Affecting an estimated 500,000 new patients each year, cervical cancer is the second most common malignancy in women worldwide and remains a leading cause of cancer-related death among women in developing countries.  In the United States, however, cervical cancer is fortunately less common, having declined over the past few decades as a result of improved screening practices, preventative immunizations, and timely treatment of invasive disease.1 In an effort to further improve outcomes, screening guidelines are currently being revised to target women most likely to benefit from assessment, while concurrently reducing potential harms associated with over-screening and over-diagnosis.2  New scanning devices, designed to detect cervical disease through optical spectroscopy, are also under investigation and may prove to be valuable diagnostic tools.3 In implementing and complying with best practices, it is imperative that healthcare professionals be well-informed regarding current and emergent screening tools and recommendations.

Pathogenesis and Etiology of Cervical Cancer
In reviewing general pathophysiology of cervical cancer in broad strokes, potentially cancerous precursor lesions found on the uterine cervix are referred to as cervical intraepithelial neoplasia (CIN), or intraepithelial squamous abnormalities that exhibit nuclear atypia.4 These lesions may be further classified as mild, moderate, or severe, based on the extent of epithelial involvement. CIN I, or mild dysplasia, typically involves one-third of the cervical epithelium; CIN II, which denotes moderate to marked dysplasia, involves two-thirds of the epithelium, while CIN III, which indicates severe dysplasia or carcinoma in situ (CIS), involves the full thickness of the epithelium.5 CIN I generally corresponds to a low-grade squamous intraepithelial lesion (LSIL), while CIN II and III are considered high-grade squamous intraepithelial lesions (HSIL).5 Experts generally believe that CIN I and II lesions typically regress or persist unchanged, while CIN III is more likely to advance to cancer. Table 1 delineates specific disease outcomes based on degree of dysplasia. Importantly, progression to cervical cancer is known to be a slow process that typically occurs over many years.1 Therefore, regular screening and management is vital in preventing progression, even among those with high-grade lesions.

As increasingly documented in published literature, strong evidence supports involvement of human papillomavirus (HPV) in the development of cervical cancer, with HPV viral DNA detected in more than 90% of premalignant and malignant cervical lesions.1 Thus far, over 100 different genotypes of HPV have been identified, with an estimated 40 having the potential to infect anogenital tissues and approximately 15  considered oncogenic.5 HPV types 6 and 11 are known to be low-risk viruses that may be associated with LSILs, but not with invasive cervical cancer. Conversely, HPV types 16 and 18 are high-risk viruses that are found in 50% to 80% of low- and high-grade lesions, as well as in up to 90% of invasive cancers.1

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While other factors (e.g., age, host immunity, smoking, oral-contraceptive use, vitamin deficiencies) are certainly involved in the carcinogenesis process,1 persistent HPV infection is considered the primary causative factor and is requisite to the development of cervical neoplasia.5 As such, HPV vaccination, which protects against commonly implicated HPV genotypes, has become a  critical public-health initiative in reducing the risk of cervical cancer development. In examining the currently available vaccinations, Gardasil® [Human Papillomavirus Quadrivalent (Types 6, 11, 16 & 18) Vaccine, Recombinant] (Merck), which covers HPV types 6, 11, 16, and 18, is indicated for use in males and females 9 to 26 years of age,6 while Cervarix® [Human Papillomavirus Quadrivalent (Types 16 & 18) Vaccine, Recombinant] (GlaxoSmithKline), which covers HPV types 16 and 18, is indicated for use in females between 9 and 25 years of age.7 According to the Centers for Disease Control and Prevention (CDC), immunization is recommended for preteens 11 or 12 years of age, as efficacy is greatest among those who are vaccinated prior to engaging in sexual activity.8

Table 1.  Disease Outcomes Based on Degree of Dysplasia5

 Degree of Dysplasia

Regression (%)

Persistence (%)

Progression to CIN III (%)

Progression to Invasive Cancer (%)
















CIN = cervical intraepithelial neoplasia
Adapted from Premalignant lesions of the cervix.  American Society for Colposcopy and Cervical Pathology (ASCCP).  Accessed January 4, 2012.  Available at: