains together are currently responsible for approximately 70% of all cervical cancers. Since the vaccine only covers some high-risk types, women should seek regular Pap smear screening, even after vaccination.

Classification

The naming and classification of cervical carcinoma percursor lesions has changed many times over the 20th century. The World Health Organization classification system was descriptive of the lesions, naming them mild, moderate or severe dysplasia or carcinoma in situ (CIS). The term, Cervical Intraepithelial Neoplasia (CIN) was developed to place emphasis on the spectrum of abnormality in these lesions, and to help standardise treatment. It classifies mild dysplasia as CIN1, moderate dysplasia as CIN2, and severe dysplasia and CIS as CIN3. The most recent classification is the Bethesda System, which divides all cervical epithelial presursor lesions into 2 groups: Low-grade Squamous Intraepithelial Lesion (LSIL) and High-grade Squamous Intraepithelial Lesion (HSIL). LSIL corresponds to CIN1, and HSIL includes CIN2 and CIN3. More recently, CIN2 and CIN3 have been combined into CIN2/3.

Signs and symptoms

The early stages of cervical cancer may be completely asymptomatic. Vaginal bleeding, contact bleeding or (rarely) a vaginal mass may indicate the presence of malignancy. Also, moderate pain during sexual intercourse and vaginal discharge are symptoms of cervical cancer. In advanced disease, metastases may be present in the abdomen, lungs or elsewhere.

Symptoms of advanced cervical cancer may include: loss of appetite, weight loss, fatigue, pelvic pain, back pain, leg pain, single swollen leg, heavy bleeding from the vagina, leaking of urine or feces from the vagina, and bone fractures.

Causes

Human papillomavirus infection

The most important risk factor in the development of cervical cancer is infection with a high-risk strain of human papillomavirus. The virus cancer link works by triggering alterations in the cells of the cervix, which can lead to the development of cervical intraepithelial neoplasia, which can lead to cancer.

Women who have many sexual partners (or who have sex with men who had many other partners) have a greater risk.

More than 150 types of HPV are acknowledged to exist (some sources indicate more than 200 subtypes). Of these, 15 are classified as high-risk types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82), 3 as probable high-risk (26, 53, and 66), and 12 as low-risk (6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 81, and CP6108), but even those may cause cancer. Types 16 and 18 are generally acknowledged to cause about 70% of cervical cancer cases. Together with type 31, they are the prime risk factors for cervical cancer.

Genital warts are caused by various strains of HPV which are usually not related to cervical cancer.

The medically accepted paradigm, officially endorsed by the American Cancer Society and other organizations, is that a patient must have been infected with HPV to develop cervical cancer, and is hence viewed as a sexually transmitted disease, but most women infected with high risk HPV will not develop cervical cancer. Use of condoms reduces, but does not always prevent transmission. Likewise, HPV can be transmitted by skin-to-skin-contact with infected areas. In males, HPV is thought to grow preferentially in the epithelium of the glans penis, and cleaning of this area may be preventative.

Cofactors

The American Cancer Society provides the following list of risk factors for cervical cancer: human papillomavirus (HPV) infection, smoking, HIV infection, chlamydia infection, dietary factors, hormonal contraception, multiple pregnancies, exposure to the hormonal drug diethylstilbestrol (DES) and a family history of cervical cancer. There is a possible genetic risk associated with HLA-B7.

There has not been any definitive evidence to support the claim that circumcision of the male partner reduces the risk of cervical cancer, although some researchers say there is compelling epidemiological evidence that men who have been circumcised are less likely to be infected with HPV. However, in men with low-risk sexual behaviour and monogamous female partners, circumcision makes no difference to the risk of cervical cancer.

Diagnosis

Visual inspection to detect precancer or cancer

Visual inspection of the cervix, using acetic acid or Lugol’s iodine to highlight precancerous lesions so they can be viewed with the “naked eye”, shifts the identification of precancer from the laboratory to the clinic. Such procedures eliminate the need for laboratories and transport of specimens, require very little equipment and provide women with immediate test results. A range of medical professionals—doctors, nurses, or professional midwives—can effectively perform the procedure, provided they receive adequate training and supervision. As a screening test, VIA performs equal to or better than cervical cytology in accurately identifying pre-cancerous lesions. This has been demonstrated in various studies where trained physicians and mid level providers correctly identified between 45% and 79% of women at high risk of developing cervical cancer. By comparison, the sensitivity of cytology has been shown to be between 47 and 62%.It should be noted, however, that cytology provides higher specificity than VIA. Like cytology, one of the limitations of VIA is that results are highly dependant on the accuracy of an individual’s interpretation. This means that initial training and on-going quality control are of paramount importance.

VIA can offer significant advantages over Pap in low-resource settings, particularly in terms of increased screening coverage, improved follow up care and overall program quality. Due to the need for fewer specialized personnel and less infrastructure, training, and equipment, with VIA public health systems can offer cervical cancer screening in more remote (and less equipped) health care settings and can achieve higher coverage. Furthermore, providers can share the results of VIA with patients immediately, making it possible to screen and treat women during the same visit. This helps ensure that follow up care can be provided on the spot and reduces the number of women who may miss out on treatment because they are not able to return to the clinic at another time. In a “screen and treat” project in Peru, for example, only 9% of women who screened positive failed to receive treatment in the single-visit approach, compared with 44% of women who were lost to treatment using a multi-visit model.

VIA has successfully been paired with cryotherapy, a relatively simple and inexpensive method of treating cervical lesions that can be performed by primary care physicians and mid-level providers.

Biopsy procedures

While the pap smear is an effective screening test, confirmation of the diagnosis of cervical cancer or pre-cancer requires a biopsy of the cervix. This is often done through colposcopy, a magnified visual inspection of the cervix aided by using a dilute acetic acid (e.g. vinegar) solution to highlight abnormal cells on the surface of the cervix.

Further diagnostic procedures are loop electrical excision procedure (LEEP) and conization, in which the inner lining of the cervix is removed to be examined pathologically. These are carried out if the biopsy confirms severe cervical intraepithelial neoplasia.

Pathologic types

Cervical intraepithelial neoplasia, the precursor to cervical cancer, is often diagnosed on examination of cervical biopsies by a pathologist. Histologic subtypes of invasive cervical carcinoma include the following: Though squamous cell carcinoma is the cervical cancer with the most incidence, the incidence of adenocarcinoma of the cervix has been increasing in recent decades.

  • squamous cell carcinoma (about 80-85%)
  • adenocarcinoma (about 15% of cervical cancers in the UK)
  • adenosquamous carcinoma
  • small cell carcinoma
  • neuroendocrine carcinoma

Non-carcinoma malignancies which can rarely occur in the cervix include

  • melanoma
  • lymphoma

Note that the FIGO stage does not incorporate lymph node involvement in contrast to the TNM staging for most other cancers.

For cases treated surgically, information obtained from the pathologist can be used in assigning a separate pathologic stage but is not to replace the

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