HPV test vs Pap: Which is better for cervical cancer screening?

January 15, 2019
Judith M. Orvos, ELS
Judith M. Orvos, ELS

a BELS-certified medical writer and editor, and an editorial consultant for Contemporary OB/GYN

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Ben Schwartz
Ben Schwartz

Ben Schwartz is Associate Editor, Contemporary OB/GYN.

Although human papillomavirus (HPV) vaccination has decreased cervical cancer morbidity and mortality, secondary prevention through screening remains an important strategy. PLUS: Does being black influence hysterectomy route and outcomes? ALSO: Syphilis in pregnancy on the rise.

Although human papillomavirus (HPV) vaccination has decreased cervical cancer morbidity and mortality, secondary prevention through screening remains an important strategy. A recent report, appearing in JAMA, examined 48-month exit round results of the Human Papillomavirus for Cervical Cancer screening trial (HPV FOCAL), which compared primary HPV testing alone with liquid-based cytology (LBC) screening for prevention of cervical intraepithelial neoplasia (CIN) grade 3 or worse. 

Participants in the publicly funded study were 16,347 women from British Columbia aged 25 to 65 who had not had a Pap test in the previous 12 months; were not pregnant, HIV-positive or receiving immunosuppressive therapy; and had no history of CIN2 in the past 5 years. They were recruited from January 2008 to May 2012, with follow-up through December 2016. Randomization was to HPV testing, LBC, or safety groups. However, after January 1, 2011, when the safety group was closed, randomization was changed to HPV testing or LBC. 

Patients in the HPV testing group who had negative results were recalled at 48 months for HPV and LBC testing. Those in the LBC group who tested negative were instructed to return at 24 months for repeat testing with LBC in accordance with the cervical cancer screening guidelines in British Columbia. 

In the first round of screening, significantly more CIN3 cases were detected in the HPV testing group than in the LBC group (absolute difference in incidence rate 2.67/1000 [95% CI, 0.53 to 4.88]). However, by 48 months, significantly fewer CIN3 cases were detected overall and across all age groups in the HPV testing group compared with LBC (absolute difference in incidence rate -3.22/1000 [95% CI, -5.12 to -1.48]). In terms of cumulative incidence of CIN3, there was no significant difference in disease detection across the groups. However, in the HPV group, the cumulative incidence rate was higher earlier in the trial at 18 months and 42 months compared to the LBC group. 

Looking at CIN2, the researchers found significantly more cases in the HPV testing group compared to those in the LBC group in the first round of screening (absolute difference in incidence rate 5.84/1000 [95% CI, 2.70 to 9.07]). But by 48 months, significantly fewer CIN2 cases were detected overall and across all ages in the HPV testing group compared with the LBC group (absolute difference in incidence rate -5.60/1000 [95% CI, -8.21 to -3.13]). Cumulative incidence of CIN2 was higher earlier in the trial at 18 and 42 months compared with the LBC group. Among baseline HPV- or LBC-negative women, rates of CIN2 positivity at 48 months were significantly higher across all age groups in the LBC group compared with those who underwent HPV testing. Cumulative incidence curves showed that women who were HPV-negative at baseline had a significantly lower risk of CIN2 at 48 months compared with cytology-negative women. 

Some of the strengths identified for the trial were that it was embedded in a well-established centralized cervical screening program, opportunistic screening not recommended through the trial was minimized by active notification by trial staff, and histopathological assessment was blinded to HPV and cytology results. Identified limitations include an exit intervention that was not the same as the baseline intervention and potential for selection bias. 

The authors believe that the findings from this study illustrate that use of primary HPV testing for women undergoing cervical cancer screening resulted in a significantly lower likelihood pf CIN3 at 48 months compared to cytology testing. However more research is necessary to understand long-term clinical outcomes and assess cost-effectiveness.


Does being black influence hysterectomy route and outcomes?

A minimally invasive approach to hysterectomy is known to cost less, result in fewer complications, and speed recovery, but previous research suggests that there may be disparities in choice of route of hysterectomy. A recent study in Obstetrics & Gynecology aimed to determine whether, in women undergoing the surgery for benign indications, race has an influence on route of hysterectomy and postoperative complications.

Using ICD-9 codes, the researchers identified patients in the American College of Surgeons National Surgical Quality Improvement Program database who had undergone hysterectomy in 2015. The primary outcome of the study was route of hysterectomy, either minimally invasive or open abdominal and the key exposure was patient race – either black or white. Surgical complications during the 30-day postoperative period were the secondary outcomes. 

Of the 15,316 patients included in the analysis, 11,330 were white (74.9%) and 3,806 black (25.1%). Black patients were younger, had higher body mass index, were more likely to have diabetes and hypertension, and had higher uterine weights and a higher incidence of prior abdominal surgery than the included white patients. White patients were more likely to have a diagnosis of endometriosis and a history of prior pelvic surgery. 

More patients in the study underwent minimally invasive hysterectomy (n=10,634 [70.3%]) than open hysterectomy (n=4.502 [29.7%]). However, black women underwent open hysterectomy at a much higher rate (50.1%) than white women (22.0%). Even after using logistic regression to account for factors associated with selection of open hysterectomy, black women still had twice the odds of having an open procedure compared to white women. Similar results were also found when the authors limited uterine weight to less than 250 g: Black women had significantly higher odds of undergoing open hysterectomy (adjust OR 1.84, 95% CI 1.61-2.11). 

In addition to having higher rates of open hysterectomy, the black patients also were more likely to experience complications when undergoing the surgery. However, the proportion with complications varied by hysterectomy type. Compared to white women, black women experienced more total complications (14.1% vs 8.6%, P < .001); more major complications, including venous thromboembolism, myocardial infarction, stroke, and pneumonia among others, (4.1% vs 2.4%, < .001);and more minor complications, including urinary tract infection, superficial wound infection and blood transfusion (11.4% vs 6.7%, < .001). While there were no significant differences in complication rates between black women and white women undergoing vaginal hysterectomies, a higher proportion of black women had minor complications (16.9% vs 11.3%, < .001) and major complications (3.3% vs 1.8%, < .001) when undergoing open hysterectomy. 

The major strength of their study, the authors said, was the reliability and accuracy of the database used to acquire the included data. Identified limitations were the potential for unmeasured bias, lack of information on the exact hospital where each hysterectomy was performed, and no information on surgeon volume or years of experience. 

The researchers noted that their findings are similar to results of previous studies and support the hypothesis that there may be clinical differences, particularly with uterine size, between white and black women that influence the surgeon’s decision on how to perform a hysterectomy. However, even after adjusting for these differences, black women still had higher odds of undergoing open hysterectomy. While the higher likelihood of open hysterectomy may be the primary cause for black women having higher odds of complications, the authors believe that further investigation is necessary. They suggest that patient lack of access to higher quality care may be a contributing factor as well. 


Syphilis in pregnancy on the rise

Rates of primary and secondary syphilis in women more than doubled between 2012 and 2016 and the rate of the disease in infants increased 86.9%. A new national case analysis by researchers from the Centers for Disease Control and Prevention (CDC) sheds light on reported risk behaviors that may be contributing to these alarming trends.

Data for the study were from the National Notifiable Diseases Surveillance System. The case reports in the system included information on demographics, stage of syphilis (primary, secondary, early-latent, or late-latent cases) and pregnancy status but not prenatal care, treatment, or pregnancy outcome. 

The authors analyzed demographic and risk behavior data on all women with syphilis from all 50 states and the District of Columbia from 2012 to 2016. Risk behavior included high-risk sexual behaviors (prior sexually transmitted disease [STD]; more than one sex partner; sex while intoxicated; anonymous sex partner; sex for drugs or money, sex with persons known to inject drugs; sex with gay, bisexual or other men who have sex with men), drug-related risk factors, history of incarceration, and human immunodeficiency virus (HIV) infection. Information on most risk factors as collected with values of “yes,” “no,” “missing,” or “unknown.” 

During the study period, the number of reported cases of syphilis among females increased 55% from 9,551 to 14,838 and the number of syphilis cases among pregnant women increased 61% from 1,561 to 2,508. However, the percentage of syphilis cases among pregnant women remained relatively stable:  16% to 18%. During this period, the proportion of pregnant women who were diagnosed with early syphilis cases (primary, secondary, or early latent syphilis) exceeded that in late latent syphilis cases, which in turn caused the rate of late latent syphilis to decrease from 65% to 42%. Early syphilis cases in pregnant women increased 43% from 1,008 to 1,443 cases over the 5-year period. 

In terms of demographics, 59% of pregnant women with syphilis were in their 20s, the highest proportion of cases was consistently among non-Hispanic blacks, and most women (56%) were from the South. Reported cases of syphilis increased in every age group, race and ethnicity group and in every geographical region. The greatest increases were seen in women aged 30 to 34 years (90%) and in Native Americans (420%). The West was the geographic region with the greatest increase. 

Looking at prevalence of risk factors, 51% (4,997/9,883) of women with syphilis reported any risk factor. The most commonly reported risk behaviors among pregnant women with syphilis were prior STD (43%) and more than one sex partner in the past 12 months (30%). Methamphetamine was the drug most commonly mentioned, used by 4.5% of pregnant women with syphilis overall and 6.3% of pregnant women with early disease. 

A few limitations to the study were identified. Among these were a lack of current data on the number of pregnancies in the United States, which prevented the authors from calculating syphilis rates per 100,000 pregnant women. Data on reported behavioral risk were also limited since they were collected via interviews and reliant on participants reporting sensitive information about which they may have feared legal repercussions. Lack of information about pregnancy outcomes precluded the authors from linking prenatal syphilis cases to reported congenital syphilis cases. 

The authors said their findings show that syphilis among pregnant women increased from 2012 to 2016. Given the trend, ob/gyns need to increase their awareness of recommendations from the CDC and the American College of Obstetricians and Gynecologists, which include screening all pregnant women for syphilis at the first prenatal visit and screening women at high risk for contracting the disease on an ongoing basis.