Studies show increase in cancer that evades Pap, confirm lethality of non-HPV disease
A type of cervical cancer often missed by Pap testing was seen at increasing rates over the past 15 years in the U.S., whereas rates of the most common histology decreased, a review of a cancer database showed.
The incidence of adenocarcinoma rose by 1.3% annually from 2002-2015 among non-Hispanic whites, including steeper rises among women ages 40 and older during some years. Rates of adenocarcinoma declined or did not change in other racial/ethnic subgroups, reported Farhad Islami, MD, PhD, of the American Cancer Society, and coauthors.
Meanwhile, diagnosis of squamous cell carcinoma (SCC) of the cervix decreased or remained stable across all subgroups. More women had advanced-stage disease at diagnosis, regardless of histology, they wrote in Preventive Medicine.
The findings underscored the importance of preventing human papillomavirus (HPV) infection, which causes most cervical cancer, and using HPV testing for diagnosis, Islami and colleagues concluded.
“Increasing or stabilized incidence trends for [adenocarcinoma] and attenuation of earlier declines for SCC in several subpopulations underscore the importance of intensifying efforts to reverse the increasing tends and further reduce the burden of cervical cancer in the U.S.,” the authors said.
An unrelated study from Spain confirmed previous evidence showing that non-HPV cervical cancer has a more aggressive clinical course and worse prognosis, including a 50% lower survival, as compared with women who have HPV-positive cervical cancer.
Over the past decade, multiple studies documented a decline in cervical cancer incidence in the U.S. Studies dating back to the 1970s showed an increased incidence of cervical adenocarcinoma, but those studies did not adequately account for hysterectomy, which introduced bias to comparisons across different subgroups, Islami and coauthors noted.
To examine contemporary trends in cervical cancer incidence, investigators queried the CDC’s U.S. Cancer Statistics Incidence Analytic Database to determine cervical cancer incidence during 1999-2015. They compared incidence by age, race/ethnicity, histology, and stage at diagnosis.
The analysis revealed 218,244 cases of cervical cancer for the period reviewed (67% SCC, 21% adenocarcinoma, 3.3% adenosquamous carcinoma, and 6.3% unknown or unspecified). For all histologies combined, cervical cancer incidence among white women declined by 4.1% a year from 1999-2003 and 1.1% a year from 2003-2013, then stabilized from 2013-2015. Among blacks and Asian/Pacific Islanders, rates declined in almost all age groups from 1999-2015. Rates also declined in Hispanics but stabilized in recent years.
Analysis by histology showed a steady rise in adenocarcinoma incidence among white women since 2002, driven by steeper increases in women ages 40 to 49 (4.4% per year since 2004) and 50-59 (5.5% per year since 2011). Rates declined or stabilized in other racial/ethnic groups. The incidence of SCC cervical cancer decreased in all racial/ethnic groups, except whites, wherein rates decreased until the current decade and then stabilized.
Of particular concern, the frequency of distant-stage cervical cancer — SCC and adenocarcinoma — increased in several age groups among whites. In general, rates remained stable in other racial/ethnic groups.
The increasing incidence of adenocarcinoma warrants attention, given that Pap testing has a lower sensitivity for detecting cervical adenocarcinoma, Islami noted. Adherence to guidelines for HPV vaccination and cervical cancer screening (with testing for HPV) affords the best assurance against continued increases.
Investigators at the Spanish Institute for Global Health (ISGlobal) in Barcelona investigated clinical and prognostic features associated with HPV-negative cervical cancer, which accounts for a small minority of all cases worldwide. Several small studies showed that HPV-negative cervical cancer suggested the disease had a more aggressive clinical course and worse prognosis, but the rarity of the cancer and the small sample sizes made the findings less than definitive, according to Jaume Ordi, MD, PhD, and colleagues at ISGlobal, writing in Modern Pathology.
To improve understanding about HPV-negative cervical cancer, investigators analyzed data for 214 patients with cervical cancers diagnosed from 2012-2015 and followed for 5 years. They found that 21 (10%) of the cancers were HPV negative.
As compared with the HPV-positive majority, HPV-negative cervical cancers were significantly more likely to be non-SCC (43% vs 19%, P<0.01), advanced stage at diagnosis (91% vs 57%, P<0.01), and have spread to lymph nodes (67% vs 36%, P<0.01). Patients with HPV-negative tumors had a median progression-free survival of 59.8 months versus 132.2 months (P<0.01) and median overall survival of 77 months versus 153.8 months (P=0.01).
“The new study confirms that HPV-negative tumors represent a more aggressive type of cancer with worse prognosis, which must be considered for the clinical management of these patients,” Ordi said in a statement.