Gupta K, Hooten TM, Naber KG,et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: a 2010 update by the Infectious Disease Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis 2011;52:e103– e120.
Intraepithelial Disease of the 19 Cervix, Vagina, and Vulva
Francisco Garcia Kenneth D. Hatch Jonathan S. Berek
Cervical intraepithelial neoplasia (CIN) most often arises in an area of metaplasia in the transformation zone at the advancing squamocolumnar junction (SCJ). Metaplasia advances from the original SCJ inward, toward the external os and over the columnar villi, to establish the transformation zone. CIN is most likely to begin either during menarche or after pregnancy, when metaplasia is most active; after menopause, metaplasia is less active and a woman has a lower risk of developing CIN.
Untreated, most CIN 1 and some CIN 2 lesions spontaneously regress; nevertheless, CIN refers to a lesion that may progress to invasive carcinoma. This term is equivalent to the term dysplasia, which means abnormal maturation; consequently, proliferating metaplasia without atypical mitotic activity should not be called dysplasia. Squamous metaplasia should not be diagnosed as dysplasia (or CIN) because it does not progress to invasive cancer.
More than 90% of CIN is attributed to human papillomavirus (HPV) infection. Only certain types of HPV cause high-grade intraepithelial lesions and cancer (HPV-16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -68). Type 16 is the most common form of HPV found in invasive cancer and in CIN 2 and CIN 3; it is found in 47% of women with cancer.
Potentially premalignant squamous lesions fall into three categories: (i) atypical squamous cells (ASC), (ii) low-grade squamous intraepithelial lesions (LSIL), and (iii) high-grade squamous intraepithelial lesions (HSIL). The ASC category is subdivided into two categories: those of unknown significance (ASC-US) and those in which high-grade lesions must be excluded (ASC-H).
The LSIL category includes CIN 1 (mild dysplasia) and the changes of HPV, termed koilocytotic atypia. The HSIL category includes CIN 2 and CIN 3 (moderate dysplasia, severe dysplasia, and carcinoma in situ).
The spontaneous regression rate of biopsy-proven CIN 1 is 60% to 85% in prospective studies. The regressions typically occur within a 2-year follow-up with cytology and colposcopy. For LSIL that persists longer than 2 years, the choice of treatment is optional. Expectant management is still appropriate in some patients, and ablative therapies, including cryotherapy and laser ablation, are acceptable treatment modalities.
When a cytologic specimen suggests the presence of HSIL, colposcopy and directed biopsy should be performed. Although high-grade CIN can be treated with a variety of techniques, the preferred treatment for CIN 2 or 3 in nonadolescent patients is loop electrosurgical excision procedure (LEEP).
Atypical endocervical cells pose a risk for adenocarcinoma in situ (AIS), which must be considered a precursor of adenocarcinoma.