Clinical utility of HPV genotyping.

Cervical cancer screening is presently done by finding abnormal cells in cervical smears (i.e., cervical cytology or Pap smears). However, cervical cytology is not full-proof. Cervical cytology is insensitive for the detection of cancer and precancer [1], requiring many rounds of screening to achieve programmatic effectiveness. It is now recognized that virtually all cervical cancers, both of the squamous and of the adenocarcinoma histologic types, are causally related to cervical infections by 14 oncogenic human papillomavirus (HPV) genotypes (HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) [2,3]. With the advent of methods that detect nearly all oncogenic HPV types in aggregate, the question has risen whether testing for oncogenic HPV can improve more reliably the detection of cervical carcinomas and their precursors (cervical intraepithelial neoplasia grade 2 [CIN2] and 3 [CIN3]). There is now compelling evidence that testing for oncogenic HPV is more sensitive and has a higher negative predictive value (NPV) for CIN2 or worse (CIN2+) compared to cervical cytology [4–6] at the cost of a small decrease in specificity and positive predictive value compared to cytology. HPV testing also implies detecting an endpoint in cervical carcinogenesis that is earlier than the development of cervical abnormalities; this translates into a longer safety margin in following up women who are HPVnegative. The sensitivity and NPV of HPV testing are so high that few cancers and CIN2+ lesions are missed. Therefore, a negative test result provides years of reassurance. Because HPV infections are so common in young women after sexual debut and precancerous lesions so rare, the use of HPV DNA testing should be delayed until 10–15 years after the average age of sexual debut in any given population. For example, in the U.S., HPV testing as an adjunct to cytology in primary screening is