Cervical Cancer: The Next Generation of Prevention, Detection, and Treatment.

Cervical cancer remains an important problem in the United States and, more significantly, the world, despite the US Food and Drug Administration’s approval of the first in-human papillomavirus (HPV) vaccine in 2006. In the United States in 2016, even with mature screening programs, an estimated 12,990 women will be diagnosed with cervical cancer and 4120 will die from the disease. 1 Worldwide, these numbers are more staggering: Cervical cancer is the fourth most frequent cancer in women, with an estimated 530,000 new cases and 270,000 deaths in 2012. 2 The treatment of cervical cancer in almost all cases will result in a loss of future fertility, as well as other significant treatment sequelae leading to a decreased quality of life. Unfortunately, cervical cancer continues to be a cancer of young women; in fact, as noted by Pelkofski et al 3 in this issue of Clinical Therapeutics, cervical cancer is the most common gynecologic malignancy in women o35 years of age. Those young women who develop cervical cancer, by virtue of their young age and the trend in the United States to delay childbearing, are at particular risk for loss of fertility, with 22% in the report from Pelkofski et al 3 having never been pregnant. In the series from Pelkofski et al, the “very young” patients (25 years or younger) were compared to the socalled "young" patients (26–35 years). While there was no difference in progression-free or overall survival between these two groups, the investigators did make some interesting observations. First, 5 of the 17 “very young” women with cervical cancer were aged 20 years or younger. It is of interest that all 5 of these women were diagnosed by Pap smear (author, personal communication), a screening procedure for which they would not be eligible under the current guideline. 4 While concerning, this finding must be placed into perspective: This is a very small-scale experience in a rural and underserved population from two mid-Atlantic university–based practices, and the findings contradict those from a larger-scale population-based study that suggests the that rate of cervical cancer in women under age 21 years is “vanishingly small.” 5 There are no data to suggest that screening in women o21 years of age affects future rates of pre-invasive disease, and screening this population may result in unnecessary procedures because younger women are more likely to clear pre-invasive disease. 6 Nonetheless, the relatively large number of young women in this series merits further consideration in future, larger-scale studies. Second, the rate of small cell carcinoma, a subtype associated with a very poor prognosis, was 4.4%, which is greater than expected in the overall cervical cancer group (expected, o3%). 7 Third, and perhaps most important, the 5-year survival rate in the entire patient group (women aged 35 years or under) in the study by Pelkofski et al 3 was surprisingly low. Despite the fact that over 80% of women had early stage disease, the 5-year survival rate in the entire cohort was 42.1%, with a 5-year survival of 46% in patients with localized disease (expected, 68% for all stages combined, 92% for localized disease). 8 Put together, these findings are hypothesis generating. It would appear, based on this small series, that cervical cancer is more aggressive in the younger age group, although the