Screening to Prevent Invasive Cervical Cancer (Resource-Stratified) SH-Shiekhhasani GYN.Oncologist TEHRAN UNIVERSITY

Cervical cancer is the fourth most common cancer and fourth leading cause of cancer-related mortality in women worldwide. Effective cervical cancer screening by (Pap) has resulted in the decline of cervical cancer incidence and mortality by 50%,Mostly in high- income countries.

high-coverage, high-quality Pap testing has not been effectively implemented in many low- and middle-income countries (LMICs) as the result of well-known limitations. 90% of the global cases of cervical cancer and related deaths occur in LMICs.

ASCO emphasizes that the primary goal of cervical cancer screening (especially in LMICs) : detection and treatment of pre-cancerous lesions to prevent progression to invasive cervical cancer and that cancer control is secondary

ASCO guidelines : HPV-based screening is the preferred approach for all resource strata. VIA is recommended in the basic resource setting, to build health care infrastructure, only until HPV testing becomes available. A large trial demonstrated that visual inspection with acetic acid (VIA) reduced mortality but not incidence VIA served only to downstage rather than prevent cancer

differences in recommendations between resource strata relate to: how many times a woman should be screened in a lifetime, over what age ranges management of HPV-positive results

GUIDELINE QUESTIONS (1)What is the best method(s) for screening for each resource stratum? (2) What is the best triage strategy for women with positive results or other abnormal results? (3) What are the best management strategies for women with precursors of cervical cancer? (4)What screening strategy should be recommended for women who have received HPV vaccination?

Maximal-Resource Setting Screening:HPV DNA testing Age:25-65y(may elect until 70y) Interval: every 5y (Evidence quality: high; Strength of recommenda-tion: strong). >= 65 and neg screening for 15 y---stop screening 65y and positive screening after 60: screening 2 & 5 & 10 y after final positive result Irregular or without screening until 65:screening once , NL, stop (Type: evidence based; Evidencequality: intermediate; Strength of recommendation: moderate)

Enhanced-Resource Setting Screening:HPV DNA testing Age:30-65y** Interval: every 5y (Type: evidence based; Evidence quality: high; Strength of recommendation: strong) two consecutive negative screening: subsequent screening every 10 years** Type: formal consensus based; Evidence quality:intermediate-low; Strength of recommendation:moderate) >= 65 and neg screening for 15 y---stop screening 65y and positive screening after 60:screening 2 & 5 & 10 y after final positive result Irregular or without screening until 65:screening once , NL, stop (Type: formal consensus based; Evidence quality: low; Strength of recom-mendation: weak)

Limited-Resource Setting Screening:HPV DNA testing Age:30-49y** Interval: every 10y= 2-3 times in lifetime** (Type: evidence based [age range],Type: formal consensus based [interval]; Evidence quality: intermediate; Strength of recommenda-tion: moderate).

Basic-Resource Setting If HPV DNA testing for screening is not available, then VIA should be offered with the goal of developing health systems and moving to HPV testing at the earliest opportunity. Age:30-49y Interval: at least 1 time in a lifetime, but not more than 3 times per lifetime(1-3 times) (Type: evidencebased; Evidencequality: interme-diate; Strength of recommendation: strong)

Women who are HIV positive screening test:HPV testing, as soon as they receive an HIV diagnosis Interval:every 2 -3 years, frequency depends on the resource level; it should be twice as many times in a lifetime as in the general Population (Type: formal consensus based ,Evidence quality: low; Strength of recommendation: weak) If HPV testing is not available, use VIA at the same intervals (Type: evidence-based; Evidence quality:low; Strength of recommendation: weak)

New guidelines for cervical screening( from Alberta and British Columbia) recommend increasing the starting age from 21 to 25 years Cervical cancer mostly has a long natural history and, is uncommon in women under age 25  years. Cervical screening among this age group has minimal impact on rates of carcinoma but does lead to over diagnosis and overtreatment of precancerous lesions that are destined to regress or not progress to cancer until later

long lead-time According to multiple epidemiologic studies, before screening, incidence of cervical cancer among unscreened populations was high from 35 to 65  years--- long lead-time from initial HPV infection There are few studies of the untreated natural history , a cohort study in New Zealand found that invasive cancer developed in 30% of women with carcinoma in situ (CINIII) over 30 years of follow-up.

Invasive cancer of the cervix is uncommon among women under <25 years, regardless of screening practices. In Canada, incidence among young women between 15 and 19  years of age has not changed since the era before widespread screening began in 1971: three per million. Among women between 20 and 24 years of age, incidence decreased from 3.2 to 1.2 per 100 000, with no change in uncommon mortality from invasive cervical cancer despite programs of annual screening

abnormal screening results and precancerous cervical lesions are commonly observed in younger women. Rates of abnormal pap tests among women 20 to 24 years vary from 7.3% in British Columbia to 23% in Newfoundland and Labrador. Most abnormalities are low grade and represent transient HPV infections that regress without intervention: few progress to highgrade precancer.

A study in California 95 women with CIN II 2Y F/UP---- in 2/3 lesion regressed No progression to invasive carcinoma Although 37% of lesions were still present, persistent lesions can be treated later without adverse physical consequence from the delay

IN FUTURE & vaccinated young women???

screening young women leads to substantial identification and overtreatment of transient changes, which could potentially cause serious harms

A study in the United Kingdom to prevent one invasive cancer in women who are 20 to 24 y would require between 12 500 and 40 000 additional screening tests and 300 - 900 excisional procedures

effect of treatment for CIN on obstetric outcomes Kyrgiou M, Athanasiou A, Paraskevaidi M, et al. Adverse obstetric outcomes after local treatment for cervical preinvasive and early invasive disease according to cone depth: systematic review and meta-analysis. BMJ2016;354:i3633. doi: 10.1136/bmj.i3633 effect of treatment for CIN on obstetric outcomes cervical excisional procedures may increase the rate of preterm birth by about 5%, depending on the depth of excision, raise the risk of perinatal death by about 0.2% in each subsequent pregnancy, the cumulative risk of cancer developing before age 30  y is <0.05%

diagnosis of cervical intraepitheleal neoplasia has substantial psychosocial impact,

The new recommended thresholds for screening are not rigid. Some factors place women at higher risk : sexual activity started early, multiple sexual partners, smoking, term pregnancy as an adolescent may consider screening young women with these risk factors earlier than age 25 years

By reducing unnecessary screening in young women: resources may be channeled to reach women who have missed recommended screening: Indigenous women, women living in rural areas some groups of immigrants first test for these women provides more value than testing women at low risk who are under the age of 25 years