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LETTERS TO THE EDITOR

Bacterial Vaginosis andInflammatory Response Showed Association With Severity ofCervical Neoplasia inHPV-Positive Women

Dear Bedrossian:

With great interest we have read the article “Bacterial

Vaginosis and Inflammatory Response Showed Associa-

tion with Severity of Cervical Neoplasia in HPV-Positive

Women” of Jucara Maria de Castro-Sobrinho et al. In

that article the authors find a strong correlation between

HPV induced cervical intraepithelial neoplastic (CIN)

lesions and BV, on the one hand, and with the presence

of inflammation, on the other. The association with the

latter was even much stronger than with the former.

The authors use an awkward way of describing micro-

flora “suggestive of/compatible with” BV, which indicates

intrinsic insecurity about their diagnosis of BV. Indeed

the suggestion of using 2 clue cells per high power field

(400x magnification) does not allow to differentiate

between “Full blown” and “Partial” BV,1 which may

have a different pathogenic potential, for instance during

pregnancy.2 Also the old way to diagnose cervicitis as 30

leukocytes per HPF, and equal this to “inflammatory

response” is not adequate as it does not to allow to differ-

entiate between possible cervicitis on the one hand and

vaginitis on the other. Differentiating between mucoid

inflammation and the proportional number of free leuko-

cytes per epithelial cell would have been a much more

accurate way.3AQ2

A typical feature of full blown bacterial vaginosis is

the paradoxal absence of inflammation, despite heavy

bacterial overgrowth. This is demonstrated by a deficient

production of interleukin 1-b, lack of interleukin 8 and,

as a consequence, a striking absence of inflammatory

cells in the vaginal fluid of women with BV.4–6 In se, the

finding that BV as well as increased inflammation are

linked to the severity of HPV induced cervical lesions is

not so new, nor unexpected, as reported by several

authors. In their article, the authors put the suggestion

forward as if the inflammation described is part of BV; in

other words, they make it seem as if they describe BV

with and without inflammation.

However, from their data it is clear that they describe BV

and inflammation as two separate, unrelated findings.

Hence, uncomplicated BV essentially being a non-

inflammatory condition, this implies that it either was coin-

ciding with another inflammatory condition like trichomoni-

asis, candidosis or aerobic vaginitis (AV), or that they failed

to describe another frequent infectious condition of the

vagina which is also devoid of lactobacilli, but, as opposed

to BV, also elicits a severe inflammatory response in the

majority of cases: aerobic vaginitis.4 Moreover, besides elic-

iting a severe interleukin response, AV also produces high

levels of sialidase similar to BV.5

All too often ignoring thiscondition causes confusion and inaccurate conclusions, as

we think is likely to be the case in this article too.

In recent work, after differentiating between both con-

ditions, we found AV, but Not BV to be a strong predic-

tor of CIN in 889 Portuguese women, confirming this

inflammatory condition may be at least as important as

noninflammatory BV in the pathogenesis of HPV induced

cervical lesions (Table T1I). Finally, as is also suggested by

the authors themselves, Not BV, but rather increased pH

Conflict of interest: No conflicts of interest to declare.AQ7Funding: No grants or funds were received for the elaboration of this

letter.AQ8*Correspondence to: Pedro Vieira Baptista, Rua Jose Pinto Miranda

14, 2500-287 Caldas da Rainha, Portugal. E-mail: [email protected]

Received 10 January 2016; Accepted 26 January 2016DOI: 10.1002/dc.23453Published online 00 Month 2016 in Wiley Online Library (wileyonli-

nelibrary.com).

VC 2016 WILEY PERIODICALS, INC. Diagnostic Cytopathology, Vol. 00, No 00 1

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and lack of lactobacillus could be the key promotor of

HPV propagation in the human cervix.

Hence, we think these authors missed an important

opportunity to show that AV may play an important role

in the pathogenesis of severe CIN lesions in HPV

infected women, and maybe even more important than

uncomplicated BV.

Gilbert G. G. Donders

Femicare VZW Clinical Research for Women,

Tienen, Belgium

Department of Obstetrics and Gynecology, Regional

Hospital H Hart Tienen, Belgium

Department of Obstetrics and Gynecology, University

Hospital Antwerp, Belgium

Pedro Vieira-Baptista*

Department of Obstetrics and Gynecology, CentroHospitalar De S~ao Jo~ao, Porto, PortugalAQ3 AQ4

References

1. Donders GG. Definition and classification of abnormal vaginal

flora. Best Pract Res Clin Obstet Gynaecol 2007;21:355–373.

2. Donders GG, Van CK, Bellen G, et al. Predictive value for preterm

birth of abnormal vaginal flora, bacterial vaginosis and aerobic

vaginitis during the first trimester of pregnancy. Bjog 2009;116:1315–1324.

3. Donders GG, Marconi C, Bellen G, Donders F Michiels T. Effect

of short training on vaginal fluid microscopy (wet mount) learning.

J Low Genit Tract Dis 2014.

4. Donders GG, Vereecken A, Bosmans E, Dekeersmaecker A,

Salembier G Spitz B. Definition of a type of abnormal vaginal flora

that is distinct from bacterial vaginosis: Aerobic vaginitis. Bjog

2002;109:34–43.

5. Marconi C, Donders GG, Bellen G, Brown DR, Parada CM Silva

MG. Sialidase activity in aerobic vaginitis is equal to levels during

bacterial vaginosis. Eur J Obstet Gynecol Reprod Biol 2013;167:

205–209.

6. Cauci S, Guaschino S, De AD, et al. Interrelationships of

interleukin-8 with interleukin-1beta and neutrophils in vaginal fluid

of healthy and bacterial vaginosis positive women. Mol HumReprod 2003;9:53–58.

Table I. Fresh Wet Mount Microscopy Findings According to the Femicare Classification System3

Compared with the Cervical Cytology FindingsIndicating LSIL (Normal Cytology (NILM), ASCUS) and >LSIL (HSIL, ASC-H, Invasive Cancer) in 889 Portuguese Women Attending ColposcopyClinicAQ6

Cervical cytology (Pap) Microbial microscopy (Fresh)

LSILn5768

> LSILn5121

OR (95% CI ) P values

Candida spp. 261 (34.0%) 43 (35.5%) 1.07 (0.72–1.60) P50.8

Bacterial vaginosis 111 (14.5%) 25 (20.7%) 1.54 (0.95–2.50) P50.1Trichomonas vaginalis 19 (2.5%) 5 (4.1% 1.70 (0.62–4.64) P50.4AV (moderate or severe) 54 (7.0%) 15 (12.4%) 1.87 (1.02–3.43) P50.045

Absent lactobacilli 254 (33.1%) 48 (39.7%) 1.33 (0.90–1.97) P50.2Inflammation (moderate or severe) 209 (27.2%) 41 (33.9%) 1.37 (0.91–2.06) P50.1AV (moderate or severe) and or bacterial vaginosis 163 (21.2%) 40 (33.1%) 1.83 (1.21–2.78) P50.005

LSIL: low grade squamous intraepithelial neoplasia, HSIL: high grade squamous intraepithelial neoplasia, AV: aerobic vaginitis. OR: Odd ratio,CL95%CI: 95% confidence intervals (Chi

2or Fisher exact test).


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Diagnostic Cytopathology DOI 10.1002/dc

DONDERS AND VIEIRA-BAPTISTA

2 Diagnostic Cytopathology, Vol. 00, No 00

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AQ1: Please check whether short title is OK as typeset.

AQ2: Please spell HPV and HPF in text.

AQ3: Please provide the department/division name for affiliation “Femicare VZW Clinical Research for Women, Tie-

nen, Belgium and check whether affiliations are OK as typeset.

AQ4: Please provide the educational qualifications in author byline for all the authors.

AQ5: Please provide the volume and page range for Ref. 3.

AQ6: Please mention the significance of bold terms in Table 1.

AQ7: Please check whether conflict of interest statement is OK as typeset.

AQ8: Please check whether funding statement is OK as typeset.


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