doi:10.1111/jog.14168 J. Obstet. Gynaecol. Res. Vol. 46, No.

2: 201–214, February 2020

Screening and management of preinvasive lesions of the

cervix: Good clinical practice recommendations from the
Federation of Obstetrics and Gynaecologic Societies of India
(FOGSI)

1 1 2 3 4
Neerja Bhatla , Seema Singhal , Usha Saraiya , Shikha Srivastava , Sarita Bhalerao , Saritha
5 6 7 8
Shamsunder , Niranjan Chavan , Partha Basu , and CN Purandare , (on behalf of FOGSI Expert
group)
1
All India Institute of Medical Sciences, 5Vardhmaan Mahaveer Medical College & Safdarjung Hospital, New Delhi, 2Breach
Candy, Saifee, Elizabeth & Cumballa Hill Hospitals, 4Reliance HNH, Saifee and Bhatia Hospitals, 6LTMMC & LTMGH, Sion,
8
Saifee Hospital, Mumbai, 3Population Services International (PSI), Delhi, India and 7Early Detection and Prevention Section
(EDP)/Screening Group (SCR) International Agency for Research on Cancer, World Health Organization, Lyon, France

Abstract
In India, there are marked variations in resources for cervical cancer screening. For the first time, resource-stratified
screening guidelines have been developed that will be suitable for low middle-income countries with similar diversities.
The current article describes the process and outcomes of these resource stratified guidelines for screening and treatment
of preinvasive lesions of cervix. Evidence from literature was collated and various guidelines were reviewed by an
expert panel. Based on the level of evidence, guidelines were developed for screening by human papillomavirus (HPV)
testing, cytology and visual inspection after appli-cation of acetic acid (VIA), and management of screen positive
lesions in different resource settings. Expert opinion was used for certain country-specific situations. The healthcare
system was stratified into two resource settings – good or limited. The mode of screening and treatment for each was
described. HPV test-ing is the preferred method for cervical cancer screening. VIA by trained providers is especially
suitable for low resource settings until an affordable HPV test becomes available. Healthcare providers can choose the
most appropriate screening and treatment modality. A single visit approach is encouraged and treatment may be offered
based on colposcopy diagnosis (‘see and treat’) or even on the basis of HPV test or VIA results (‘screen and treat’), if
compliance cannot be ensured. The Federation of Obsterician and Gyn-aecologists of India Good Clinical Practice
Recommendations (FOGSI) GCPR are appropriately designed for countries with varied resource situations to ensure an
acceptable cervical cancer prevention strategy.

Key words: cervical cancer screening, good clinical practice, prevention, recommendations, resource-based, single
visit approach.

Received: June 14 2019.

Accepted: November 13 2019.
Correspondence: Dr Neerja Bhatla, Department of Obstetrics & Gynaecology, Room no 3081 Teaching Block, All India Institute of
Medical Sciences, New Delhi, India. Email: neerja.bhatla07@gmail.com
Members of FOGSI Expert Group: Agarwal P, Arora M, Bhatla N, Basu P, Bhalerao S, Batra S, Banerjee D, Chavan N, Dhorepatil B,
Gupta B, Gandhi G, Gupta K, Ganesh P, Joshi S, Kriplani A, Khanna R, Kumar S, Maheshwari A, Meena J, Nayak B, Natarajan J,
Pai R, Pathak R, Prabhu RB, Peedicayil A, Rajaram S, Sekhon R, Shamsunder S, Srivastava S, Singh U, Singhal S, Saraiya U, Zutshi V.

© 2019 Japan Society of Obstetrics and Gynecology 201

N. Bhatla et al.
Introduction
Cervical cancer is a major public health problem, being the
1
second most common cancer among Indian women. India
contributes to one quarter of the global burden with 96 922
1
incident cases and 60 078 deaths in 2018. The age-
standardized incidence and mortal-ity rates in India (ASR)
are 14.7/100 000 and 9.2/100 000 women, respectively.
1 with reference to study designs and participants,
There are regional variations in ASR, from 24.3/100 000 in
2 were evaluated for quality, and strength was assigned to
Aizawl to 5.6/100 000 in Dibrugarh district. The 5-year
relative survival rate for cancer cervix in India continues to
be low, approximately 46% (range 34–60%), predomi-
3 guidelines appropriate for resource-constrained situations
nantly because of late detection.
In developed countries, establishment of national
screening programs with population-based invitation of
eligible women and a recall system for screen posi-tives
4 synopsis was prepared and circulated in the group.
resulted in prevention of almost 70% of cervical cancer.
India is a land of diversity with enormous variations in
sociocultural practices and healthcare infrastructure.
5 various algorithms was discussed and subse-quent
Shortage of trained manpower and infrastructure has
limited the establishment of effec-tive, standardized,
cytology-based screening program, which is currently used
only for opportunistic screen-ing. Ministry of Health and
Family Welfare (MoHFW), Govt. of India has formulated
operational framework for screening of cervical cancer
based on visual inspection of cervix after application of
6
acetic acid (VIA) in 2016. However, in urban settings the
option of high-risk human papillomavirus (HPV) test-ing is
now available in many cities.
In the absence of national guidelines, healthcare
providers have been following different international
recommendations, which were limited in their appli-
cability to the Indian setting. Therefore, a need was felt for
an expert group to develop evidence-based
recommendations that are suitable for diverse resource
situations. The current article describes the process and
outcomes of resource stratified guidelines for screening and
treatment of preinvasive lesions of cervix. Though
developed in India they are also suit-able for low and
middle income countries (LMICs) with similar diversities.
Methods
A panel of gynecologists, gynecologic oncologists and
public health experts with experience in cervical cancer
prevention from all regions of the country was consti-tuted.
Relevant questions were formulated and
202
distributed among the experts who reviewed the liter-ature
intervention, comparisons, outcomes (PICOS). Studies
7
each practice recommendation. Previously publi-shed
guidelines by major international organizations as well as
by the World Health Organiza-tion 2014, Government of
India 2016 and the American
Society of Clinical Oncology (ASCO) 2016 were ana-lyzed
6,8,9
for their applicability in the Indian context. A
Thereafter, in a face-to-face meeting, the document with
comments were circulated until unanimous agreement was
reached. The draft recommendations were posted online on
the Federation of Obsterician
and Gynaecologists of India (FOGSI) website for pub-lic
10,11
comments. The final consensus document was
presented and was then approved at the FOGSI Man-aging
Committee Meeting in January 2018.
Results and Discussion
Resource stratification
Initially the expert panel planned to stratify the healthcare
system into four groups in accordance with ASCO resource
9
stratified clinical practice guidelines, but later for easy
understanding and usability, resource stratification was
simplified into two strata as good and limited resource
settings. Settings with-out lack of facilities including
trained doctors, labora-tories and equipment are considered
good resource settings. Settings that lack any of these are
termed limited resource settings.
The suggested modalities for screening and triage in each
setting are shown in Table 1. Considering the var-iations in
cervical cancer screening practices, expert group agreed to
suggest preferred and acceptable modalities for follow-up
and treatment. Single visit approach (SVA), in which
screening and treatment can be completed at the same
sitting, was identified as the preferred modality for all
resource settings, especially when patient is likely to be lost
to follow-up.
Choosing an appropriate screening modality
The three main modalities of screening in use are HPV
testing, cytology and visual inspection with
© 2019 Japan Society of Obstetrics and Gynecology
 Cervical Cancer Screening & Management of CIN

Table 1 Resource-based strategies for cervical cancer screening and management of CIN
Good Resource settings Limited Resource settings
Screening modality HPV testing VIA (visual inspection of cervix with acetic
•Primary HPV testing acid)
•Co-testing (HPV and cytology) Affordable HPV test (if available),
Cytology including self-sampling, can be used
VIA
Triage tool For ASCUS cytology: Colposcopy if available
‡
High-risk HPV test Biopsy
For HPV test:
†
Cytology newer modalities
Or HPV Genotyping for types 16/18
‡
Or colposcopy and biopsy
‡
Or VIA and biopsy
Management options All CIN2 and CIN3 can be treated by LEEP. All grades of CIN fulfilling the criteria for
§
for histopathology CKC can be performed for AIS or if early ablation should be treated by cryotherapy
proved CIN invasive cancer is suspected. or thermal ablation.
CIN1 can be followed up and be treated All grades of CIN not fulfilling the criteria
if it progresses or persists after should be treated by LEEP.
2 years. CKC can be performed for AIS or if early
Cryotherapy or thermal ablation can be invasive cancer is suspected.
performed for all grades of CIN as an
alternative to LEEP, provided the
§
criteria for ablation are fulfilled.
Approaches to reduce the ‘See-and-Treat’ strategy is preferred to treat ‘See-and-Treat’ strategy should be followed,
number of visits women with colposcopically suspected if colposcopy facilities are available.
high-grade lesions. Treatment with If colposcopy is not available, VIA or HPV
LLETZ/LEEP or ablation depending on positive women may be offered imme-
suitability of lesion for ablative treatment. diate treatment (‘Screen-and-Treat’). All
Histopathology report should be reviewed cases should initially be assessed for
at follow-up. suitability of ablative treatment
(cryotherapy or thermal ablation).
Eligibility of HPV positive women to be
assessed after applying 5% acetic acid
(VIA). A punch biopsy should be
obtained prior to ablative treatment and
the report reviewed at follow-up.
LLETZ/LEEP, large loop excision of transformation zone/loop electrosurgical excision procedure; CKC, cold knife colonization; CIN, cer-vical intra
epithelial lesion.; †Newer modalities (p16, Ki 67 testing, mRNA testing, E6, E7 protein testing).; ‡Biopsy from any abnormal area(s). and §Criteria for
ablation: (i) Lesion should be entirely visible and not occupy more than two quadrants of cervix, (ii) The entire lesion should be located on ecto cervix
without any vaginal or endo-cervical extension, (iii) Lesion should be entirely covered by largest cryotherapy probe available, (iv) No suspicion of
invasive disease, (v) Contraindicated in cases with post coital or postmenopausal bleed-ing, obvious cervical growth, irregular surface or bleeds on
touch.

acetic acid (VIA). Figure 1 describes the algorithm to
choose the most appropriate screening modality. Vali-dated
primary HPV screening, the most effective method, was
recommended for screening in good resource settings.
However, the centers with an established cytology program
with good quality con-trol may continue with cytology. In
limited resource settings one may screen with VIA.
There is ample evidence that HPV testing is the most
sensitive modality, suitable for screening in all resource
12,13
settings. In an Indian study, even a single round of
HPV testing was shown to significantly reduce the
14
incidence of cervical cancer. However, it
is expensive and not widely available. It is rec-ommended
for women aged over 30 years using vali-dated tests.
Validated tests are those that have demonstrated efficacy in
randomized controlled trials or have shown test accuracy
comparable to a vali-dated test. The results of such tests are
generally reported as detected/not detected for a pool of 13
or 14 high-risk HPV genotypes; some also report indi-
vidual genotypes for the most oncogenic types (HPV
16/18). Example of validated tests are Hybrid Cap-ture 2,
careHPV, Cobas, Xpert, Cervista, APTIMA etc. HPV tests
based on routine polymerase chain reaction (PCR)
detecting only a few genotypes should not be

© 2019 Japan Society of Obstetrics and Gynecology 203

N. Bhatla et al.
Figure 1 : How to choose the most appropriate screening modality?
advised as they are of high analytical sensitivity and a
positive result has little clinical relevance. Affording
centers/individuals, can consider co-testing with both
cytology and HPV test or switch over to primary HPV
15
testing. The incremental benefit of co-testing over HPV
test alone is, however, small.
Cytology facilities are available in most cities and
tertiary hospitals, but cytology has an inherent fal-
lacy of low sensitivity (60–70%), which therefore
13,14,16
necessitates frequent rounds of testing. Its
major advantage lies in its high specificity (93.5%). Liquid
based cytology (LBC) does not improve the sensitivity of
conventional cytology, though it does decrease the rates of
unsatisfactory smears and also allows the same sample to
17
be used for HPV test-ing. Centers with established
cytology programs should assess quality indicators
including diagnostic accuracy, training, coverage, etc. If
these are found adequate they may continue with the same.
If not, they should consider switching to primary HPV
screening or even substitute or supplement with VIA. VIA
has sensitivity comparable to cytology but poorer
16
specificity. It can be used in all resource settings by all
levels of healthcare providers. How-ever, a larger number
of women will require further triage by colposcopy because
of its low specificity
204
16
and high false positivity. Currently it is the only test that
can be used in low resource settings with considerable
accuracy and safety but in future, the availability of
affordable HPV testing may change this paradigm.
Whenever possible, colposcopy should be used to obtain
a guided biopsy; if not available, biopsy can be guided by
VIA too. It is advisable to link screening with treatment by
minimizing the number of visits to the clinics, especially
when there is a risk of loss to follow up. When screening
and treatment can be com-pleted in the same sitting, the
strategy is known as the single visit approach (SVA).
Biopsy can be reviewed post-hoc for adequacy of treatment
and to rule out invasive cancer. Women with high-grade
abnormalities on cytology (ASC-H or HSIL) and an
abnormal colposcopy can be treated without waiting for
18
histopathological verification. Such an approach is known
as ‘See-and-Treat’. It is also applicable to women who are
HPV or VIA positive and are referred for colposcopy. In
low resource settings where colposcopy facilities are not
available, treat-ment by cryotherapy or thermal ablation
based on abnormal HPV test or VIA is also admissible and
is known as a ‘Screen-and-Treat’ strategy. This will ensure
that women with cervical intraepithelial
© 2019 Japan Society of Obstetrics and Gynecology
 Cervical Cancer Screening & Management of CIN

neoplasia (CIN) lesions that fulfill the criteria do not remain
untreated. With this there is an acceptable risk of over-
treatment and the referral is minimized to only those with
large, suspicious or endocervical lesions.
Age of screening
To be most cost-effective, the age of starting and stop-ping
screening is determined by the age-specific can-cer burden.
In India, the burden of cervical cancer under the age of 30
years is very low and it is negligi-ble under the age of 25
19
years. According to Globocan 2018, the age standardized
incidence rate below 29 years is 0.46/100 000 women and
below 24 years, is as low as 0.06 per 100 000 women.
1 last 5 years.
There-fore, screening should not be initiated before 25
years in asymptomatic women, regardless of the age of ini-
tiation of sexual activity/resources. In limited resource
settings, screening is recommended after the age of 30
years. If only one round of screening is
feasible, it should be targeted at women between the age of
14
35–40 years.
The upper age limit is decided based on life expec-tancy.
If screening was continued till 90 years, the estimated
chance of preventing cervical cancer was only 1.6 cases per
20
1000 women with substantial bur-den of colposcopies.
Therefore, women over 65 years with previously adequate
negative screening and no history of CIN2+ within the last
20,21
20 years need not be screened further. Adequate
negative prior screening is defined as three consecutive
negative cytology or two consecutive negative co-tests
within
10 years, with the last test having taken place within the
20,21
In women who have undergone
hysterectomy with a report of CIN2+ lesions, screen-ing
should be continued for 20 years from the age of surgery.
Women who underwent hysterectomy for any other benign
disease need not continue screening.
The screening age and periodicity recommenda-tions for
each resource setting are depicted in Table 2.

Table 2 Resource-based cervical cancer screening recommendations

Good resource settings Limited resource settings
Target age group (years) 25–65 years 30–65 years (NB: In post-menopausal
women, screening with VIA may not
be as effective)
Age to start (years) Cytology at 25 years
Primary HPV testing/co-testing VIA at 30 years
at 30 years
Frequency Primary HPV testing or co-testing – Every 5 years (at least 1–3 times in a
every 5 years lifetime)
Cytology alone – every 3 years
Age to stop (years) 65 years, with consistent negative results in last 15 years
Women with no prior screening should undergo tests once at 65 years and, if
negative, they should exit screening
Follow up after treatment (method HPV testing (preferred) or cytology or VIA, 12 months
and interval) colposcopy, 12 months
Screening following abnormal
reports ≥ CIN 2+, irrespective of 20 years
method of treatment
Screening in hysterectomized
women Following hysterectomy in which cervix was removed for benign causes: no need for
screening, unless there is history of previous cervical intraepithelial neoplasia.

Absence of cervix must be confirmed by clinical records or examination. If

Follow up in women with CIN in
hysterectomy HPE report
Screening of immunocompromised
women
indications for hysterectomy unclear, screening may be performed at
clinician’s discretion.
Need to be screened with HPV at 6 months and 18 months.
Start within 1 year of initiation of Start within 1 year of initiation of
sexual activity or as soon as HIV is sexual activity or as soon as HIV is
detected in sexually active women detected in sexually active women
HPV testing/co-testing/cytology/ VIA/affordable HPV testing
VIA (if available)
Every 2–3 years Every 3 years (at least twice as often
as general population)

© 2019 Japan Society of Obstetrics and Gynecology 205

N. Bhatla et al.
VIA every 5 years, starting from 30 upto 65 years is the
recommended screening modality by Government of
6
India. The accuracy of VIA in postmenopausal women
decreases as the transformation zone (TZ) recedes into the
endocervical canal. Other resource-based guidelines have
recommended screen-ing at least one to three times till the
8,9
age of 50 years. In a randomized trial in India, a single
round of VIA based screening led to 30% reduction in
cervical cancer incidence and a 42% reduction in cervical
cancer mortality. The maximum reduction in the incidence
of cervical cancer was seen among women aged 30–39
21
years. Another study demon-strated 25–31% reduction in
the lifetime risk of invasive cervical cancer with VIA, 30–
36% reduction with HPV DNA testing, carried out once at
the age of 35 years. Two rounds of screening done at the
22
age of 35 and 40 years reduced lifetime risk by 40%.
Screening paradigms
The efficacy of the cervical cancer screening modali-ties;
co- testing, primary HPV testing, cytology and VIA are
investigated in large clinical trials and based on the
generated evidence, clinical practice points are formulated
as shown in Table 3.
Co-testing with HPV testing and cytology
The combination of a highly sensitive validated HPV test
with highly specific cytology every 5 years is the most
effective and preferred screening modality in India. Co-
testing can detect 51% more cases of CIN2/3 or invasive
23
cancer than cytology alone. Schiffman et al. investigated
the relative performance of each component and found that
the first co-test could detect 67.9% cases likely to progress
in next 10 years. Only a small fraction, i.e., 3.5% cases of
preinvasive and 5.9% cases of invasive disease were
detected in women who were HPV−/cytology+ results and
15
were actually benefited by adding cytol-ogy to HPV test.
Although this number may be small (five cases/million
women/year) and the com-bination is costly but considering
that in India major-ity of the women will be possibly
having infrequent screening or even once in a life-time
screening, it is prudent to use co-testing. Management of
women with abnormal co-testing based on specific
abnormal-ity and resource availability is depicted in Figure
2.
Primary HPV testing
Primary HPV testing alone has replaced cytology in the
cervical cancer screening programs in various
206
24,25
countries including Australia and some parts of Europe.
In an RCT the detection rates of high-
grade precancer/cancer (CIN2+) lesions in the initial rounds
were higher in the HPV arm than cytology but were either
same or lower in the subsequent rounds of screening with
greater sensitivity (ratio = 1.29, 95% CI, 1.18–1.39) and
26
lower specificity (ratio = 0.94, 95% CI 0.92–0.96).
Another study observed the cumulative incidence rates of
CIN3 and cancer in HPV negative women aged >25 years
as low as 0.34% (95% CI, 0.10–0.65), in cytology-negative
women 0.78%(95% CI, 0.53–1.09) and least in co-test
27
negative women 0.30% (95% CI, 0.05–0.62). How-ever,
this small decrease in cancer risk associated with co-testing
may not be affordable in developing coun-tries with
important competing health priorities. HPV test also
provides better reassurance that high-grade lesion is
currently absent and thus provides an oppor-tunity to safely
extend the screening intervals to 5 years or even 10 years.
Compared to Pap test, HPV test misses fewer
28
adenocarcinomas or adenocarci-nomas in situ.
The specificity and positive predictive value of HPV test
are low. To reduce referral to colposcopy, HPV positive
women may be triaged with another test (cytology or VIA
or HPV 16/18 genotyping), and triage positive cases may
29
then be referred to colpos-copy. The risk of CIN3+ in
HPV 16/18 positive cases is 21.1% while it is 5.4% with
27
other non-16/18 strains. Hence HPV 16,18 positive
women may be immediately referred to colposcopy and
those with other strains may have cytology or VIA. In
12
good resource settings, women should be screened every 5
years with an approved HPV test or co-test. FOGSI Good
Clinical Practice Recommendations (GCPR) rec-ommends
VIA as a feasible option to triage HPV posi-tive cases
where genotyping or good quality cytology are not
available. Direct colposcopy is acceptable for noncompliant
cases (Fig. 2).
Cytology as the primary screening modality
Cytology-based programs have reduced the burden of
cervical cancer in developed countries. The sensi-tivity of a
single Pap test for detection of CIN2/3 reportedly ranges
30
from 51% to 53% but the specificity is as high as 96.3%.
Therefore, currently cytology is best used as a triage tool
for HPV positive cases to reduce unnecessary
12
colposcopy. The GCPR provide algorithms for the
management of women with both
squamous and glandular abnormalities in different age
10,11
groups.
© 2019 Japan Society of Obstetrics and Gynecology
 Cervical Cancer Screening & Management of CIN

†
Table 3 Resource-based good clinical practice recommendations for cervical cancer screening and treatment of preinvasive lesions

FOGSI good clinical practice recommendation

1. In limited resource settings, women should be screened with VIA, at least one to three times in a lifetime, every 5 years
(Level A).
In good resource settings, women should be screened every 5 years with a validated HPV test or co-test (HPV +
cytology) (Level A).
2. HPV positive cases should be triaged with either HPV genotyping or cytology. Referral to colposcopy if HPV 16/18
positive or cytology result is abnormal (ASCUS or worse). Others should have a repeat HPV test after 1 year.
Colposcopy referral if the HPV test is persistently positive (Level A).
In limited resource settings, VIA can be used to triage HPV positive women. Direct colposcopy is an
acceptable option where compliance is an issue (Level B).
3. Women with co-testing (HPV + cytology)
Women with both HPV positive and cytology abnormal report should be advised colposcopy and directed biopsy
(Level A).
Women with HPV positive and cytology negative report should be advised HPV genotyping or repeat co-testing
after 1 year, depending on the availability of resources (Level B).
Women with HPV negative and cytology abnormal report should be advised further follow-up depending on the type of
cytological abnormality. All cases with ASC-H, HSIL, atypical glandular cells or suspected cancer on cytology
should be referred to colposcopy irrespective of HPV test result (Level A).
4. Women with ASCUS cytology:
Women aged 30–64 years with ASCUS cytology should be triaged preferably with HPV test, or if not
available with repeat cytology at 1 year (Level A).
Younger women should be followed up with annual cytology for 2 years (Level A).
If compliance is a concern, or HPV test is not available, colposcopy/VIA and directed biopsy is an acceptable option for
all age groups (Level C).
Women with LSIL cytology:
Women with LSIL cytology should be managed preferably with colposcopy (Level A).
If compliance is an issue, ‘See-and-Treat’ approach is an acceptable option (Level C).
Colposcopy in younger women with LSIL cytology should be done only when cytology results are persistent or severe
(Level B).
In postmenopausal women, LSIL cytology should be triaged with either colposcopy or reflex HPV or repeat cytology
(Level B).
Women with ASC-H or HSIL cytology:
Colposcopy should be done with special emphasis on visualization of the transformation zone (TZ) and
endocervical evaluation for managing women with ASC-H or HSIL (Level A).
Women with atypical glandular cells with any of the sub-categories should be evaluated with colposcopy and
directed biopsy along with endocervical sampling. Cold knife colonization or LEEP is required if the cytology is
repeatedly showing glandular abnormalities (Level A).
If colposcopy normal endometrial and adnexal pathology should be ruled out (Level B).
5. VIA based screening
VIA based screening is the most feasible modality in low resource settings and also in good resource settings with high
volume of patients (Level B).
VIA positive cases, depending on their compliance and need, can be either managed with colposcopy and biopsy or
can be treated in the same sitting with ablation if eligibility criteria for ablative treatment are fulfilled (Level C).

6. HIV positive women can be screened with any available modality (Level A).
Screen positive HIV positive women should be managed in the same way as general population (Level A).
7. In women with CIN1 preceded by ASCUS or LSIL cytology treatment in form of excision or ablation is
warranted if it persists for 2 years (Level A).
In women with CIN1 preceded by ASC-H or HSIL cytology should be followed up either with yearly co-testing or
with 6-monthly cytology for 2 years. If the abnormality persists, a diagnostic excisional procedure should be advised.
Alternatively, if the patient cannot follow up, a diagnostic excisional procedure can be recommended (Level B).

Patients with CIN2/3 who have type I transformation zone on colposcopy should be managed by either excision
(LEEP) or ablation of the TZ (cryotherapy or thermal ablation). Conversely, if TZ is type II or III on colposcopy or
endocervical sampling shows CIN2/3 or in recurrent CIN, excisional procedure (either cold knife conization or LEEP)
should be performed (Level B).
†Level A: Recommendations are based on good and consistent scientific evidence; Level B: Recommendations are based on limited or
inconsistent scientific evidence; Level C: Recommendations are based primarily on consensus and expert opinion.

© 2019 Japan Society of Obstetrics and Gynecology 207

N. Bhatla et al.

Figure 2 (a) Management of abnormal primary HPV testing. HR HPV, high-risk HPV; VIA, visual inspection after appli-cation of
acetic acid; NILM, negative for intra epithelial lesion or malignancy; CIN, cervical intra epithelial neoplasia.
(b) Management of abnormal co-testing. ASCUS, atypical squamous cells of undetermined significance; HSIL, high-grade
squamous intra epithelial lesion.

Management of cytology showing atypical squamous cells
with undetermined significance Atypical squamous cells
with undetermined significance (ASCUS) cytol-ogy is seen
in 2.8% of women between 30 and
64 years and 23–74% of these women are HPV posi-
31,32
tive. The ASCUS/LSIL Triage Study (ALTS)
investigated triage of ASCUS cytology either with
reflex HPV or repeat cytology at 6 months or immedi-ate
colposcopy. The detection of cumulative cases of CIN3+
was highest in HPV triage group (72.3%), followed by
conservative management (55%), and least(54.6%) in
immediate colposcopy group. HPV tri-age could detect
92.4% of the CIN3 cases. Repeat cytology needed two
visits to demonstrate similar

208 © 2019 Japan Society of Obstetrics and Gynecology

sensitivity (95.4%) and would have to refer a large number
of cases (67.1%) for colposcopy and thus was not cost-
33
effective compared to HPV testing. There-fore, HPV
triage is equally sensitive as immediate col-poscopy and
32
also reduces unnecessary colposcopy referrals. Women
aged 30–64 years with ASCUS should be triaged
preferably with HPV test or if not available with repeat
cytology at 1 year and women ≤30 years with ASCUS or
low grade squamous intra-epithelial lesion (LSIL) should
be followed with annual cytology for 2 years. However,
where compli-ance is a concern or HPV testing is not
available, col-poscopy/VIA and directed biopsy is
acceptable for all age groups (Fig. 3).
Management of LSIL cytology In the ALTS trial, 1572
women with LSIL were followed either with colpos-copy
or HPV or with repeat cytology at 6 months. More than
80% were HPV positive thus obviating the need for HPV
triage in women with LSIL.
34
Thus col-poscopy is
preferred for managing women with LSIL cytology. If
colposcopy is not readily available or if
Figure 3 Management of abnormal cytology test. (a) Management of ASCUS. ASCUS, atypical squamous cells of un determined
significance; LSIL, low grade squamous intra epithelial lesion; VIA, visual inspection after application of acetic acid; HSIL, high-
grade squamous intra epithelial lesion. (b) Management of LSIL. (c) Management of ASC-H/ HSIL. ASC-H, atypical squamous
cells cannot exclude HSIL. (d) Management of HSIL.
© 2019 Japan Society of Obstetrics and Gynecology
Cervical Cancer Screening & Management of CIN
the accuracy of cytology is uncertain, HPV testing may be
used for triage. If compliance is an issue, ‘See-and-Treat’
approach is acceptable (Fig. 3). Colposcopy and treatment
may do more harms than benefits in women aged <30 years
because of higher regression (70% with CIN2) and lower
35
progression (0.5% with CIN3) rates. Therefore,
colposcopy should be done with severe/persistent cytology
results. Immediate colposcopy is also preferred in post-
menopausal women. However, due to likelihood of
regression of transformation zone (TZ), use of endocervical
specu-lum for clear delineation is highly desirable.
Management of women with ASC-H (atypical squamous
cells: Cannot exclude high-grade squamous intraepithelial
lesion) or high-grade squamous intraepithelial lesion
cytology HPV triage is not advisable because 65.8% of
ASC-H and 89–97% of high-grade squamous intra-
epithelial lesion (HSIL) cytology are HPV positive and are
managed with immediate colposcopy with endo-cervical
35
evaluation. If TZ is not visualized, diagnostic excisional
procedure is preferred except during
209
N. Bhatla et al.
Figure 4 Management of abnormal VIA test. VIA, visual inspection of cervix after application of acetic acid; CIN, cervical intra
epithelial neoplasia.
pregnancy. In noncompliant cases, SVA with cervical
ablation is acceptable if criteria is fulfilled, but without a
diagnostic specimen (Fig. 3). In younger women with
normal colposcopy and Type-I TZ after a high-grade
smear, regular follow-up is emphasized and a diagnostic
excisional procedure is recommended when an abnormal
screening test persists for 2 years.
Management of women with glandular cell abnormalities
About 30% women aged >40 years with
atypical glandular cytology will have preinvasive or
36,37
invasive disease. Majority of these lesions are squa-
mous lesions but the probability of finding endometrial
malignancy is 2–3%, cervical adenocarcinoma in situ is 3–
4%, invasive adenocarcinoma cervix is 2% and cervi-cal
38
squamous cell carvcinoma is 1%. Hence, a thor-ough
evaluation to rule out endometrial, ovarian or cervical
38
malignancy is essential. Women with atypi-cal glandular
cells with any of the sub-categories should be evaluated
with colposcopy and directed biopsy along with
endocervical sampling (Fig. 3).
VIA as the primary screening modality
VIA is a promising tool for screening in low-
resource settings because it is economical, with minimal
39,40
loss to follow up. The pooled sensitiv-
ity and specificity of VIA to detect CIN2+ ranged
210
19
from 16% to 82.6%, and 82.1% to 96.8%, respec-tively.
VIA when compared with cytology has higher sensitivity
(90% vs 50%) but lower specificity
(37% vs 93.5%) thus raising the burden of false posi-tive
19,40,41
cases. VIA permits an SVA for screening
in LMICs because of instant results and linkage with
7,8,16
treatment. VIA-positive cases can be either
managed with colposcopy and biopsy or can be treated in
the same sitting with ablation, if criteria are fulfilled (Fig.
4).
Screening in HIV Infected Women
Infection with HIV increases a woman’s lifetime risk of
developing cervical cancer and approxi-mately 10% HIV
positive women develop CIN2+ each year compared to 1–
42
2% HIV negative women. The prevalence of invasive
cervical can-
cer was 4% and CIN2+ lesions was 8.5% among HIV
positive women.
42,43
Women who are HIV pos-
itive should begin screening with any of the screen-ing
modalities as soon as they are diagnosed with HIV. The
expert group has endorsed the recommen-dations by WHO
and ASCO that the screening frequency in HIV+ women
7,9
should be twice as often as the general population.
ART(antiretroviral
© 2019 Japan Society of Obstetrics and Gynecology
 Cervical Cancer Screening & Management of CIN

Figure 5 Management of women with CIN on histology. CIN, cervical intraepithelial neoplasia; ASC-H, atypical squa-mous cells
cannot exclude HSIL; HSIL, high-grade squamous intra epithelial lesion. (a) Management of women with CIN-1. (b) Management
of women with CIN2/3

therapy) services should be integrated with cervical Management of CIN

44
cancer screening program. Screen positive cases
should be managed in the same way as general The aim of CIN management is to prevent progression
population (Tables 2 and 3). of disease while avoiding over-treatment of lesions that

© 2019 Japan Society of Obstetrics and Gynecology 211

N. Bhatla et al.
 45
might otherwise regress. CIN1 preceded by ASCUS or
LSIL cytology is likely to progress to CIN2/3 in 4–13%
cases in next 2 years. Thus treatment by ablation or exci-
sion is warranted if the abnormality persists for 2 years.
46
The risk of progression of CIN1 when pre-ceded by ASC-H
or HSIL is more than 15%, thus imme-diate colposcopy
46
examination is advised. About 40–58% of CIN2 will
regress and only 22% will progress to CIN3; the
cumulative incidence of invasive disease in untreated CIN3
47
is 31% after 10 years. Patients with CIN2/3 with type-I or
type-II TZ on colposcopy may be treated by excision or
ablation. Risk of invasive cancer is as high as 7% in
women with type-III TZ on colposcopy or in recurrent
CIN, therefore excisional procedures with either
LLETZ/LEEP (large loop excision of TZ) or cold knife
colonization are performed and ablation should be avoided
47
in such situation.
In women ≤30 years the probability of regression is
higher and 70% of CIN2 lesions would regress. There-fore,
conservative management is preferred and treat-ment is
45,47
advisable when CIN2 persists for over 24 months. The
management of CIN depending on the severity and age
group is depicted in Figure 5 and summarized in Table 3.
The FOGSI recommendations have been drafted to
empower healthcare professionals with evidence-based
simplified algorithms applicable in daily practice regard-
less of available resources. However, dissemination to
remote areas still remains a challenge. Expanding access
through newer technologies such as mHealth is being
considered.
Conclusion and Perspective
Implementation of universal screening for cervical can-cer
irrespective of resources is the need of the hour. The
screening effort should be linked with optimum treatment
and follow-up. The FOGSI recommenda-tions not only
empower clinicians with the option of using any available
modality, but also provide a com-prehensive overview of
follow-up and treatment. Thus they are suitable not only for
India but also for many LMICs with similar diverse
practices and inequality.
Acknowledgments
The contributions of Sankaranarayanan R, Ahuja M, Joshi
R, Purandare N and Natarajan J to development of the
GCPR are deeply appreciated.
212
Contributions of PSI (Population Services Interna-tional
India) are appreciated for arranging the expert group
meeting.
Disclosure
None declared.
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214 © 2019 Japan Society of Obstetrics and Gynecology