Haematology+Oncology_News

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H aematology & O ncology N ews • Vol. 9 • No. 1 • 2016

ACOG recommends against annual cervical cancer screening

A history of having had the HPV vaccine series doesn’t obviate the need for screening or change the basic recommendations for screen- ing type or interval, according to the ACOG document. Even the 9-valent vaccine doesn’t cover all cancer-associated HPV. And many women may have had the series after al- ready acquiring an HPV infection, which reduces the vaccine’s efficacy. Finally, the ACOG committee noted that, “long-term efficacy of the vaccine remains incompletely established. Al- though HPV vaccination is an important step toward cervical cancer prevention, it does not remove the need for routine cervical cancer screening.” After age 65 years, screening can be discontinued for women with who have had consecutive negative testing in the prior 10 years. For women who have had grade 2 or 3 cervical intraepithelial neo- plasia (CIN), or adenocarcinoma in situ, screening needs to continue for 20 years after spontaneous regression or treatment. “Women aged 65 years and older do get cervical cancer,” the ACOG committee members wrote. “Women in this age group represent 14% of the US female popula- tion but have 19.6% of the new cases of cervical cancer.” However, since most cases occur in inadequately or unscreened women, and because of the long latency of HPV-driven cancers, “screening women in this age group would prevent very few cases ... [and the slight gain] would come at significant cost, including an increase in required colposcopy procedures.” Changes in most risk factors, including new sexual partners, are not a reason to start screening again in older women because of the long disease latency, according to the ACOG recommendations. Dr Rabin added, “I recon- sider this in certain instances if their status changes, especially if there is immunosuppres- sion, being with a high-risk partner, or having multiple sexual partners.” The guidelines recommend more frequent screening for women previously treated for CIN 2, CIN 3, or cancer; those with HIV infection; those who are immunocompro- mised, including have received solid organ transplants; and those who were exposed to diethylstilbestrol in utero. Women who’ve had a total hysterectomy and no history of CIN 2 or greater don’t need screening, but those who have had a high- grade CIN should continue it, as there can be a recurrence in the vaginal cuff even years later.

BY MICHELE G. SULLIVAN Frontline Medical News From Obstetrics and Gynecology C ervical cancer screening should begin at age 21 years and continue even beyond a woman’s reproductive years, but yearly testing is neither necessary nor recommended for most women, according to new guidelines issued by the American College of Obstetri- cians and Gynecologists. Since cervical cancer is “a rather indolent disease,” more frequent testing is much more likely to result in anxiety and unnecessary treat- ment than in preventing cancers, according to the document, which was published online in Obstetrics and Gynecology (2016;127:e1–20). “Annual screening leads to a very small increase in cases of cancer prevented at the cost of a very large excess of procedures and treatments and should not be performed,” members of the ACOG Committee on Prac- tice Bulletins–Gynecology wrote. Excisional procedures can confer an increased risk of preterm birth – another serious consideration when determining the frequency of screening. And, wrote the committee, the psychosocial aspects of earlier screening must also be taken into account. “The emotional effect of labelling an ado- lescent with a sexually transmitted infection and potential precancer must be considered, because adolescence is a time of heightened concern for self-image and emerging sexuality,” they wrote. Recommendations in this set of guidelines dif- fer slightly from those published in 2015 by the Society of GynecologicOncology (SGO) and the American Society for Colposcopy and Cervical Pathology (ASCCP). Both the SGO andACOG documents take into account the recently ap- proved HPV DNA test, which is indicated as a primary cervical cancer screening tool. The test detects 14 high-risk HPV types, and specifically identifies HPV 16 and 18. A positive result for either of those types should prompt a colposcopy; women who test positive for any of the other 12 high-risk types should have a Pap test. The SGO guidelines say that primary HPV testing alone can be considered for women beginning at age 25 years. The ACOG docu- ment also notes that HPV testing alone can be considered an alternative for women older

21–29 years, cervical cytology alone is suffi- cient for these women, and primary HPV co- testing is not appropriate. The recommended screening interval is every 3 years. HPV testing is more sensitive than is cytol- ogy but less specific, the authors said. And because women in this age group often have noncarcinogenic, transient HPV infections, co-testing could drive more testing and inter- ventions without decreasing cancer incidence. For women aged 30–65 years, however, HPV testing combined with cervical cytology is the optimum choice and should be conducted every 5 years. If cytology alone is performed, however, the recommended interval is every 3 years. Any woman in this age group who has an HPV-positive co-test with negative cytology should be retested with both methods in 12 months. A colposcopy is recommended if the repeat cervical cytology test result is unspeci- fied atypical squamous cells or higher, or if the HPV test result is still positive. Otherwise, the next co-testing can occur 3 years later. As an alternative strategy, an immediate HPV genotyping can be performed; if high-risk strains are present, an immediate colposcopy is indicated.

than 25 years but stresses that cytology alone or co-testing remain the options specifically recommended in current major society guide- lines. If screening with the primary HPV test is used, it should be performed according to the SGO guidance, the ACOG document states. Dr Jill Rabin favours the ACOG recommen- dations over HPV-only testing. She is a profes- sor of obstetrics and gynaecology and cochief of the division of ambulatory care, Women’s Health Programs – Prenatal Care Assistance Program Services at Northwell Health, New Hyde Park, New York “I know certain groups – and not just SGO – go with just the HPV-only test, but I can’t bring myself to do that,” she said in an interview. “Most of the literature agrees that you need to look at both cytology and HPV testing to get the best results. And all cervical cancer is not driven by HPV infections.” The ACOG document stresses that sexual initiation – whatever the age – should not be the precipitating factor for the first cervical cancer screening. HPV infections are normally acquired very quickly after vaginal intercourse begins, although nearly all cases are naturally cleared within a couple of years. From ages

KIR2DL5B genotype predicts outcome in chronic phase CML BY JENNIFER SHEPPHIRD Frontline Medical News From Blood T he presence of KIR2DL5B was associated with lower rates of major molecular response KIR genotypes, KIR2DL2pos and KIR2DS3pos, were also associated with inferior achievement of MMR, probably because of their associa- tion with KIR2DL5B due to linkage disequilibrium among KIR genes, according to the investigators.

samples available for genotyping. KIR genotype frequencies ob- served in this study were similar to other white populations reported in the Allele Frequency Database. Early molecular response was also significantly associated with treat- ment outcomes, independent of KIR prognostic significance, and may add additional prognostic information, available 3 months after treatment commences. “In contrast, KIR2DL5B can iden- tify, at baseline, the 20% of patients with a transformation risk of [about] 10% over 2 years versus the 80% of patients with a transformation risk of less than 3%,” the authors wrote. They suggest that KIR2DL5B, com- bined with other predictive markers, may enable targeted early interven- tions to improve outcomes.

Even with the potent second-generation TKI [tyrosine kinase inhibitor] nilotinib, KIR genotypes, a predetermined genetic host factor, may still be one of the most discriminatory prognostic markers available at baseline.

(MMR), transformation-free sur- vival, and event-free survival (but not overall survival) in patients with chronic phase-chronic myeloid leukaemia (CP-CML) treated with sequential imatinib/nilotinib, ac- cording to researchers. Univariate analysis demonstrated a significant association between KIR2DL5B and achievement of a major molecular response, with hazard ratio 0.423 (95% CI, 0.262–0.682; P < 0.001). Other

inhibitory KIR receptor, the absence of which may increase efficiency of NK-mediated killing of leukaemic stem cells, researchers suggested. The Therapeutic Intensification in De Novo Leukaemia (TIDEL-II) study included 210 patients with CP-CML who were treated with imatinib initially, and nilotinib sub- sequently if predetermined molecu- lar targets were not met. The KIR substudy included 148 patients with

( Blood 2015 Dec 17. doi:10.1182/ blood-2015-07-655589). Killer immunoglobulin-like recep- tors (KIRs) contribute to natural killer (NK) cell-mediated killing of tumour cells, in both activating and inhibi- tory roles. Normal cells are spared through actions of inhibitory KIRs. Although the mechanism underlying the association between KIR2DL5B and CP-CML treatment outcomes is still unclear, the gene encodes an

“Our findings suggest that even with the potent second-generation TKI [tyrosine kinase inhibitor] nilo- tinib, KIR genotypes, a predeter- mined genetic host factor, may still be one of the most discriminatory prognostic markers available at base- line,” wrote Dr David T. Yeung of the department of genetics and molecu- lar pathology, Centre for Cancer Bi- ology and the University of Adelaide, South Australia, and colleagues