CERVICAL CANCER SCREENING

KENYA NATIONAL CANCER SCREENING GUIDELINES I 39

CERVICAL CANCER SCREENING

Introduction

Cervical cancer is a consequence of long-term infection with human papillomavirus

(HPV). Globally, it ranks 4th in both incidence and cancer-related mortality amongst

women with an estimated 569,847 new cases new cases and 311,365 deaths annual-

ly. It accounts for 13.1% of all new female cancers globally. In Eastern Africa, cervical

cancer remains the most common cancer in women with estimated age-standardized

incidence and mortality rates of 40.1 and 30.0 per 100,000 respectively (GLOBOCAN,

2018).

In Kenya, cervical cancer contributes 5,250 (12.9%) of the new cancer cases annually and 3,286 (11.84%) of all cancer deaths annually. It is the leading cause of cancer relat- ed deaths in Kenya and the 2nd most common cancer among females. (GLOBOCAN,

2018).

According to the World Health Organization (WHO), over 1 million women worldwide are currently living with cervical cancer, many of whom have no access to health ser- vices for prevention, curative treatment or palliative care. As a result, many present late when treatment is more difficult and expensive and chances of cure are abysmal. Screening allows for treatment in the asymptomatic precancerous stage (WHO, 2014). Unfortunately, according to the Kenya STEPwise survey for NCDs Risk Factors 2015 report (KNBS, 2015), only 16.4% of women aged 30 – 49 years had ever been screened for cervical cancer.

HPV is the primary cause of 99.7% of all cervical cancers and is sexually transmitted. Infection with one or more of the 15 high-risk oncogenic types (types 16, 18, 31, 33,

35, 39, 41, 51, 52, 56, 58, 59, 66, 67 and 68) usually results in invasive cervical cancer after 10-20 years. Globally, about 70% of all cases of cervical cancer are caused by HPV types 16 and 18. With the increasing availability of vaccines against high-risk HPV, there exists great potential to reduce the incidence of cervical and other anogenital cancers (ACCP 2004, WHO 2006).

The lifetime risk for HPV infection among sexually active women is 50-70%. By the age of 50 years, at least 80% of women will have acquired genital HPV infection. For- tunately, over 80% of HPV infections are transient, asymptomatic and resolve sponta- neously in 2-3 years due to the natural cell-mediated immunity, hence the majority of women who get infected with high-risk oncogenic HPV types do not develop cervical cancer. Of the 20% of infections that persist, the HPV viral gene is incorporated into the DNA of cervical cells stimulating abnormal cell division. This may cause mild cyto-

logical abnormalities and/or mild cervical intraepithelial neoplasia (CIN 1), which usually clears spontaneously in about 60% of women in 2-3 years. In about 40% of women, the abnormalities progress to high grade squamous intraepithelial lesions (HSIL) or CIN 2/3 and carcinoma-in-situ (CIS) that subsequently progress to invasive cancer. About 40% and 30% of CIN 2 and CIN 3, respectively spontaneously regress to normal.

The presence of additional co-factors is necessary for the HPV infection to progress to invasive cervical cancer is implied by the fact that not all persistent HPV infections prog- ress to cervical cancer (Mati, 1984; Berraho, 2017)

RISK FACTORS FOR CERVICAL CANCER:

• Early initiation of sexual intercourse
• Having multiple sexual partners
• Having a sexual partner with multiple sexual partners
• Co-infection with other sexually transmitted infections, such as  

Chlamydia trachomatis and herpes simplex virus type 2

• Multiparity

• Immunosuppression due to HIV/AIDS infection

• Tobacco use

RATIONALE FOR SCREENING

Screening programmes continue to have a vital role, allowing for early detection and treatment in order to achieve a maximal impact on cervical cancer prevention. The natural history of cervical cancer is many years to decades, with a long precancerous, preclinical phase, allowing for testing (screening) for precancerous lesions and cancer. When screening detects precancerous lesions, these can easily be treated and cancer avoided. Screening can also detect cancer at an early stage, enabling women to receive treatment when it is highly effective (WHO, 2014).

The increasing availability of HPV vaccination for girls and the potential for reduction of the possibility of developing cervical cancer later in life, however, does not eliminate the need for regular screening when women get older.

The success of a screening programme in reaching its aims is dependent on achieving adequate coverage. While the screening programme will be introduced incremental- ly depending on health service capacity, the ultimate goal is to screen at least 70% of women, nationally, within the target age group within 10 years of initiating the programme (IAEA, 2016).

WHO SHOULD BE SCREENED AND WHEN?

Any woman who has ever had sexual intercourse is eligible for cervical cancer screening

The target population for screening is women aged 25 to 49 years

Women aged 50-65 years are still at risk of cervical cancer and can therefore receive screening every 5 years on individual resources

Screening interval is 5 years among women who test negative for HIV For HIV positive clients and other special groups refer to special group

section

SCREENING METHODS FOR CERVICAL CANCER

For the Kenyan screening programme, this guideline recommends the following:

1. HPV testing is recommended as the primary screening method for women above 30 years of age.

2. Where HPV testing is not yet available, or loss-to-follow-up is a risk, then Visual Inspection with Acetic acid (VIA) or Visual Inspection with Acetic acid and Visual Inspection with Lugol’s iodine (VIA/VILI) is recommended as the primary screening method

3. Pap smear is recommended as a primary screening method in the following situations:

a. For women not eligible for VIA or VIA/VILI because their squamo-columnar junction (SCJ) is not visible, and HPV screening not accessible

b. As a primary test in women under 30 years of age

c. As a co-test with HPV in HIV positive women where the

resources are available

PLANNING FOR CERVICAL CANCER SCREENING

This decision-mak- ing flowchart has been developed to assist administrators/ managers at County

& facility level to choose an appro- priate screening strategy

SOURCE: Adapted from WHO Guide- line for Screening and Treatment of

Precancerous Lesions for Cervical Cancer Prevention 2073

CLINICIAN ALGORITHM FOR CHOICE OF SCREENING TEST

How old is the client?

<30 years 30 – 49 years

Cytology or VIA

or VIA/VILI

Is HPV test available?

Yes No

See HPV Algorithm

See VIA and VIA/VILI

algorithim

Molecular HPV testing methods are based on the detection of DNA from high-risk HPV types in vaginal and/or cervical samples. Since persistent HPV infection is the cause of nearly all cases of cervical cancer, a positive test result indicates that she may have an existing lesion or may be at risk for future pre-cancer and cancer.

HPV TEST

HPV testing algorithm

Source: WHO Guideline for Screening and Treatment of Precancerous Lesions for Cervical

Cancer Prevention 2073

Who should be tested?

HPV testing should be reserved for women over the age of 30 years. Testing women younger than 30 years old is not advised because many young women are infected with HPV most of which will be spontaneously resolved by age 30 years. This will therefore lead to a high number of false positive results resulting in unnecessary procedures which overwhelm the health system, with little impact on the inci- dence.

How to screen

HPV sample collection can be done by the client (self-collected) or by a health pro- vider according to the manufacturers’ instructions.

A health-care provider can collect a sample of cells with or without a speculum, by inserting the provided swab or other appropriate device deep into the vagina, and then placing it in a container with a preservative solution.

For self-collected samples, the woman can be given the sample-collection kit with instructions for use. This strategy offers greater convenience to women and can be implemented at substantially lower cost to the healthcare system.

Follow-up after Results:

• For woman who is High-risk HPV (HR-HPV) negative, re-testing

should be done after 5 years (after 2 years for HIV positive).

• If the test is HR-HPV positive, colposcopy, VIA or VIA/VILI and further

management is advised (See algorithm for HPV Test)

VISUAL INSPECTION METHODS

VIA/VILI algorithm

Source: WHO Guideline for Screening and Treatment of Precancerous Lesions for Cervical

Cancer Prevention 2073

Visual Inspection With Acetic Acid (VIA)

Description

Visual inspection with acetic acid (VIA) is a method for detecting early cell changes that

are visible when using a speculum to inspect the cervix with the naked eye after apply-

ing dilute (3-5%) acetic acid to it. It requires training and supervision of primary care

providers, as well as ongoing quality control and quality assurance. It is quite inexpen-

sive, utilizes locally sourced supplies (vinegar and cotton), and does not require labora-

tory services. It can be performed by trained providers, with adequate visual acuity, at

any level of the health system.

VIA is appropriate to use in women whose squamocolumnar junction (SCJ) is visible, typically in those younger than 5O. This is because the SCJ gradually recedes into the endocervical canal when menopause occurs, making it possible to miss lesions when relying on visual inspection.

How to screen?

The provider performs a speculum examination, identifying the SCJ and carefully in-

specting the cervix for visual signs suspicious for cancer or pre-cancer. A 3-5% acetic

acid solution is liberally applied to the cervix with a large cotton swab. After removing

the cotton swab, the provider waits for at least one minute. Acetowhite changes on the

cervix indicate likely cervical pre-cancer or cancer. If these changes are seen in the trans-

formation zone and have well-defined borders, they are considered a positive result. If

no persistent acetowhite changes are noted, a negative result is reported. The one-min-

ute waiting time allows for any areas that became faintly white due to inflammation or

physiological cell changes (metaplasia) to recede.

Follow-up after Results:

• For woman who is VIA negative, re-testing should be done 5 years. If HIV

positive, test every year.

• If the test is VIA positive, treat as appropriate (See algorithm)

VIA testing can detect both early changes and those representing more advanced pre-cancer.

A single visit approach using the ‘screen & treat’ strategy is recommended to avoid loss to follow up.

If the cervix shows any unusual signs or the provider suspects cancer, the patient can be referred for further diagnostic tests (colposcopy and/or biopsy).

Visual Inspection With Acetic Acid (VIA) And Visual

Inspection With Lugol’s Iodine (VILI) Testing

Description

Visual inspection with Lugol’s iodine (VILI) – also

known as Schiller’s test, uses Lugol’s iodine instead

of acetic acid. VILI should only be done after VIA in

a co-test strategy as it improves the specificity of

the testing. Many guidelines now recommend the

use of VIA alone as there is little difference in the

sensitivity and specificity when combined. Howev-

er, this guideline recommends the continued use

of both VIA and VILI as a co-test as the shift may

affect quality of results.

How to screen?

VILI involves looking at the cervix after swabbing it with Lugol’s iodine. Squamous epi-

thelium contains glycogen, whereas precancerous lesions and invasive cancer contain

little or no glycogen. Iodine is glycophilic and is taken up by the squamous epitheli-

um, staining it mahogany brown or black. Columnar epithelium does not change color,

as it has no glycogen. Immature metaplasia and inflammatory lesions are at most only

partially glycogenated and, when stained, appear as scattered, ill-defined uptake areas.

Precancerous lesions and invasive cancer do not take up iodine (as they lack glycogen)

and appear as well-defined, thick, mustard or saffron yellow areas.

Results interpretations

• VIA/VILI test is interpreted as positive if either of the tests is positive

• If the test is VIA/VILI positive, treat as appropriate (See VIA/VILI

algorithm)

• For woman who is VIA and VILI negative, retest after 5 years. If HIV

positive, retest every year.

Exclusion Criteria for VIA/VILI

• Women who are very ill

• Women who are in 2nd & 3rd trimester of pregnancy

• Women less than 6 weeks after delivery

• Women with cauliflower-like growth or ulcer; fungating mass

• Women with previous history of treatment of cancerous lesions

• Women with known allergy to acetic acid

• Women with a history of total hysterectomy

CYTOLOGY-BASED SCREENING

Cytology algorithm

Cytology

Normal

ASCUS or greater

Rescreen every

3-5 years

Colposcopy

Colposcopy positive

Biopsy No Biopsy

Colposcopy negative

Rescreen within

3 years

Suspicious for cancer

Refer to appropriate diagnosis and treatment

Eligible for cryotherapy, treat with cryotherapy

Not eligible for cryotherapy, treat with LEEP

If CIN2+, treat with cryotherapy or LEEP

Post-treatment follow-up at

1 year

SOURCE: Adapted from WHO Guideline for Screening and Treatment of Precancerous Lesions for Cervical Cancer

If CIN2 or less, rescreen within 3 years

Prevention 2073

Cytology-based screening involves taking a sample of cells from the entire transforma- tion zone. The cells are either fixed on a slide at the facility (Pap smear) or placed in a transport medium (liquid-based cytology- LBC) and then sent to the laboratory for microscopic examination. Well-implemented cytology programmes have successfully prevented cervical cancer in developed countries; however, they require highly skilled personnel and logistics which have been challenging in low-resource settings.

How to screen

Collection of a cytology sample requires a speculum and adequate lighting to visualize

the entire surface of the cervix. The provider takes specimens from the face of the cervix

and the endocervix using a spatula or brush and transfers the specimen to a slide (Pap

smear) or a preservative solution (LBC). The sample must be appropriately labelled and

transported to the laboratory, where expert cytotechnologists are needed to process

and interpret it. If abnormal cells are seen on microscopic examination, the extent of

their abnormality is classified using the Bethesda System.

SCREEENING AT VARIOUS HEALTHCARE LEVELS

Sample processing: Accredited lab by

HEALTHCARE LEVEL VIA HPV PAP SMEAR
& PERSONNEL
Level 1 A self-collected sample collection
Level 2 + A sample collection
Level 3 + A sample collection
Level 4 + A sample collection +
Level s + A sample collection +
Personnel required Trained nurse, Sample collection: Client, Nurse, Clinical Trained nurse,
clinical officers, officer, Medical officer clinical officers,
medical medical officers
officers, MOH gynecologist
gynecologist

KEY POINTS

• Screening all women in the target age group, followed by treatment of detected precancerous lesions can prevent the majority of cervical cancers.

• Decisions on which screening and treatment approach to use in a particular county or health-care facility are based on various factors, including, potential for loss to follow-up, cost, and availability of the necessary equipment and human resources.

• Every woman in the target age group (25-49 years) should have a cervical cancer screening test performed at least once when most benefit can be achieved.

• HPV testing is recommended as the primary screening method

• Where HPV testing is not yet available, or loss-to-follow-up is a risk, then Visual Inspection with Acetic acid (VIA) or Visual Inspection with Acetic acid and Visual Inspection with Lugol’s iodine (VIA/VILI) is recommended as the primary screening method

• A “screen-and-treat” approach is recommended

• Any suspected cancer case after screening should immediately be

referred for diagnosis and treatment of cancer.

RECOMMENDATIONS FOR SPECIAL POPULATIONS:

Women who are HIV positive or immunosuppressed for any other reasons.

• Begin cervical cancer screening at the point of diagnosis or at 25

years, whichever comes earlier

• Screening should continue throughout their lifetime

• Screening frequency should be yearly if using VIA or VIA/VILI, every

2 years if using HPV testing and yearly if using cytology.

Women who are pregnant

• Screening can be done during the 1st trimester

• Treatment for precancerous lesions should NOT be performed

during pregnancy.

• For suspicious lesions in pregnancy, a biopsy can be done at any

trimester by an obstetrician/gynecologist.

Post-partum women

• Cervical cancer screening can commence 6 weeks after delivery.

Women who have had total abdominal hysterectomies (with no history of �CIN2)

• Screening should be discontinued in women who have received a total hysterectomy for benign causes with no history of gynecological malignancy.

• Women who have received a subtotal hysterectomy (with an intact

cervix) should continue to receive routine screening.

NOTE

Women who have received HPV vaccination

• Women who have been vaccinated should receive routine screening

as per the national guidelines above.

Women 50-64 years:

• Screening should be done at 5-year intervals on an individualized

basis using HPV and cytology methods.

Women 65years and above

• Screening is not recommended

MANAGEMENT OF CERVICAL PRE-CANCEROUS LESIONS

Treatment of precancerous lesions is a key consideration for the success of any cervical cancer prevention and screening program. A ‘screen and treat’ strategy is usually com- posed of two phases; the screening test followed by treatment of cervical intraepithelial lesions. Most screen-and- treat strategies to prevent cervical cancer will usually involve treatment with cryotherapy, or LEEP when a patient is not eligible for cryotherapy. Oth- er treatment methods include cold knife conization and thermo-coagulation.

Points to note:

• Before treatment, ALL women who have screened positive with any

test, especially HPV testing, should undergo VIA to determine their

eligibility for treatment (i.e. cryotherapy versus LEEP) and to rule out

large lesions of cervical cancer.

Women who are VIA positive will then be treated while those who are

VIA negative will not be treated.

• Women presenting for treatment of pre-cancerous lesions should be

offered HIV counseling and testing.

• ALL women with suspected cancer should be referred immediately for

colposcopy with biopsy and further management by specialists

• All women who have had treatment for precancerous lesions should

receive post-treatment follow-up screening at one year after the

treatment.

A) CRYOTHERAPY

This is an ablative form of treatment for precancerous lesions of the cervix which freezes cells using a cryoprobe with a tip made of highly conductive metal (usually silver and copper), that makes direct surface contact with the ectocervical lesion. Carbon dioxide or Nitrous oxide are usually the coolants of choice. Cells reduced to -20°C for one or more minutes will undergo cryonecrosis.

Cryotherapy is highly effective with cure rates of 85-90% for lesions occupying less than

75% of the cervix; however, for larger lesions the cure rate is reduced. When cryotherapy

is indicated, only healthcare providers (including nurses or midwives) trained in cryo-

therapy should perform the procedure.

Exclusion Criteria for Cryotherapy Eligibility Criteria for Cryotherapy
• Women with a history of prior treatment for precancer

• Women with suspected cancer

• Women with known pregnancy and until 6

weeks postpartum

• Women with a lesion occupying more than75% of the surface area of the cervix

• The cryotherapy probe does not cover the lesion or leaves space of more than 2mm

• The lesion extends more than 2mm into cervical canal or onto the vaginal wall

• Women with a positive test and an entirely visible lesion on the ectocervix, not extending to the vaginal wall or into the endocervix

• The lesion can be adequately covered with a 2.5 cm cryotherapy probe

• Women with no evidence of pelvic inflammatory diseases or cervicitis and with no polyps

• Women who are not pregnant

• Women who have given consent for treatment

Cryotherapy Procedure:

1. Explain why the treatment is recommended and describe the procedure including side effects and reassure her.

2. Check that instruments and supplies are available and arrange on high level disinfected tray. Check that cryotherapy instrument is ready to use, that gas (C02) is turned on at the cylinder and the pressure reads at least

40-70 kg/cm2. Set timer to 0. Insert high-level disinfected cryotip into protective sleeve. Remove protective cover from end of probe.

3. Check that the woman has emptied her bladder if more than 30 minutes since VIA test. Help her onto examining table and once in lithotomy position, drape her.

4. Wash hands thoroughly with soap and water and dry. Wear a pair of examination or high-level disinfected surgical gloves on both hands.

5. Insert speculum and adjust the speculum so that the entire cervix can be seen.Fix the speculum blades in the open position so that the speculum will remain in place with the cervix in view.

6. Move the light source so that you can see the cervix clearly. Use a clean cotton swab to remove any discharge, blood or mucus from the cervix. Dispose of swab.

7. Identify the cervical os, SCJ and site and size of the lesion. Apply dilute acetic acid with a clean swab so that lesion can be seen clearly.

8. Point probe at ceiling. Press freeze button for 1 second and then defrost button for 1 second.

9. Screw cryotip with sleeve onto end of probe.

10. Apply the cryotip to the cervix ensuring that the nipple is placed squarely onto

the os. Check to be sure the cryotip is not touching the vaginal walls.

11. Set timer for 3 minutes. Press freeze button. Apply pressure to the cervix as the gas begins to flow to the cryoprobe. Watch as the ice ball

develops. Use “freeze-clear-freeze technique,” (double-freeze) and freeze cervix

for 3 minutes. Adequate freezing has been achieved when the margin of the

ice ball extends 4-5 mm past the outer edge of the cryotip. After 3 minutes, al

low time for adequate thawing before removing the probe from the cervix.

12. After thawing, repeat the procedure. Inspect the cervix carefully to ensure that

a hard, white completely frozen ice ball is present.

13. Close master cylinder valve.

14. Inspect cervix for bleeding. If there is bleeding, apply pressure to area using

clean cotton swab.

15. Remove the speculum and place it in 0.5% chlorine solution for 10 minutes for

decontamination.

Post-cryotherapy Tasks

1. Light source, cryogun, regulator and gas cylinder should be wiped with 0.5%

chlorine solution or 60-90% ethyl, isopropyl alcohol.

2. Wash hands thoroughly with soap and water and dry with clean, dry cloth or air dry.

3. Women may be provided with a supply of sanitary pads to prevent the secretions

staining their clothes

4. Advise the woman about post-treatment care, warning signs and follow up

instructions, as follows:

• Women may experience some mild cramps and a clear or lightly

blood-stained watery discharge for up to 4-6 weeks after treatment.

• They should be advised not to use a vaginal douche or tampons or to

have sexual intercourse for one month after treatment. If it is not

possible to abstain, condoms may be used from 2 weeks post treatment.

Appointments should be made for a follow-up visit one year after treatment.

Cervical lesions persist or recur in about 5-10% of HIV-negative cryotherapy clients. Re-

peat VIA one year after cryotherapy to assess the persistence or recurrence of lesions.

Retreatment is carried out if lesions persist but VIA negative women will require annual

screening for 5 years after which they may be referred back to the screening program.

B) LOOP ELECTROSURGICAL EXCISION PROCEDURE (LEEP)

LEEP, also referred to as Large Loop Excision of the Transformation Zone (LLETZ), is an excisional method of treatment of precancerous lesions. It is the treatment of choice for cervical lesions that do not meet the eligibility criteria for cryotherapy, or when a histo- logical specimen is needed.

It involves removal of abnormal areas of the cervix by applying a low voltage high frequency alternating current to a thin wire loop electrode and slowly passing it through the cervix. The loop cuts and coagulates at the same time. LEEP is successful in eradicating pre-cancer in over 90% of cases. However, unlike cryotherapy, LEEP requires more highly skilled personnel, electricity and local anesthesia including colposcopy. Clients requiring LEEP should be referred to appropriately trained personnel.

C) COLD KNIFE CONISATION

Cold knife conisation is the removal of a cone-shaped area from the cervix including the ectocervix and endocervix. It is usually done under general or regional anesthesia by gynaecologists and gynaeoncologists trained in the procedure and able to recognize and manage its complications, in an equipped surgical facility. Because of the possible side effects, cold knife conisation should be reserved for cases that cannot be managed with cryotherapy or LEEP excision. The extent of conisation depends on the size of the lesion; the woman’s desire to have more children, and the likelihood of finding invasive cancer. The tissue removed is then subjected to histopathology.

D) THERMOCOAGULATION

The use of thermocoagulation for the treatment of CIN is as effective as other methods, such as cryotherapy and LEEP, with the advantage of being rapid and is also associat- ed to a low occurrence of side effects [Dolman et al, 2017]. It is a low-cost and simple treatment method comparable to cryotherapy. While cryotherapy is a highly effective intervention with a good cure rate, the low availability of refrigerant gas makes its use challenging in LMIC [Elit et al, 2011]. In this regard, thermocoagulation represents an attractive alternative for the treatment of cervical precancerous lesions especially where electricity is available.

This method involves destruction of precancerous lesions in the transformation zone with temperatures between 100 – 120°C. It is a 20 second treatment procedure, followed by 20 seconds of waiting, followed by another 20 second treatment procedure. It re- quires electricity and overall takes about 1 minute to perform. Thermocoagulation is currently under review by World Health Organization as an alternative to cryotherapy where electricity is available.

POST-TREATMENT SCREENING

Screening for cervical cancer after treatment for pre-cancerous lesions focuses on a distinct sub-set of women and thus requires unique considerations as compared with primary screening.

A study on post treatment testing in HIV+ women done in Western Kenya found that HPV test had the highest sensitivity and specificity. The second-best ap- proach was found to be a co-test of VIA and pap smear (Orang’o, 2017). Where HPV test and pap smear are not available, this guideline recommends perform- ing VIA and referring women for pap smear.

HIV status

Negative

HPV or Cytology

Positive
HPV (prefered) or VIA/Cytology co-test

REFERENCES

Alliance for Cervical Cancer Prevention. Planning and Implementing Cervical Cancer Prevention and Control Programs: a Manager’s Manual. ACCP, 2004.

Berraho, M., Amarti-Riffi, A., El-Mzibri, M., Bezad, R., Benjaafar, N., Benideer, A., . . . Nejjari, C. (2017). HPV and cofactors for invasive cervical cancer in Morocco: A multicentre case-control study. BMC Cancer, 17(1). doi:10.1186/s12885-017-3425-z

Carozzi F, Confortini M, Dalla Palma P, et al: Use of p16-INK4A overexpression to increase the specificity of human papillomavirus testing: A nested substudy of the NTCC randomised controlled trial. Lancet Oncol 9:937-945, 2008

Carozzi F, Gillio-Tos A, Confortini M, et al: Risk of high-grade cervical intraepithelial neoplasia during follow-up in HPV-positive women according to baseline p16-INK4A results: A prospective analysis of a nested substudy of the NTCC randomised controlled trial. Lancet Oncol 14:168-176, 2013 DOI 10.1186/s12905-016-0355

Dolman L, Suvaget C, Muwonge R, et al. Meta-analysis of the efficacy of cold coagulation as a treatment method for cervical intraepithelial neoplasia: a systematic review. BJOG. 2014;121:929-42.

Elit L, Jimenez w, McAlpine J, et al. Cervical cancer prevention in low-resource settings. J Obstet Gynaecol can. 2011;33(3):272-9.

GLOBOCAN 2018. Estimated cancer incidence, mortality and prevalence worldwide in 2018.

Goldie SJ, Kuhn L, Denny L, Pollack A, Wright TC. Policy analysis of cervical cancer screening strategies in low-resource settings: clinical benefits and cost-effectiveness. JAMA. 2001; 285 (24):3107-15.

IAEA 2016; International Atomic Energy Agency (IAEA) imPACT study

Report – Kenya, 2016 10. Ikenberg H, Bergeron C, Schmidt D, et

al: Screening for cervical cancer precursors with p16/Ki-67 dual-stained

cytology: Results of the PALMS study. J Natl Cancer Inst 105:1550-1557, 2013

Jeronimo J, Castle PE, Temin S, et al: Secondary prevention of cervical cancer: ASCO resource-stratifed clinical practice guideline. J Glob Oncoldoi: 10.1200/JGO.2016.006577

KNBS, 2015 The Kenya STEPwise survey for non-communicable diseases risk factors 2015 report. 2015[cited 2018 Oct 2]. Available on https://www.knbs.or.ke/kenya-stepwise-survey-for-non-communica- ble-diseases-risk-factors-2015-report/

Mati JKG, Mbugua S, Ndavi M. Control of cancer of the cervix: Feasibility of screening for premalignant lesions in an African environment. In: Virus Associated Cancers in Africa. International Agency for Research on Cancer 1984; 63: 451-463.

Ministry of Health (MOH). Mortality Trends in Kenya 2012-2016: Cause of death, trends, and data quality. 2018

Orang’O, E. O., Liu, T., Christoffersen-Deb, A., Itsura, P., Oguda, J., Washington, S., . . . Rositch, A. F. (2017). Use of visual inspection with acetic acid, Pap smear, or high-risk human papillomavirus testing in women living with HIV/AIDS for posttreatment cervical cancer screening. Aids, 31(2), 233-240. doi:10.1097/qad.0000000000001327

Qiao YL, Jeronimo J, Zhao FH, et al: Lower cost strategies for triage of human papillomavirus DNA-positive women. Int J Cancer

134:2891-2901, 2014,

Sankaranarayanan R, Esmy PO, Rajkumar R, Muwonge R,

Swaminathan R, Shanthakumari S, Fayette JM, Cherian J Effect of visual

screening on cervical cancer incidence and mortality in Tamil Nadu,

India: a cluster-randomised trial. Lancet. 2007; 370(9585):398.

Saslow D, Solomon D, Lawson HW, et al: American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer. CA Cancer J Clin

62:147-172, 2012, Murphy J, Kennedy EB, Dunn S, et al: Cervical screening: A guideline for clinical practice in Ontario. J ObstetGynaecol Can 34:453-458, 2012

Schiffman M, Wentzensen N, Wacholder S, Kinney W, Gage JC, Castle PE. Human papillomavirus testing in the prevention of cervical cancer. J Natl Cancer Inst 2011; 103:368-83.

Silkensen SL, Schiffman M, Sahasrabuddhe V, Flanigan JS.Is It Time to Move Beyond Visual Inspection With Acetic Acid for Cervical

Cancer Screening?Glob Health SciPract. 2018 Jun 29;6 (2):242-246. doi:

10.9745/GHSP-D-18-00206. Print 2018 Jun 27.

Valdez M, Jeronimo J, Bansil P, et al: Effectiveness of novel, lower cost

molecular human papillomavirus-based tests for cervical cancer

screening in rural china. Int J Cancer 138:1453-1461, 2016

Viviano, M., Kenfack,B., Catarino, R., Tincho, E., Temogne, L., Benski, A., Tebeu, P., Meyer-Hamme, U., Vassilakos, P and Patrick Petignat. Feasibility of thermocoagulation in a screen-and-treat approach for the treatment of cervical precancerous lesions in sub-Saharan Africa. BMC Women’s Health (2017) 17:2

Whitlock EP, Vesco KK, Eder M, Lin JS, Senger CA, Burda BU.

Liquid-based cytology and human papillomavirus testing to screen for

cervical cancer: a systematic review for the U.S. Preventive Services

Task Force. Ann Intern Med 2011; 155:687-97.

WHO Comprehensive cervical cancer control: a guide to essential practice, 2014

WHO Guidelines for Screening and Treatment of Precancerous Lesions for Cervical Cancer Prevention. (2013). Retrieved from http://www. who.int/reproductivehealth/publications/cancers/screening_and_ treatment_of_precancerous_lesions/en/

WHO guidelines for treatment of cervical intraepithelial neoplasia 2-3 and adenocarcinoma in situ: cryotherapy, large loop excision of the transformation zone, and cold knife conization.* Available online: www.who.int/reproductivehealth/publications/cancers/treatment_ CIN_2-3/en/index.html

WHO. Preparing for the introduction of HPV vaccines: policy and programme guidance for countries, Geneva, 2006.

WHO/PAHO guide: Monitoring national cervical cancer prevention and control programmes: quality control and quality assurance for visual inspection with acetic acid (VIA)-based programmes (2013).3

Zhao FH, Jeronimo J, Qiao YL, et al: An evaluation of novel, lower-cost molecular screening tests for human papillomavirus in rural China. Cancer Prev Res (Phila) 6:938-948, 2013

 

We've got the answer