D S a ana Kuma i Chin am. (2025). Non Squamous His ology in Ce ical Cance : P ognos ic Insigh s om
Ins i u ional S udy. MAR Oncology and Hema ology. (2025) 5:08
Non Squamous His ology in Ce ical Cance : P ognos ic Insigh s om
Ins i u ional S udy
D Mohanap iya A1, D S a ana Kuma i Chin am*
1. Senio Residen , Depa men o Radia ion Oncology, GSL Medical College, Rajahmund y, India.
*Co espondence o: D S a ana Kuma i Chin am, Assis an p o esso , Depa men o Radia ion
Oncology, GSL Medical College, Rajahmund y, India.
Copy igh .
© 2025 D S a ana Kuma i Chin am This is an open access a icle dis ibu ed unde he C ea i e Commons
A ibu ion License, which pe mi s un es ic ed use, dis ibu ion, and ep oduc ion in any medium, p o ided
he o iginal wo k is p ope ly ci ed.
Recei ed: 02 Sep 2025
Published: 10 Sep 2025
MAR Oncology and Hema ology (2025) 5:08
Resea ch A icle
D S a ana Kuma i Chin am, MAR Oncology and Hema ology (2025) 5:08.
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D S a ana Kuma i Chin am. (2025). Non Squamous His ology in Ce ical Cance : P ognos ic Insigh s om
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Abs ac
Backg ound: Non-squamous his ologies in ca cinoma ce ix, including adenoca cinoma (AC)
and adenosquamous ca cinoma (ASC), ep esen a clinically and biologically dis inc subg oup
wi h epo edly in e io ou comes compa ed o squamous cell ca cinoma (SCC). Limi ed da a
exis ega ding hei ea men ou comes in he Indian popula ion. This s udy aimed o e alua e
he clinical p o ile, ea men esponse, pa e ns o ailu e, and su i al ou comes in pa ien s
wi h non-squamous ca cinoma o he ce ix ea ed a ou e ia y ca e cen e .
Me hods: This e ospec i e s udy included pa ien s wi h his ologically con i med non-
squamous ce ical cance ea ed wi h de ini i e o adju an adio he apy be ween Janua y
2020 and Decembe 2024. Clinical cha ac e is ic, pa hological, and ea men de ails we e
collec ed. Disease- ee su i al (DFS), o e all su i al (OS), and pa e ns o ailu e we e
analyzed. S a is ical analysis was pe o med using he unpai ed - es .
Resul s: A o al o 34 pa ien s we e included, wi h a mean age o 48.6 yea s. Adenoca cinoma
was he mos common his ology (21 pa ien s ,61.8%), ollowed by adenosquamous ca cinoma
in 7 (20.6%) and o he a e sub ypes (6 pa ien s,17.6%). The mos common s age a he
p esen a ion was FIGO IIB. Twel e pa ien s (35.3%) unde wen p ima y su ge y ollowed by
adju an he apy, and 22 (64.7%) ecei ed de ini i e concu en chemo adia ion (CCRT).
A e a median ollow-up o 28 mon hs, he mean DFS and OS we e 27.2 and 29 mon hs,
espec i ely. Pa ien s unde going su ge y had nume ically highe DFS and OS (30.4 and 34.3
mon hs) compa ed o hose ecei ing de ini i e CCRT (25.5 and 26.1 mon hs), hough no
s a is ically signi ican (p = 0.63 o DFS; p = 0.34 o OS). Failu e pa e ns showed sligh ly
highe ecu ence in he su ge y g oup (5 pa ien s, 41.6%) compa ed o he CCRT g oup (3
pa ien s, 13.6%).
Conclusion: Non-squamous ce ical cance s exhibi ela i ely poo e ou comes and dis inc
ailu e pa e ns. While p ima y su ge y may o e a su i al ad an age in ea ly-s age disease,
CCRT emains he mains ay o ad anced s ages. Tailo ed ea men app oaches and
molecula p o iling a e wa an ed o op imize ou comes in his high- isk subg oup.
Key wo ds: Ce ical cance , adenoca cinoma, adenosquamous ca cinoma, chemo adia ion,
su ge y, su i al, ecu ence pa e n, non-squamous his ology.
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In oduc ion
Ce ical cance emains a majo global heal h bu den, anking as he ou h mos common cance among
women wo ldwide. Acco ding o GLOBOCON 2022, he e we e app op ia ely 662301 new cases and 348874
dea hs globally, wi h a signi ican p opo ion in low- and middle- income coun ies [1]. In India, ce ical
cance con inues o be he second mos common cance among women, wi h app oxima ely 127526 new cases
and 79906 dea hs [2].
His ologically, squamous cell ca cinoma (SCC) is he p edominan sub ype, accoun ing o app op ia ely 80%
o cases globally, while adenoca cinoma (AC) and adenosquamous comp ises a ound 15-20%[3]. In India, he
dis ibu ion sligh ly di e s, wi h squamous his ology accoun ing o app oxima ely 89.5% o ce ical cance ,
adenoca cinoma o 6-7%, and adenosquamous ca cinoma o abou 1%[4]. Al hough ela i ely uncommon,
he incidence o adenoca cinoma is ising, pa icula ly in younge women, due o i s associa ion wi h high-
isk HPV ype 18 and limi ed cy ology based sc eening p og ams.
Non squamous his ologies, including adenoca cinoma and adenosquamous ca cinoma, exhibi dis inc clinical
and biological cha ac e is ics compa ed o SCC. They a e o en conside ed less adiosensi i e, ha e a highe
likelihood o p esen ing a an ad anced s age, and g ea e endency o dis an me as ases, pa icula ly lungs
and pa a ao ic lymph nodes [5,6]. S udies ha e epo ed in e io local con ol, disease- ee su i al (DFS),
and o e all su i al (OS) o adenoca cinoma compa ed o SCC, e en wi h s anda d concu en chemo
adia ion (CCRT) p o ocols[7]. Howe e , ea men s a egies o non-squamous his ologies emain
con o e sial, wi h some expe s ad oca ing o p ima y su ge y o in ensi ied sys emic he apy in selec ed
cases.
Indian da a on non-squamous ce ical cance s a e spa se, as mos s udies p ima ily ocus on SCC. Some
e ospec i e s udies sugges ha adenoca cinoma and adenosquamous ca cinoma ha e wo se ou comes and
a dis inc ecu ence pa e n. Gi en hese challenges, ou s udy aims o analyze he clinical p o ile, ea men
esponse, pa e ns o ailu e, and su i al ou comes in pa ien s wi h non-squamous ca cinoma o he ce ix
ea ed a ou ins i u ion.
Ma e ial and Me hods
S udy design
This is a e ospec i e obse a ional s udy conduc ed a he Depa men o Radia ion Oncology , ou ins i u e,
a e ia y ca e cen e in India. The s udy was app o ed by he ins i u ional E hics Commi ee.
All pa ien s diagnosed wi h ca cinoma ce ix wi h non-squamous his ology who ecei ed de ini i e o
adju an adio he apy be ween 2020- 2024 we e included in he analysis. Pa ien s wi h his ology o squamous
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cell ca cinoma we e excluded.
Da a collec ion
Clinical and ea men de ails we e collec ed om hospi al medical eco ds and adio he apy depa men
egis y. Demog aphics , clinical p esen a ion, his opa hology, ea men de ails ( su ge y de ails, ype o
adia ion- adical o adju an , EBRT echniques & dose, concu en chemo he apy, b achy he apy) and ollow
up da a i.e. de ails o ecu ence (si e and ime), disease s a us, su i al ou come.
T ea men P o ocol
Pa ien s wi h ea ly-s age who we e ope able unde wen adical hys e ec omy wi h pel ic lymph node
dissec ion. Su gical his opa hology was e iewed o isk ac o s including umou size, deep s omal in asion,
posi i e ma gins, pa ame ial in ol emen , lympho ascula space in asion (LVSI), and lymph node s a us.
Pa ien s wi h high- isk o in e media e- isk ea u es pos su ge y ecei ed adju an ex e nal beam adio he apy
(EBRT) wi h o wi hou concu en chemo he apy (CCRT). De ini i e CCRT is ecei ed by pa ien s who we e
unsui able o su ge y o wi h locally ad anced disease.
All pa ien s unde wen pel ic EBRT o a dose o 45-50.4 Gy in 25-28 ac ions, using ei he 3D con o mal
adio he apy (3DCRT) o in ensi y modula ed adio he apy (IMRT). Concu en chemo he apy wi h weekly
Cispla in (40mg/m2) was gi en o eligible pa ien s wi h adequa e enal unc ion and hema ological pa ame e s.
High-dose a e in aca i a y b achy he apy (ICRT) was adminis e ed in 3 ac ions, o ally ~21Gy, p esc ibing
o poin A.
Follow-up p o ocol and Ou come Assessmen
Pa ien s we e ollowed up e e y 3 mon hs o he i s 2 yea s,e e y 6 mon hs o he nex 3 yea s, and annually
he ea e , o un il disease ecu ence o dea h. Follow-up assessmen s included clinical examina ion, imaging
(ul asound/CT/MRI as app op ia e) when indica ed. Ou comes measu ed included, DFS i.e. Time om
ea men comple ion o ecu ence o las ollow-up, OS i.e. Time om diagnosis o dea h om any cause o
las ollow-up and Pa e n o ailu e - Local, egional, o dis an ecu ence.
Resul s
A o al o 34 pa ien s wi h non-squamous his ology o ca cinoma ce ix we e ea ed a ou ins i u ion be ween
Janua y 2020 and Decembe 2024. The mean age a p esen a ion was 48.6 yea s ( 33-70 yea s), wi h he
majo i y o pa ien s (14) alling in he 41-50-yea age g oup, ollowed by hose aged 31-40 (8) and 51-60 yea s
(8). The mos common s age a p esen a ion was FIGO s age IIB (13, 38.2%), ollowed by IIIC1 (8, 23.5%).
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Among he his ological sub ypes, adenoca cinoma was mos equen , seen in 21 pa ien s (61.8%), ollowed
by adenosquamous ca cinoma in 7 pa ien s (20.6%). Ra e sub ypes (17.6%) included adenoca cinoma wi h
neu oendoc ine di e en ia ion (1 pa ien , 2.9%), papilla y se ous ype adenoca cinoma (1, 2.9%),
neu oendoc ine ca cinoma (1, 2.9%), papilla y squamo ansi ional ca cinoma (1, 2.9%),
squamo ansi ional ca cinoma (1, 2.9%), and leiomyosa coma (1, 2.9%). Twel e pa ien s (35.3%) unde wen
p ima y su ge y ollowed by adju an he apy, while he emaining 22 (64.7%) ecei ed de ini i e CCRT
(Table 1).
A e a median ollow-up o 28 mon hs, he o e all mean DFS o he en i e coho was 27.2 mon hs, and he
mean OS was 29 mon hs. In he su gical subg oup, he mean DFS and OS we e 30.4 and 34.3 mon hs,
espec i ely. Fi e pa ien s in his g oup de eloped disease ecu ence, wi h a mean ime o local elapse o 7.3
mon hs and dis an ailu e a 5.7 mon hs. The mean OS o hose who ailed in he su gical subg oup was 14.6
mon hs. Among pa ien s ea ed wi h de ini i e CCRT, he mean DFS and OS we e 25.5 mon hs and 26.1
mon hs, espec i ely (Table 2). Th ee pa ien s expe ienced ecu ence in his g oup, wi h mean ime o local
ailu e o 9 mon hs and dis an ailu e o 10.5 mon hs; he mean OS o h ee pa ien s was 12.7 mon hs. O e all,
4 pa ien s had isola ed local elapse, 2 de eloped dis an me as ases and 2 expe ienced bo h local and dis an
ailu e. Common si es o dis an ailu e being li e ollowed by lung and bone.
Al hough he mean DFS and OS we e longe in pa ien s unde going p ima y su ge y (30.4 and 34.3 mon hs,
espec i ely) compa ed o hose ea ed wi h de ini i e CCRT (25.5 and 26.1 mon hs, espec i ely), hei
di e ence did no each s a is ical signi icance, by using unpai ed - es show p=0.63 o DFS and p=0.34 o
OS. Howe e , he nume ical end a ou s he su ge y g oup in bo h DFS and OS. Addi ionally, ailu e pa e n
di e ed sligh ly be ween wo g oups, wi h a nume ically highe ailu e a e obse ed in he su gical g oup (5
pa ien s, 41.6% s 3 pa ien s, 13.6%), possibly e lec ing his ological agg essi eness.
Table 1. Pa ien Cha ac e is ics and T ea men de ails (n=34)
Cha ac e is ic
Numbe o pa ien s (n)
Pe cen age (%)
Age a p esen a ion (yea s)
Mean / Range
48.6 / 33 - 70
31 - 40
8
23.5
41 - 50
14
41.2
51 - 60
8
23.5
61 - 70
4
11.8
His ology
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Adenoca cinoma (AC)
21
61.8
Adenosquamous ca cinoma
7
20.6
AC wi h Neu oendoc ine di e en ia ion
1
2.9
AC wi h papilla y se ous ype
1
2.9
Leiomyosa coma
1
2.9
Neu oendoc ine Ca cinoma
1
2.9
Papilla y Squamo ansi ional ca cinoma
1
2.9
Squamo ansi ional ca cinoma
1
2.9
FIGO S age (2018)
I
5
14.7
IIA
4
11.8
IIB
13
38.2
IIIB
1
2.9
IIIC1
8
23.5
IVA
3
8.9
P ima y ea men
De ini i e CCRT
22
64.7
P ima y su ge y + Adju an RT/CCRT
12
35.3
Table 2: Su i al Ou comes
G oup
Mean DFS (mon hs)
Mean OS (mon hs)
En i e coho
27.2
29
Su ge y
30.4
34.3
CCRT
25.5
26.1
Discussion
Non-squamous his ologies in ca cinoma ce ix, including adenoca cinoma, adenosquamous ca cinoma, and
a e sub ypes such as neu oendoc ine o sa coma oid a ian s, ep esen a biologically and clinically dis inc
subg oup compa ed o he p edominan squamous cell ca cinoma. In ou s udy o 34 pa ien s ea ed be ween
Janua y 2021 and Decembe 2024, adenoca cinoma was he mos common sub ype (61.7%), ollowed by
adenosquamous ca cinoma (20.5%) and o he a e a ian s.
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The median age a p esen a ion was 48.6 yea s, wi h he majo i y in he 41–50 age g oup. This aligns wi h
p e iously epo ed ends indica ing ha adenoca cinoma ends o p esen in sligh ly younge pa ien s
compa ed o squamous his ology [8]. Mos pa ien s p esen ed a ad anced s ages, wi h IIB being he mos
common, ollowed by IIIC1.
The op imal managemen o non-squamous his ologies emains con o e sial due o hei ela i ely lowe
adiosensi i i y and highe endency o dis an ailu e. In ou coho , 12 pa ien s unde wen p ima y su ge y,
while 22 ecei ed adical concu en chemo adio he apy. Pa ien s ea ed wi h su ge y showed a nume ically
highe mean OS (34.3 mon hs) and DFS (30.4 mon hs) compa ed o hose who ecei ed adical CCRT (OS
26.1 mon hs; DFS 25.5 mon hs). Despi e his end, he di e ence did no each s a is ical signi icance, likely
due o he small sample size.
Failu e pa e ns also a ied be ween he wo g oups. Among su gical pa ien s, 5 expe ienced elapse (local o
dis an ), wi h a sho e ime o dis an ailu e (mean: 5.7 mon hs). In he CCRT subg oup, 3 pa ien s elapsed,
wi h a sligh ly delayed mean ime o dis an ailu e (10.5 mon hs), al hough hese di e ences we e no
s a is ically signi ican . The OS o hose who expe ienced elapse was no ably poo in bo h g oups (14.6
mon hs pos - elapse in he su ge y g oup s. 12.7 mon hs in CCRT g oup).
Ou indings a e in conco dance wi h global da a sugges ing ha adenoca cinoma and adenosquamous
his ologies ha e in e io local con ol and su i al ou comes compa ed o squamous ca cinoma. S udies such
as by Yokoi e al. and Seamon e al. ha e highligh ed he limi a ions o adio he apy in hese sub ypes, wi h
su gical in e en ion o e ing be e con ol in ea ly-s age disease. Howe e , o locally ad anced disease,
concu en chemo adia ion emains he s anda d o ca e, hough wi h modes ou comes[9,10] [11,12].
The inc easing ecogni ion o HPV-independen pa hways, pa icula ly in non-squamous his ologies like
gas ic- ype adenoca cinoma and clea cell ca cinoma, u he unde sco es he need o molecula p o iling
and pe sonalized ea men s a egies[13]. Al hough HPV is implica ed in he pa hogenesis o mos
adenoca cinomas, ce ain sub ypes a e HPV-nega i e and ca y a wo se p ognosis[14,15].
Limi a ions
This s udy is limi ed by i s e ospec i e na u e and small sample size. Addi ionally, he his ological
he e ogenei y wi hin he non-squamous ca ego y makes ou come compa isons complex. P ospec i e
mul icen ic s udies wi h molecula co ela ion a e wa an ed o alida e he indings.
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Conclusion
Non-squamous his ologies in ca cinoma ce ix ep esen a high- isk subg oup wi h ela i ely poo e
ou comes. While p ima y su ge y may o e su i al bene i s in selec ed cases, especially in ea ly-s age
disease, he ole o chemo adia ion emains cen al in locally ad anced cases. Tailo ed s a egies, including
adju an he apy and molecula -based isk s a i ica ion, may help imp o e ou comes in he u u e.
Decla a ion o pa ien consen
Consen o ms ob ained om all pa ien s app op ia ely in which hey ha e gi en hei consen o clinical
in o ma ion o be epo ed in he s udy.
Funding
Nil.
Con lic s o in e es
The e a e no con lic s o in e es .
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Med onic
