Medical brain notes 42

  Cervical Disease and Neoplasia Although the incidence and mortality from cervical   cancer have decreased substantially in the past sev-eral decades among women in the United States, cervical cancer remains the third most common gynecologic cancer. In countries where cytologic screening is not widely available, cervical cancer remains common. Worldwide, it is the second most common cancer among women, the third most common cause of cancer-related death, and the most common cause of mortality from gynaecologic  malignancy.   Cervical cancer can be thought of as a “controllable” cancer. It is preceded by an identifiable precursor lesion ( cervical intraepithelial neoplasia, CIN ) that may (but not always) progress to invasive cancer. CIN can be easily detected by an inexpensive and noninvasive screening test (Pap test) that may be augmented with adjunctive tests such as HPV DNA typing and a follow-up diagnostic procedure (colposcopy). CIN is treatable with simple and...

  CERVICAL INTRAEPITHELIAL NEOPLASIA   Etiology   Cervical cancer and CIN are caused by human papillo-mavirus (HPV). Of the approximately 80 types of HPV, about 30 infect the anogenital tract. Approximately 15 of these types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82) are associated with cancer and are known as  high-risk HPV types.  The majority of cervical cancers are caused by just four of these high-risk HPV types: 16, 18, 31, and 45. Low-risk HPV types are not associated with cancer. However, low-risk types 6 and 11 are associ-ated with  genital warts  ( condylomata acuminata ) and with low-grade squamous intraepithelial lesions.   HPV infects the cells of the cervix. The size and shape of the cervix change depending on age, hormonal status, and number of children (parity). In reproductive-age women, the cervix measures 7–8 mm at its widest point. The upper part of the cervix that opens into the endome-trial cavity is cal...

  Risk Factors   Several factors have been identified that may increase the risk of cervical neoplasia (Box 43.1). A higher incidence of HPV infection and progression of intraepithelial neo-plasia is seen in immunosuppressed patients, including those infected with HIV as well as those who are organ transplant recipients, who have chronic renal failure or a history of Hodgkin lymphoma, or have undergone  immunosuppressive therapy for other reasons. Another factor is cigarette smoking.     Box 43.1 Risk Factors for Cervical Neoplasia More than 1 sexual partner or have a male sexual partner who has had sex with more than  1  person First intercourse at an early age (younger than  18  years) Male sexual partner who has had a sexual part-ner with cervical cancer Smoking Human immunodeficiency virus (HIV) infection Organ (especially kidney) transplant STD infection Diethylstilbestrol (DES) exposure History of cervical cancer or high-grade squa-mous...

  lassification   The goal of all cervical cancer classification systems is to establish management guidelines that decrease the like-lihood of progression of precursor lesions to more advanced lesions. The 2001 Bethesda System is the most widely used system in the United States for reporting and classifying cervical cytologic studies. Established in 1988 and updated in 1991 and 2001, The Bethesda Classification outlines the various possible results of the Pap test, specifies accepted methodologies of reporting the Pap results, and provides for interpretation of findings. This categorization allows for defined management options regarding the initial results of the Pap test (Box 43.2).   The classification used by the Bethesda system divides epithelial lesions into two categories: squamous lesions and glandular lesions. In both categories, lesions are either precancerous or cancerous. Squamous precursor lesions are described as either  atypical squamous cells (ASC),l...

  Evaluation of Abnormal Pap Test Results   An abnormal cervical cytologic finding from a Pap test should be followed by visual inspection of the vagina and a bimanual examination. The first objective is to exclude the presence of invasive carcinoma. Once this has been accomplished, the objectives are to determine the grade and distribution of the intraepithelial lesion. Options for evaluation include repeat cytology, HPV DNA testing, colposcopy with directed biopsies, and endocervical assessment.     COLPOSCOPY AND ENDOCERVICAL CURETTAGE   Colposcopy with directed biopsy  has been the criterionof disease detection and remains the technique of choice for treatment decisions. A  colposcope  is a binocular stereomi-croscope with variable magnification (usually 7 ×  to 15 × ) and a light source with a green filter to aid in the identification of abnormal appearing blood vessels that may be associated with intraepithelial neoplasia. With colposco...

  Management Guidelines for Cervical Epithelial Cell Abnormalities   The American Society for Colposcopy and Cervical Pa-thology (ASCCP) issues guidelines and protocols for the appropriate management of women with cervical cytologic or histologic abnormalities. The most recent updates to these recommendations occurred in 2006 and were published in 2007. These guidelines, including practice algorithms, are available at  www.asccp. org/concensus/ cytological/shtml.  The following sections summarize these guidelines.     LOW-GRADE SQUAMOUS INTRAEPITHELIAL LESIONS AND ATYPICAL SQUAMOUS CELL OF UNDETERMINED SIGNIFICANCE   A patient with an ASC-US result should either undergo HPV DNA testing or repeat cytology at 6 and 12 months following the abnormal Pap test result. The rationale for HPV DNA testing is that a negative result obviates the need for colposcopy; patients with ASC-US who are nega-tive for high-risk HPV DNA may be followed routinely. Women who s...

  Treatment   Both excisional and ablative techniques are used to treat CIN. The underlying concept in the treatment of CIN is that excision or ablation of the precursor lesion prevents progression to carcinoma.      Ablative methods  destroy the  affected cervical tissue and include cryotherapy, laser ablation, electrofulguration, and cold coagulation, all of which are outpatient procedures that can be performed with regional anesthesia. Ablative methods should be used only with an adequate colposcopy and appropriate correlation between Pap test results and colposcopically directed biopsy.   Laser therapy is now only rarely performed in the United States.  Cryotherapy  is a commonly used out-patient method used to treat persistent CIN 1. The pro-cedure involves covering the SCJ and all identified lesions with a stainless steel probe, which is then supercooled with liquid nitrogen or compressed gas (carbon dioxide or nitrous oxide). The ...

  Follow-up After treatment for noninvasive epithelial cell abnormalities, either by ablation or excision, a period of follow-up Pap tests every 6 months for 2 years is generally recommended, with variations depending on the severity of the lesion treated. Most patients may return to a routine screening thereafter. If a subsequent Pap test is abnormal, it is evaluated in the same manner as a new abnormal Pap test. The importance of follow-up should be stressed to the patient, because of the greater risk of recurrent abnormalities.

  CERVICAL CARCINOMA   Between 1950 and 1992, the death rate from cervical can-cer declined by 74%. The main reason for this steep decrease is the increasing use of the Pap test for cervical cancer screening. The death rate continues to decline by approximately 4% per year. Despite the progress made in early detection and treatment, approximately 11,000 new cases of invasive cervical carcinoma are diagnosed annually with 3870 deaths.   The average age at diagnosis for invasive cervical can-cer is approximately 50 years, although the disease may occur in the very young as well as the very old patient. In studies following patients with advanced CIN, this precur-sor lesion precedes invasive carcinoma by approximately 10 years. In some patients, however, this time of progres-sion may be considerably less.   The etiology of cervical cancer is HPV in more than 90% of the cases. The two major histologic types of inva-sive cervical carcinomas are squamous cell carcinomas an...